CONSORT: May stereotactic intracavity administration of antibiotics shorten the course of systemic antibiotic therapy for brain abscesses?

PubMed

Yu, Xin; Liu, Rui; Wang, Yaming; Zhao, Hulin; Chen, Jinhui; Zhang, Jianning; Hu, Chenhao

2017-05-01

Despite advances in surgical techniques in the management of the brain abscess, continuous systemic long-term antibiotics are necessary and crucial. This study was designed to evaluate the effect of intracavity administration of high-dose antibiotics on the course of antibiotic therapy. Between 2003 and 2013, 55 patients with bacterial brain abscesses (83 abscesses) were treated with stereotactic aspiration and intracavity injection of high-dose antibiotics combined with a short course systemic antibiotic therapy. Antibiotics of one-eighth daily systemic dosage were injected into the abscess cavity after stereotactic aspiration and intravenous antibiotics were given in all patients for 3 to 4 weeks. The results of the group treated with stereotactic aspiration and intracavity injection of antibiotic solution were compared to the results of our previous patients treated by stereotactic aspiration only. Thirty-nine males and 16 females (age ranging from 1.5 to 76 years; mean age 38.7 years) were included in this study. During the follow-up (mean 26.2 months, ranging from 6 to 72 months), all the abscesses subsided with no recurrence. No adverse effects related to topical use of antibiotics occurred. At the end of follow-up, 38 patients had good outcomes, 11 had mild neurological deficits, 3 had moderate deficits, 1 was in vegetative state, and 2 died of accidents not related to brain abscesses. Compared with conventional stereotactic aspiration and drainage, intracavity injection of antibiotics shorted the course of consecutive systemic intravenous antibiotics by average 10.8 days without an increase of the recurrence rate of abscesses. Our results indicate that topical application of antibiotics into the brain abscess cavity helps to reduce the length of systemic antibiotic therapy, decreases the abscess recurrence rate, avoids the side effects of long-term high dose antibiotics, shortens the hospitalization and reduces treatment costs.

Cervical necrotizing fasciitis as a complication of acute epiglottitis managed with minimally aggressive surgical intervention: Case report.

PubMed

Gollapalli, Rajesh Babu; Naiman, Ana Nusa; Merry, David

2015-07-01

Cervical necrotizing fasciitis secondary to epiglottitis is rare. The standard treatment of this severe condition has long been early and aggressive surgical debridement and adequate antimicrobial therapy. We report the case of an immunocompetent 59-year-old man who developed cervical necrotizing fasciitis as a complication of acute epiglottitis. We were able to successfully manage this patient with conservative surgical treatment (incision and drainage, in addition to antibiotic therapy) that did not involve aggressive debridement.

Antibiotic Desensitization Therapy in Secondary Syphilis and Listeria Infection: Case Reports and Review of Desensitization Therapy

PubMed Central

Magpantay, Gil; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

2011-01-01

Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting. PMID:22187514

Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy

PubMed Central

2013-01-01

Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has

Comparative outcomes of β-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches.

PubMed

Lee, Boeun; Tam, Idy; Weigel, Bernard; Breeze, Janis L; Paulus, Jessica K; Nelson, Jason; Allison, Genève M

2015-08-01

β-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with β-lactam antibiotics as OPAT. We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug. Four hundred patients were identified (cefazolin n = 38, ceftriaxone n = 104, ertapenem n = 128 and oxacillin n = 130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; P < 0.001). Thirty-day all-cause readmissions were similar (cefazolin 21%, ceftriaxone 14%, ertapenem 20% and oxacillin 15%; P = 0.46). In 400 OPAT courses, 37 out of 50 antibiotic switches were accomplished without readmission. Adverse drug events (ADEs) were the most common reason for outpatient antibiotic switches (31/37, 84%). The ADE rate was higher for the oxacillin group (cefazolin 2.0 versus ceftriaxone 1.5 versus ertapenem 2.9 versus oxacillin 8.4 per 1000 OPAT days; P < 0.001). OPAT with β-lactam antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States.

PubMed

Thomas, Zachariah; Bandali, Farooq; Sankaranarayanan, Jayashri; Reardon, Tom; Olsen, Keith M

2015-12-01

The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Multicenter, prospective, observational, 72-hour snapshot study. Sixty-seven ICUs from 32 hospitals in the United States. Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. None. Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate. Half of all

Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections.

PubMed

Grossman, Chagai; Keller, Nathan; Bornstein, Gil; Ben-Zvi, Ilan; Koren-Morag, Nira; Rahav, Galia

2017-06-01

Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia. A cross-sectional study was conducted during January 2010-December 2011 at the medical wards of the Chaim Sheba Medical Center, Israel. The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed. A total of 681 eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in 138 (20.2%) patients (95% C.I. 17.2-23.2). The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria. Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination. Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.

[Prophylactic antibiotic treatment of neutropenic patients].

PubMed

Telekes, András; Hegedüs, Márta

2004-07-11

There is no special signs of neutropenia therefore it is usually diagnosed due to an acute infection or laboratory control. Infections acquired during chemotherapy induced myelosuppression may further deteriorate the neutropenia in cancer patients. There are many possible cause of fever in cancer patients but in case of neutropenia infection is the most likely reason. If febrile neutropenia occurs immediately broad spectrum intravenous antibiotic treatment should be initiated. Recently introduced aggressive chemotherapy protocols further increased the number of neutropenic patients. Therefore it would be important to prevent febrile neutropenia. Unfortunately the available data still insufficient to make any conclusions regarding the efficacy of short or long term prophylactic treatment. While there are generally accepted recommendations of empiric antibiotic therapy no such options are available regarding prophylactic treatments. The decision regarding prophylactic treatment (similarly to empiric therapy) should be based on the resistance of the dominant pathogens in a therapeutic unit. Several study had been conducted regarding prophylactic administration of antibiotics the results however contradictory. Considering the advantages and disadvantages, the prophylactic antibiotic treatment of neutropenic patients could be suggested only in certain cases.

[LOCAL ANTIBIOTIC THERAPY OF OSTEOMYELITIS USING NONABSORBABLE IMPLANT (REVIEW)].

PubMed

Tuleubaev, B; Saginova, D; Abiyev, T; Davletbaev, M; Koshanova, A

2016-06-01

Despite the variety of treatments available, including surgical procedures and antimicrobial therapy, bone infections is still a medical problem, because they are difficult to treat. Optimal treatment should stabilize the bone, promote the biological recovery of bone defects and destroy bacterial infection. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. In contrast, the antibiotic impregnated bone cements or fillers can act as a local anti-infective drug delivery system, which not only fills the dead space after debridement, but also provide high concentrations of antibiotics in a potential site of infection, no increase levels of antibiotics in serum. The review analyzed the use of antibiotic-impregnated cement as local delivery of antibiotics systems. Gentamycin impregnated polymethylmethacrylate (PMMA) beads, for the topical treatment of orthopedic infections clinically used for over 30 years. Application of antibiotic delivery systems using cement in the infected region is common method of treatment that continues to improve. On the downside of PMMA is that the material does not biodegradable requires subsequent invasive procedures necessary to remove the implant.

[Health economics and antibiotic therapy].

PubMed

Leclercq, P; Bigdéli, M

1995-01-01

In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications. Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions. After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation. An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria. The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations. If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician.

[The effect of group-based psychodrama therapy on decreasing the level of aggression in adolescents].

PubMed

Karataş, Zeynep; Gökçakan, Dan Zafer

2009-01-01

This study aimed to examine the effect of group-based psychodrama therapy on the level aggression in adolescents. The study included 23 students from Nezihe Yalvac Anatolian Vocational High School of Hotel Management and Tourism that had high aggression scores. Eleven of the participants (6 female, 5 male) constituted the experimental group and 12 (6 male, 6 female) were in the control group. The 34-item Aggression Scale was used to measure level of aggression. We utilized mixed pattern design including experiment-control, pre-test and post test and follow up. The experimental group participated in group-based psychodrama therapy once a week for 90 minutes, for 14 weeks in total. The Aggression Scale was administered to the experimental and control groups before and after treatment; it was additionally administered to the experimental group 16 weeks after treatment. Data were analyzed using ANCOVA and dependent samples t tests. Our analysis shows that group-based psychodrama had an effect on the experimental group in terms of total aggression, anger, hostility, and indirect aggression scores (F=65.109, F=20.175, F=18.593, F=40.987, respectively, P<.001). There was no effect of the group-based treatment on verbal or physical aggression scores. Follow-up indicated that the effect of the therapy was still measureable 16 weeks after the cessation of the therapy. Results of the present study indicate that group-based psychodrama therapy decreased the level of aggression in the experimental group. Current findings are discussed with reference to the literature. Recommendations for further research and for psychiatric counselors are provided.

Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: A meta-analysis

PubMed Central

Wang, Jun; He, Xiao Dong; Zhang, You Cheng

2012-01-01

BACKGROUND: The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial. AIM: To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures. METHODS: Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate. RESULTS: Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare. CONCLUSION: Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed. PMID:22312607

Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: a meta-analysis.

PubMed

Wang, Jun; He, Xiao Dong; Zhang, You Cheng

2012-02-01

The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial. To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures. Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate. Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare. Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed.

Two-stage revision of infected hip arthroplasty using an antibiotic-loaded spacer: retrospective comparison between short-term and prolonged antibiotic therapy.

PubMed

Hsieh, Pang-Hsin; Huang, Kuo-Chin; Lee, Po-Cheng; Lee, Mel S

2009-08-01

The optimal duration of systemic antibiotic therapy in patients with prosthetic hip infection (PHI) undergoing staged exchange arthroplasty (SEA) has not been determined. We hypothesized that with an antibiotic-loaded cement spacer (ALCS), in the interim, short-term antibiotic therapy is as effective as a conventional prolonged treatment course. We reviewed 99 patients with PHI who were managed with SEA using an ALCS from February 2002 to October 2005. A standard (4-6 week) antibiotic treatment course was administered in the first 46 patients and a short-term (1 week) therapy was adopted in the subsequent 53 patients. Eight patients (four in each group) had persistent infection following the first attempt of surgery and antibiotic treatment; in three of them the infection was cured by additional debridement prior to re-implantation. Forty-two (91%) patients in the long-term group and 47 (89%) patients in the short-term group were free of infection (P = 0.67) at an average follow-up of 43 months (range, 24-60 months). Five (11%) patients developed complications related to prolonged antibiotic therapy. The short-term treatment resulted in a shorter hospital stay (18 versus 43 days, P < 0.001) and a lower direct medical cost (US$13 732 versus US$21 756, P < 0.001). Short-term antibiotic therapy was not associated with a higher rate of treatment failure. Given the higher costs and incidence of complications, protracted courses of antibiotic administration may not necessarily be routine practice in patients with PHI undergoing SEA, provided that an ALCS is used.

Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.

PubMed

Park, H C; Kim, M J; Lee, B H

2017-12-01

Uncomplicated appendicitis may resolve spontaneously or require treatment with antibiotics or appendicectomy. The aim of this randomized trial was to compare the outcome of a non-antibiotic management strategy with that of antibiotic therapy in uncomplicated appendicitis. Patients presenting to a university teaching hospital with CT-verified uncomplicated simple appendicitis (appendiceal diameter no larger than 11 mm and without any signs of perforation) were randomized to management with a no-antibiotic regimen with supportive care (intravenous fluids, analgesia and antipyretics as necessary) or a 4-day course of antibiotics with supportive care. The primary endpoint was rate of total treatment failure, defined as initial treatment failure within 1 month and recurrence of appendicitis during the follow-up period. Some 245 patients were randomized within the trial, and followed up for a median of 19 months. The duration of hospital stay was shorter (mean 3·1 versus 3·7 days; P < 0·001) and the medical costs lower (€1181 versus 1348; P < 0·001) among those randomized to therapy without antibiotics. There was no difference in total treatment failure rate between the groups: 29 of 124 (23·4 per cent) in the no-antibiotic group and 25 of 121 (20·7 per cent) in the antibiotic group (P = 0·609). Eighteen patients (9 in each group) had initial treatment failure, 15 of whom underwent appendicectomy and three received additional antibiotics. Thirty-six patients (20 in the no-antibiotic group, 16 in the antibiotic group) experienced recurrence, of whom 30 underwent appendicectomy and six received further antibiotics. Treatment failure rates in patients presenting with CT-confirmed uncomplicated appendicitis appeared similar among those receiving supportive care with either a no-antibiotic regimen or a 4-day course of antibiotics. Registration number: KCT0000124 ( http://cris.nih.go.kr). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Antibiotic therapy for Shigella dysentery.

PubMed

Prince Christopher R H; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-01-20

antibiotic superior in efficacy in treating Shigella dysentery, but heterogeneity for some comparisons limits confidence in the results. All the antibiotics studied were safe. There was inadequate evidence regarding the role of antibiotics in preventing relapses. Antibiotics reduce the duration of Shigella dysentery.Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.

Antibiotic therapy for Shigella dysentery.

PubMed

Christopher, Prince Rh; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-08-04

antibiotic superior in efficacy in treating Shigella dysentery, but heterogeneity for some comparisons limits confidence in the results. All the antibiotics studied were safe. There was inadequate evidence regarding the role of antibiotics in preventing relapses. Antibiotics reduce the duration of Shigella dysentery.Regularly updated local or regional antibiotic sensitivity patterns to different species and strains of Shigella are required to guide empiric therapy. More trials adhering to standard guidelines are required to evaluate the role of antibiotics in the treatment of severe forms of Shigella dysentery and in groups who are at high risk of complications.

Localized severe aggressive periodontitis. Disease progression and tooth preservation: a short case report over 14 years.

PubMed

Pelka, Matthias; Petschelt, Anselm

2009-04-01

A case of a 31-year-old female with aggressive periodontitis over 14 years is presented. From 1993 to 2000, no periodontal therapy occurred; disease development and progression could be reconstructed upon radiographic findings. In 2000, full-mouth disinfection therapy and antibiotic therapy was performed, as well as regenerative surgical treatments. Seven years after surgical treatment, stable periodontal conditions and clear bone regeneration in the surgical areas was evident.

Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis.

PubMed

Omidvari, K; de Boisblanc, B P; Karam, G; Nelson, S; Haponik, E; Summer, W

1998-08-01

Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.

Antibiotic therapy for preventing infections in people with acute stroke.

PubMed

Vermeij, Jan-Dirk; Westendorp, Willeke F; Dippel, Diederik Wj; van de Beek, Diederik; Nederkoorn, Paul J

2018-01-22

Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review. To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms. We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field. Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke. Two review authors independently selected

Empiric Antibiotic Therapy of Nosocomial Bacterial Infections.

PubMed

Reddy, Pramod

2016-01-01

Broad-spectrum antibiotics are commonly used by physicians to treat various infections. The source of infection and causative organisms are not always apparent during the initial evaluation of the patient, and antibiotics are often given empirically to patients with suspected sepsis. Fear of attempting cephalosporins and carbapenems in penicillin-allergic septic patients may result in significant decrease in the spectrum of antimicrobial coverage. Empiric antibiotic therapy should sufficiently cover all the suspected pathogens, guided by the bacteriologic susceptibilities of the medical center. It is important to understand the major pharmacokinetic properties of antibacterial agents for proper use and to minimize the development of resistance. In several septic patients, negative cultures do not exclude active infection and positive cultures may not represent the actual infection. This article will review the important differences in the spectrum of commonly used antibiotics for nosocomial bacterial infections with a particular emphasis on culture-negative sepsis and colonization.

Recurrent uncomplicated cystitis in women: allowing patients to self-initiate antibiotic therapy.

PubMed

2014-02-01

Acute uncomplicated cystitis is a lower urinary tract infection occurring in the absence of anatomic or functional abnormalities of the urinary tract or any other complicating factors.The organism responsible is often an enterobacterium, especially Escherichia coli. What is the role of antibiotic therapy for non-pregnant women with recurrent acute uncomplicated cystitis? We reviewed the available evidence using the standard Prescrire methodology. A single oral dose of fosfomycin trometamol is the antibiotic of choice for treating an episode of acute uncomplicated cystitis. Alternative antibiotics are certain fluoroquinolones or co-trimoxazole (a fixed-dose combination of sulfamethoxazole and trimethoprim). For recurrent acute uncomplicated cystitis, cranberry juice has modest efficacy in reducing the frequency of episodes. A number of non-drug measures are typically proposed, although their effects are unproven: drinking sufficient fluids and urinating regularly; urinating after sexual intercourse; and avoiding spermicides. The strategy that results in the lowest antibiotic exposure is a short course of antibiotics for each episode of urinary tract infection, initiated as soon as clinical symptoms appear. Long-term antibiotic therapy is sometimes offered. According to one systematic review, women taking long-term prophylactic antibiotic therapy had about 6 times fewer clinical recurrences than with placebo. According to one randomised trial, 3 g of fosfomycin trometamol taken as a single dose every ten days reduced the frequency of recurrence, resulting in 0.14 episodes of infection per year on average versus about 3 episodes with placebo (p < 0.001). The amount of antibiotic used when fosfomycin trometamol is taken every 10 days for 6 months is equivalent to treatment of 18 acute episodes of cystitis. When cystitis appears to be associated with sexual intercourse, two small randomised trials suggest that routine postcoital antibiotic treatment is more effective

Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent.

PubMed

Lewis, Susan J; Mueller, Bruce A

2014-01-01

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT. We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients. © 2014 Wiley Periodicals, Inc.

Nanoengineered drug delivery systems for enhancing antibiotic therapy.

PubMed

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

2015-03-01

Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

PubMed Central

Maselli, Diego J.; Keyt, Holly; Restrepo, Marcos I.

2017-01-01

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases. PMID:28509852

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.

PubMed

Maselli, Diego J; Keyt, Holly; Restrepo, Marcos I

2017-05-16

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa , Methicillin-resistant Staphylococcus aureus , Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

PubMed

Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G

2017-11-25

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Diagnosis and treatment of patients with prostatic abscess in the post-antibiotic era.

PubMed

Ackerman, Anne Lenore; Parameshwar, Pooja S; Anger, Jennifer T

2018-02-01

We reviewed the pathogenesis, clinical presentation, treatment options and outcomes of prostatic abscess in the post-antibiotic era, focusing on how patient risk factors and the emergence of multidrug-resistant organisms influence management of the condition. A MEDLINE search for "prostate abscess" or "prostatic abscess" was carried out. Prostate abscess is no longer considered a consequence of untreated urinary infection; now, men with prostatic abscess are typically debilitated or immunologically compromised, with >50% of patients having diabetes. In younger men, prostatic abscess can be the initial presentation of such chronic conditions. In older men, prostatic abscess is increasingly a complication of benign prostatic hyperplasia or prostate biopsy. Diagnosis is based on a physical examination, leukocytosis, leukocyturia and transrectal ultrasound, with magnetic resonance imaging serving as the preferred confirmatory imaging modality. Treatment of prostatic abscess is changing as a result of the emergence of atypical and drug-resistant organisms, such as extended-spectrum β-lactamase-producing enterobacteriaceae and methicillin-resistant Staphylococcus aureus. As many as 75% of infections are resistant to first-generation antibiotics, necessitating aggressive therapy with broad-spectrum parenteral antibiotics, such as third-generation cephalosporins, aztreonam or antibiotic combinations. A total of 80% of patients require early surgical drainage, frequently through a transurethral approach. In the post-antibiotic era, prostatic abscess is evolving from an uncommon complication of urinary infection to a consequence of immunodeficiency, growing antibiotic resistance and urological manipulation. This condition, primarily affecting patients with chronic medical conditions rendering them susceptible to atypical, drug-resistant organisms, requires prompt aggressive intervention with contemporary antibiotic therapy and surgical drainage. © 2017 The Japanese

Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis.

PubMed

Hu, Z; Huang, P; Zhou, Z; Li, W; Xu, J; Xu, K; Wang, J; Zhang, H

2018-06-01

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM-HCC. Synchronous PM-HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE. Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338). Prognosis of synchronous PM-HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes

PubMed Central

Abeles, Shira R.; Ly, Melissa; Santiago-Rodriguez, Tasha M.; Pride, David T.

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

PubMed

Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

Implementation of treatment guidelines to support judicious use of antibiotic therapy.

PubMed

Deuster, S; Roten, I; Muehlebach, S

2010-02-01

Judicious use of antibiotics is essential considering the growth of antimicrobial resistance and escalating costs in health care. This intervention study used treatment guidelines to improve antibiotic therapy by changing prescribing practice. A before-after intervention study was performed in a 550-bed tertiary care teaching hospital in Switzerland, with an additional follow-up analysis 1 year later. The pre-intervention phase included chart analysis of current antibiotic use in 100 consecutive patients from the representative medical and surgical wards included in the study. Treatment guidelines were defined, taking into account published guidelines, the local antibacterial sensitivity of the pathogens, and the hospital antibiotic formulary defined by the drug and therapeutics committee. The guidelines were presented to the medical residents on a pocket card. They were informed and educated by the pharmacist (intervention). In the post-intervention phase immediately after the instruction, and in the follow-up phase 1 year later, a prospective analysis of antibiotic prescription was performed by chart review of 100 antibacterial treatments in consecutive patients to detect changes in antibiotic prescribing (treatment) and to determine whether these changes were sustained. The pre-intervention review of antibiotic use showed the need for therapy improvements in urinary tract infections (UTI) and hospital-acquired pneumonia (HAP). In the post-intervention phase 100% of UTI were treated as recommended, compared to 30% before the intervention (P < 0.001). The follow-up analysis showed a decrease in guideline adherence to 39% in patients with UTI. Before implementation of the clinical guidelines, HAP was inappropriately treated like community-acquired pneumonia (CAP). Immediately after the intervention, 50% of HAP patients were treated as recommended, and 1 year later (follow-up phase) 56% of HAP patients received the recommended antibiotic medication. This change in

Effect of an Undergraduate Special Problems Elective upon Student Knowledge of Antibiotic Therapy.

ERIC Educational Resources Information Center

MacCosbe, Paul E.; Segelman, Alvin B.

1984-01-01

The knowledge of antibiotic therapy among students taking an elective course in antibiotic prescription following a course in antibiotics and infectious diseases was compared with those not taking the follow-up elective course, and it was determined that the elective course reinforced existing knowledge. (MSE)

Streamlining antibiotic therapy with procalcitonin protocols: consensus and controversies.

PubMed

Haubitz, Sebastian; Mueller, Beat; Schuetz, Philipp

2013-04-01

Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate biomarker for likelihood and severity of bacterial infections. In community-acquired pneumonia and other respiratory infections, PCT-guided antibiotic therapy algorithms resulted in reduced antibiotic exposure while maintaining a similar or even better level of safety compared with standard care. Reductions in antibiotic use translate into lower treatment costs, decreased risk of side effects and decreased bacterial multiresistance. This is especially important, as acute respiratory infections represent the most frequent reason for antibiotic prescriptions worldwide. Still, there is some controversy about the benefits of PCT measurement in sepsis patients in the intensive care unit and for nonrespiratory infections. Highly sensitive PCT assays are readily available in many hospitals today, and point-of-care assays with high enough sensitivity for antibiotic guidance are expected to be available soon. Herein, the authors provide an overview of recent studies evaluating PCT in different clinical situations and an outlook of currently enrolling or upcoming interventional trials.

Evaluation of an antibiotic intravenous to oral sequential therapy program.

PubMed

Pablos, Ana I; Escobar, Ismael; Albiñana, Sandra; Serrano, Olga; Ferrari, José M; Herreros de Tejada, Alberto

2005-01-01

This study was designed to analyse the drug consumption difference and economic impact of an antibiotic sequential therapy focused on quinolones. We studied the consumption of quinolones (ofloxacin/levofloxacin and ciprofloxacin) 6 months before and after the implementation of a sequential therapy program in hospitalised patients. It was calculated for each antibiotic, in its oral and intravenous forms, in defined daily dose (DDD/100 stays per day) and economical terms (drug acquisition cost). At the beginning of the program ofloxacin was replaced by levofloxacin and, since their clinical uses are similar, the consumption of both drugs was compared during the period. In economic terms, the consumption of intravenous quinolones decreased 60% whereas the consumption of oral quinolones increased 66%. In DDD/100 stays per day, intravenous forms consumption decreased 53% and oral forms consumption increased 36%. Focusing on quinolones, the implementation of a sequential therapy program based on promoting an early switch from intravenous to oral regimen has proved its capacity to alter the utilisation profile of these antibiotics. The program has permitted the hospital a global saving of 41420 dollars for these drugs during the period of time considered. Copyright (c) 2004 John Wiley & Sons, Ltd.

A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens

PubMed Central

Wittebole, Xavier; De Roock, Sophie; Opal, Steven M

2014-01-01

The seemingly inexorable spread of antibiotic resistance genes among microbial pathogens now threatens the long-term viability of our current antimicrobial therapy to treat severe bacterial infections such as sepsis. Antibiotic resistance is reaching a crisis situation in some bacterial pathogens where few therapeutic alternatives remain and pan-resistant strains are becoming more prevalent. Non-antibiotic therapies to treat bacterial infections are now under serious consideration and one possible option is the therapeutic use of specific phage particles that target bacterial pathogens. Bacteriophage therapy has essentially been re-discovered by modern medicine after widespread use of phage therapy in the pre-antibiotic era lost favor, at least in Western countries, after the introduction of antibiotics. We review the current therapeutic rationale and clinical experience with phage therapy as a treatment for invasive bacterial infection as novel alternative to antimicrobial chemotherapy. PMID:23973944

An office model of outpatient parenteral antibiotic therapy.

PubMed

Tice, A D

1991-01-01

This office-based program for parenteral therapy began with the im administration of therapy to outpatients in 1981. Since then it has expanded in scope and staff and has provided more than 1,200 courses of i.v. antibiotics. The success of the program is dependent on patients' ability to provide i.v. medication to themselves. These patients are trained and cared for by a team consisting of a physician who specializes in infectious diseases, nurses trained in i.v. techniques, a pharmacist, and microbiologists who are all part of a practice of the subspecialty of infectious diseases. This office model has resulted in excellent quality of care for patients who have experienced few adverse effects or complications. The cost savings of an office program are significant compared to hospitalization for i.v. administration of antibiotics, but issues related to reimbursement are a constant issue.

[Rational antibiotic therapy in the dental office: Practical guidelines for decision-making].

PubMed

Zadik, Y

2016-04-01

Although most dental and periodontal diseases are caused by bacteria, the usual therapy is mechanical/surgical rather than antimicrobial medications. However, sometimes antibiotic administration may be necessary in addition to or as an alternative to the surgical/mechanical treatment. Many studies have shown that the misuse of antibiotics by dentists may be mostly attributed to unnecessity or inefficient regimen, and could contribute to bacterial resistance to antibiotics. The article presents practical guidelines to the administration of antibiotics in the dental office.

Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial.

PubMed

Oliveira, Carolina F; Botoni, Fernando A; Oliveira, Clara R A; Silva, Camila B; Pereira, Helena A; Serufo, José C; Nobre, Vandack

2013-10-01

We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis. Randomized open clinical trial. Two university hospitals in Brazil. Patients with severe sepsis or septic shock. Patients were randomized in two groups: the procalcitonin group and the C-reactive protein group. Antibiotic therapy was discontinued following a protocol based on serum levels of these markers, according to the allocation group. The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25% shorter than in the C-reactive protein group. For both groups, at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and/or bacteremia at inclusion, and patients with evident resolution of the infectious process had antibiotics stopped after 7 days, despite biomarkers levels. Ninety-four patients were randomized: 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group. The mean age was 59.8 (SD, 16.8) years. The median duration of antibiotic therapy for the first episode of infection was 7.0 (Q1-Q3, 6.0-8.5) days in the procalcitonin group and 6.0 (Q1-Q3, 5.0-7.0) days in the C-reactive protein group (p=0.13), with a hazard ratio of 1.206 (95% CI, 0.774-1.3; p=0.13). Overall, protocol overruling occurred in only 13 (13.8%) patients. Twenty-one patients died in each group (p=0.836). C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients, causing no apparent harm.

DRESS syndrome due to antibiotic therapy of osteoarticular infections in children: two case reports.

PubMed

Ramírez, A; Abril, J C; Cano, J

2015-01-01

Osteoarticular infection in children frequently occurs before 10 years of age. Surgical drainage is sometimes required, whereas acute osteomyelitis can be treated with antibiotic therapy alone. The duration of antibiotic therapy varies, 2 weeks is sufficient for septic arthritis, whereas 6 weeks is often required for complicated cases. Some of these antibiotic drugs present direct complications with low clinical impact in certain individuals. Hypersensitivity to these drugs causes different reactions in children. DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe and potentially life-threatening drug reaction. It is characterised by high fever, malaise, lymphadenopathy and skin rash. From a clinical perspective, these symptoms can lead to an exacerbation of the initial infectious process for which treatment was commenced. The liver is the organ most often affected in DRESS syndrome associated with haematological changes, potentially similar to sepsis. We present two cases of children with osteoarticular infections who developed DRESS syndrome after antibiotic therapy. Both patients made a complete recovery after cessation of the antibiotic drugs used. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

PubMed

Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

2012-12-01

It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

[Simple parameters of antibiotic utilization and diagnostic background of antimicrobial therapy in Hungarian hospitals in 1995].

PubMed

Almási, I; Ternák, G

1997-02-23

This paper is published as second part of a survey on antibiotic utilisation of 8 Hungarian hospitals in January, 1995. The length of hospital stay of the patients receiving systemic antibiotic treatment was significantly higher (P < 0.0001) than those of not receiving such treatment. After exclusion of the patients suffering from nosocomial infections, average of the excess of hospital days was 4.65. Comparing the figures of patients receiving one or more antibiotic/one hospital stay and the rate of monotherapy and combined therapy and number of used antibiotics/100 discharged patients or/100 patients treated with antibiotics it was found that these indexes were most favourable in that hospital, where antibiotic policy was in function. Examining diagnoses (perioperative profilaxis 32.7%, pneumonia 13.3% of the 753 diagnoses) and drugs (metronidazol 26.3%, aminoglycosides 20% of the 1455 antibiotics) most frequently found in cases of combined antibiotic therapy it was concluded that parallel treatment with two or more antibiotic was often unjustified. Only 11% of antibiotics was used as directed against known bacteria. It was found that the rate of the achieved microbiological examinations and targeted therapy was low even if microbiological samples were easy to obtain. It was not the main purpose of the survey to get data of the clinical diagnostic background of antibiotic therapy, but indirect signs showed that these drugs were often used without sufficient clinical evidences (anamnesis, physical status, labor, X-ray and other tests) of infection. Authors recommend further survey in order to find out the causes of insufficiency of diagnoses. They also propose elaboration of diagnostic protocols.

Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci

PubMed Central

Dastgheyb, Sana S.; Eckmann, David M.; Composto, Russell J.

2013-01-01

Staphylococcal infections have become difficult to treat due to antibiotic insensitivity and resistance. Antimicrobial combination therapies may minimize acquisition of resistance and photodynamic therapy is an attractive candidate for these combinations. In this manuscript, we explore combined use of antibiotics and meso-tetra (4-aminophenyl) porphine (TAPP), a cationic porphyrin, for treatment of Staphylococcus aureus contamination. We characterize the antimicrobial activity of photoactivated TAPP and show that activity is largely lost in the presence of a radical scavenger. Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for Staphylococcus aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis. Chloramphenicol + methylene blue, another photosensitizer, also show additivity against Staphylococcus aureus. In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. aureus. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentration levels of photo-activated TAPP could be used to boost the activity of waning antibiotics. This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy. PMID:24148969

An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients.

PubMed

McCaig, D J; Stewart, D; Harvey, Y; Downie, G; Scott, C J

1995-11-01

The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.

Practical Considerations and the Intestinal Microbiome in Disease: Antibiotics for IBD Therapy.

PubMed

Fedorak, Richard N; Ismond, Kathleen P

2016-01-01

The inflammatory bowel diseases, Crohn's and ulcerative colitis, have been treated with a range of antibiotics for inducing and maintaining remission, as well as the prevention of post-operative symptoms. To date, many studies have been performed assessing the efficacy of antibiotics when used alone, in combination with other antibiotics, or as an adjunctive therapy to other pharmaceutical treatments. Literature evidence supporting the use of antibiotics in IBD can be ambiguous, especially when considering the potential role of dysbiosis in the gastrointestinal tract. The review considers the systemic effect of antibiotics and the evidence base for their efficacy in the treatment of IBD. © 2016 S. Karger AG, Basel.

Consensus on diagnosis and empiric antibiotic therapy of febrile neutropenia

PubMed Central

Giurici, Nagua; Zanazzo, Giulio A.

2011-01-01

Controversial issues on the management of empiric therapy and diagnosis of febrile neutropenia (FN) were faced by a Consensus Group of the Italian Association of Pediatric Hematology-Oncology (AIEOP). In this paper we report the suggestions of the consensus process regarding the role of aminoglycosides, glycopeptides and oral antibiotics in empiric therapy of FN, the rules for changing or discontinuing the therapy as well as the timing of the blood cultures. PMID:21647277

Is there an improvement of antibiotic use in China? Evidence from the usage analysis of combination antibiotic therapy for type I incisions in 244 hospitals.

PubMed

Zhou, Wen-Juan; Luo, Zhen-Ni; Tang, Chang-Min; Zou, Xiao-Xu; Zhao, Lu; Fang, Peng-Qian

2016-10-01

The improvement of antibiotic rational use in China was studied by usage analysis of combination antibiotic therapy for type I incisions in 244 hospitals. Five kinds of hospitals, including general hospital, maternity hospital, children's hospital, stomatological hospital and cancer hospital, from 30 provinces were surveyed. A systematic random sampling strategy was employed to select outpatient prescriptions and inpatient cases in 2011 and 2012. A total of 29 280 outpatient prescriptions and 73 200 inpatient cases from 244 hospitals in each year were analyzed. Data were collected with regards to the implementation of the national antibiotic stewardship program (NASP), the overall usage and the prophylactic use of antibiotic for type I incisions. Univariate analysis was used for microbiological diagnosis rate before antimicrobial therapy, prophylactic use of antibiotics for type I incision operation, and so on. For multivariate analysis, the use of antibiotics was dichotomized according to the guidelines, and entered as binary values into logistic regression analysis. The results were compared with the corresponding criteria given by the guidelines of this campaign. The antibiotic stewardship in China was effective in that more than 80% of each kind of hospitals achieved the criteria of recommended antibiotics varieties. Hospital type appeared to be a factor statistically associated with stewardship outcome. The prophylactic use of antibiotics on type I incision operations decreased by 16.22% (P<0.05). The usage of combination antibiotic therapy for type I incisions was also decreased. Region and bed size were the main determinants on surgical prophylaxis for type I incision. This national analysis of hospitals on antibiotic use and stewardship allows relevant comparisons for bench marking. More efforts addressing the root cause of antibiotics abuse would continue to improve the rational use of antibiotics in China.

Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis.

PubMed

Eickholz, Peter; Siegelin, Yasemin; Scharf, Susanne; Schacher, Beate; Oremek, Gerhard M; Sauer-Eppel, Hildegund; Schubert, Ralf; Wohlfeil, Martin

2013-04-01

Assessment of the effect of non-surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. Overall, 31 ChP and 29 AgP were examined clinically prior to and 12 weeks after SRP (subgingival scaling of all pockets within 2 days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12 weeks after the first SRP visit. Serum elastase, C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed. At baseline, serum elastase, CRP, and LBP were significantly (p < 0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL-6 were significantly (p < 0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p < 0.001). A significant difference was observed regarding change of serum elastase 12 weeks after SRP between AgP and ChP (p = 0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth. SRP results in serum elastase reduction in AgP but not in ChP. © 2013 John Wiley & Sons A/S.

Antibiotic resistance rates in causative agents of infections in diabetic patients: rising concerns.

PubMed

Boyanova, Lyudmila; Mitov, Ivan

2013-04-01

The vicious cycle is that hyperglycemia (≥11.1 mmol/l) or other diabetes-associated factors facilitate or worsen the development of infections and vice versa, the infections deteriorate the glycemic control of the patients. Diabetic patients are prone to some infections, infection recurrences and poor outcomes. Immunocompromised state and frequent antibiotic use are associated with antibiotic resistance of the bacterial pathogens, such as Mycobacterium tuberculosis (in some studies), methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii, bacteria in diabetic foot infections and different opportunistic and rare pathogens or multidrug-resistant strains. Prompt diagnostics and susceptibility testing, early and aggressive surgical and/or antibiotic therapy, and, importantly, good glycemic control are of utmost importance for treatment of antibiotic-resistant infections in diabetic patients.

Systematic review of duration and choice of systemic antibiotic therapy for acute haematogenous bacterial osteomyelitis in children.

PubMed

Howard-Jones, Annaleise R; Isaacs, David

2013-09-01

Historically, children with acute osteomyelitis received 4-6 weeks of parenteral antibiotics; however, evidence to guide optimal duration of therapy is limited. This study aims to summarise the available evidence on the duration and choice of antimicrobial therapy for acute haematogenous osteomyelitis in children. We systematically reviewed the literature on children with acute osteomyelitis to determine if shorter durations of antibiotic treatment compared with protracted treatment gave different cure rates. We also analysed studies for choice of antibiotics to determine differences in success rates. Randomised controlled trials, cohort studies, case-control studies and case series were eligible for inclusion. We identified six randomised controlled trials, three of which addressed duration of antibiotic use and three choice of antibiotic for acute osteomyelitis in children. We found 28 observational studies, 20 of which focused on duration and 22 of which allowed analysis of choice of antibiotic. A range of therapy durations and types of antibiotics were assessed. Only one small study looked at treatment of neonates. The quality of evidence on antibiotic treatment for acute osteomyelitis is limited, allowing only weak (GRADE 2B) recommendations. Our review suggests that early transition from intravenous to oral therapy, after 3-4 days in patients responding well, followed by oral therapy to a total of 3 weeks may be as effective as longer courses for uncomplicated acute osteomyelitis. This recommendation does not apply to neonates. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Systemic antibiotics in periodontics.

PubMed

Slots, Jørgen

2004-11-01

This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession.

Antibiotic therapy in ventilator-associated tracheobronchitis: a literature review.

PubMed

Alves, Abel Eduardo; Pereira, José Manuel

2018-03-01

The concept of ventilator-associated tracheobronchitis is controversial; its definition is not unanimously accepted and often overlaps with ventilator-associated pneumonia. Ventilator-associated tracheobronchitis has an incidence similar to that of ventilator-associated pneumonia, with a high prevalence of isolated multiresistant agents, resulting in an increase in the time of mechanical ventilation and hospitalization but without an impact on mortality. The performance of quantitative cultures may allow better diagnostic definition of tracheobronchitis associated with mechanical ventilation, possibly avoiding the overdiagnosis of this condition. One of the major difficulties in differentiating between ventilator-associated tracheobronchitis and ventilator-associated pneumonia is the exclusion of a pulmonary infiltrate by chest radiography; thoracic computed tomography, thoracic ultrasonography, or invasive specimen collection may also be required. The institution of systemic antibiotic therapy does not improve the clinical impact of ventilator-associated tracheobronchitis, particularly in reducing time of mechanical ventilation, hospitalization or mortality, despite the possible reduced progression to ventilator-associated pneumonia. However, there are doubts regarding the methodology used. Thus, considering the high prevalence of tracheobronchitis associated with mechanical ventilation, routine treatment of this condition would result in high antibiotic usage without clear benefits. However, we suggest the institution of antibiotic therapy in patients with tracheobronchitis associated with mechanical ventilation and septic shock and/or worsening of oxygenation, and other auxiliary diagnostic tests should be simultaneously performed to exclude ventilator-associated pneumonia. This review provides a better understanding of the differentiation between tracheobronchitis associated with mechanical ventilation and pneumonia associated with mechanical ventilation, which

Ticarcillin in Combination with Cephalothin or Gentamicin as Empiric Antibiotic Therapy in Granulocytopenic Cancer Patients

PubMed Central

Schimpff, Stephen C.; Landesman, Sheldon; Hahn, Davis M.; Standiford, Harold C.; Fortner, Clarence L.; Young, Viola Mae; Wiernik, Peter H.

1976-01-01

Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although Staphylococcus aureus was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by S. aureus but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients. PMID:795372

Non-adherence to antibiotic therapy in patients visiting community pharmacies.

PubMed

Fernandes, Milene; Leite, Andreia; Basto, Maria; Nobre, Miguel Araújo; Vieira, Nuno; Fernandes, Rui; Nogueira, Paulo; Nicola, Paulo Jorge; Jorge, Paulo

2014-02-01

Patient non-adherence to antibiotic therapy may lead to therapeutic failure, re-infection, and bacterial resistance. Assessing the factors associated with this problem is important for promoting rational use of antibiotics. This study aimed to measure prevalence and reasons for non-adherence to antibiotic treatment and to identify associated factors. Patients were recruited for the study in community pharmacies in Lisbon, Portugal, from February to April, 2009. Data from prescriptions for oral antibiotics were collected for adult subjects. Adherence to treatment was assessed with a modified Portuguese version of the Morisky scale. Factors associated with non-adherence were identified through bivariate analysis and logistic regression models. A total of 243 patients were included in the study. They had a mean age 46.5 ± 16.6 years and 74.5 % of the sample was female. The prevalence of non-adherence was 57.7 % and was related to delays and failures in taking the prescribed medicine. Increasing age (OR 0.97), difficulty in buying the antibiotic (OR 2.34), duration of treatment (OR 1.28), difficulty with ingestion (OR 3.08), and satisfaction with the information given by physician (OR 0.33) were identified as independent factors associated with non-adherence. Non-adherence to antibiotics is common in the community setting. Factors related to the antibiotic, the patient, and the patient-physician relationship should be addressed to promote adherence. Pharmacists should provide information to patients about correct use of antibiotics and address barriers to adherence.

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

PubMed

Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

2016-11-01

There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia.

PubMed

Acharya, Deepa; Harper, David G; Achtyes, Eric D; Seiner, Stephen J; Mahdasian, Jack A; Nykamp, Louis J; Adkison, Lesley; Van der Schuur White, Lori; McClintock, Shawn M; Ujkaj, Manjola; Davidoff, Donald A; Forester, Brent P

2015-03-01

Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Twenty-three participants admitted to McLean Hospital (Belmont, MA, USA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI, USA), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory-Short Form, Neuropsychiatric Inventory-Nursing Home Version, Cornell Scale for Depression in Dementia, and the Clinical Global Impression Scale at baseline, during, and after the ECT course. Regression analyses revealed a significant decrease from baseline to discharge on the Cohen-Mansfield Agitation Inventory (F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory (F(4,31) = 14.6; p < 0.001). There was no statistically significant change in scores on the Cornell Scale for Depression in Dementia. The Clinical Global Impression scores on average changed from a rating of "markedly agitated/aggressive" at baseline to "borderline agitated/aggressive" at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants because of recurrence of agitation and for three participants because of adverse events. Electroconvulsive therapy may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. Copyright © 2014 John Wiley & Sons, Ltd.

Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution?

PubMed Central

Cheesman, Matthew J.; Ilanko, Aishwarya; Blonk, Baxter; Cock, Ian E.

2017-01-01

The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field. PMID:28989242

Developing New Antimicrobial Therapies: Are Synergistic Combinations of Plant Extracts/Compounds with Conventional Antibiotics the Solution?

PubMed

Cheesman, Matthew J; Ilanko, Aishwarya; Blonk, Baxter; Cock, Ian E

2017-01-01

The discovery of penicillin nearly 90 years ago revolutionized the treatment of bacterial disease. Since that time, numerous other antibiotics have been discovered from bacteria and fungi, or developed by chemical synthesis and have become effective chemotherapeutic options. However, the misuse of antibiotics has lessened the efficacy of many commonly used antibiotics. The emergence of resistant strains of bacteria has seriously limited our ability to treat bacterial illness, and new antibiotics are desperately needed. Since the discovery of penicillin, most antibiotic development has focused on the discovery of new antibiotics derived from microbial sources, or on the synthesis of new compounds using existing antibiotic scaffolds to the detriment of other lines of discovery. Both of these methods have been fruitful. However, for a number of reasons discussed in this review, these strategies are unlikely to provide the same wealth of new antibiotics in the future. Indeed, the number of newly developed antibiotics has decreased dramatically in recent years. Instead, a reexamination of traditional medicines has become more common and has already provided several new antibiotics. Traditional medicine plants are likely to provide further new antibiotics in the future. However, the use of plant extracts or pure natural compounds in combination with conventional antibiotics may hold greater promise for rapidly providing affordable treatment options. Indeed, some combinational antibiotic therapies are already clinically available. This study reviews the recent literature on combinational antibiotic therapies to highlight their potential and to guide future research in this field.

Antimicrobial Therapy for Legionnaire's Disease: Antibiotic Stewardship Implications.

PubMed

Cunha, Cheston B; Cunha, Burke A

2017-03-01

Legionnaire's disease is a common cause of community-acquired pneumonia (CAP). Although no single clinical feature is diagnostic, if characteristic extrapulmonary findings are present a presumptive clinical syndromic diagnosis is possible. Depending on geographic location, season, and physician awareness, Legionnaire's disease may be included in the differential diagnosis of CAP. Some antibiotics effective against Legionella sp are also effective in treating the typical bacterial causes of CAP. From an antimicrobial stewardship program (ASP) perspective, monotherapy is preferred to double-drug therapy. From an ASP and pharmacoeconomic standpoint, monotherapy with doxycycline or a respiratory quinolone provides optimal cost effective therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Continuous alternating inhaled antibiotic therapy in CF: A single center retrospective analysis.

PubMed

Van de Kerkhove, C; Goeminne, P C; Kicinski, M; Nawrot, T S; Lorent, N; Van Bleyenbergh, P; De Boeck, K; Dupont, L J

2016-11-01

The efficacy of inhaled antibiotics to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been well established. Few data are available on the value of continuous alternating inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management of CF. To investigate the effect of CAIT on clinical outcome in adult CF patients treated at the University Hospital Leuven. Patients with a documented CF diagnosis who received inhaled antibiotics between March 2010 and January 2015 were retrospectively evaluated. In patients receiving CAIT patient characteristics, recorded spirometry data and number of IV antibiotic days were collected retrospectively at fixed time intervals, from 6months before to one year after the start of the 2nd inhaled antibiotic. For patients on inhaled antibiotic monotherapy (IAMT), the same data were obtained at similar intervals during the study period. A total of 49 of 89 patients using chronic inhaled antibiotic therapy received CAIT. Patients receiving CAIT had a lower baseline FEV 1 and were more likely to be homozygous for F508del compared to patients receiving IAMT. FEV 1 deteriorated on average by a factor of 0.904 per year (95% CI: 0.851-0.960) prior to the start of CAIT. The initiation of CAIT was associated with an average improvement in FEV 1 by a factor of 1.148 per year (95% CI: 1.068-1.236, p=0.0002). The analysis of specific types of antibiotics revealed evidence of positive effects of adding COLI to TOBI and COLI to AZLI. We found no effect of the initiation of CAIT on the number of IV antibiotic days (p=0.80). CF patients with more advanced lung disease are more likely to receive CAIT. In this patient group, CAIT was associated with a significant improvement in FEV 1 . Further data are warranted to identify the value of CAIT. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis.

PubMed

Jepsen, Karin; Jepsen, Søren

2016-06-01

This review gives an update of the current scientific evidence on the efficacy of the adjunctive use of systemic and local antibiotics/antimicrobials in the treatment of periodontitis. In particular, it addresses whether their use can improve the results of nonsurgical mechanical therapy in mild-to-moderate forms of the disease. Large numbers of randomized clinical trials and systematic reviews with meta-analyses have clearly established that adjunctive systemic antibiotics, combined with mechanical debridement, offer clinical improvements additional to those obtained with scaling and root planing alone. These effects are more pronounced in aggressive periodontitis and in initially deep pockets, whereas more limited additional improvements, of 0.3 mm for additional pocket reduction and 0.2 mm for additional clinical attachment gain, have been documented for moderately deep sites (4-6 mm) in patients with chronic periodontitis. The marginal clinical benefit in patients with moderate disease has to be balanced against possible side effects. Notably, it has to be realized that an increasing number of warnings have been articulated against the unrestricted use of antibiotics in treating periodontal diseases because of the emerging global public health issue of bacterial resistance. The effects of the adjunctive local administration of antimicrobials have also been very well documented in several systematic reviews. Overall, in persistent or recurrent localized deep sites, the application of antimicrobials by sustained-delivery devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and 0.3 mm in clinical attachment level gain. In conclusion, the slight additional benefits of adjunctive antimicrobials, which were shown for moderate forms of periodontitis, have to be balanced against their side effects and therefore their prescription should be limited as much as possible. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rapid resolution of cellulitis in patients managed with combination antibiotic and anti-inflammatory therapy.

PubMed

Dall, Lawrence; Peterson, Sandford; Simmons, Tom; Dall, Amy

2005-03-01

There is some evidence to suggest that host inflammatory response has some effect on the clinical manifestations of cellulitis. The objective of this pilot study was to investigate whether the addition of oral nonsteroidal anti-inflammatory (NSAI) therapy to antibiotic treatment hastens resolution of cellulitis-related inflammation. Patients presenting in the emergency department with signs and symptoms of class II cellulitis were assigned to receive treatment with either antibiotic therapy alone (intravenous, supplemented with oral cephalexin or an equivalent) for 10 days (n = 33) or antibiotic therapy for 10 days plus an oral anti-inflammatory (ibuprofen 400 mg every 6 hours) for 5 days (n = 31). Patients were discharged as soon as possible to complete their therapy on an outpatient basis. The addition of an oral anti-inflammatory agent significantly (P < .05) shortened the time to regression of inflammation and complete resolution of cellulitis. Twenty-four of 29 evaluable patients (82.8%) who received supplemental anti-inflammatory treatment showed regression of inflammation within 1 to 2 days compared with only 3 of 33 patients (9.1%) treated without an anti-inflammatory in the same time frame. All patients receiving adjunctive anti-inflammatory treatment experienced complete resolution of cellulitis in 4 to 5 days or less, while 24.2% (8/33) of patients treated with antibiotic alone required 6 to 7 days, and 6.1% (2/33) required 7 days or more (P < .05). This small preliminary study provides some promising data, suggesting that the supplemental use of anti-inflammatory therapy may hasten the time to regression of inflammation and complete resolution of cellulitis.

Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis.

PubMed

Lascarrou, Jean Baptiste; Lissonde, Floriane; Le Thuaut, Aurélie; Bachoumas, Konstantinos; Colin, Gwenhael; Henry Lagarrigue, Matthieu; Vinatier, Isabelle; Fiancette, Maud; Lacherade, Jean Claude; Yehia, Aihem; Joret, Aurélie; Lebert, Christine; Bourdon, Sandra; Martin Lefèvre, Laurent; Reignier, Jean

2017-08-01

To determine the proportion of patients with documented bacterial aspiration pneumonia among comatose ICU patients with symptoms suggesting either bacterial aspiration pneumonia or non-bacterial aspiration pneumonitis. Prospective observational study. University-affiliated 30-bed ICU. Prospective cohort of 250 patients admitted to the ICU with coma (Glasgow Coma Scale score ≤ 8) and treated with invasive mechanical ventilation. None. The primary outcome was the proportion of patients with microbiologically documented bacterial aspiration pneumonia. Patients meeting predefined criteria for aspiration syndrome routinely underwent telescopic plugged catheter sampling during bronchoscopy before starting probabilistic antibiotic treatment. When cultures were negative, the antibiotic treatment was stopped. Of 250 included patients, 98 (39.2%) had aspiration syndrome, including 92 before mechanical ventilation discontinuation. Telescopic plugged catheter in these 92 patients showed bacterial aspiration pneumonia in 43 patients (46.7%). Among the remaining 49 patients, 16 continued to receive antibiotics, usually for infections other than pneumonia; of the 33 patients whose antibiotics were discontinued, only two subsequently showed signs of lung infection. In the six patients with aspiration syndrome after mechanical ventilation, and therefore without telescopic plugged catheter, antibiotic treatment was continued for 7 days. Mechanical ventilation duration, ICU length of stay, and mortality did not differ between the 43 patients with bacterial aspiration pneumonia and the 49 patients with non-bacterial aspiration pneumonitis. The 152 patients without aspiration syndrome did not receive antibiotics. Among comatose patients receiving mechanical ventilation, those without clinical, laboratory, or radiologic evidence of bacterial aspiration pneumonia did not require antibiotics. In those with suspected bacterial aspiration pneumonia, stopping empirical antibiotic therapy

Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children

PubMed Central

Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Zhou, Zongguang

2017-01-01

Importance Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. Objective To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. Data Sources The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Study Selection Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data Extraction and Synthesis Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. Main Outcomes and Measures The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. Results A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2�

[Domiciliary parenteral antibiotic therapy: a prospective analysis of the last 12 years].

PubMed

Peláez Cantero, M J; Madrid Rodríguez, A; Urda Cardona, A L; Jurado Ortiz, A

2014-08-01

Parenteral antibiotic treatment has been classically developed in hospitals and is considered as a hospital procedure. The development of Hospital at Home Units (HHU) has led to an increase in outpatient parenteral antibiotic therapy (OPAT) in paediatrics patients. The objective of this study is to describe our experience, as an HHU integrated within a Paediatric Department, in home antimicrobial therapy over a period of 12 years. This prospective and descriptive study included every patient with a disease requiring parenteral antimicrobial therapy who was admitted to our HHU from January 2000 to December 2012. During the study there were 163 cases on OPAT. The mean age of the patients was 11.1 years, and the sample group was comprised of 33 males and 22 feamales. The main sources of the treated infections were respiratory tract (76%), catheter-related bloodstream (9.2%), and urinary tract infections (5.5%). Amikacin was the most widely used antibiotic. Almost all treatments (96.6%) were via an intravenous route. Catheter-associated complications were more common than drug-associated complications. Successful at-home treatment was observed in 90.2% of cases. OPAT is a good and safe alternative in many paediatric diseases. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis.

PubMed

Kip, Michelle M A; Kusters, Ron; IJzerman, Maarten J; Steuten, Lotte M G

2015-01-01

Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital stay. Limiting antibiotic treatment duration is highly important because antibiotic over-use may cause patient harm, prolonged hospital stay, and resistance development. Several systematic reviews show that a PCT algorithm for antibiotic discontinuation is safe, but upfront investment required for PCT remains an important barrier against implementation. The current study investigates to what extent this PCT algorithm is a cost-effective use of scarce healthcare resources in ICU patients with sepsis compared to current practice. A decision tree was developed to estimate the health economic consequences of the PCT algorithm for antibiotic discontinuation from a Dutch hospital perspective. Input data were obtained from a systematic literature review. When necessary, additional information was gathered from open interviews with clinical chemists and intensivists. The primary effectiveness measure is defined as the number of antibiotic days, and cost-effectiveness is expressed as incremental costs per antibiotic day avoided. The PCT algorithm for antibiotic discontinuation is expected to reduce hospital spending by circa € 3503 per patient, indicating savings of 9.2%. Savings are mainly due to reductions in length of hospital stay, number of blood cultures performed, and, importantly, days on antibiotic therapy. Probabilistic and one-way sensitivity analyses showed the model outcome to be robust against changes in model inputs. Proven safe, a PCT algorithm for antibiotic discontinuation is a cost-effective means of reducing antibiotic exposure in adult ICU patients with sepsis, compared to current practice. Additional resources required for PCT are more than offset by downstream cost

[Hot rods in the ICU : What is the antibiotic mileage of your renal replacement therapy?

PubMed

Kielstein, J T; Kruse, A K; Anderson, N; Vaitiekunas, H; Scherneck, S

2017-05-08

We would neither be disappointed nor upset if the gas mileage on the sticker of a car didn't match our personal, real-life fuel consumption. Depending on our daily route to work, our style of accelerating and the number of passengers in our carpool, the gas mileage will vary. As soon as the falcon wing door of our car is closed and entrance to the ICU is granted, we tend to forget all of this, even though another hot rod is waiting there for us. Renal replacement therapy is like a car; it fulfills goals, such as the removal of uremic toxins and accumulated fluids, but it also "consumes" (removes) antibiotics. Unlike catecholamines, where we have the mean arterial pressure on our ICU dashboard, we do not have a gauge to measure antibiotic "consumption", i.e. elimination by renal replacement therapy. This manuscript describes the principles and basic knowledge to improve dosing of antibiotics in critically ill patients undergoing renal replacement therapy. As in modern cars, we briefly touch on hybrid therapies combining renal replacement therapy with extracorporeal lung support or adsorbent technologies that remove cytokines or bacteria. Further, the importance of considering body size and body composition is addressed, especially for choosing the right initial dose of antibiotics. Lastly we point out the dire need to increase the availability of timely and affordable therapeutic drug monitoring on the most commonly used antiinfectives, ideally using point-of-care devices at the bedside.

Gram-negative bacteremia: which empirical antibiotic therapy?

PubMed

Shoai Tehrani, M; Hajage, D; Fihman, V; Tankovic, J; Cau, S; Day, N; Visseaux, C; Carbonnelle, E; Kouatchet, A; Cattoir, V; Nhan, T X; Corvec, S; Jacquier, H; Jauréguy, F; Le Monnier, A; Morand, P; Zahar, J R

2014-04-01

Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be recommended any longer as empirical antibiotic therapy for community-acquired Gram-negative bacteremia (CA-GNB). We conducted a multicenter prospective descriptive study including patients with CA-GNB. Two hundred and nineteen patients were included. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated species in 63% (n=138) and 11% (n=24) of the cases, respectively. The prevalence of cefotaxime-resistance reached 18% (n=39) mostly due to intrinsic resistance (27 cases, 12%). The presence of invasive material (P<0.001), the origin of the patient (Paris region or West of France) (P=0.006), and home health care (P<0.001) were variables predicting resistant GNB. The negative predictive value for resistance in patients with invasive material coming from the West of France, or without invasive material and with home health care was 94%. The positive predictive value for patients with invasive material living in Paris, or without invasive material and with home health care only reached 58 and 54%, respectively. Using 3GC for CA-GNB due to cefotaxime-resistant strains was relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our study highlights the role of local epidemiology; before any changes to first-line antibiotic therapy, local epidemiological data should be taken into account. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Minimally invasive flap surgery and enamel matrix derivative in the treatment of localized aggressive periodontitis: case report.

PubMed

Kaner, Doğan; Bernimoulin, Jean-Pierre; Kleber, Bernd-Michael; Friedmann, Anton

2009-02-01

Localized aggressive periodontitis is a distinct entity of periodontal disease and is characterized by deep vertical bony defects that typically affect the first molars and incisors of young patients. Therapy is usually aimed at reducing the pathogenic microflora through scaling and root planing and the administration of systemic antibiotics. However, conservative periodontal therapy may result in reparative wound healing with limited regeneration of the lost tissues. Periodontal surgery combined with enamel matrix derivative has been introduced as a method to promote regeneration of the lost periodontium and has been studied extensively in the treatment of chronic periodontitis. This case report describes the treatment of a 27-year-old patient displaying severe localized aggressive periodontitis with documented disease progression. After initial therapy consisting of scaling and root planing and systemic administration of amoxicillin and metronidazole, the vertical defects were treated by minimally invasive access flaps combined with application of enamel matrix derivative. Clinical, microbiologic, and radiographic findings are reported for up to 1.5 years after initial therapy, indicating good efficacy of the therapeutic strategy and stability of the treatment outcome.

Time to Guideline-Based Empiric Antibiotic Therapy in the Treatment of Pneumonia in a Community Hospital: A Retrospective Review.

PubMed

Erwin, Beth L; Kyle, Jeffrey A; Allen, Leland N

2016-08-01

The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines for hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health care-associated pneumonia (HCAP) stress the importance of initiating prompt appropriate empiric antibiotic therapy. This study's purpose was to determine the percentage of patients with HAP, VAP, and HCAP who received guideline-based empiric antibiotic therapy and to determine the average time to receipt of an appropriate empiric regimen. A retrospective chart review of adults with HAP, VAP, or HCAP was conducted at a community hospital in suburban Birmingham, Alabama. The hospital's electronic medical record system utilized International Classification of Diseases, Ninth Revision (ICD-9) codes to identify patients diagnosed with pneumonia. The percentage of patients who received guideline-based empiric antibiotic therapy was calculated. The mean time from suspected diagnosis of pneumonia to initial administration of the final antibiotic within the empiric regimen was calculated for patients who received guideline-based therapy. Ninety-three patients met the inclusion criteria. The overall guideline adherence rate for empiric antibiotic therapy was 31.2%. The mean time to guideline-based therapy in hours:minutes was 7:47 for HAP and 28:16 for HCAP. For HAP and HCAP combined, the mean time to appropriate therapy was 21:55. Guideline adherence rates were lower and time to appropriate empiric therapy was greater for patients with HCAP compared to patients with HAP. © The Author(s) 2015.

How to measure the impacts of antibiotic resistance and antibiotic development on empiric therapy: new composite indices.

PubMed

Hughes, Josie S; Hurford, Amy; Finley, Rita L; Patrick, David M; Wu, Jianhong; Morris, Andrew M

2016-12-16

We aimed to construct widely useable summary measures of the net impact of antibiotic resistance on empiric therapy. Summary measures are needed to communicate the importance of resistance, plan and evaluate interventions, and direct policy and investment. As an example, we retrospectively summarised the 2011 cumulative antibiogram from a Toronto academic intensive care unit. We developed two complementary indices to summarise the clinical impact of antibiotic resistance and drug availability on empiric therapy. The Empiric Coverage Index (ECI) measures susceptibility of common bacterial infections to available empiric antibiotics as a percentage. The Empiric Options Index (EOI) varies from 0 to 'the number of treatment options available', and measures the empiric value of the current stock of antibiotics as a depletable resource. The indices account for drug availability and the relative clinical importance of pathogens. We demonstrate meaning and use by examining the potential impact of new drugs and threatening bacterial strains. In our intensive care unit coverage of device-associated infections measured by the ECI remains high (98%), but 37-44% of treatment potential measured by the EOI has been lost. Without reserved drugs, the ECI is 86-88%. New cephalosporin/β-lactamase inhibitor combinations could increase the EOI, but no single drug can compensate for losses. Increasing methicillin-resistant Staphylococcus aureus (MRSA) prevalence would have little overall impact (ECI=98%, EOI=4.8-5.2) because many Gram-positives are already resistant to β-lactams. Aminoglycoside resistance, however, could have substantial clinical impact because they are among the few drugs that provide coverage of Gram-negative infections (ECI=97%, EOI=3.8-4.5). Our proposed indices summarise the local impact of antibiotic resistance on empiric coverage (ECI) and available empiric treatment options (EOI) using readily available data. Policymakers and drug developers can use the

Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies.

PubMed

Taylor, Patrick K; Yeung, Amy T Y; Hancock, Robert E W

2014-12-10

The growth of bacteria as structured aggregates termed biofilms leads to their protection from harsh environmental conditions such as physical and chemical stresses, shearing forces, and limited nutrient availability. Because of this highly adapted ability to survive adverse environmental conditions, bacterial biofilms are recalcitrant to antibiotic therapies and immune clearance. This is particularly problematic in hospital settings where biofilms are a frequent cause of chronic and device-related infections and constitute a significant burden on the health-care system. The major therapeutic strategy against infections is the use of antibiotics, which, due to adaptive resistance, are often insufficient to clear biofilm infections. Thus, novel biofilm-specific therapies are required. Specific features of biofilm development, such as surface adherence, extracellular matrix formation, quorum sensing, and highly regulated biofilm maturation and dispersal are currently being studied as targets to be exploited in the development of novel biofilm-specific treatments. Using Pseudomonas aeruginosa for illustrative purposes, this review highlights the antibiotic resistance mechanisms of biofilms, and discusses current research into novel biofilm-specific therapies. Copyright © 2014 Elsevier B.V. All rights reserved.

[Adequacy of antibiotic therapy for urinary tract infection in a Medical Department from the university hospital of Lille: A retrospective cohort study].

PubMed

Deconinck, L; Maillard, H; Lemaitre, M; Barbottin, E; Bakhache, E; Galperine, T; Puisieux, F; Hatron, P-Y; Lambert, M

2015-11-01

The main objective of the study was to assess the adequacy of antibiotic therapy for urinary tract infections (UTI) in a French hospital medical department. The secondary objective was to identify factors associated with inadequacy of the antibiotic therapy. A retrospective single centre cohort study was performed in the Post-Emergency Medicine Department (PEMD) of the university hospital of Lille. All patients presenting with an UTI from May 2012 to April 2014 were included. Adequacy of antibiotic therapy was assessed with reference to local guidelines. Factors associated with inadequacy of antibiotic prescription were determined using a multivariate logistic regression model. Two hundred and twenty-eight patients were included. The antibiotic prescription was fully adequate in 173 patients (76%) with appropriate use of a single or a combination antibiotic therapy in 96%, appropriate drug in 80%, appropriate dosage in 89% and appropriate route of administration in 95%. The risk for antibiotic inadequacy was significantly higher in patients with cystitis than in those with pyelonephritis (OR 12.01; 95% CI 4.17-34.65), when antibiotics were prescribed in the Emergency Department (OR 6.84; 95% CI 2.29-20.47) or before hospital admission (OR 382.46; 95% CI 19.61≥999.99) compared to when antibiotics were first administered in the PEMD, and in patients with severe UTI (OR 19.55; 95% CI 2.79-137.01). Adequacy of antibiotic therapy for UTI is relatively high in our study, reflecting the effective dissemination of antibiotic guidelines. However, antibiotic therapy is still inappropriate in cystitis, severe UTI and in case of prescription before the admission in the PEMD. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

What exactly distinguishes aggressive from chronic periodontitis: is it mainly a difference in the degree of bacterial invasiveness?

PubMed

Van der Velden, Ubele

2017-10-01

At the International Workshop for Classification of Periodontal Diseases and Conditions in 1999, the classification of aggressive and chronic periodontitis that is presently used was introduced. A literature review of papers published in 2015 and having aggressive periodontitis in the title revealed that most studies use this terminology but it is questionable whether all established criteria were really applied correctly. Review of the literature showed no qualitative differences between aggressive and chronic periodontitis regarding bacterial and viral aspects. It is also unlikely that that there are major immunologic differences between aggressive and chronic periodontitis. Neutrophil function can be compromised in both conditions but may be more genetically related in aggressive periodontitis and be associated more with lifestyle factors in chronic periodontitis. In general, genetics plays a more important role in aggressive periodontitis than in chronic periodontitis. It is likely that periodontitis progresses by recurrent acute episodes during which invasion of bacteria into the connective tissue may occur. Two cases are presented for which invasive periodontitis is treated with systemic antibiotics, showing remarkable periodontal healing in terms of probing attachment gain, as well as radiographic bone gain. Periodontitis in an active state with bacterial invasion is probably accompanied with a significant increase in subgingival temperature. It is hypothesized that elevated subgingival temperature may help to distinguish between bacterial and nonbacterial invasive periodontitis. Scaling and root planing during a burst of disease activity may result in removal of connective tissue fiber attachment and down-growth of epithelium, thereby preventing the reattachment of connective tissue. Because the burst of disease is accompanied by an increase of temperature, assessment of the temperature may help in deciding whether or not to prescribe systemic antibiotics

Epidemiology, antibiotic therapy and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in cancer patients.

PubMed

Bodro, Marta; Gudiol, Carlota; Garcia-Vidal, Carolina; Tubau, Fe; Contra, Anna; Boix, Lucía; Domingo-Domenech, Eva; Calvo, Mariona; Carratalà, Jordi

2014-03-01

Infection due to the six ESKAPE pathogens has recently been identified as a serious emerging problem. However, there is still a lack of information on bacteremia caused by these organisms in cancer patients. We aimed to assess the epidemiology, antibiotic therapy and outcomes of bacteremia due to drug-resistant ESKAPE pathogens (rESKAPE) in patients with cancer. All episodes of bacteremia prospectively documented in hospitalized adults with cancer from 2006 to 2011 were analyzed. Of 1,148 episodes of bacteremia, 392 (34 %) were caused by ESKAPE pathogens. Fifty-four episodes (4.7 %) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium 0, methicillin-resistant Staphylococcus aureus (MRSA) 13, extended-spectrum beta-lactamase (ESLB)-producing Klebsiella pneumoniae 7, carbapenem-resistant Acinetobacter baumannii 4, carbapenem- and quinolone-resistant Pseudomonas aeruginosa 18 and derepression chromosomic ß-lactam and ESBL-producing Enterobacter species 12. Risk factors independently associated with rESKAPE bacteremia were comorbidities, prior antibiotic therapy, urinary catheter and urinary tract source. Inappropriate empirical antibiotic therapy was more frequent in patients with rESKAPE bacteremia than in the other cases (55.6 % vs. 21.5 %, p < 0.001). Persistence of bacteremia (25 % vs. 9.7 %), septic metastasis (8 % vs. 4 %) and early case-fatality rate (23 % vs. 11 %) were more frequent in patients with rESKAPE bacteremia than in patients with other etiologies (p < 0.05). Bacteremia due to rESKAPE pathogens in cancer patients occurs mainly among those with comorbidities who have received prior antibiotic therapy and have a urinary tract source. These patients often receive inappropriate empirical antibiotic therapy and have a poor outcome.

De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study.

PubMed

Moraes, Rafael Barberena; Guillén, Julián Alberto Viteri; Zabaleta, William Javier Castillo; Borges, Flavia Kessler

2016-09-01

To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates.

The Efficacy of Perioperative Antibiotic Therapy in Tonsillectomy Patients.

PubMed

Orłowski, Krzysztof; Lisowska, Grażyna; Misiołek, Hanna; Paluch, Zbigniew; Misiołek, Maciej

2016-01-01

While the results of early research suggested that perioperative antibiotic prophylaxis in tonsillectomy patients is associated with many benefits, these data were not confirmed by further studies and meta-analyses. The aim of this study was to investigate the usefulness and efficacy of antibiotic monotherapy in the healing of surgical wounds of patients undergoing bilateral resection of the palatine tonsils, based on an analysis of selected objective and subjective characteristics of wound healing during the postoperative period. The study included 50 men and women who underwent routine resection of the palatine tonsils. The patients were randomized into two groups: Group I, undergoing tonsillectomy with cefuroxime prophylaxis (n = 25), and Group II, who were not given perioperative antibiotic therapy (n = 25). The severity of signs and complaints recorded on postoperative days 1-10 was scored on 3- and 10-item scales. The only significant intergroup differences pertained to problems with swallowing food and fluids on postoperative days 4-6, 8 and 9 (less prevalent in Group II), postoperative use of analgesics on postoperative day 9 (less frequent in Group II), the degree of mucosal swelling in the operated area on postoperative days 3 and 7 (less severe in Group II), and the amount of fibrin covering the tonsillar niches on the third postoperative day (significantly higher in Group I). The administration of antibiotics for prevention or control of infection should be preceded by a comprehensive analysis of the potential benefits and risks. Perioperative use of antibiotics is justified only in selected cases, i.e. in individuals with comorbidities.

Empirical Comparison of Three Treatments for Adolescent Males with Physical and Sexual Aggression: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

ERIC Educational Resources Information Center

Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Murphy, Christopher J.; Hunter, Linda A.; Siv, Alexander M.

2005-01-01

This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

[Urinary pneumococcal or Legionella antigen detection tests and low-spectrum antibiotic therapy for community-acquired pneumonia].

PubMed

Roger, P-M; Risso, K; Hyvernat, H; Landraud, L; Vassallo, M; Dellamonica, J; de Salvador, F; Cua, E; Bernardin, G

2010-06-01

We performed urinary antigen tests for pneumococcus and Legionella for patients with community-acquired pneumonia (CAP), to prescribe a documented antibiotic therapy. We report the efficiency of low-spectrum antibiotic treatment, illustrating the inappropriateness of bacteriological respiratory sampling. Patients with CAP were enrolled from three different units; the pneumonia severity index was used to assess the disease. Respiratory samples were also listed. Low-spectrum antibiotic therapy was amoxicillin for pneumococcal infection, and macrolides or non-anti-pneumococcal fluoroquinolone for legionellosis. Six hundred and seventy-five CAP were diagnosed during the study period,, 150 with positive urinary antigen tests (23%), among which 108 pneumococcal infections (73%), 40 legionellosis (26%), and two mixed infections. The pneumonia severity index was 106+/-38. Amoxicillin was prescribed in 108 cases, fluoroquinolone in 24 cases, macrolide in 18 cases. The outcome was favourable for 138 patients (92%). Eighty three respiratory samples allowed identification of a bacterium for 58 patients (39%), among which 24 strains were not in the antibiotic spectrum: Haemophilus influenzae and Pseudmomonas aeruginosa in six cases, Staphylococcus aureus in five cases, Klebsiella pneumoniae in two cases, and another Gram negative bacillus in five cases. These strains were resistant in vitro to the prescribed treatment in 19/24 cases (79%). One out of 12 patients who died had a respiratory sample positive for Enterobacter spp strain resistant to the ongoing antibiotic treatment. The low-spectrum antibiotic therapy based on urinary antigen tests is efficient, and demonstrates respiratory tract colonisation with bacteriological strains usually considered as pathogenic.

Paradoxically aggressive multiple sclerosis in the face of natalizumab therapy.

PubMed

Berger, J R

2008-06-01

In the pivotal trials of natalizumab in the treatment of relapsing-remitting multiple sclerosis (AFFIRM and SENTINEL), a dramatic reduction in relapse rate, new or enlarging T2-hyperintense lesions, and mean number of gadolinium-enhancing lesions was observed. While both relapses and new MRI lesions were observed in these trials, there has been no comment on the presence of aggressive disease in the face of natalizumab treatment. I report a 31-year-old woman with relapsing remitting MS of 12 years duration who developed aggressive demyelinating disease four months after the initiation of natalizumab. The clinical worsening was accompanied by a significant increase in new large T2-hyperintense signal abnormalities and in both solid and C-shaped contrast-enhancing lesions. Neither the clinical severity nor the striking MRI abnormalities had been noted earlier in her disease course. Neutralizing antibodies to natalizumab were not detected. She subsequently responded to combination therapy of pulsed methylprednisolone and daily glatiramer acetate.

Use of Prophylactic Antibiotics to Prevent Abscess Formation Following Hepatic Ablation in Patients with Prior Enterobiliary Manipulation

PubMed Central

Richter, Michael; Aloia, Thomas A.; Conrad, Claudius; Ahrar, Kamran; Gupta, Sanjay; Vauthey, Jean-Nicolas; Huang, Steven Y.

2016-01-01

Introduction Prior enterobiliary manipulation confers a high risk for liver abscess formation after hepatic ablation. We aimed to determine if prophylactic antibiotics could prevent post-ablation abscess in patients with a history of hepaticojejunostomy. Materials and Methods This single-institution retrospective study identified 262 patients who underwent 307 percutaneous liver ablation sessions between January 2010 and August 2014. Twelve (4.6%) patients with prior hepaticojejunostomy were included in this analysis. Ten (83>%) had received an aggressive prophylactic antibiotic regimen consisting of levofloxacin, metronidazole, neomycin, and erythromycin base. Two (16.6%) had received other antibiotic regimens. Clinical, laboratory, and imaging findings were used to identify abscess formation and antibiotic-related side effects. Results Twelve ablation sessions were performed during the period studied. During a mean follow-up period of 440 days (range, 77–1784 days), post-ablation abscesses had developed in 2 (16.6 %) patients, who both received the alternative antibiotic regimens. None of the 10 patients who received the aggressive prophylactic antibiotic regimen developed liver abscess. One of the 10 patients who received the aggressive prophylactic antibiotic regimen developed grade 2 antibiotic-related diarrhea and arthralgia. Conclusion An aggressive regimen of prophylactic antibiotics may be effective in preventing liver abscess formation after liver ablation in patients with prior hepaticojejunostomy. PMID:26984694

Use of Prophylactic Antibiotics to Prevent Abscess Formation Following Hepatic Ablation in Patients with Prior Enterobiliary Manipulation.

PubMed

Odisio, Bruno C; Richter, Michael; Aloia, Thomas A; Conrad, Claudius; Ahrar, Kamran; Gupta, Sanjay; Vauthey, Jean-Nicolas; Huang, Steven Y

2016-08-01

Prior enterobiliary manipulation confers a high risk for liver abscess formation after hepatic ablation. We aimed to determine if prophylactic antibiotics could prevent post-ablation abscess in patients with a history of hepaticojejunostomy. This single-institution retrospective study identified 262 patients who underwent 307 percutaneous liver ablation sessions between January 2010 and August 2014. Twelve (4.6 %) patients with prior hepaticojejunostomy were included in this analysis. Ten (83> %) had received an aggressive prophylactic antibiotic regimen consisting of levofloxacin, metronidazole, neomycin, and erythromycin base. Two (16.6 %) had received other antibiotic regimens. Clinical, laboratory, and imaging findings were used to identify abscess formation and antibiotic-related side effects. Twelve ablation sessions were performed during the period studied. During a mean follow-up period of 440 days (range, 77-1784 days), post-ablation abscesses had developed in 2 (16.6 %) patients, who both received the alternative antibiotic regimens. None of the 10 patients who received the aggressive prophylactic antibiotic regimen developed liver abscess. One of the 10 patients who received the aggressive prophylactic antibiotic regimen developed grade 2 antibiotic-related diarrhea and arthralgia. An aggressive regimen of prophylactic antibiotics may be effective in preventing liver abscess formation after liver ablation in patients with prior hepaticojejunostomy.

Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

PubMed

Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

2012-11-01

Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

PubMed

Pouwels, K B; Van Kleef, E; Vansteelandt, S; Batra, R; Edgeworth, J D; Smieszek, T; Robotham, J V

2017-05-01

Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature. Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes. Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

[Antibiotics, azelaic acid and benzoyl peroxide in topical acne therapy].

PubMed

Fluhr, Joachim W; Degitz, Klaus

2010-03-01

Benzoyl peroxide was introduced as a basic treatment already in acne therapy 1934. The mechanism of action is the reduction of anaerobe bacteria by strong oxidation processes. No resistancies have been ever reported. BPO is available in 2.5, 5 and 10 % formulations. Its efficacy is slightly related to the strength of concentrations, but the side effect profile with burning, erythema and desquamation is increasing with concentrations. BPO 5% mostly is efficient enough to control acne of grades I to II according to the Kligman & Plewig classification. BPO my bleach clothes and hair. It is the most costeffective topical drug in acne of grades I-II. Inflammatory acne of the papular-pustular type I-II can also be treated by topical antibiotics such as erythromycin, clindamycin, and, less frequent and today not anymore recommended tetracyclines. Mechanism of action is not alone an antibacterial but anti inflammatory effect. The efficacy and penetration of the topical antibiotics between the groups are similar. Randomized studies have shown that concentrations of 2-4% are equivalent to oral tetracycline and minocycline in mild to moderate acne. Combinatory formulations with BPO and with retinoids enhance the efficacy significantly. Topical antibiotics plus BPO show less bacterial resistancies as topical antibiotics alone. Antibiotics should therefore not be used as monotherapy. Moreover gram negative folliculitis may develop. Azelaic acid is acting as an antimicrobial and can also reduce comedones. It can also be used in pregnancy and during the lactation period.

Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates.

PubMed

Song, Zhiqiang; Zhou, Liya; Zhang, Jianzhong; He, Lihua; Bai, Peng; Xue, Yan

2016-10-01

Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates. This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing. Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126-30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014). Despite good compliance and

Effects of One-Week Empirical Antibiotic Therapy on the Early Development of Gut Microbiota and Metabolites in Preterm Infants.

PubMed

Zhu, Danping; Xiao, Sa; Yu, Jialin; Ai, Qing; He, Yu; Cheng, Chen; Zhang, Yunhui; Pan, Yun

2017-08-14

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.

Patient and physician predictors of patient receipt of therapies recommended by a computerized decision support system when initially prescribed broad-spectrum antibiotics: a cohort study

PubMed Central

Lye, David C.; Arah, Onyebuchi A

2016-01-01

Objective Antibiotic computerized decision support systems (CDSSs) were developed to guide antibiotic decisions, yet prescriptions of CDSS-recommended antibiotics have remained low. Our aim was to identify predictors of patients' receipt of empiric antibiotic therapies recommended by a CDSS when the prescribing physician had an initial preference for using broad-spectrum antibiotics. Methods We conducted a prospective cohort study in a 1 500-bed tertiary-care hospital in Singapore. We included all patients admitted from October 1, 2011 through September 30, 2012, who were prescribed piperacillin-tazobactam or carbapenem for empiric therapy and auto-triggered to receive antibiotic recommendations by the in-house antibiotic CDSS. Relevant data on the patient, prescribing and attending physicians were collected via electronic linkages of medical records and administrative databases. To account for clustering, we used multilevel logistic regression models to explore factors associated with receipt of CDSS-recommended antibiotic therapy. Results One-quarter of the 1 886 patients received CDSS-recommended antibiotics. More patients treated for pneumonia (33.2%) than sepsis (12.1%) and urinary tract infections (7.1%) received CDSS-recommended antibiotic therapies. The prescribing physician – but not the attending physician or clinical specialty – accounted for some (13.3%) of the variation. Prior hospitalization (odds ratio [OR] 1.32, 95% CI, 1.01-1.71), presumed pneumonia (OR 6.77, 95% CI, 3.28-13.99), intensive care unit (ICU) admission (OR 0.38, 95% CI, 0.21-0.66), and renal impairment (OR 0.70, 95% CI, 0.52-0.93) were factors associated with patients’ receipt of CDSS-recommended antibiotic therapies. Conclusions We observed that ICU admission and renal impairment were negative predictors of patients’ receipt of CDSS-recommended antibiotic therapies. Patients admitted to ICU and those with renal impairment might have more complex clinical conditions that

Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children: A Meta-analysis.

PubMed

Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Li, Yuan; Zhou, Zongguang

2017-05-01

Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a

Importance of nondrug costs of intravenous antibiotic therapy.

PubMed

van Zanten, Arthur R H; Engelfriet, Peter M; van Dillen, Karin; van Veen, Miriam; Nuijten, Mark J C; Polderman, Kees H

2003-12-01

costs) were calculated this resulted in average costs of 5.65, 7.28, 5.36 and 3.83, respectively, for administration of each dose of antibiotics. These costs represent between 11% and 53% of the total daily costs of antibiotic therapy. Compared with the acquisition costs, these indirect costs ranged from 13% to 113%. Not included in this comparison is the time required for insertion of an IV catheter, which was found to be 10:15 +/- 6:31 min with an average calculated cost of 9.17. Total costs of IV antibiotic administration are formed not only by the costs of the drugs themselves, but also, to a substantial degree, by the time expended by medical and nursing staff, costs of disposable materials and overhead costs. Physicians making decisions regarding the use of specific medications in intensive care unit patients should take these factors into account. Use of IV antibiotics is associated with considerable workload and additional costs that can exceed the acquisition costs of the medications themselves.

Adjunct Antimicrobial Therapy and Periodontal Surgery to Treat Generalized Aggressive Periodontitis: A Case Report.

PubMed

Irokawa, Daisuke; Makino-Oi, Asako; Fujita, Takahisa; Yamamoto, Shigeki; Tomita, Sachiyo; Saito, Atsushi

2016-01-01

Here we report a case of generalized aggressive periodontitis treated with periodontal therapy including adjunct antimicrobial therapy and periodontal surgery. The patient was a 22-year-old woman who presented with the chief complaint of gingival recession. Baseline examination revealed generalized plaque deposition and gingival inflammation. Thirty-nine percent of the sites had a probing depth (PD) of 4-6 mm and 2% a PD of ≥7 mm; 63% exhibited bleeding on probing (BOP). Radiographic examination revealed vertical bone loss in the molars and horizontal bone loss in other teeth. Microbiological examination of subgingival plaque revealed the presence of Aggregatibacter actinomycetemcomitans and Tannerella forsythia. Oral health-related quality of life was assessed as a measure of patient-reported outcome. Based on a clinical diagnosis of generalized aggressive periodontitis, initial periodontal therapy and adjunct antimicrobial therapy were implemented. After reducing inflammation and subgingival bacteria, open flap debridement was performed for teeth with a PD of ≥4 mm. Reevaluation showed no sites with a PD of ≥5 mm, a minimal level of BOP, and a marked reduction in the level of the targeted periodontal pathogens. The patient's oral health-related quality of life was slightly worsened during supportive periodontal therapy (SPT). Implementation of adjunct antimicrobial therapy targeting periodontal pathogens and subsequent periodontal surgery resulted in improvement in periodontal and microbiological parameters. This improvement has been adequately maintained over a 2-year period. However, additional care is necessary to further improve the patient's oral health-related quality of life during SPT.

Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia.

PubMed

Esposito, Susanna; Garziano, Micaela; Rainone, Veronica; Trabattoni, Daria; Biasin, Mara; Senatore, Laura; Marchisio, Paola; Rossi, Marta; Principi, Nicola; Clerici, Mario

2015-09-03

Several attempts to improve immune function in young children have been made and encouraging results have been collected with pidotimod (PDT), a synthetic dipeptide molecule that seems to have immunomodulatory activity on both innate and adaptive responses. Until now, the effects of PDT on the immune system have only been studied in vivo after long-term administration to evaluate whether its immunomodulatory activity might prevent the development of infections. This study was planned to evaluate the immunomodulatory activity of PDT administered together with standard antibiotic therapy in children hospitalized for community-acquired pneumonia (CAP). A total of 20 children hospitalized for community-acquired pneumonia (CAP) were randomized at a 1:1 ratio to receive either standard antibiotics plus pidotimod (PDT) or standard antibiotics alone to evaluate the immunomodulatory activity of PDT. Blood samples for the evaluation of immunological parameters were drawn at the time of recruitment (T0) (i.e., before therapy administration), at T3 and T5 (i.e., 3 and 5 days after the initiation of therapy) as well as at T21 (i.e., 7 days after the therapy ended). Following pneumococcal polysaccharide stimulation, the percentage of dendritic cells (DCs) expressing activation and costimulatory molecules was significantly higher in children receiving PDT plus antibiotics than in the controls. A significant increase in tumor necrosis factor-α and/or interleukin-12 secretion and expression of toll like receptor 2 was observed in PDT-treated children compared with controls; this was followed by an increased release of proinflammatory cytokines by monocytes. In the PDT-treated group, mRNA expression of antimicrobial peptides and genes involved in the inflammatory response were also augmented in comparison with the controls. These results demonstrate, for the first time, that PDT administered together with standard antibiotics is associated with a favorable persistent

Stenting versus aggressive medical therapy for intracranial arterial stenosis.

PubMed

Chimowitz, Marc I; Lynn, Michael J; Derdeyn, Colin P; Turan, Tanya N; Fiorella, David; Lane, Bethany F; Janis, L Scott; Lutsep, Helmi L; Barnwell, Stanley L; Waters, Michael F; Hoh, Brian L; Hourihane, J Maurice; Levy, Elad I; Alexandrov, Andrei V; Harrigan, Mark R; Chiu, David; Klucznik, Richard P; Clark, Joni M; McDougall, Cameron G; Johnson, Mark D; Pride, G Lee; Torbey, Michel T; Zaidat, Osama O; Rumboldt, Zoran; Cloft, Harry J

2011-09-15

Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial. We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.).

Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

NASA Astrophysics Data System (ADS)

Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

2017-06-01

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

Variability in Antibiotic Use Across PICUs.

PubMed

Brogan, Thomas V; Thurm, Cary; Hersh, Adam L; Gerber, Jeffrey S; Smith, Michael J; Shah, Samir S; Courter, Joshua D; Patel, Sameer J; Parker, Sarah K; Kronman, Matthew P; Lee, Brian R; Newland, Jason G

2018-06-01

To characterize and compare antibiotic prescribing across PICUs to evaluate the degree of variability. Retrospective analysis from 2010 through 2014 of the Pediatric Health Information System. Forty-one freestanding children's hospital. Children aged 30 days to 18 years admitted to a PICU in children's hospitals contributing data to Pediatric Health Information System. To normalize for potential differences in disease severity and case mix across centers, a subanalysis was performed of children admitted with one of the 20 All Patient Refined-Diagnosis Related Groups and the seven All Patient Refined-Diagnosis Related Groups shared by all PICUs with the highest antibiotic use. The study included 3,101,201 hospital discharges from 41 institutions with 386,914 PICU patients. All antibiotic use declined during the study period. The median-adjusted antibiotic use among PICU patients was 1,043 days of therapy/1,000 patient-days (interquartile range, 977-1,147 days of therapy/1,000 patient-days) compared with 893 among non-ICU children (interquartile range, 805-968 days of therapy/1,000 patient-days). For PICU patients, the median adjusted use of broad-spectrum antibiotics was 176 days of therapy/1,000 patient-days (interquartile range, 152-217 days of therapy/1,000 patient-days) and was 302 days of therapy/1,000 patient-days (interquartile range, 220-351 days of therapy/1,000 patient-days) for antimethicillin-resistant Staphylococcus aureus agents, compared with 153 days of therapy/1,000 patient-days (interquartile range, 130-182 days of therapy/1,000 patient-days) and 244 days of therapy/1,000 patient-days (interquartile range, 203-270 days of therapy/1,000 patient-days) for non-ICU children. After adjusting for potential confounders, significant institutional variability existed in antibiotic use in PICU patients, in the 20 All Patient Refined-Diagnosis Related Groups with the highest antibiotic usage and in the seven All Patient Refined-Diagnosis Related Groups shared

Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

PubMed Central

Gjini, Erida; Brito, Patricia H.

2016-01-01

Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes. PMID:27078624

RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance.

PubMed

Alam, Md Kausar; Alhhazmi, Areej; DeCoteau, John F; Luo, Yu; Geyer, C Ronald

2016-03-17

Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, β-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protocol for extended antibiotic therapy after laparoscopic cholecystectomy for acute calculous cholecystitis (Cholecystectomy Antibiotic Randomised Trial, CHART).

PubMed

Pellegrini, Pablo; Campana, Juan Pablo; Dietrich, Agustín; Goransky, Jeremías; Glinka, Juan; Giunta, Diego; Barcan, Laura; Alvarez, Fernando; Mazza, Oscar; Sánchez Claria, Rodrigo; Palavecino, Martin; Arbues, Guillermo; Ardiles, Victoria; de Santibañes, Eduardo; Pekolj, Juan; de Santibañes, Martin

2015-11-18

Acute calculous cholecystitis represents one of the most common complications of cholelithiasis. While laparoscopic cholecystectomy is the standard treatment in mild and moderate forms, the need for antibiotic therapy after surgery remains undefined. The aim of the randomised controlled Cholecystectomy Antibiotic Randomised Trial (CHART) is therefore to assess if there are benefits in the use of postoperative antibiotics in patients with mild or moderate acute cholecystitis in whom a laparoscopic cholecystectomy is performed. A single-centre, double-blind, randomised trial. After screening for eligibility and informed consent, 300 patients admitted for acute calculus cholecystitis will be randomised into two groups of treatment, either receiving amoxicillin/clavulanic acid or placebo for 5 consecutive days. Postoperative evaluation will take place during the first 30 days. Postoperative infectious complications are the primary end point. Secondary end points are length of hospital stay, readmissions, need of reintervention (percutaneous or surgical reinterventions) and overall mortality. The results of this trial will provide strong evidence to either support or abandon the use of antibiotics after surgery, impacting directly in the incidence of adverse events associated with the use of antibiotics, the emergence of bacterial resistance and treatment costs. This study and informed consent sheets have been approved by the Research Projects Evaluating Committee (CEPI) of Hospital Italiano de Buenos Aires (protocol N° 2111). The results of the trial will be reported in a peer-reviewed publication. NCT02057679. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality.

PubMed

Díaz-Martín, Ana; Martínez-González, María Luisa; Ferrer, Ricard; Ortiz-Leyba, Carlos; Piacentini, Enrique; Lopez-Pueyo, Maria Jesus; Martín-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antoni; Garnacho-Montero, José

2012-11-18

Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

PubMed

Herath, Samantha C; Poole, Phillippa

2013-11-28

.The development of antibiotic resistance in the community is of major concern. One study found newly colonised patients to have higher rates of antibiotic resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. Use of continuous prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All trials of continuous antibiotics used macrolides hence the noted benefit applies only to the use of continuous macrolide antibiotics. The impact of pulsed antibiotics remains uncertain and requires further research.The trials in this review included patients who were frequent exacerbators and needed treatment with antibiotics or systemic steroids, or who were on supplemental oxygen. There were also older individuals with a mean age of 66 years. The results of these trials apply only to the group of patients who were studied in these trials and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse.

Antibiotic Therapy of Staphylococcal Infections

PubMed Central

Hawks, Gordon H.

1965-01-01

The antibiotic treatment of staphylococcal infections remains a problem. Isolation of the organism and sensitivity testing are necessary in the choice of antibiotic. Penicillin G is the most effective penicillin against non-penicillinase-producing staphy-lococci; for the penicillinase producers there is very little to choose between the semisynthetic penicillins, methicillin, cloxacillin, nafcillin and oxacillin. For patients who are hypersensitive to penicillin, the bacteriostatic drugs (erythromycin, novobiocin, tetracycline, chloramphenicol, oleandomycin) are useful for mild infections, while for more severe illness the bactericidal drugs (vancomycin, ristocetin, kanamycin, bacitracin, neomycin) have been used successfully. Acute staphylococcal enterocolitis is probably best treated by a semisynthetic penicillin. Other antibiotics which have been found useful, with clinical trials, for staphylococcal infections are cephalosporin, fucidin, cephaloridine and lincomycin. The latter drug has been reported of value in the treatment of osteomyelitis. There is little justification for the prophylactic use of antibiotics to prevent staphylococcal infection. Surgical drainage is still an important adjunct in the treatment of many staphylococcal infections. PMID:5318575

Emergency Department Management of Patients With Febrile Neutropenia: Guideline Concordant or Overly Aggressive?

PubMed

Baugh, Christopher W; Wang, Thomas J; Caterino, Jeffrey M; Baker, Olesya N; Brooks, Gabriel A; Reust, Audrey C; Pallin, Daniel J

2017-01-01

The Infectious Diseases Society of America and the American Society of Clinical Oncology recommend risk stratification of patients with febrile neutropenia (FN) and discharge with oral antibiotics for low-risk patients. We studied guideline concordance and clinical outcomes of FN management in our emergency department (ED). Our urban, tertiary care teaching hospital provides all emergency and inpatient services to a large comprehensive cancer center. We performed a structured chart review of all FN patients seen in our ED from January 2010 to December 2014. Using electronic medical records, we identified all visits by patients with fever and an absolute neutrophil count of <1000 cells/mm 3 and then included only patients without a clear source of infection. Following national guidelines, we classified patients as low or high risk and assessed guideline concordance in disposition and parenteral versus oral antibiotic therapy by risk category as our main outcome measure. Of 173 qualifying visits, we classified 44 (25%) as low risk and 129 (75%) as high risk. Management was guideline concordant in 121 (70%, 95% confidence interval [CI] = 63% to 77%). Management was guideline discordant in 43 (98%, 95% CI = 88% to 100%) of low-risk patients versus 9 (7%, 95% CI = 3% to 13%) of high-risk patients (relative risk [RR] = 14, 95% CI = 7.5 to 26). Of 52 guideline-discordant cases, 36 (83%, 95% CI = 72% to 93%) involved low-risk cases with treatment that was more aggressive than recommended. Guideline concordance was low among low-risk patients, with management tending to be more aggressive than recommended. Unless data emerge that undermine the guidelines, we believe that many of these hospitalizations and parenteral antibiotic regimens can be avoided, decreasing the risks associated with hospitalization, while improving antibiotic stewardship and patient comfort. © 2016 by the Society for Academic Emergency Medicine.

[Antibiotics in the critically ill].

PubMed

Kolak, Radmila R

2010-01-01

Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy

PubMed Central

Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.

2014-01-01

Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

[Special characteristics of antibiotic therapy in the elderly].

PubMed

Stock, Ingo

2012-03-01

The ever-increasing proportion of elderly people in the general population represents physicians and pharmacists with new challenges. Older people suffer more frequently than younger persons from bacterial diseases, and they have a higher tendency to develop more severe or progressive forms of these illnesses. Bacterial diseases of the urinary tract, respiratory tract, skin and soft tissues are especially common in old age. In general, most antibacterial agents are also promising agents for the therapy of bacterial diseases in the elderly. Prior to initiating therapy, however, the modified organ functions of the elderly have to be considered carefully. Depending on the individual and the antibacterial agent, a dose adjustment may be necessary. To reduce the high mortality rate characteristic for many infectious diseases in the elderly, antibacterial therapy ought to be carefully calculated and initiated as quickly as possible. It has to be born in mind that some side effects of antibiotics are more common and more severe in old age. Since older people often take several drugs simultaneously, the probability for the occurrence of side effects and drug interactions in this population is greatly increased. Significant compliance problems may also arise.

Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

PubMed

Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

2018-05-01

To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study.

PubMed

Gattarello, Simone; Lagunes, Leonel; Vidaur, Loreto; Solé-Violán, Jordi; Zaragoza, Rafael; Vallés, Jordi; Torres, Antoni; Sierra, Rafael; Sebastian, Rosa; Rello, Jordi

2015-09-10

We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000-2002 and 2008-2014, and the impact of the improvement in antibiotic strategies on outcomes. This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000-2002 database (CAPUCI I group) were paired with 72 from the 2008-2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1%) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7%); prevalence of shock was 59.7%, while 73.6% of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7% versus 16.7%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5% in CAPUCI I and 92.7% in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3% and 37.5 versus 63.9%; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95% CI 0.07-0.74) and early antibiotic treatment (OR 0.07, 95% CI 0.02-0.22) were independently associated with decreased intensive care unit mortality. In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.

Pilot study evaluating the effect of massage therapy on stress, anxiety and aggression in a young adult psychiatric inpatient unit.

PubMed

Garner, Belinda; Phillips, Lisa J; Schmidt, Hans-Martin; Markulev, Connie; O'Connor, Jenny; Wood, Stephen J; Berger, Gregor E; Burnett, Peter; McGorry, Patrick D

2008-05-01

The aim of the present pilot study was to examine the effectiveness of a relaxation massage therapy programme in reducing stress, anxiety and aggression on a young adult psychiatric inpatient unit. This was a prospective, non-randomized intervention study comparing treatment as usual (TAU) with TAU plus massage therapy intervention (MT) over consecutive 7 week blocks (May-August 2006). MT consisted of a 20 min massage therapy session offered daily to patients during their period of hospitalization. The Kennedy Nurses' Observational Scale for Inpatient Evaluation (NOSIE), the Symptom Checklist-90-Revised (SCL-90-R), the State-Trait Anxiety Inventory (STAI) and stress hormone (saliva cortisol) levels were used to measure patient outcomes at admission and discharge from the unit. The Staff Observation Aggression Scale-Revised (SOAS-R) was used to monitor the frequency and severity of aggressive incidents on the unit. There was a significant reduction in self-reported anxiety (p < 0.001), resting heart rate (p < 0.05) and cortisol levels (p < 0.05) immediately following the initial and final massage therapy sessions. Significant improvements in hostility (p = 0.007) and depression scores (p < 0.001) on the SCL-90-R were observed in both treatment groups. There was no group x time interaction on any of the measures. Poor reliability of staff-reported incidents on the SOAS-R limited the validity of results in this domain. Massage therapy had immediate beneficial effects on anxiety-related measures and may be a useful de-escalating tool for reducing stress and anxiety in acutely hospitalized psychiatric patients. Study limitations preclude any definite conclusions on the effect of massage therapy on aggressive incidents in an acute psychiatric setting. Randomized controlled trials are warranted.

Prospective open-label randomized comparative, non-inferiority study of two initial antibiotic strategies for patients with nursing- and healthcare-associated pneumonia: Guideline-concordant therapy versus empiric therapy.

PubMed

Matsuda, Shuichi; Ogasawara, Takashi; Sugimoto, Shunsuke; Kato, Shinpei; Umezawa, Hiroki; Yano, Toshiaki; Kasamatsu, Norio

2016-06-01

The nursing- and healthcare-associated pneumonia guideline, proposed by the Japan Respiratory Society, recommends that patients at risk of exposure to drug-resistant pathogens, classified as treatment category C, be treated with antipseudomonal antibiotics. This study aimed to prove the non-inferiority of empirical therapy in our hospital compared with guideline-concordant therapy. This was a randomized controlled trial conducted from December 2011 to December 2012. Patients were randomized to the Guideline group receiving guideline-concordant therapy, and the Empiric group treated with sulbactam/ampicillin or ceftriaxone. The primary endpoint was in-hospital relapse of pneumonia and mortality within 30 days, with a predefined non-inferiority margin of 10%. The secondary endpoints included duration, adverse effects, and cost of antibiotic therapy. One hundred and eleven patients were assigned to the Guideline group (n = 55) and the Empiric group (n = 56; 3 of which were excluded). The incidence of relapse and death within 30 days was similar in the Guideline and the Empiric groups (31% vs. 26%, risk difference -4.5%, 95% CI -21.5% to 12.5%). While the duration of antibiotic therapy was slightly shorter in the Guideline group than in the Empiric group (7 vs. 8 days), there were no significant differences in adverse effects or cost. The efficacy of empiric therapy was comparable to guideline-concordant therapy, although non-inferiority was not proven. The administration of broad-spectrum antibiotics to patients at risk of exposure to drug-resistant pathogens may not necessarily improve the prognosis. UMIN000006792. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

De-escalating therapy in gastric aggressive lymphoma.

PubMed

Cuccurullo, Rosanna; Govi, Silvia; Ferreri, Andrés J M

2014-07-21

The treatment of primary gastric diffuse large B-cell lymphoma (DLBCL) has changed radically over the last 10-15 years, with the abandonment of routine gastrectomy in favor of more conservative therapies. Low-level evidence suggests that consolidation radiotherapy could be avoided in patients with limited-stage DLBCL of the stomach who achieve complete remission after rituximab-CHOP combination. Small, recent prospective trials suggest that selected patients with limited-stage Helicobacter pylori (H. pylori)-positive DLBCL of the stomach and favorable prognostic factors can be managed with antibiotics alone, with excellent disease control and cure rates, keeping chemo-radiotherapy for unresponsive patients. This recommendation should equally regard patients with mucosa-associated lymphoid tissue-related or de novo DLBCL. Future studies should be focused on the establishment of reliable variables able to distinguish the best candidates for exclusive treatment with H. pylori eradication from those who need for conventional chemo-immunotherapy.

Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

PubMed

Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

2010-05-01

No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (antibiotic therapy (>7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with antibiotic treatment (OR 0.6; 95% CI 0.1-2.9) or >14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

Newly approved antibiotics and antibiotics reserved for resistant infections: Implications for emergency medicine.

PubMed

Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa

2017-01-01

Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

PubMed

Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

2017-07-01

Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p < 0.01; respectively). Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis

PubMed Central

Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O’Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman T.; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.

2011-01-01

OBJECTIVES To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months. METHODS Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months. RESULTS By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events. CONCLUSIONS Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment. PMID:22183975

Subinhibitory antibiotic therapy alters recurrent urinary tract infection pathogenesis through modulation of bacterial virulence and host immunity.

PubMed

Goneau, Lee W; Hannan, Thomas J; MacPhee, Roderick A; Schwartz, Drew J; Macklaim, Jean M; Gloor, Gregory B; Razvi, Hassan; Reid, Gregor; Hultgren, Scott J; Burton, Jeremy P

2015-03-31

The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections. Antibiotics are the mainstay treatment for bacterial infections; however, evidence is emerging that argues these agents may have off-target effects if sublethal concentrations are present. Most studies have focused on changes occurring in vitro, leaving questions regarding the clinical relevance in vivo. We utilized a murine urinary tract infection model to explore the potential impact of low-dose antibiotics on pathogenesis. Using this model, we showed that subinhibitory antibiotics prime uropathogens for adherence and invasion of murine urothelial tissues. These changes in initial colonization promoted the establishment of chronic infection. Furthermore, treatment of chronically infected mice with subtherapeutic ciprofloxacin served to exacerbate infection. A part of these changes was

Long-Term Clinical Response to Treatment and Maintenance of Localized Aggressive Periodontitis: A Cohort Study

PubMed Central

Miller, Karina A. F. S.; Branco-de-Almeida, Luciana S.; Wolf, Sandra; Hovencamp, Nicole; Treloar, Tina; Harrison, Peter; Aukhil, Ikramuddin; Gong, Yan; Shaddox, Luciana M.

2016-01-01

Aim To evaluate long-term clinical response to periodontal therapy and maintenance in localized aggressive periodontitis (LAP). Materials and Methods One hundred forty-one African-Americans diagnosed with LAP, aged 5–25 years, were enrolled. Patients underwent periodontal mechanical debridement plus one week of amoxicillin/metronidazole. Mechanical therapy was repeated as needed and clinical parameters were recorded at baseline, 3, 6, 12, 18, and 24 months, and 2 additional annual follow-up visits after treatment. Radiographs from primary dentition of patients with LAP in permanent dentition, and additional healthy siblings (HS) were analyzed retrospectively. Results Periodontal therapy significantly improved probing depth and clinical attachment level up to 4 years (mean reductions: 2.18 ± 1.03 and 2.80 ± 1.43 mm, respectively). Percentage of affected sites was reduced at all timepoints and maintained up to 4 years. Noncompliance with antibiotics/appointments negatively affected the treatment response. Ninety percent of LAP patients in permanent dentition and 32% of HS presented radiographic bone loss in primary dentition. Conclusions Mechanical debridement with one-week of systemic antibiotics along with proper periodontal maintenance was effective in the treatment and successful maintenance of LAP for up to 4 years. LAP in permanent dentition may be preceded in the primary dentition. Clinicaltrials.gov #NCT01330719. PMID:27767222

PIRATE project: point-of-care, informatics-based randomised controlled trial for decreasing overuse of antibiotic therapy in Gram-negative bacteraemia.

PubMed

Huttner, Angela; Albrich, Werner C; Bochud, Pierre-Yves; Gayet-Ageron, Angèle; Rossel, Anne; Dach, Elodie von; Harbarth, Stephan; Kaiser, Laurent

2017-07-13

Antibiotic overuse drives antibiotic resistance. The optimal duration of antibiotic therapy for Gram-negative bacteraemia (GNB), a common community and hospital-associated infection, remains unknown and unstudied via randomised controlled trials (RCTs). This investigator-initiated, multicentre, non-inferiority, informatics-based point-of-care RCT will randomly assign adult hospitalised patients receiving microbiologically efficacious antibiotic(s) for GNB to (1) 14 days of antibiotic therapy, (2) 7 days of therapy or (3) an individualised duration determined by clinical response and 75% reduction in peak C reactive protein (CRP) values. The randomisation will occur in equal proportions (1:1:1) on day 5 (±1) of efficacious antibiotic therapy as determined by antibiogram; patients, their physicians and study investigators will be blind to treatment duration allocation until the day of antibiotic discontinuation. Immunosuppressed patients and those with GNB due to complicated infections (endocarditis, osteomyelitis, etc) and/or non-fermenting bacilli ( Acinetobacter spp, Burkholderia spp, Pseudomonas spp) Brucella spp, Fusobacterium spp or polymicrobial growth with Gram-positive organisms will be ineligible. The primary outcome is incidence of clinical failure at day 30; secondary outcomes include clinical failure, all-cause mortality and incidence of Clostridiumdifficile infection in the 90-day study period. An interim safety analysis will be performed after the first 150 patients have been followed for ≤30 days. Given a chosen margin of 10%, the required sample size to determine non-inferiority is roughly 500 patients. Analyses will be performed on both intention-to-treat and per-protocol populations. Ethics approval was obtained from the cantonal ethics committees of all three participating sites. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. This trial is registered at www

Prophylactic broad spectrum antibiotics as a new anti-myeloma therapy.

PubMed

Valkovic, Toni; Nacinovic, Antica Duletic; Petranovic, Duska

2013-12-01

Multiple myeloma is a common, yet incurable, haematological neoplasm. The reciprocal communication between malignant plasma cells, other cell types, and the extracellular matrix in the bone marrow micro-eco system is mediated by cell-cell and cell-matrix adhesion, as well as the production of different soluble factors, and is crucial for tumour growth and drug resistance. Inflammation and pro-inflammatory cytokines contribute to the clonal expansion of neoplastic plasmacytes. This extremely complex pathogenesis of multiple myeloma gives us the opportunity to promote numerous novel drugs and approaches based on the paradigm of targeted therapy. Immune dysfunction is a hallmark of multiple myeloma. Intrinsic and therapy-related immunosuppression leads to an increased risk of recurrent infection, the major cause of mortality. However, little data is available regarding the possible influence of infection on the biology and progression of multiple myeloma. Some authors have shown that pathogenic microorganisms can activate tool-like receptors on myeloma cells, as well as the robust production of pro-inflammatory cytokines; together these factors can contribute to myeloma growth, survival, and progression. Therefore, we proposed a simple, inexpensive, and new approach for anti-myeloma therapy that, to the best of our knowledge, is the first one concerning the prophylactic, long-term use of broad-spectrum antibiotics during the course of disease regardless of the chosen concomitant regimens. Prophylactic treatment with antibiotics should suppress the pro-inflammatory milieu produced during recurrent bacterial infections and prevent the activation of tool-like receptors on tumour cells, which are important factors responsible for tumour growth and survival in patients with multiple myeloma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

PubMed

Ball, P; Baquero, F; Cars, O; File, T; Garau, J; Klugman, K; Low, D E; Rubinstein, E; Wise, R

2002-01-01

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

PubMed

Tissot-Dupont, H; Casalta, J P; Gouriet, F; Hubert, S; Salaun, E; Habib, G; Fernandez-Gerlinger, M P; Mainardi, J L; Tattevin, P; Revest, M; Lucht, F; Botelho-Nevers, E; Gagneux-Brunon, A; Snygg-Martin, U; Chan, K L; Bishara, J; Vilacosta, I; Olmos, C; San Román, J A; López, J; Tornos, P; Fernández-Hidalgo, N; Durante-Mangoni, E; Utili, R; Paul, M; Baddour, L M; DeSimone, D C; Sohail, M R; Steckelberg, J M; Wilson, W R; Raoult, D

2017-10-01

The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general practitioners (GP): A retrospective cohort study.

PubMed

Barbieri, John S; Hoffstad, Ole; Margolis, David J

2016-12-01

Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. We conducted a retrospective cohort study using the Health Improvement Network database. The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. The Health Improvement Network does not include information on acne severity and clinical outcomes. Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial.

PubMed

Salminen, Paulina; Paajanen, Hannu; Rautio, Tero; Nordström, Pia; Aarnio, Markku; Rantanen, Tuomo; Tuominen, Risto; Hurme, Saija; Virtanen, Johanna; Mecklin, Jukka-Pekka; Sand, Juhani; Jartti, Airi; Rinta-Kiikka, Irina; Grönroos, Juha M

2015-06-16

An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of

Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.

PubMed

Wallace, Carol A; Giannini, Edward H; Spalding, Steven J; Hashkes, Philip J; O'Neil, Kathleen M; Zeft, Andrew S; Szer, Ilona S; Ringold, Sarah; Brunner, Hermine I; Schanberg, Laura E; Sundel, Robert P; Milojevic, Diana; Punaro, Marilynn G; Chira, Peter; Gottlieb, Beth S; Higgins, Gloria C; Ilowite, Norman T; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J

2012-06-01

To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months. Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months. By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events. Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms. Copyright © 2012 by the American College of Rheumatology.

Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory Activities of Antibiotics.

PubMed

Huckle, Anthony W; Fairclough, Lucy C; Todd, Ian

2018-05-01

Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice. Copyright © 2018 by Daedalus Enterprises.

Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

PubMed

Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

2016-06-01

Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.

PubMed

Conese, Massimo; Castellani, Stefano; Lepore, Silvia; Palumbo, Orazio; Manca, Antonio; Santostasi, Teresa; Polizzi, Angela Maria; Copetti, Massimiliano; Di Gioia, Sante; Casavola, Valeria; Guerra, Lorenzo; Diana, Anna; Montemurro, Pasqualina; Mariggiò, Maria Addolorata; Gallo, Crescenzio; Maffione, Angela Bruna; Carella, Massimo

2014-01-01

In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and

Evaluation of Genome-Wide Expression Profiles of Blood and Sputum Neutrophils in Cystic Fibrosis Patients Before and After Antibiotic Therapy

PubMed Central

Conese, Massimo; Castellani, Stefano; Lepore, Silvia; Palumbo, Orazio; Manca, Antonio; Santostasi, Teresa; Polizzi, Angela Maria; Copetti, Massimiliano; Di Gioia, Sante; Casavola, Valeria; Guerra, Lorenzo; Diana, Anna; Montemurro, Pasqualina; Mariggiò, Maria Addolorata; Gallo, Crescenzio; Maffione, Angela Bruna; Carella, Massimo

2014-01-01

In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to “healthy” condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before

Appropriateness of antibiotic prescription for targeted therapy of infections caused by multidrug-resistant bacteria: assessment of the most common improper uses in a tertiary hospital in southern Italy.

PubMed

Viceconte, Giulio; Maraolo, Alberto Enrico; Iula, Vita Dora; Catania, Maria Rosaria; Tosone, Grazia; Orlando, Raffaele

2017-09-01

A huge proportion of antibiotic therapies for infections caused by multidrug-resistant bacteria (MDR) are inappropriate. In this study, we described the most common causes of inappropriateness of definitive antibiotic regimes in a large university hospital in southern Italy and we evaluated the impact on microbial eradication, length of stay, 30-day readmission and mortality. We retrospectively assessed 45 patients who received a definitive antibiotic therapy after isolation of multidrug-resistant Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. strains between 2014 and 2015. From the literature, we set a series of criteria to retrospectively determine the appropriateness of the therapy. In all, 61% of the prescribed antibiotic regimes were found to be inappropriate, especially due to incorrect drug dosage. It emerged that meropenem was the antibiotic most frequently inappropriately used. In 46% of infections caused by MDR but not extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenems were inappropriately administered. Microbial eradication was achieved in 87% of the appropriate therapy group compared to 31% of the inappropriate therapy group (chi-square=6.750, p<0.027). No statistically significant association was found between inappropriate therapy and the length of stay (chi-square=3.084, p=0.101) and 30-day readmission (p=0.103). Definitive antibiotic therapy in infections caused by multidrug-resistant bacteria in a large university hospital is often inappropriate, especially due to the drug dosing regimen, particularly in the case of meropenem and colistin. This inappropriateness has a significant impact on post-treatment microbial eradication in specimens collected after antibiotic therapy.

Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

PubMed Central

Chauhan, Ashwini; Lebeaux, David; Ghigo, Jean-Marc

2012-01-01

Biofilms that develop on indwelling devices are a major concern in clinical settings. While removal of colonized devices remains the most frequent strategy for avoiding device-related complications, antibiotic lock therapy constitutes an adjunct therapy for catheter-related infection. However, currently used antibiotic lock solutions are not fully effective against biofilms, thus warranting a search for new antibiotic locks. Metal-binding chelators have emerged as potential adjuvants due to their dual anticoagulant/antibiofilm activities, but studies investigating their efficiency were mainly in vitro or else focused on their effects in prevention of infection. To assess the ability of such chelators to eradicate mature biofilms, we used an in vivo model of a totally implantable venous access port inserted in rats and colonized by either Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, or Pseudomonas aeruginosa. We demonstrate that use of tetrasodium EDTA (30 mg/ml) as a supplement to the gentamicin (5 mg/ml) antibiotic lock solution associated with systemic antibiotics completely eradicated Gram-positive and Gram-negative bacterial biofilms developed in totally implantable venous access ports. Gentamicin-EDTA lock was able to eliminate biofilms with a single instillation, thus reducing length of treatment. Moreover, we show that this combination was effective for immunosuppressed rats. Lastly, we demonstrate that a gentamicin-EDTA lock is able to eradicate the biofilm formed by a gentamicin-resistant strain of methicillin-resistant S. aureus. This in vivo study demonstrates the potential of EDTA as an efficient antibiotic adjuvant to eradicate catheter-associated biofilms of major bacterial pathogens and thus provides a promising new lock solution. PMID:23027191

Treating Comorbid Anxiety and Aggression in Children

ERIC Educational Resources Information Center

Levy, Karyn; Hunt, Caroline; Heriot, Sandra

2007-01-01

Objective: The aim of the study was to evaluate the effectiveness of an intervention that targeted both anxious and aggressive behaviors in children with anxiety disorders and comorbid aggression by parent report. Method: The effects of a cognitive-behavioral therapy intervention targeting comorbid anxiety and aggression problems were compared…

INTRAVENOUS REGIONAL ANTIBIOTIC PERFUSION THERAPY AS AN ADJUNCTIVE TREATMENT FOR DIGITAL LESIONS IN SEABIRDS.

PubMed

Fiorello, Christine V

2017-03-01

Foot infections are a common problem among seabirds in wildlife rehabilitation. Pododermatitis and digital infections are often challenging to treat because of the presence of suboptimal substrates, abnormal weight-bearing due to injuries, and suboptimal nutritional or health status. Seabirds represent the majority of animals requiring rehabilitation after oil spills, and foot problems are a common reason for euthanasia among these birds. Antibiotic intravenous regional perfusion therapy is frequently used in humans and other species to treat infections of the distal extremities, but it has not been evaluated in seabirds. During the 2015 Refugio oil spill response, four birds with foot lesions (pododermatitis, osteomyelitis, or both) were treated with ampicillin/sulbactam administered intravenously to the affected limb(s) in addition to systemic antibiotics and anti-inflammatories. Three of the birds, all brown pelicans ( Pelecanus occidentalis ) recovered rapidly and were released. Two of these birds had acute pododermatitis and were treated once with intravenous regional perfusion. They were released approximately 3 wk after the perfusion therapy. The third pelican had osteomyelitis of a digit. It was treated twice with intravenous regional perfusion and was released about 1 mo after the initial perfusion therapy. The fourth bird, a Pacific loon ( Gavia pacifica ), was treated once with perfusion therapy but did not respond to treatment and was euthanatized. No serious adverse effects were observed. This technique should be explored further in avian species.

Biomarker-guided antibiotic therapy—strengths and limitations

PubMed Central

Salluh, Jorge; Martin-Loeches, Ignacio; Póvoa, Pedro

2017-01-01

Biomarkers as C-reactive protein (CRP) and procalcitonin (PCT) emerged as tools to help clinicians to diagnose infection and to properly initiate and define the duration of antibiotic therapy. Several randomized controlled trials, including adult critically ill patients, showed that PCT-guided antibiotic stewardship was repeatedly associated with a decrease in the duration of antibiotic therapy with no apparent harm. There are however some relevant limitations in these trials namely the low rate of compliance of PCT-guided algorithms, the high rate of exclusion (without including common clinical situations and pathogens) and the long duration of antibiotic therapy in control groups. Such limitations weakened the real impact of such algorithms in the clinical decision-making process and strengthened the concept that the initiation and the duration of antibiotic therapy cannot depend solely on a biomarker. Future efforts should address these limitations in order to better clarify the role of biomarkers on the complex and multifactorial issue of antibiotic management and to deeply understand its potential effect on mortality. PMID:28603723

Duration of oral antibiotic therapy for the treatment of adult acne: a retrospective analysis investigating adherence to guideline recommendations and opportunities for cost-savings.

PubMed

Straight, Chelsey E; Lee, Young H; Liu, Guodong; Kirby, Joslyn S

2015-05-01

The duration of oral antibiotic acne therapy for adolescents compared with guidelines was recently investigated; however it was uncertain if duration of antibiotics for adult acne therapy differed. This study aimed to evaluate duration of oral antibiotics for adult acne compared with guidelines and determine possible cost-savings. This was a retrospective cohort study of MarketScan Commercial Claims and Encounters database that incorporated claims data to determine duration and costs of antibiotic treatment among adults ages 21 years and older. Of 17,448 courses, 84.5% (14,737) aligned with duration guidelines, although 12,040 (69.0%) courses did not include concomitant topical retinoid therapy. Mean savings of $592.26 per person could result if prolonged courses met guidelines. Mean (median) costs of generic and branded formulations for the most frequent course duration (90-179 days) were $103.77 ($54.27) and $1421.61 ($1462.25), respectively. Actual patient prescription adherence is uncertain and database lacks information regarding acne severity, patient physical characteristics, and clinical outcomes. The majority of oral antibiotic course durations follow guidelines, although topical retinoids are underused. Costs of antibiotic therapy were lower for shorter courses and those using generic medications; the cost-effectiveness of these modifications has not been investigated. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Antibiotics in aggressive periodontitis, is there a clinical benefit?

PubMed

Rajendra, Anjana; Spivakovsky, Silvia

2016-12-01

Data sourcesMedline, Embase and CENTRAL databases were searched up to December 2014. Unpublished data were sought by searching a database listing unpublished studies OpenGray [http://www.opengrey.eu/], formerly OpenSIGLE.Study selectionRandomised clinical trials assessing treatment of patients with AgP comparing scaling and root planing (SRP) alone with SRP plus a single antibiotic or a combination of drugs with a minimum of three months follow-up were considered. Studies specifically designed to evaluate smokers or subjects with diabetes mellitus and HIV/AIDS were not included.Data extraction and synthesisTwo researchers independently screened titles, abstracts and full texts of the search results. The studies, which fulfilled inclusion criteria, underwent validity assessment and data extraction using a specifically designed form. The quality of included studies was assessed using the Cochranes collaboration tool for risk of bias. Only two of the 11 included trials were considered at a low risk of bias. The data extracted from ten studies was analysed by pair-wise meta-analyses and the data extracted from five studies was included in Bayesian network meta-analyses pooled estimates. The six studies evaluated in the pairwise meta-analyses were excluded in the pooled estimates because four studies included patients with advanced disease only and one study did not present average data for pocket depth (PD) and clinical attachment level (CAL) and another one for using a different mechanical treatment.ResultsFourteen studies reporting 11 randomised clinical trials with a total of 388 patients were included in the review. Nine of 11 studies reported a statistically significant greater gain in full mouth mean clinical attachment (CA) and reduction in probing depth (PD) when a systemic antibiotic was used. From those studies the calculated mean difference for CA gained was 1.08 mm (p < 0.0001) and for PD reduction was 1.05 mm (p< 0.00001) for SRP + Metronidazole (Mtz). For

Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

PubMed

Fitzpatrick, J M; Biswas, J S; Edgeworth, J D; Islam, J; Jenkins, N; Judge, R; Lavery, A J; Melzer, M; Morris-Jones, S; Nsutebu, E F; Peters, J; Pillay, D G; Pink, F; Price, J R; Scarborough, M; Thwaites, G E; Tilley, R; Walker, A S; Llewelyn, M J

2016-03-01

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Prophylactic antibiotics in dermatological surgery.

PubMed

Lee, Michael R; Paver, Robert

2016-05-01

This is a review of the common pathogens of surgical site infections, antibiotic coverage for particular anatomical sites, mechanisms by which surgical site infections occur and the latest data and recommendations for prophylactic antibiotics in the prevention of surgical site infections, infective endocarditis and haematogenous joint infections. Recent evidence-based guidelines on surgical prophylaxis is for restricted indications and a shorter duration of antibiotic prophylaxis in situations where no clinical benefit of prolonged therapy has been proven, in order to minimise the potential adverse ecological and clinical effects associated with antibiotic therapy. This review recommends the cautious use of prophylactic antibiotics in dermatological surgery to help prevent the growing problem of bacterial resistance as well as other morbidity and health-care costs. © 2015 The Australasian College of Dermatologists.

Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

PubMed

Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

2018-06-01

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

Does vaginal irrigation with saline solution in women with infectious vaginitis contribute to the clinical and microbiological results of antibiotic therapy?

PubMed

Derbent, Aysel Uysal; Ulukanlıgil, Mustafa; Keskin, Esra Aktepe; Soylu, Gül; Kafalı, Hasan

2012-01-01

To compare the clinical and microbiological results between patients with infectious vaginitis receiving vaginal irrigation with saline or no irrigation before standard antibiotic therapy. Women with vaginitis (n = 109) were randomized to receive vaginal irrigation with saline or no irrigation before standard antibiotic therapy. The vaginal symptoms perceived by subjects and clinical findings were assessed with a standardized scale during four follow-up visits, and Gram stain Nugent scores and vaginal fluid cultures were analyzed at each visit. Vaginal discharge (z = 7.159; p < 0.001), pruritus (z = 5.169; p < 0.001), itching (z = 2.969; p < 0.003) and odor scores (z = 2.303; p < 0.021) were significantly reduced in the study group compared to the control group between the first visit and 3-5 days after irrigation, before the start of antibiotic therapy. The second and third visits (15 and 30-45 days after antibiotic therapy) showed that the patients' symptoms and amounts of visible vaginal discharge did not differ between the two groups. Moreover, the microbiological cures of patients in each group did not differ at these visits (z = 0.447; p = 0.655). Vaginal irrigation with saline significantly reduces self-reported symptoms in the short term but has no effect on long-term clinical and laboratory results in women with infectious vaginitis. Copyright © 2012 S. Karger AG, Basel.

The efficacy of combined therapy with metronidazole and broad-spectrum antibiotics on postoperative outcomes for pediatric patients with perforated appendicitis.

PubMed

Shang, Qingjuan; Geng, Qiankun; Zhang, Xuebing; Guo, Chunbao

2017-11-01

The aim of this study was to evaluate the efficacy of combined therapy with metronidazole and broad-spectrum antibiotics for patients with perforated appendicitis who underwent surgical intervention.Broad-spectrum antibiotic therapy is warranted in the treatment of perforated appendicitis. Metronidazole has been used as anaerobic antimicrobial therapy. However, few studies about the use of metronidazole in perforated appendicitis have been reported.The medical records of 249 patients treated with metronidazole combined with broad-spectrum antibiotics following perforated appendicitis surgery were reviewed retrospectively and compared with the medical records of 149 patients treated only with broad-spectrum antibiotics. Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including postoperative complications and length of hospital stay, were compared between the 2 groups.No differences were found between the use of combined therapy with metronidazole and the use of solely broad-spectrum antibiotic agents with regard to postoperative duration of intravenous antibiotic treatment (6.8 ± 1.3 vs 7.9 ± 2.1 days, respectively, P = .18), inflammation variables at POD 5 (white blood cell [WBC] [risk ratio [RR], 1.06; 95% confidence interval [CI], 0.67-1.93, P = .15] and C-reactive protein [CRP] [RR, 1.18; 95% CI, 0.73-2.25, P = .36]) (Table 2), and the mean postoperative length of hospital stay (LOS) (RR, 0.68, 95% CI, 0.41-0.94, P = .41). There were also no differences in the incidence of postoperative complications, including the intra-abdominal or pelvic abscess rate (7[7.1%] vs 9[9.2%], respectively, P = .40), the incidence of wound infection (14[14.3%] vs 15[15.3%], respectively, P = .50), and the 30-day readmission rate (9[9.2%] vs 12[12.2%], respectively, P = .32).Regarding overall postoperative outcomes and complications, our study demonstrated no beneficial clinical effects of

The efficacy of combined therapy with metronidazole and broad-spectrum antibiotics on postoperative outcomes for pediatric patients with perforated appendicitis

PubMed Central

Shang, Qingjuan; Geng, Qiankun; Zhang, Xuebing; Guo, Chunbao

2017-01-01

Abstract The aim of this study was to evaluate the efficacy of combined therapy with metronidazole and broad-spectrum antibiotics for patients with perforated appendicitis who underwent surgical intervention. Broad-spectrum antibiotic therapy is warranted in the treatment of perforated appendicitis. Metronidazole has been used as anaerobic antimicrobial therapy. However, few studies about the use of metronidazole in perforated appendicitis have been reported. The medical records of 249 patients treated with metronidazole combined with broad-spectrum antibiotics following perforated appendicitis surgery were reviewed retrospectively and compared with the medical records of 149 patients treated only with broad-spectrum antibiotics. Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including postoperative complications and length of hospital stay, were compared between the 2 groups. No differences were found between the use of combined therapy with metronidazole and the use of solely broad-spectrum antibiotic agents with regard to postoperative duration of intravenous antibiotic treatment (6.8 ± 1.3 vs 7.9 ± 2.1 days, respectively, P = .18), inflammation variables at POD 5 (white blood cell [WBC] [risk ratio [RR], 1.06; 95% confidence interval [CI], 0.67–1.93, P = .15] and C-reactive protein [CRP] [RR, 1.18; 95% CI, 0.73–2.25, P = .36]) (Table 2), and the mean postoperative length of hospital stay (LOS) (RR, 0.68, 95% CI, 0.41–0.94, P = .41). There were also no differences in the incidence of postoperative complications, including the intra-abdominal or pelvic abscess rate (7[7.1%] vs 9[9.2%], respectively, P = .40), the incidence of wound infection (14[14.3%] vs 15[15.3%], respectively, P = .50), and the 30-day readmission rate (9[9.2%] vs 12[12.2%], respectively, P = .32). Regarding overall postoperative outcomes and complications, our study demonstrated no beneficial

Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity

PubMed Central

Hannan, Thomas J.; MacPhee, Roderick A.; Schwartz, Drew J.; Macklaim, Jean M.; Gloor, Gregory B.; Razvi, Hassan; Reid, Gregor; Hultgren, Scott J.; Burton, Jeremy P.

2015-01-01

ABSTRACT The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections. PMID:25827417

Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy.

PubMed

Trabattoni, D; Clerici, M; Centanni, S; Mantero, M; Garziano, M; Blasi, F

2017-06-01

The morbidity and mortality of community-acquired pneumonia (CAP) are still elevated and two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvants, including corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects but their efficacy is only partial. We examined the immunomodulatory activity of Pidotimod (PDT), a synthetic dipeptide molecule in adult patients hospitalized for CAP. Sixteen patients with a diagnosis of CAP and a PSI score III or IV and/or a CURB-65 0-2 were randomized to receive either levofloxacin 500 mg b.i.d. alone or levofloxacin plus PDT (800mg, 2 daily doses). Blood samples were drawn at baseline (T0), before initiation of therapy, as well as 3 (T3), and 5 (T5) days after initiation of therapy. Immunologic and clinical parameters were analyzed at each time point. Supplementation of antibiotic therapy with PDT resulted in an upregulation of antimicrobial and of immunomodulatory proteins as well as in an increased percentage of Toll like receptor (TLR)2- and TLR4, and of CD80- and CD86-expressing immune cells. Notably, Pidotimod supplementation was also associated with a robust reduction of TNFα-producing immune cells. No significant differences were observed in clinical parameters. These results confirm that supplementation of antibiotic therapy with Pidotimod in patients with CAP results in a potentially beneficial modulation of innate immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries.

PubMed

Anjum, Nadeem; Ren, Jianan; Wang, Gefei; Li, Guanwei; Wu, Xiuwen; Dong, Hu; Wu, Qin; Li, Jieshou

2017-12-01

Preoperative bowel preparation with or without oral antibiotics is controversial in terms of postoperative surgical site infections. This study aimed to evaluate the efficacy of oral antibiotics as adjunct therapy to systemic antibiotics with mechanical bowel preparation for preventing surgical site infections in clean contaminated, contaminated, and dirty colorectal procedures. This was a single-center, prospective randomized study. This study was conducted at the General Surgery Department at Jinling Hospital, Nanjing University, China, from July 15, 2014 to January 20, 2016. Patients aged ≥18 years scheduled for abdominal surgery with clean-contaminated, contaminated, and dirty wounds were selected. Patients were randomly assigned to receive preoperative mechanical bowel preparation or mechanical bowel preparation with oral antibiotics. The primary outcome was the rate of surgical site infections. The secondary outcomes were extra-abdominal complications, duration of postoperative ileus, and readmission rate. Ninety-five patients were allocated to each group. Eight and 26 surgical site infections (8.42% vs 27.3 %, p = 0.004) occurred in the mechanical bowel preparation with oral antibiotics and mechanical bowel preparation groups. Thirteen extra-abdominal complications were reported: 6 in the mechanical bowel preparation with oral antibiotics group and 7 in the mechanical bowel preparation group (6.3% vs 7.3%, p = 0.77). Postoperative ileus duration did not differ between groups (p = 0.23). There were 4 readmissions in the mechanical bowel preparation group and none in the mechanical bowel preparation with oral antibiotics group (p = 0.04). On multivariable analysis, blood loss ≥500 mL (OR, 5.1; 95% CI, 1.27-20.4; p = 0.02), ASA score ≥3 (OR, 3.9; 95% CI, 1.2-12.5; p = 0.01), contaminated types (OR, 3.6; 95% CI, 1.5-8.6; p = 0.01), and administration of preoperative oral antibiotics (OR, 0.20; 95% CI, 0.06-0.60; p = 0.005) independently affected the

Electroconvulsive Therapy for Agitation and Aggression in Dementia: A Systematic Review.

PubMed

van den Berg, Julia F; Kruithof, Henk C; Kok, Rob M; Verwijk, Esmée; Spaans, Harm-Pieter

2018-04-01

Many patients with dementia develop agitation or aggression in the course of their disease. In some severe cases, behavioral, environmental, and pharmacological interventions are not sufficient to alleviate these potentially life-threatening symptoms. It has been suggested that in those cases, electroconvulsive therapy (ECT) could be an option. This review summarizes the scientific literature on ECT for agitation and aggression in dementia. We performed a systematic review in accordance with PRISMA guidelines. A search was conducted in Ovid MEDLINE, EMBASE, and PsycINFO. Two reviewers extracted the following data from the retrieved articles: number of patients and their age, gender, diagnoses, types of problem behavior, treatments tried before ECT, specifications of the ECT treatment, use of rating scales, treatment results, follow-up data, and adverse effects. The initial search yielded 264 articles, 17 of which fulfilled the inclusion criteria. Of these studies, one was a prospective cohort study, one was a case-control study, and the others were retrospective chart reviews, case series, or case reports. Clinically significant improvement was observed in the majority (88%) of the 122 patients described, often early in the treatment course. Adverse effects were most commonly mild, transient, or not reported. The reviewed articles suggest that ECT could be an effective treatment for severe and treatment-refractory agitation and aggression in dementia, with few adverse consequences. Nevertheless, because of the substantial risk of selection bias, the designs of the studies reviewed, and their small number, further prospective studies are needed to substantiate these preliminary positive results. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

[A study of non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections in women (the NAPRUTI study)].

PubMed

Beerepoot, M A J; Stobberingh, E E; Geerlings, S E

2006-03-11

Patient enrolment in the 'Non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections' (NAPRUTI) study was started in September 2005. In this study of women with recurrent urinary-tract infections we aim to investigate the effect of 12 months of non-antibiotic prophylaxis in comparison with antibiotic prophylaxis on the rate of recurrence of urinary-tract infections and the development of antibiotic resistance. The study consists of two interlinked, randomised, clinical non-inferiority trials. In one trial, 280 premenopausal women will receive either cranberry capsules (twice daily 500 mg) or standardised antibiotic therapy (once daily 480 mg trimethoprim-sulfamethoxazole). In the other trial, 280 postmenopausal women will receive either oral lactobacilli (twice daily a capsule with > 10(9) colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14) or standardised antibiotic therapy. Non-inferiority of non-antibiotic prophylaxis would be attractive given its potential to reduce the prevalence of microbial resistance to antibiotics significantly.

Prophylactic antibiotic therapy prior to dental treatment for patients with end-stage renal disease.

PubMed

Werner, C W; Saad, T F

1999-01-01

In the United States, there is a large and growing population of patients undergoing dialysis because of end-stage renal disease (ESRD). These patients present special management considerations for dentists, including antibiotic prophylaxis for the prevention of bacterial endocarditis (BE). ESRD patients, particularly those with an arteriovenous shunt for hemodialysis access, are predisposed to valvular endocarditis. Thus, BE prevention is the primary goal of antibiotic prophylaxis prior to dental or other invasive procedures in these patients. Bacteremia may predispose to infection of synthetic vascular access grafts, although this form of endovascular infection in ESRD patients has not been as well-characterized as BE. Antibiotic prophylaxis may be of some benefit for prevention of synthetic graft infections as well as BE. Poor dentist and physician compliance with BE prophylaxis regimens, as well as errors in dosing, timing, or duration of prophylaxis, have been reported. These problems are of particular concern in the treatment of chronically ill patients. In this article, we review the rationale for prophylactic antibiotic therapy prior to dental procedures in ESRD patients with vascular access. We also elaborate on the current American Heart Association guidelines for BE prophylaxis, and address special considerations for ESRD patients.

Impact of prospective verification of intravenous antibiotics in an ED.

PubMed

Hunt, Allyson; Nakajima, Steven; Hall Zimmerman, Lisa; Patel, Manav

2016-12-01

Delay in appropriate antibiotic therapy is associated with an increase in mortality and prolonged length of stay. Automatic dispensing machines decrease the delivery time of intravenous (IV) antibiotics to patients in the emergency department (ED). However, when IV antibiotics are not reviewed by pharmacists before being administered, patients are at risk for receiving inappropriate antibiotic therapy. The objective of this study was to determine if a difference exists in the time to administration of appropriate antibiotic therapy before and after implementation of prospective verification of antibiotics in the ED. This retrospective, institutional review board-approved preimplementation vs postimplementation study evaluated patients 18years or older who were started on IV antibiotics in the ED. Patients were excluded if pregnant, if the patient is a prisoner, if no cultures were drawn, or if the patient was transferred from an outside facility. Appropriate antibiotic therapy was based on empiric source-specific evidence-based guidelines, appropriate pharmacokinetic and pharmacodynamic properties, and microbiologic data. The primary end point was the time from ED arrival to administration of appropriate antibiotic therapy. Of the 1628 evaluated, 128 patients met the inclusion criteria (64 pre vs 64 post). Patients were aged 65.2±17.0years, with most of infections being pneumonia (44%) and urinary tract infections (18%) and most patients being noncritically ill. Time to appropriate antibiotic therapy was reduced in the postgroup vs pregroup (8.1±8.6 vs 15.2±22.8hours, respectively, P=.03). In addition, appropriate empiric antibiotics were initiated more frequently after the implementation (92% post vs 66% pre; P=.0001). There was no difference in mortality or length of stay between the 2 groups. Prompt administration of the appropriate antibiotics is imperative in patients with infections presenting to the ED. The impact of prospective verification of

A call for antibiotic alternatives research

USDA-ARS?s Scientific Manuscript database

The persistence and spread of antibiotic resistance and decreased profitability of new antibiotics have created the dangerous prospect of ineffective therapies against bacterial diseases. The discovery, development, and application of effective antibiotic alternatives, especially in agriculture, sho...

Decision and cost analysis of empirical antibiotic therapy of acute sinusitis in the era of increasing antimicrobial resistance: do we have an additional tool for antibiotic policy decisions?

PubMed

Babela, Robert; Jarcuska, Pavol; Uraz, Vladimir; Krčméry, Vladimír; Jadud, Branislav; Stevlik, Jan; Gould, Ian M

2017-11-01

No previous analyses have attempted to determine optimal therapy for upper respiratory tract infections on the basis of cost-minimization models and the prevalence of antimicrobial resistance among respiratory pathogens in Slovakia. This investigation compares macrolides and cephalosporines for empirical therapy and look at this new tool from the aspect of potential antibiotic policy decision-making process. We employed a decision tree model to determine the threshold level of macrolides and cephalosporines resistance among community respiratory pathogens that would make cephalosporines or macrolides cost-minimising. To obtain information on clinical outcomes and cost of URTIs, a systematic review of the literature was performed. The cost-minimization model of upper respiratory tract infections (URTIs) treatment was derived from the review of literature and published models. We found that the mean cost of empirical treatment with macrolides for an URTIs was €93.27 when the percentage of resistant Streptococcus pneumoniae in the community was 0%; at 5%, the mean cost was €96.45; at 10%, €99.63; at 20%, €105.99, and at 30%, €112.36. Our model demonstrated that when the percentage of macrolide resistant Streptococcus pneumoniae exceeds 13.8%, use of empirical cephalosporines rather than macrolides minimizes the treatment cost of URTIs. Empirical macrolide therapy is less expensive than cephalosporines therapy for URTIs unless macrolide resistance exceeds 13.8% in the community. Results have important antibiotic policy implications, since presented model can be use as an additional decision-making tool for new guidelines and reimbursement processes by local authorities in the era of continual increase in antibiotic resistance.

SAFETY AND UTILITY OF ACUTE ELECTROCONVULSIVE THERAPY FOR AGITATION AND AGGRESSION IN DEMENTIA

PubMed Central

Acharya, Deepa; Harper, David G.; Achtyes, Eric D.; Seiner, Stephen J.; Mahdasian, Jack A.; Nykamp, Louis J.; Adkison, Lesley; Van der Schuur White, Lori; McClintock, Shawn M.; Ujkaj, Manjola; Davidoff, Donald A.; Forester, Brent P.

2015-01-01

Objective Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Methods Twenty-three participants admitted to McLean Hospital (Belmont, MA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory (CMAI)-short form, Neuropsychiatric Inventory (NPI)-Nursing Home Version, Cornell Scale for Depression in Dementia (CSDD), and the Clinical Global Impression Scale (CGI) at baseline, during, and after the ECT course. Results Regression analyses revealed a significant decrease from baseline to discharge on the CMAI (F(4, 8) =13.3; p=0.006) and NPI (F(4, 31)= 14.6; p<0.001). There was no statistically significant change in scores on the CSDD. The CGI scores on average changed from a rating of “markedly agitated/aggressive” at baseline to “borderline agitated/aggressive” at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants due to recurrence of agitation and for three participants due to adverse events. Conclusions ECT may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. PMID:24838521

Impact of Radiation Therapy on Aggressive Care and Quality of Life near Death

PubMed Central

Li, David; Prigerson, Holly G.; Kang, Josephine; Maciejewski, Paul K.

2016-01-01

Context Radiation therapy (RT) is used with palliative intent in patients with advanced stage cancer. Prior studies, primarily in patients with poor performance status (PS), suggest that RT is associated with aggressive medical care, which may impact patients’ quality of life near death (QoD) adversely. Objective This study examines associations between RT use and patients’ receipt of aggressive care and QoD based on patients’ PS. Methods Multi-institutional, prospective cohort study of patients with end-stage cancers (N=312) and identified as terminally ill at study enrollment. RT use (n=24; 7.7%) and Eastern Cooperative Oncology Group (ECOG) PS were assessed at study entry (median = 3.8 months before death). Aggressive care near death was operationalized as use of mechanical ventilation and/or resuscitation in the last week of life. QoD was determined using validated caregiver ratings of patients’ physical and mental distress in their final week. Results RT use was associated with higher QoD (8/8, 100.0%, versus 58/114, 50.9%; p=0.006) among patients with good PS (ECOG=1), more aggressive care near death (3/9, 33.3%, versus 6/107, 5.6%; p=0.020) among patients with moderate PS (ECOG=2), and lower QoD (1/7, 14.3%, versus 28/51, 54.9%; p=0.046) among patients with poor PS (ECOG=3). Conclusions Targeted use of RT in end-of-life cancer care may benefit patients with good PS, but its use may adversely affect patients with poorer PS. Decisions about RT use in this setting should consider likely end-of-life outcomes based on patients’ current PS. PMID:27720786

Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy.

PubMed

Cosgrove, Sara E; Li, David X; Tamma, Pranita D; Avdic, Edina; Hadhazy, Eric; Wakefield, Teresa; Gherna, Michael; Carroll, Karen C

2016-09-01

Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) is a rapid diagnostic assay that can identify certain organisms growing in blood cultures 30-90 min from the time of positive Gram-stain. Existing studies have demonstrated a clinical utility with this assay when antibiotic stewardship programs assist clinicians with interpreting the results. However, the benefit of these rapid assays in the absence of concomitant antibiotic stewardship involvement is unclear. In this randomized study of 220 patients with enterococcal or streptococcal bacteremia, we found that PNA FISH, in the absence of concomitant input from an antibiotic stewardship program, had no impact on time to effective or optimal therapy, length of hospital stay, or in-hospital mortality. Our results suggest that in the absence of guidance from an antibiotic stewardship program, the clinical benefits of rapid diagnostic microbiological tools may be reduced. Copyright © 2016 Elsevier Inc. All rights reserved.

[Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid].

PubMed

Worret, Wolf-Ingo; Fluhr, Joachim W

2006-04-01

Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite the fact that only few randomized trials have been published, BPO is considered the standard in topical acne treatment. Anaerobic bacteria are reduced by oxidative mechanisms and the induction of resistant strains is reduced. Topical formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect is dose-dependent, but the irritation increases with higher concentrations. Usually 5 % BPO is sufficient to control acne grade I-II. Due to its strong oxidative potential, patients should be advised that BPO may bleach colored and dark clothing, bedding and even hair. BPO is safe for use in pregnant and lactating females because it is degraded to benzoic acid. It is a cost-effective treatment for acne grade I-II. Patients with papulopustular acne grade I-II, particularly with marked inflammation, show satisfactory improvement with topical antibiotic treatment. The following compounds are available and effective: erythromycin, clindamycin and tetracycline (the latter being less frequently used). A review in 1990 suggested that topical tetracycline was ineffective in the treatment of acne. Along with eliminating Propionibacterium acnes, the main mechanism of topical antibiotics is their antiinflammatory effect. All three penetrate the epidermal barrier well and are similarly efficacious. Randomized trials have shown that in concentrations of 2-4 %, their effects are comparable to oral tetracycline and minocycline. Combination therapy with retinoids or benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and reduce comedones, while topical antibiotics primarily address inflammation. One side effect of topical antibacterial treatment is an increase in drug-resistant resident skin flora with gram-negative microorganisms prevailing, which can lead to gram-negative folliculitis. All three antibiotics fluoresce under black light which may produce interesting

Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

PubMed

Castagnola, Elio; Caviglia, Ilaria; Pescetto, Luisa; Bagnasco, Francesca; Haupt, Riccardo; Bandettini, Roberto

2015-01-01

Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

Impact of antibiotic restrictions: the ethical perspective.

PubMed

Garau, J

2006-08-01

Antibiotic restrictions present difficult choices for physicians, patients and payors. Physicians must choose between the welfare of the patient and the directive of healthcare systems to restrict antibiotics. These may be supported with incentives or penalties, causing a conflict of interest. The patient has an expectation of best care, but will often be unaware of antibiotic restriction policies and is therefore not fully informed about his/her treatment. For payors, reducing the volume of antibiotic prescribing and/or prescribing less expensive antibiotics are apparently attractive targets for cost savings. However, we are only now beginning to understand the downstream consequences of restricting antibiotics on outcomes and costs. We are hampered by the lack of a universal ethical framework and information on outcomes. In addition, the concept of 'effective' or 'best' therapy will vary among different groups. Balancing the risks of treating or not treating with antibiotics is complex. Suboptimal therapy, that fails to eradicate the bacterial infection, exposes the patient to the risk of poor outcome, adverse events and the wider risk of antimicrobial resistance. Failure to treat where the risk of a poor outcome exceeds the risk of an adverse event is also ethically unacceptable. The key to rational antibiotic prescribing is to identify those patients who need antibiotic therapy and optimise therapy to achieve the fastest bacterial and clinical cure. We are only now beginning to assemble the information and tools to be able to make such decisions. Above all, we should treat on the basis of knowledge.

The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review.

PubMed

Russell, Christopher J; Shiroishi, Mark S; Siantz, Elizabeth; Wu, Brian W; Patino, Cecilia M

2016-03-08

Ventilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines. We conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook's "Risk of Bias" assessment tool. Six studies met full inclusion criteria. For the systemic review's primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis. There is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled

Prospective Evaluation of Self-Reported Aggression in Transgender Persons.

PubMed

Defreyne, Justine; T'Sjoen, Guy; Bouman, Walter Pierre; Brewin, Nicola; Arcelus, Jon

2018-05-01

Although research on the relation between testosterone and aggression in humans is inconclusive, guidelines (including the World Professional Association for Transgender Health Standards of Care, edition 7) have warned for an increase in aggression in transgender men taking testosterone treatment. To investigate the association between levels of testosterone and aggression in treatment-seeking transgender people and explore the role of mental health psychopathology (anxiety and depressive symptoms) and social support in aggression in this population. Every transgender person invited for assessment at a national transgender health clinic in the United Kingdom during a 3-year period (2012-2015) completed self-report measures for interpersonal problems, including levels of aggression (Inventory of Interpersonal Problems [IIP-32]), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), social support (Multidimensional Scale of Perceived Social Support), and experiences of transphobia before and 1 year after the initiation of gender-affirming hormonal therapy. Correlations between prospective scores for the IIP-32 factor "too aggressive" and prospective levels of sex steroids, prospective psychological (HADS), and baseline psychosocial measurements were tested. Prospective scores for the factor "too aggressive" were not correlated to prospective serum testosterone levels. Results of 140 people (56 transgender men, 84 transgender women) were analyzed. A prospective increase in scores for the factor "too aggressive" of the IIP-32 in transgender men 1 year after being treated with testosterone treatment or a decrease of the IIP-32 aggression scores in transgender women 1 year after gender-affirming hormonal therapy was not found. However, a positive correlation was found between increasing HADS anxiety scores and increasing scores for the IIP-32 "too aggressive" score in the entire study population and a positive correlation with lower support

Demographics and microbiology of otorrhea through patent tubes failing ototopical and/or oral antibiotic therapy.

PubMed

Fishman, Inessa; Sykes, Kevin J; Horvat, Rebecca; Selvarangan, Rangaraj; Newland, Jason; Wei, Julie L

2011-12-01

Posttympanostomy tube otorrhea (PTTO) results in significant health care cost and decreased satisfaction with care. The authors reviewed PTTO failing initial ototopical and/or oral antibiotic therapy and microbiology/susceptibility data from cultures. Case series with chart review. A community university satellite ambulatory clinic and the outpatient clinic of a children's hospital. Review of 202 patients with 228 discrete episodes of culture-positive otorrhea from January 2004 to January 2009. PTTO occurred an average of 13 months after tube placement. Median otorrhea duration was 21 days (mean, 42 days). A mean of 1.6 visits (range, 1-6) to the pediatric otolaryngology office was required for PTTO resolution. Ototopical therapy was reported used in 198 of 228 (87%) episodes of otorrhea prior to pediatric otolaryngology visit. Nearly 50% of patients were prescribed at least 1 or more courses of systemic antibiotics. Staphylococcus aureus accounted for 52% of the organisms cultured, with 57% methicillin-resistant S aureus (MRSA). S aureus resistance to clindamycin was high (49%) and resistance to levofloxacin was low (1.8%). MRSA was 68% clindamycin resistant, much higher than both ours and the children's hospital's clindamycin resistance rate of MRSA cultured from all other body sites. PTTO that presents as having failed ototopical and/or oral antibiotics most commonly consists of S aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. MRSA is highly prevalent in this population. It is not necessary to culture PTTO that presents to an otolaryngology office, as resistance to levofloxacin was only 1.8%. It is unclear why the same fluoroquinolone ototopical therapy that failed initially is often successful in treating PTTO after otolaryngologist visit.

Antibiotics for acute pyelonephritis in children.

PubMed

Strohmeier, Yvonne; Hodson, Elisabeth M; Willis, Narelle S; Webster, Angela C; Craig, Jonathan C

2014-07-28

Urinary tract infection (UTI) is one of the most common bacterial infections in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent kidney damage. There remains uncertainty regarding the optimum antibiotic regimen, route of administration and duration of treatment. This is an update of a review that was first published in 2003 and updated in 2005 and 2007. To evaluate the benefits and harms of antibiotics used to treat children with acute pyelonephritis. The aspects of therapy considered were 1) different antibiotics, 2) different dosing regimens of the same antibiotic, 3) different duration of treatment, and 4) different routes of administration. We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of articles and conference proceedings without language restriction to 10 April 2014. Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected. Four authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI). This updated review included 27 studies (4452 children). This update included evidence from three new studies, and following re-evaluation, a previously excluded study was included because it now met our inclusion criteria.Risk of bias was assessed as low for sequence generation (12 studies), allocation concealment (six studies), blinding of outcome assessors (17 studies), incomplete outcome reporting (19 studies) and selective outcome reporting (13 studies). No study was blinded for participants or investigators. The 27 included studies evaluated 12 different

Impact of acute antibiotic therapy on the pulmonary exacerbation endpoint in cystic fibrosis clinical trials.

PubMed

Mayer-Hamblett, Nicole; Saiman, Lisa; Lands, Larry C; Anstead, Michael; Rosenfeld, Margaret; Kloster, Margaret; Fisher, Leigh; Ratjen, Felix

2013-09-01

In a chronic disease setting such as cystic fibrosis (CF), antibiotics are often prescribed for emergent symptoms and it is unclear whether this affects endpoints in a clinical trial. Pulmonary exacerbations (PEs) are defined episodes of acute worsening and a key clinical efficacy measure in CF. Our hypothesis was that acute antibiotics given for illnesses not meeting the PE definition may alter estimates of treatment effect that do not account for this antibiotic use. A randomized, placebo-controlled trial of azithromycin (AZ) including 260 participants with CF was utilized for this study. PEs were defined using a priori criteria. Physician initiated antibiotic therapy (PIT) not meeting the PE endpoint was characterized and its impact on treatment effect assessed. 40% (104/260) of participants were prescribed 188 courses of PIT in the absence of a PE; 19% (25/129) of placebo and 10% (13/131) of AZ participants received ≥2 courses of PIT and never fulfilled the PE definition (9% difference, 95% confidence interval: 1%, 18%, p = 0.04). Accounting for PIT through use of a composite endpoint including time to PE or need for repeated PIT altered treatment effect estimates (a 56% reduction in the event rate comparing AZ to placebo [p < 0.0001] as compared to a 50% reduction not accounting for PIT [p = 0.003]). PIT is common in CF and may impact treatment effect estimates. Optimization of the PE endpoint to include meaningful events necessitating treatment may improve our ability to conduct efficient trials by reducing the sample size 30-50%, ultimately enabling rapid evaluation of new therapies. Copyright © 2013 Elsevier Inc. All rights reserved.

Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure.

PubMed

Kim, Carole H; Chen, Monica F; Coleman, Anne L

2017-02-22

search results, assessed risk of bias, and extracted data using methods expected by Cochrane. We contacted study authors to try to obtain missing information or information to clarify risk of bias. We conducted a meta-analysis for any outcomes that were reported by at least two studies. Outcomes reported from single studies were summarized in the text. We assessed the certainty of the evidence using GRADE. We included three trials with a total of 95 randomized participants in this review and identified one ongoing trial. The studies were conducted in South Africa, India, and the Netherlands. Out of the 92 analyzed participants, 91 participants were diagnosed with endophthalmitis following cataract surgery. In the remaining participant, endophthalmitis was attributable to penetrating keratoplasty. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged one trial to be at overall low risk of bias and two studies to be at overall unclear risk of bias due to lack of reporting of study methods. None of the three trials had been registered in a clinical trial register.While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low-certainty evidence suggested no difference in combined success when comparing adjunctive steroid antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low-certainty evidence from two studies showed that a higher proportion of participants who received adjunctive dexamethasone had a good visual outcome (Snellen visual acuity 6/6 to 6/18) at three months compared with those in the antibiotics

Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure

PubMed Central

Kim, Carole H; Chen, Monica F; Coleman, Anne L

2017-01-01

steroids. Data collection and analysis Two review authors independently screened the search results, assessed risk of bias, and extracted data using methods expected by Cochrane. We contacted study authors to try to obtain missing information or information to clarify risk of bias. We conducted a meta-analysis for any outcomes that were reported by at least two studies. Outcomes reported from single studies were summarized in the text. We assessed the certainty of the evidence using GRADE. Main results We included three trials with a total of 95 randomized participants in this review and identified one ongoing trial. The studies were conducted in South Africa, India, and the Netherlands. Out of the 92 analyzed participants, 91 participants were diagnosed with endophthalmitis following cataract surgery. In the remaining participant, endophthalmitis was attributable to penetrating keratoplasty. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged one trial to be at overall low risk of bias and two studies to be at overall unclear risk of bias due to lack of reporting of study methods. None of the three trials had been registered in a clinical trial register. While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low-certainty evidence suggested no difference in combined success when comparing adjunctive steroid antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low-certainty evidence from two studies showed that a higher proportion of participants who received adjunctive dexamethasone had a good visual

Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial.

PubMed

Schuetz, Philipp; Christ-Crain, Mirjam; Wolbers, Marcel; Schild, Ursula; Thomann, Robert; Falconnier, Claudine; Widmer, Isabelle; Neidert, Stefanie; Blum, Claudine A; Schönenberger, Ronald; Henzen, Christoph; Bregenzer, Thomas; Hoess, Claus; Krause, Martin; Bucher, Heiner C; Zimmerli, Werner; Müller, Beat

2007-07-05

Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections. We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections <28 days of duration. Patients with no informed consent, not fluent in German, a previous hospital stay within 14 days, severe immunosuppression or chronic infection, intravenous drug use or a terminal condition are excluded. Randomization to either guidelines-enforced management or procalcitonin-guided antibiotic therapy is stratified by centre and type of lower respiratory tract infections. During hospitalization, all patients are reassessed at days 3, 5, 7 and at the day of discharge. After 30 and 180 days, structured phone interviews by blinded medical students are conducted. Depending on the randomization allocation, initiation and discontinuation of antibiotics is encouraged or discouraged based on evidence-based guidelines or procalcitonin cut off ranges, respectively. The primary endpoint is the risk of combined disease-specific failure after 30 days. Secondary outcomes are antibiotic exposure, side effects from antibiotics, rate and duration of hospitalization, time to clinical stability, disease activity scores and cost effectiveness. The study hypothesis is that procalcitonin-guidance is non

Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

PubMed

Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

2013-01-01

This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

Scope of photodynamic therapy in periodontics.

PubMed

Kumar, Vivek; Sinha, Jolly; Verma, Neelu; Nayan, Kamal; Saimbi, C S; Tripathi, Amitandra K

2015-01-01

Periodontal disease results from inflammation of the supporting structure of the teeth and in response to chronic infection caused by various periodontopathic bacteria. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. However, the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. Photodynamic therapy (PDT) is a powerful laser-initiated photochemical reaction, involving the use of a photoactive dye (photosensitizer) activated by light of a specific wavelength in the presence of oxygen. Application of PDT in periodontics such as pocket debridement, gingivitis, and aggressive periodontitis continue to evolve into a mature clinical treatment modality and is considered as a promising novel approach for eradicating pathogenic bacteria in periodontitis.

A retrospective analysis of the duration of oral antibiotic therapy for the treatment of acne among adolescents: investigating practice gaps and potential cost-savings.

PubMed

Lee, Young H; Liu, Guodong; Thiboutot, Diane M; Leslie, Douglas L; Kirby, Joslyn S

2014-07-01

Duration of oral antibiotic therapy in acne has not been widely studied. Recent guidelines suggest it should be limited to 3 to 6 months. We sought to compare the duration of oral antibiotic use with recent guidelines and determine the potential cost-savings related to shortened durations. This is a retrospective cohort study from the MarketScan Commercial Claims and Encounters database. Claims data were used to determine duration and costs of antibiotic therapy. The mean course duration was 129 days. The majority (93%) of courses were less than 9 months. Among the 31,634 courses, 18,280 (57.8%) did not include concomitant topical retinoid therapy. The mean (95% confidence interval) duration with and without topical retinoid use was 133 (131.5-134.7) days and 127 (125.4-127.9) days, respectively. The mean excess direct cost of antibiotic treatment for longer than 6 months was $580.99/person. Claims cannot be attributed to a specific diagnosis or provider. The database does not provide information on acne severity. Duration of antibiotic use is decreasing when compared with previous data. However, 5547 (17.53%) courses exceeded 6 months, highlighting an opportunity for reduced antibiotic use. If courses greater than 6 months were shortened to 6 months, savings would be $580.99/person. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Anthrax prevention and treatment: utility of therapy combining antibiotic plus vaccine.

PubMed

Klinman, Dennis M; Yamamoto, Masaki; Tross, Debra; Tomaru, Koji

2009-12-01

The intentional release of anthrax spores in 2001 confirmed this pathogen's ability to cause widespread panic, morbidity and mortality. While individuals exposed to anthrax can be successfully treated with antibiotics, pre-exposure vaccination can reduce susceptibility to infection-induced illness. Concern over the safety and immunogenicity of the licensed US vaccine (Anthrax Vaccine Adsorbed (AVA)) has fueled research into alternatives. Second-generation anthrax vaccines based on purified recombinant protective antigen (rPA) have entered clinical trials. These rPA vaccines induce neutralizing antibodies that prevent illness, but the magnitude and duration of the resultant protective response is modest. Efforts are underway to bolster the immunogenicity of rPA by combining it with adjuvants and other immunostimulatory agents. Third generation vaccines are under development that utilize a wide variety of immunization platforms, antigens, adjuvants, delivery methods and routes of delivery to optimize the induction of a protective immunity. For the foreseeable future, vaccination will rely on first and second generation vaccines co-administered with immune adjuvants. Optimal post-exposure treatment of immunologically naive individuals should include a combination of vaccine plus antibiotic therapy.

Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

PubMed

Hadinoto, Kunn; Cheow, Wean Sin

2014-04-01

Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified. Copyright © 2014 Elsevier B.V. All rights reserved.

WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics.

PubMed

Carlet, Jean; Rambaud, Claude; Pulcini, Céline

2012-07-09

Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians.

A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

PubMed

Paajanen, Hannu; Grönroos, Juha M; Rautio, Tero; Nordström, Pia; Aarnio, Markku; Rantanen, Tuomo; Hurme, Saija; Dean, Kirsti; Jartti, Airi; Mecklin, Jukka-Pekka; Sand, Juhani; Salminen, Paulina

2013-02-08

Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting

Impact of procalcitonin-guided therapy for hospitalized community-acquired pneumonia on reducing antibiotic consumption and costs in Japan.

PubMed

Ito, Akihiro; Ishida, Tadashi; Tokumasu, Hironobu; Washio, Yasuyoshi; Yamazaki, Akio; Ito, Yuhei; Tachibana, Hiromasa

2017-03-01

This study aimed to investigate the usefulness of procalcitonin-guided therapy in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening prognosis. 352 hospitalized community-acquired pneumonia patients in an observational cohort study in which procalcitonin was measured three times serially, on admission (Day 1) and 2-3 days (Day 3) and 6-8 days (Day 7) after admission, between October 2010 and February 2016 were reviewed retrospectively. Antibiotics could be stopped if Day 7 procalcitonin was <0.25 ng mL -1 or ≤10% of the higher value of procalcitonin on Day 1 or 3. Antibiotic duration and costs and recurrence and mortality rates were evaluated in mild to moderate or severe pneumonia by theoretical procalcitonin guidance for community-acquired pneumonia treatment. Using theoretical procalcitonin guidance, antibiotic duration could be reduced from 12.6 to 8.6 days (P < 0.001), while costs could be reduced from 45,833 to 38,952 yen (P = 0.005). Among the patients in whom theoretical procalcitonin guidance could be adopted, recurrence rates (5.6% vs. 8.1%, P = 0.15) and mortality rates (0% vs. 5.1%, P = 0.07) did not worsen between the group having the same antibiotic durations as with theoretical procalcitonin guidance in actual practice (N = 71) and the group having durations more than 2 days longer in actual practice than in theoretical procalcitonin guidance (N = 198). There was no significant difference in pneumonia severity using A-DROP, CURB-65, and PSI between two groups. Procalcitonin-guided therapy may be useful in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening the prognosis. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Antibiotic prescribing for endodontic therapies: a comparative survey between general dental practitioners and final year Bachelor of Dental Surgery students in Cardiff, UK.

PubMed

Al Masan, A A; Dummer, P M H; Farnell, D J J; Vianna, M E

2018-07-01

To evaluate the views of final year dental surgery students (BDS; G1) at Cardiff University and general dental practitioners (GDPs; G2) within the geographic area of Cardiff, Wales, on antibiotic prescribing for endodontic conditions, and investigate the potential differences between the two groups. A cross-sectional online questionnaire-based survey of 12 qualitative and quantitative questions was distributed to 76 final year BDS Cardiff University students and 55 dental practices within Cardiff, UK. Six questions recorded general information, and the remaining questions included a series of hypothetical clinical scenarios, where the participants were asked to state whether they would or would not prescribe antibiotics. The data were analysed using spss version 23 to produce descriptive statistics, contingency tables and to run chi-square (χ²) tests, Fisher's exact tests and relative risk calculations. The response rate was 60% (n = 79). All G1 participants were aware of the consequences of antibiotic overuse. Approximately 60% of responders were aware of guidelines for antibiotic use in endodontic therapies, and 83% would only use antibiotics for a limited selection of patients (e.g. patients with systemic complications). G1 responses to clinical scenarios indicated overall that they were comparable to the ideal answers except for acute apical abscess (64% believed that antibiotics were indicated). The majority of G2 were aware of the consequences of antibiotic overuse. Only 28% of G2 were aware of guidelines for antibiotic use in endodontic therapies. Overall responses revealed that antibiotics would be prescribed for: systemic complications (78%), acute apical abscess (72%) and symptomatic apical periodontitis (28%). The clinical scenarios revealed G1 were more likely to prescribe antibiotics compared to G2 for cases of necrotic pulp with symptomatic apical periodontitis without systemic complications (incorrect answer) and less likely to other clinical

Antibiotic treatment for Helicobacter pylori: Is the end coming?

PubMed Central

Kim, Su Young; Choi, Duck Joo; Chung, Jun-Won

2015-01-01

Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID:26558152

Do we treat our patients or rather periodontal microbes with adjunctive antibiotics in periodontal therapy? A 16S rDNA microbial community analysis.

PubMed

Hagenfeld, Daniel; Koch, Raphael; Jünemann, Sebastian; Prior, Karola; Harks, Inga; Eickholz, Peter; Hoffmann, Thomas; Kim, Ti-Sun; Kocher, Thomas; Meyle, Jörg; Kaner, Doğan; Schlagenhauf, Ulrich; Ehmke, Benjamin; Harmsen, Dag

2018-01-01

Empiric antibiotics are often used in combination with mechanical debridement to treat patients suffering from periodontitis and to eliminate disease-associated pathogens. Until now, only a few next generation sequencing 16S rDNA amplicon based publications with rather small sample sizes studied the effect of those interventions on the subgingival microbiome. Therefore, we studied subgingival samples of 89 patients with chronic periodontitis (solely non-smokers) before and two months after therapy. Forty-seven patients received mechanical periodontal therapy only, whereas 42 patients additionally received oral administered amoxicillin plus metronidazole (500 and 400 mg, respectively; 3x/day for 7 days). Samples were sequenced with Illumina MiSeq 300 base pairs paired end technology (V3 and V4 hypervariable regions of the 16S rDNA). Inter-group differences before and after therapy of clinical variables (percentage of sites with pocket depth ≥ 5mm, percentage of sites with bleeding on probing) and microbiome variables (diversity, richness, evenness, and dissimilarity) were calculated, a principal coordinate analysis (PCoA) was conducted, and differential abundance of agglomerated ribosomal sequence variants (aRSVs) classified on genus level was calculated using a negative binomial regression model. We found statistically noticeable decreased richness, and increased dissimilarity in the antibiotic, but not in the placebo group after therapy. The PCoA revealed a clear compositional separation of microbiomes after therapy in the antibiotic group, which could not be seen in the group receiving mechanical therapy only. This difference was even more pronounced on aRSV level. Here, adjunctive antibiotics were able to induce a microbiome shift by statistically noticeably reducing aRSVs belonging to genera containing disease-associated species, e.g., Porphyromonas, Tannerella, Treponema, and Aggregatibacter, and by noticeably increasing genera containing health

Continuous versus intermittent antibiotics for bronchiectasis.

PubMed

Donovan, Tim; Felix, Lambert M; Chalmers, James D; Milan, Stephen J; Mathioudakis, Alexander G; Spencer, Sally

2018-06-03

Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events. To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events. On 1 August 2017 and 4 May 2018 we searched the Cochrane Airways Review Group Specialised Register (CAGR), CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. On 25 September 2017 and 4 May 2018 we also searched www.clinicaltrials.gov, the World Health Organization (WHO) trials portal, conference proceedings and the reference lists of existing systematic reviews. We planned to include randomised controlled trials (RCTs) of adults or children with bronchiectasis that compared continuous versus intermittent administration of long-term prophylactic antibiotics of at least three months' duration. We considered eligible studies reported as full-text articles, as abstracts only and unpublished data. Two review authors independently screened the search results and full-text reports. We identified 268 unique records. Of these we retrieved and examined 126 full-text reports, representing 114 studies, but none of these studies

Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

PubMed Central

Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

2014-01-01

There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing.

PubMed Central

Kerr, J. R.; Barr, J. G.; Smyth, E. T.; O'Hare, J.; Bell, P. M.; Callender, M. E.

1993-01-01

Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown. These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects. An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses. Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken. The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison. The breakdown cost for gentamicin is presented to illustrate the method. The costing of adverse effects has not been attempted. We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use. These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital. PMID:8516976

Negative Pressure Wound Therapy Reduces the Effectiveness of Traditional Local Antibiotic Depot in a Large Complex Musculoskeletal Wound Animal Model

DTIC Science & Technology

2012-09-01

in particular, local antibiotic delivery via polymethylmethacrylate (PMMA) bone cement and negative pressure wound therapy (NPWT). In cases with gross...release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacoki- netic study. J Bone Joint Surg Br. 1978;60-B:270 275. 7...diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992;278:244 252. Stinner et al J Orthop Trauma Volume

Multifaceted antibiotic treatment analysis of methicillin-sensitive Staphylococcus aureus bloodstream infections.

PubMed

Weber, Zhanni; Ariano, Robert; Lagacé-Wiens, Philippe; Zelenitsky, Sheryl

2016-12-01

Given the overall prevalence and poor prognosis of Staphylococcus aureus bloodstream infections (BSIs), the study of treatment strategies to improve patient outcomes is important. The aim of this study was to conduct a multifaceted antibiotic treatment analysis of methicillin-sensitive S. aureus (MSSA) BSI and to characterise optimal early antibiotic therapy (within the first 7 days of drawing the index blood culture) for this serious infection. Antibiotic selection was categorised as optimal targeted (intravenous cloxacillin or cefazolin), optimal broad (piperacillin/tazobactam or meropenem), adequate (vancomycin) or inadequate (other antibiotics or oral therapy). A TSE (timing, selection, exposure) score was developed to comprehensively characterise early antibiotic therapy, where higher points corresponded to prompt initiation, optimal antibiotic selection and longer exposure (duration). Amongst 71 cases of complicated MSSA-BSI, end-of-treatment (EOT) response (i.e. clinical cure) was improved when at least adequate antibiotic therapy was initiated within 24 h [71.7% (33/46) vs. 48.0% (12/25); P = 0.047]. Clinical cure was also more likely when therapy included ≥4 days of optimal targeted antibiotics within the first 7 days [74.4% (29/39) vs. 50.0% (16/32); P = 0.03]. The TSE score was an informative index of early antibiotic therapy, with EOT cure documented in 72.0% (36/50) compared with 42.9% (9/21) of cases with scores above and below 15.2, respectively (P = 0.02). In multivariable analysis, lower Charlson comorbidity index, presence of BSI on admission, and optimising early antibiotic therapy, as described above, were associated with clinical cure in patients with MSSA-BSI. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Grievances in cases using antibiotics due to orodental problems and assessment of the need for antibiotics.

PubMed

Kandemir, S; Ergül, N

2000-04-01

To assess the complaints of patients who were prescribed antibiotics following orodental problems and the need for antibiotics prescribed for this purpose. Examinations were carried out in the Department of Oral Diagnosis and Radiology, Ege University, Turkey. A total of 203 patients (129 females and 74 males) between 8-70 years of age (mean age 37.7 +/- 13.9). Examination and report. Frequency of unnecessary antibiotic use. Antibiotic therapy was not necessary for 151 (74.4 per cent) cases. Antibiotics were unnecessarily prescribed in 45 cases of acute irreversible pulpitis, 10 chronic apical abscess, 6 acute apical paradontitis, 7 gingivitis, 10 periodontitis, 4 epulis, 2 TMJ (temporomandibular junction) dysfunction, 2 sharp ridge of alveolar bone, 1 burning mouth syndrome and 1 recurrent aphthous stomatitis. In 108 (53.2 per cent) of the cases, the prescribed antibiotics were found to be penicillins, 102 of which were broad-spectrum. It was also determined that only 6 (7.7 per cent) of the 78 cases diagnosed as acute apical abscess were given drainage as local therapy. Principles for treating dental infections suggest that an antibiotic should only be used to supplement and not substitute for conventional surgical methods. Therefore, in cases with acute apical abscess, mechanical treatment (drainage) should be the first step. Inappropriate antibiotic use is quite widespread in dentistry. Dentists should avoid inappropriate use of antibiotics. To prevent inappropriate administration, necessary precautions need to be taken against dispensing antibiotics without prescription.

Empirical mono- versus combination antibiotic therapy in adult intensive care patients with severe sepsis - A systematic review with meta-analysis and trial sequential analysis.

PubMed

Sjövall, Fredrik; Perner, Anders; Hylander Møller, Morten

2017-04-01

To assess benefits and harms of empirical mono- vs. combination antibiotic therapy in adult patients with severe sepsis in the intensive care unit (ICU). We performed a systematic review according to the Cochrane Collaboration methodology, including meta-analysis, risk of bias assessment and trial sequential analysis (TSA). We included randomised clinical trials (RCT) assessing empirical mono-antibiotic therapy versus a combination of two or more antibiotics in adult ICU patients with severe sepsis. We exclusively assessed patient-important outcomes, including mortality. Two reviewers independently evaluated studies for inclusion, extracted data, and assessed risk of bias. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated and the risk of random errors was assessed by TSA. Thirteen RCTs (n = 2633) were included; all were judged as having high risk of bias. Carbapenems were the most frequently used mono-antibiotic (8 of 13 trials). There was no difference in mortality (RR 1.11, 95% CI 0.95-1.29; p = 0.19) or in any other patient-important outcomes between mono- vs. combination therapy. In TSA of mortality, the Z-curve reached the futility area, indicating that a 20% relative risk difference in mortality may be excluded between the two groups. For the other outcomes, TSA indicated lack of data and high risk of random errors. This systematic review of RCTs with meta-analysis and TSA demonstrated no differences in mortality or other patient-important outcomes between empirical mono- vs. combination antibiotic therapy in adult ICU patients with severe sepsis. The quantity and quality of data was low without firm evidence for benefit or harm of combination therapy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial.

PubMed

Cranendonk, Duncan R; Opmeer, Brent C; Prins, Jan M; Wiersinga, W Joost

2014-05-05

Recommended therapy duration for patients hospitalized with cellulitis is 10-14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation. This study will compare in hospitalized patients the safety and effectiveness of shortening antibiotic therapy for cellulitis from 12 to 6 days. In a multicenter, randomized, double-blind, non-inferiority trial, adult patients admitted with cellulitis will be included. Cellulitis is defined as warmth, erythema, and induration of the skin and/or subcutaneous tissue, with or without pain (including erysipelas). All patients will initially be treated with intravenous flucloxacillin, and will be evaluated after 5-6 days. Those who have improved substantially (defined as being afebrile, and having a lower cellulitis severity score) will be randomized at day 6 between additional 6 days of oral flucloxacillin (n = 198) or placebo (n = 198). Treatment success is defined as resolution of cellulitis on day 14 (disappearance of warmth and tenderness, improvement of erythema and edema), without the need of additional antibiotics for cellulitis by day 28. Secondary endpoints are relapse rate (up to day 90), speed of recovery (using a cellulitis severity score until day 28, and VAS scores on pain and swelling until day 90), quality of life (using the SF-36 and EQ-5D questionnaires) and costs (associated with total antibiotic use and health-care resource utilization up to day 90). Inclusion is planned to start in Q2 2014. ClinicalTrials.gov (NCT02032654) and the Netherlands Trial Register (NTR4360).

Osmotic therapies added to antibiotics for acute bacterial meningitis

PubMed Central

Wall, Emma Cb; Ajdukiewicz, Katherine Mb; Bergman, Hanna; Heyderman, Robert S; Garner, Paul

2018-01-01

Background Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes. This is an update of a Cochrane Review first published in 2013. Objectives To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability. Search methods We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015). Selection criteria Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. Data collection and analysis Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence. Main results We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates. Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272

Antibiotic-non-antibiotic combinations for combating extremely drug-resistant Gram-negative 'superbugs'.

PubMed

Schneider, Elena K; Reyes-Ortega, Felisa; Velkov, Tony; Li, Jian

2017-02-28

The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis. The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post-antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant (XDR) Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non-antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens. This review surveys the available literature on the potential benefits of employing antibiotic-non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by 'superbugs'. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Antibiotic Resistance in Sepsis Patients: Evaluation and Recommendation of Antibiotic Use

PubMed Central

Pradipta, Ivan Surya; Sodik, Dian Chairunnisa; Lestari, Keri; Parwati, Ida; Halimah, Eli; Diantini, Ajeng; Abdulah, Rizky

2013-01-01

Background: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics. Aims: We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis. Materials and Methods: A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data. Results: A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%. Conclusions: The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients. PMID:23923107

Music therapy to promote prosocial behaviors in aggressive adolescent boys--a pilot study.

PubMed

Rickson, Daphne J; Watkins, William G

2003-01-01

This pilot study was undertaken to investigate whether music therapy is effective in promoting prosocial behaviors in aggressive adolescent boys who have social, emotional, and learning difficulties. Fifteen subjects (aged 11-15 years), enrolled at a special residential school in New Zealand, were randomly assigned to music therapy treatment groups (n = 6, n = 5), and a waitlist control group (n = 4). Examination of demographic data identified differences between groups for diagnosis (p =.044), with Group 1 all having Attention Deficit Hyperactivity Disorder (ADHD), and for age (p =.027), with Group 2 having a mean age 1.38 years older. Measures included parent and teacher versions of the Developmental Behaviour Checklist (DBC-P & DBC-T) (Einfeld & Tonge, 1994; Einfeld, Tonge, & Parmenter, 1998). While no definite treatment effects could be detected, results suggest that a music therapy program promoting autonomy and creativity may help adolescents to interact more appropriately with others in a residential villa setting, but might also lead to a temporary mild increase in disruptive behavior in the classroom. A more highly structured program and smaller group numbers may be advantageous for boys who have ADHD.

Optimising patient safety when using elastomeric pumps to administer outpatient parenteral antibiotic therapy.

PubMed

Oliver, Gemma

2016-10-27

Outpatient parenteral antibiotic therapy (OPAT) is a growing area of practice that has numerous benefits for both patients and the healthcare system. In order for OPAT services to be successful, strategies need to be in place to maximise efficiency while providing safe, high-quality care. The use of elastomeric pumps to deliver intravenous (IV) antibiotics can have many benefits for OPAT services; they are cost-effective, easy to use and allow the patient to be fully ambulant. However, plans need to be put in place to make sure their use is safe and effective. This article discusses the use of elastomeric pumps by a UK-based OPAT team and the governance processes the team put in place to optimise patient safety when using elastomeric pumps to deliver IV antibiotics. Furthermore, with experience of using elastomeric pumps for more than 4 years the OPAT team was asked to evaluate an elastomeric pump new to the UK market: the Accufuser pump (Vygon (UK) Limited). By collecting data on its use it was found to be safe and easy to use. The team felt that the Accufuser pump ran to time in 96% of completed evaluations and considered it to be clinically acceptable in all responses.

Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicenter noninferiority randomized clinical trial (HiTEMP study).

PubMed

van der Does, Yuri; Limper, Maarten; Jie, Kim E; Schuit, Stephanie C E; Jansen, Henry; Pernot, Niki; van Rosmalen, Joost; Poley, Marten J; Ramakers, Christian; Patka, Peter; van Gorp, Eric C M; Rood, Pleunie P M

2018-06-02

Overuse of broad-spectrum antibiotics in emergency departments(EDs) results in antibiotic resistance. We determined if procalcitonin(PCT)-guided therapy can be used to reduce antibiotic regimens in EDs by investigating efficacy, safety and accuracy. This was a noninferiority multicenter randomized clinical trial, performed in two Dutch hospitals. Adult patients with fever ≥38.2°C(100.8°F) in triage were randomized between standard diagnostic workup(control group) and PCT-guided therapy, defined as standard workup with addition of one single PCT measurement. Treatment algorithm encouraged withholding antibiotic regimens with PCT<0.5μg/L, and starting antibiotic regimens PCT≥0.5μg/L. Exclusion criteria were immunocompromised conditions, pregnancy, moribund patients, patients <72h after surgery or requiring primary surgical intervention. Primary outcomes were efficacy, defined as number of prescribed antibiotic regimens; safety, defined as combined-safety-endpoint(CSE) consisting of 30-days mortality, intensive-care unit admission, ED-return-visit within 2 weeks; accuracy, defined as sensitivity, apecificity and area-under-the-curve(AUC) of PCT for bacterial infections. Noninferiority margin for safety outcome was 7.5%. Between August 2014 and January 2017, 551 patients were included. In the PCT-guided group(n=275) 200(73%)patients were prescribed antibiotic regimens, in the control group(n=276) 212(77%)(p=0.28). There was no significant difference in CSE between the PCT-guided group, 29(11%), and control group, 46(16%)(p=0.16), with a noninferiority margin of 0.46%(n=526). AUC for confirmed bacterial infections for PCT was 0.681(95%CI0.633-0.730), for CRP 0.619(95%CI 0.569-0.669).: CONCLUSIONS.: PCT-guided therapy was noninferior in terms of safety, but did not reduce prescription of antibiotic regimens in an ED population with fever. In this heterogeneous population, the accuracy of PCT in diagnosing bacterial infections was poor. TRIAL REGISTRATION IN

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PubMed

Elting, L S; Rubenstein, E B; Rolston, K; Cantor, S B; Martin, C G; Kurtin, D; Rodriguez, S; Lam, T; Kanesan, K; Bodey, G

2000-11-01

To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Think twice: A cognitive perspective of an antibiotic timeout intervention to improve antibiotic use.

PubMed

Jones, Makoto; Butler, Jorie; Graber, Christopher J; Glassman, Peter; Samore, Matthew H; Pollack, Lori A; Weir, Charlene; Goetz, Matthew Bidwell

2017-07-01

To understand clinicians' impressions of and decision-making processes regarding an informatics-supported antibiotic timeout program to re-evaluate the appropriateness of continuing vancomycin and piperacillin/tazobactam. We implemented a multi-pronged informatics intervention, based on Dual Process Theory, to prompt discontinuation of unwarranted vancomycin and piperacillin/tazobactam on or after day three in a large Veterans Affairs Medical Center. Two workflow changes were introduced to facilitate cognitive deliberation about continuing antibiotics at day three: (1) teams completed an electronic template note, and (2) a paper summary of clinical and antibiotic-related information was provided to clinical teams. Shortly after starting the intervention, six focus groups were conducted with users or potential users. Interviews were recorded and transcribed. Iterative thematic analysis identified recurrent themes from feedback. Themes that emerged are represented by the following quotations: (1) captures and controls attention ("it reminds us to think about it"), (2) enhances informed and deliberative reasoning ("it makes you think twice"), (3) redirects decision direction ("…because [there was no indication] I just [discontinued] it without even trying"), (4) fosters autonomy and improves team empowerment ("the template… forces the team to really discuss it"), and (5) limits use of emotion-based heuristics ("my clinical concern is high enough I think they need more aggressive therapy…"). Requiring template completion to continue antibiotics nudged clinicians to re-assess the appropriateness of specified antibiotics. Antibiotic timeouts can encourage deliberation on overprescribed antibiotics without substantially curtailing autonomy. An effective nudge should take into account clinician's time, workflow, and thought processes. Published by Elsevier Inc.

Optimal Duration of Antibiotic Therapy in Patients With Hematogenous Vertebral Osteomyelitis at Low Risk and High Risk of Recurrence.

PubMed

Park, Ki-Ho; Cho, Oh-Hyun; Lee, Jung Hee; Park, Ji Seon; Ryu, Kyung Nam; Park, Seong Yeon; Lee, Yu-Mi; Chong, Yong Pil; Kim, Sung-Han; Lee, Sang-Oh; Choi, Sang-Ho; Bae, In-Gyu; Kim, Yang Soo; Woo, Jun Hee; Lee, Mi Suk

2016-05-15

The optimal duration of antibiotic treatment for hematogenous vertebral osteomyelitis (HVO) should be based on the patient's risk of recurrence, but it is not well established. A retrospective review was conducted to evaluate the optimal duration of antibiotic treatment in patients with HVO at low and high risk of recurrence. Patients with at least 1 independent baseline risk factor for recurrence, determined by multivariable analysis, were considered as high risk and those with no risk factor as low risk. A total of 314 patients with microbiologically diagnosed HVO were evaluable for recurrence. In multivariable analysis, methicillin-resistant Staphylococcus aureus infection (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.16-5.87), undrained paravertebral/psoas abscesses (aOR, 4.09; 95% CI, 1.82-9.19), and end-stage renal disease (aOR, 6.58; 95% CI, 1.63-26.54) were independent baseline risk factors for recurrence. Therefore, 191 (60.8%) patients were classified as low risk and 123 (39.2%) as high risk. Among high-risk patients, there was a significant decreasing trend for recurrence according to total duration of antibiotic therapy: 34.8% (4-6 weeks [28-41 days]), 29.6% (6-8 weeks [42-55 days]), and 9.6% (≥8 weeks [≥56 days]) (P = .002). For low-risk patients, this association was still significant but the recurrence rates were much lower: 12.0% (4-6 weeks), 6.3% (6-8 weeks), and 2.2% (≥8 weeks) (P = .02). Antibiotic therapy of prolonged duration (≥8 weeks) should be given to patients with HVO at high risk of recurrence. For low-risk patients, a shorter duration (6-8 weeks) of pathogen-directed antibiotic therapy may be sufficient. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Topical antibiotics: therapeutic value or ecologic mischief?

PubMed

Del Rosso, James Q; Kim, Grace K

2009-01-01

Based on antibiotic prescribing data from 2003, dermatologists account annually for 8-9 million prescriptions for oral antibiotics, and 3-4 million prescriptions for topical antibiotics. Overall, much of the emphasis on concerns related to emergence of clinically significant antibiotic-resistant bacterial strains focuses on use of systemic antibiotics, however, topical antibiotic use may also have potential implications. The following article discusses the perspectives of the authors related to the potential therapeutic benefits and ecologic implications ("ecologic mischief") of topical antibiotic therapy for specific indications encountered in ambulatory dermatology practice.

Role of (18)F-FDG PET/CT in the evaluation of response to antibiotic therapy in patients affected by infectious spondylodiscitis.

PubMed

Niccoli Asabella, Artor; Iuele, Francesca; Simone, Francesco; Fanelli, Margherita; Lavelli, Valentina; Ferrari, Cristina; Di Palo, Alessandra; Notaristefano, Antonio; Merenda, Nunzio Clemente; Rubini, Giuseppe

2015-01-01

Spondylodiscitis is characterized by infection involving the intervertebral disc and adjacent vertebrae. It can occur anywhere in the vertebral column but more commonly involves lumbar spine. Our aim was to evaluate the usefulness of (18)F-FDG PET/CT to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis and to compare the role of (18)F-FDG PET/CT and MRI in post-treatment evaluation. 15 patients (12M, 3F), with mean age 65±13 years old, with typical clinical symptoms of Infectious Spondylodiscitis (pain, fever and increase of inflammatory indexes) and confirmed by blood culture or vertebral biopsy underwent within three day-interval a (18)F-FDG PET/CT and Magnetic Resonance (MR) at "baseline" and after antibiotic therapy. Semiquantitative parameters at (18)F-FDG PET/CT "baseline" SUVmax1, MTV1 and TLG1 and after therapy SUVmax2, MTV2 and TLG2 of involved vertebrae were calculated. Follow-up period of at least three months was available for all patients. T-student test for paired groups was performed to compare baseline and after therapy (18)F-FDG PET/CT semiquantitative parameters. According to (18)F-FDG PET/CT parameters all patients showed a response to antibiotic therapy. All patients were positive at "baseline" MRI of the spine, while at follow-up, 7/15 patients showed MR signs of infection and were considered "positive" and 8/15 showed resolution of infectious condition and, therefore they were considered "negative". A statistical significant difference between (18)F-FDG PET/CT "baseline" and after antibiotic therapy was found for all semiquantitative parameters: SUVmax (t=5.8, P=0.01); MTV (t=5.17, P=0.001); TLG (t=5,26, P=0,001). The comparison between the "baseline" and "after treatment" (18)F-FDG semiquantitative parameters showed a significant reduction of all parameters. This reduction was relevant also in patients with positive post-treatment MRI. This can be probably related to the tissue remodeling in

Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

PubMed Central

Amann, Birgit H.

2016-01-01

Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when

Dynamics of success and failure in phage and antibiotic therapy in experimental infections.

PubMed

Bull, J J; Levin, Bruce R; DeRouin, Terry; Walker, Nina; Bloch, Craig A

2002-11-26

In 1982 Smith and Huggins showed that bacteriophages could be at least as effective as antibiotics in preventing mortality from experimental infections with a capsulated E. coli (K1) in mice. Phages that required the K1 capsule for infection were more effective than phages that did not require this capsule, but the efficacies of phages and antibiotics in preventing mortality both declined with time between infection and treatment, becoming virtually ineffective within 16 hours. We develop quantitative microbiological procedures that (1) explore the in vivo processes responsible for the efficacy of phage and antibiotic treatment protocols in experimental infections (the Resistance Competition Assay, or RCA), and (2) survey the therapeutic potential of phages in vitro (the Phage Replication Assay or PRA). We illustrate the application and utility of these methods in a repetition of Smith and Huggins' experiments, using the E. coli K1 mouse thigh infection model, and applying treatments of phages or streptomycin. 1) The Smith and Huggins phage and antibiotic therapy results are quantitatively and qualitatively robust. (2) Our RCA values reflect the microbiological efficacies of the different phages and of streptomycin in preventing mortality, and reflect the decline in their efficacy with a delay in treatment. These results show specifically that bacteria become refractory to treatment over the term of infection. (3) The K1-specific and non-specific phages had similar replication rates on bacteria grown in broth (based on the PRA), but the K1-specific phage had markedly greater replication rates in mouse serum.

Effects of inappropriate empirical antibiotic therapy on mortality in patients with healthcare-associated methicillin-resistant Staphylococcus aureus bacteremia: a propensity-matched analysis.

PubMed

Yoon, Young Kyung; Park, Dae Won; Sohn, Jang Wook; Kim, Hyo Youl; Kim, Yeon-Sook; Lee, Chang-Seop; Lee, Mi Suk; Ryu, Seong-Yeol; Jang, Hee-Chang; Choi, Young Ju; Kang, Cheol-In; Choi, Hee Jung; Lee, Seung Soon; Kim, Shin Woo; Kim, Sang Il; Kim, Eu Suk; Kim, Jeong Yeon; Yang, Kyung Sook; Peck, Kyong Ran; Kim, Min Ja

2016-07-15

The purported value of empirical therapy to cover methicillin-resistant Staphylococcus aureus (MRSA) has been debated for decades. The purpose of this study was to evaluate the effects of inappropriate empirical antibiotic therapy on clinical outcomes in patients with healthcare-associated MRSA bacteremia (HA-MRSAB). A prospective, multicenter, observational study was conducted in 15 teaching hospitals in the Republic of Korea from February 2010 to July 2011. The study subjects included adult patients with HA-MRSAB. Covariate adjustment using the propensity score was performed to control for bias in treatment assignment. The predictors of in-hospital mortality were determined by multivariate logistic regression analyses. In total, 345 patients with HA-MRSAB were analyzed. The overall in-hospital mortality rate was 33.0 %. Appropriate empirical antibiotic therapy was given to 154 (44.6 %) patients. The vancomycin minimum inhibitory concentrations of the MRSA isolates ranged from 0.5 to 2 mg/L by E-test. There was no significant difference in mortality between propensity-matched patient pairs receiving inappropriate or appropriate empirical antibiotics (odds ratio [OR] = 1.20; 95 % confidence interval [CI] = 0.71-2.03). Among patients with severe sepsis or septic shock, there was no significant difference in mortality between the treatment groups. In multivariate analyses, severe sepsis or septic shock (OR = 5.45; 95 % CI = 2.14-13.87), Charlson's comorbidity index (per 1-point increment; OR = 1.52; 95 % CI = 1.27-1.83), and prior receipt of glycopeptides (OR = 3.24; 95 % CI = 1.08-9.67) were independent risk factors for mortality. Inappropriate empirical antibiotic therapy was not associated with clinical outcome in patients with HA-MRSAB. Prudent use of empirical glycopeptide therapy should be justified even in hospitals with high MRSA prevalence.

Antibiotics for PANDAS? Limited Evidence: Review and Putative Mechanisms of Action.

PubMed

Burchi, Elisabetta; Pallanti, Stefano

2018-05-03

Antibiotics have been used extensively by clinicians to treat patients with PANDAS or PANS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome, respectively). This review examines the best-quality evidence supporting the practice-based use of antibiotics in these psychiatric conditions. PubMed was searched for English-language articles published between January 1994 and July 2017 using the search terms [PANDAS OR PANS OR new-onset pediatric OCD] AND [antibiotics OR macrolides OR beta-lactams]. Randomized clinical trials, observational studies, and case reports concerning antibiotic use in PANDAS/PANS were reviewed. Four publications were included in the quantitative synthesis. The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. Although the single studies conveyed no statistically significant results, there is some evidence for efficacy of antibiotic therapy in reducing neuropsychiatric symptoms in the PANDAS/PANS population. Whereas the use of eradicating antibiotic therapy during active infections in PANDAS/PANS is well established, there is still a need for studies that improve the quality of evidence supporting use of antibiotics in this population independent of ongoing infections. Studies that compare antibiotics with other therapies, as well as studies that assess safety and efficacy of long-term use of antibiotic therapy in PANDAS/PANS, are still lacking. However, the available research supports evidence of a subgroup in the pediatric OCD population that is sensitive to antibiotic treatment and immunomodulatory therapy, independent of ongoing infectious conditions. Thus, more studies are warranted in the overall OCD spectrum. © Copyright 2018 Physicians Postgraduate Press, Inc.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

PubMed

Sippola, S; Grönroos, J; Tuominen, R; Paajanen, H; Rautio, T; Nordström, P; Aarnio, M; Rantanen, T; Hurme, S; Salminen, P

2017-09-01

An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Antibiotic therapy prior to hospital admission is associated with reduced septic shock and need for mechanical ventilation in patients with community-acquired pneumonia.

PubMed

Amaro, Rosanel; Sellarés, Jacobo; Polverino, Eva; Cillóniz, Catia; Ferrer, Miquel; Fernández-Barat, Laia; Mensa, Josep; Niederman, Michael S; Torres, Antoni

2017-05-01

A subgroup of patients admitted to the hospital with a diagnosis of community-acquired pneumonia (CAP) have received antibiotic therapy prior to admission for the current episode of pneumonia. The objective of this study was to assess the clinical course of patients receiving antibiotics prior to admission, compared to patients not previously treated. An observational cohort of 3364 CAP patients consecutively admitted to our hospital, and prospectively included, were studied. We collected clinical, microbiological and biochemical parameters, focusing on recent antibiotics received prior to admission. 610 (18%) patients received antibiotics prior to hospital admission for the current CAP episode. Patients with previous antibiotic use developed septic shock less frequently (4% vs. 7%, p = 0.007) and required invasive ventilation less often (3% vs. 6%, p = 0.002). After adjustment by different covariate factors and propensity score, antibiotic therapy was still independently associated with a lower incidence of septic shock at admission (OR 0.54 [95% CI 0.31-0.95], p = 0.03) and less need for invasive ventilation (OR 0.38 [95% CI 0.16-0.91], p = 0.03). In this cohort, recent use of antibiotics before hospital admission in CAP seems to be associated with a lower incidence of septic shock on admission and a lower need for invasive ventilation. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Non-antibiotic treatments for bacterial diseases in an era of progressive antibiotic resistance.

PubMed

Opal, Steven M

2016-12-16

The emergence of multi-drug resistant (MDR) microbial pathogens threatens the very foundation upon which standard antibacterial chemotherapy is based. We must consider non-antibiotic solutions to manage invasive bacterial infections. Transition from antibiotics to non-traditional treatments poses real clinical challenges that will not be easy to solve. Antibiotics will continue to reliably treat some infections (e.g., group A streptococci and Treponema pallidum) but will likely need adjuvant therapies or will need to be replaced for many bacterial infections in the future.

Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children with ADHD

PubMed Central

Blader, Joseph C.; Pliszka, Steven R.; Jensen, Peter S.; Schooler, Nina R.; Kafantaris, Vivian

2010-01-01

OBJECTIVES The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol’s methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy

Procalcitonin Biomarker Algorithm Reduces Antibiotic Prescriptions, Duration of Therapy, and Costs in Chronic Obstructive Pulmonary Disease: A Comparison in the Netherlands, Germany, and the United Kingdom.

PubMed

van der Maas, Marloes E; Mantjes, Gertjan; Steuten, Lotte M G

2017-04-01

Antibiotics are often recommended as treatment for patients with chronic obstructive pulmonary disease (COPD) exacerbations. However, not all COPD exacerbations are caused by bacterial infections and there is consequently considerable misuse and overuse of antibiotics among patients with COPD. This poses a severe burden on healthcare resources such as increased risk of developing antibiotic resistance. The biomarker procalcitonin (PCT) displays specificity to distinguish bacterial inflammations from nonbacterial inflammations and may therefore help to rationalize antibiotic prescriptions. We report in this study, a three-country comparison of the health and economic consequences of a PCT biomarker-guided prescription and clinical decision-making strategy compared to current practice in hospitalized patients with COPD exacerbations. A decision tree was developed, comparing the expected costs and effects of the PCT algorithm to current practice in the Netherlands, Germany, and the United Kingdom. The time horizon of the model captured the length of hospital stay and a societal perspective was also adopted. The primary health outcome was the duration of antibiotic therapy. The incremental cost-effectiveness ratio was defined as the incremental costs per antibiotic day avoided. The incremental cost savings per day on antibiotic therapy avoided were (in Euros) €90 in the Netherlands, €125 in Germany, and €52 in the United Kingdom. Probabilistic sensitivity analyses showed that in the majority of simulations, the PCT biomarker strategy was superior to current practice (the Netherlands: 58%, Germany: 58%, and the United Kingdom: 57%). In conclusion, the PCT biomarker algorithm to optimize antibiotic prescriptions in COPD is likely to be cost-effective compared to current practice. Both the percentage of patients who start with antibiotic treatment as well as the duration of antibiotic therapy are reduced with the PCT decision algorithm, leading to a decrease in

Cycling Empirical Antibiotic Therapy in Hospitals: Meta-Analysis and Models

PubMed Central

Abel, Sören; Viechtbauer, Wolfgang; Bonhoeffer, Sebastian

2014-01-01

The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden. Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance. However, theoretical and clinical studies came to different conclusions regarding the usefulness of rotating first-line therapy (cycling). Here, we performed a quantitative pathogen-specific meta-analysis of clinical studies comparing cycling to standard practice. We searched PubMed and Google Scholar and identified 46 clinical studies addressing the effect of cycling on nosocomial infections, of which 11 met our selection criteria. We employed a method for multivariate meta-analysis using incidence rates as endpoints and find that cycling reduced the incidence rate/1000 patient days of both total infections by 4.95 [9.43–0.48] and resistant infections by 7.2 [14.00–0.44]. This positive effect was observed in most pathogens despite a large variance between individual species. Our findings remain robust in uni- and multivariate metaregressions. We used theoretical models that reflect various infections and hospital settings to compare cycling to random assignment to different drugs (mixing). We make the realistic assumption that therapy is changed when first line treatment is ineffective, which we call “adjustable cycling/mixing”. In concordance with earlier theoretical studies, we find that in strict regimens, cycling is detrimental. However, in adjustable regimens single resistance is suppressed and cycling is successful in most settings. Both a meta-regression and our theoretical model indicate that “adjustable cycling” is especially useful to suppress emergence of multiple resistance. While our model predicts that cycling periods of one month perform well, we expect that too long cycling periods are detrimental. Our results suggest that �

Dual antibiotics for bronchiectasis.

PubMed

Felix, Lambert M; Grundy, Seamus; Milan, Stephen J; Armstrong, Ross; Harrison, Haley; Lynes, Dave; Spencer, Sally

2018-06-11

Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation of the smaller airways and associated with a mortality rate greater than twice that of the general population. Antibiotics serve as front-line therapy for managing bacterial load, but their use is weighed against the development of antibiotic resistance. Dual antibiotic therapy has the potential to suppress infection from multiple strains of bacteria, leading to more successful treatment of exacerbations, reduced symptoms, and improved quality of life. Further evidence is required on the efficacy of dual antibiotics in terms of management of exacerbations and extent of antibiotic resistance. To evaluate the effects of dual antibiotics in the treatment of adults and children with bronchiectasis. We identified studies from the Cochrane Airways Group Specialised Register (CAGR), which includes the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine (AMED), and PsycINFO, as well as studies obtained by handsearching of journals/abstracts. We also searched the following trial registries: US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. We imposed no restriction on language of publication. We conducted our search in October 2017. We searched for randomised controlled trials comparing dual antibiotics versus a single antibiotic for short-term (< 4 weeks) or long-term management of bronchiectasis diagnosed in adults and/or children by bronchography, plain film chest radiography, or high-resolution computed tomography. Primary outcomes included exacerbations, length of hospitalisation, and serious adverse events. Secondary outcomes were response rates, emergence of resistance to antibiotics, systemic markers of infection, sputum

Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial

PubMed Central

Lee, Myeong Soo; Lee, Jung-Sook

2010-01-01

We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control. PMID:18955314

Platelet gel biotechnology applied to regenerative surgery of intrabony defects in patients with refractory generalized aggressive peridontitis. Case report.

PubMed

Mauro, S; Orlando, L; Panzoni, R; Orlando, P F

2003-01-01

Platelet gel biotechnology, a method which has all the components of "tissue engineering" techniques, potentiates the already known healing process of guided tissue regeneration procedures (GTR) by multiplying the number of molecules that activate the healing response and by grafting in the host site various cell types, among which stem cells. Here are reported cases of patients affected by refractory generalized aggressive periodontitis treated with the association GTR and platelet gel biotechnology to verify if the contribution of the gel would produce superior results than those obtained by surgery alone which had been previously applied to the same sites with negative results. Three patients in therapy from 4 to 11 years, already subjected to surgery (GTR) and antibiotic therapy, were reoperated with the adjunct of autologous platelet gel. At a distance of 15.2 months (range 11-17 months) the operated sites showed a reduction in probing pocket depth of 3.4 mm (range 2.8-4.8 mm) and a gain in clinical attachment level of 3.1 mm (range 3-3.5 mm). The association of platelet gel biotechnology with GTR in the surgical treatment of intrabony defects of refractory generalized aggressive periodontitis patients seems to produce results similar to those reported for patients with chronic adult periodontitis. The observations at 15.2 months indicate that there is a stability over time of the results in those sites where previous surgical therapy had shown relapse.

Principles of Antibiotic Management of Community-Acquired Pneumonia.

PubMed

Bender, Michael T; Niederman, Michael S

2016-12-01

Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae . We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Surveillance of life-long antibiotics: a review of antibiotic prescribing practices in an Australian Healthcare Network.

PubMed

Lau, Jillian S Y; Kiss, Christopher; Roberts, Erika; Horne, Kylie; Korman, Tony M; Woolley, Ian

2017-01-18

The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not "life-long" course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6 month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1 year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged courses of antibiotics were used mainly to

Individualizing duration of antibiotic therapy in community-acquired pneumonia.

PubMed

Aliberti, Stefano; Ramirez, Julio; Giuliani, Fabio; Wiemken, Timothy; Sotgiu, Giovanni; Tedeschi, Sara; Carugati, Manuela; Valenti, Vincenzo; Marchioni, Marco; Camera, Marco; Piro, Roberto; Del Forno, Manuela; Milani, Giuseppe; Faverio, Paola; Richeldi, Luca; Deotto, Martina; Villani, Massimiliano; Voza, Antonio; Tobaldini, Eleonora; Bernardi, Mauro; Bellone, Andrea; Bassetti, Matteo; Blasi, Francesco

2017-08-01

International experts suggest tailoring antibiotic duration in community-acquired pneumonia (CAP) according to patients' characteristics. We aimed to assess the effectiveness of an individualized approach to antibiotic duration based on time in which CAP patients reach clinical stability during hospitalization. In a multicenter, non-inferiority, randomized, controlled trial hospitalized adult patients with CAP reaching clinical stability within 5 days after hospitalization were randomized to a standard vs. individualized antibiotic duration. In the Individualized group, antibiotics were discontinued 48 h after the patient reached clinical stability, with at least five days of total antibiotic treatment. Early failure within 30 days was the primary composite outcome. 135 patients were randomized to the Standard group and 125 to the Individualized group. The trial was interrupted by the safety committee because of an apparent inferiority of the Individualized group over the Standard treatment: 14 (11.2%) patients in the Individualized group experienced early failure vs. 10 (7.4%) patients in the Standard group, p = 0.200, at the intention-to-treat analysis. 30-day mortality rate was four-time higher in the Individualized group than the Standard group. Shortening antibiotic duration according to patients' characteristics still remains an open question. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of Adverse Events With Antibiotic Use in Hospitalized Patients.

PubMed

Tamma, Pranita D; Avdic, Edina; Li, David X; Dzintars, Kathryn; Cosgrove, Sara E

2017-09-01

Estimates of the incidence of overall antibiotic-associated adverse drug events (ADEs) in hospitalized patients are generally unavailable. To describe the incidence of antibiotic-associated ADEs for adult inpatients receiving systemic antibiotic therapy. Retrospective cohort of adult inpatients admitted to general medicine wards at an academic medical center. At least 24 hours of any parenteral or oral antibiotic therapy. Medical records of 1488 patients were examined for 30 days after antibiotic initiation for the development of the following antibiotic-associated ADEs: gastrointestinal, dermatologic, musculoskeletal, hematologic, hepatobiliary, renal, cardiac, and neurologic; and 90 days for the development of Clostridium difficile infection or incident multidrug-resistant organism infection, based on adjudication by 2 infectious diseases trained clinicians. In 1488 patients, the median age was 59 years (interquartile range, 49-69 years), and 758 (51%) participants were female. A total of 298 (20%) patients experienced at least 1 antibiotic-associated ADE. Furthermore, 56 (20%) non-clinically indicated antibiotic regimens were associated with an ADE, including 7 cases of C difficile infection. Every additional 10 days of antibiotic therapy conferred a 3% increased risk of an ADE. The most common ADEs were gastrointestinal, renal, and hematologic abnormalities, accounting for 78 (42%), 45 (24%), and 28 (15%) 30-day ADEs, respectively. Notable differences were identified between the incidence of ADEs associated with specific antibiotics. Although antibiotics may play a critical role when used appropriately, our findings underscore the importance of judicious antibiotic prescribing to reduce the harm that can result from antibiotic-associated ADEs.

Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center.

PubMed

Marín, Mar; Gudiol, Carlota; Garcia-Vidal, Carol; Ardanuy, Carmen; Carratalà, Jordi

2014-05-01

Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the

Evaluation of Two Treatments for Reactive and Proactive Aggression in Preschool

ERIC Educational Resources Information Center

Whitaker, Regina Navonne

2010-01-01

Previous research has indicated that preschoolers identified for aggressive behavior would benefit from family, group, or individual therapy. However, there remains an important gap in the current literature regarding treatments for aggressive behavior based on the subtype of aggression. The purpose of this pilot study was to examine if 2…

Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: an interventional study

PubMed Central

2009-01-01

Introduction The acronym SAPHO was introduced in 1987 to unify the various descriptions of a seronegative arthritis associated with skin manifestations and to show synovitis, acne, pustulosis, hyperostosis, and osteitis with and without sterile multifocal osteomyelitis. The etiology of SAPHO syndrome is unknown, but an association with infection by semipathogenic bacteria like Propionibacterium acnes has been suggested. We conducted an interventional study of SAPHO patients receiving antibiotics. Methods Thirty-seven patients met the clinical criteria of SAPHO syndrome, 21 of them underwent a needle biopsy of the osteitis lesion, and 14 of them showed positive bacteriological cultures for P. acnes. Thirty patients (14 bacteriological positive and 16 without biopsy) were treated with antibiotics for 16 weeks. The activity of skin disease and osteitis were assessed by a physician using a scoring model (from 0 to 6). In addition, patients completed a Health Assessment Score (HAS, from 0 to 6). The erythrocyte sedimentation rate was determined and a MRI (of the osteitis lesion, radiologic activity score from 0 to 2) was performed in week 1 (W1), week 16 (W16), and week 28 (W28, 12 weeks after antibiotics). Results Twenty-seven patients continued the medication (azithromycin, n = 25, 500 mg twice a week; clindamycin, n = 1, 300 mg daily; or doxycycline, n = 1, 100 mg daily) for 16 weeks. After W16 the scores for MRI (1.5 to 1.1, P = 0.01), skin activity (3.2 to 1.2, P = 0.01), osteitis activity (4.0 to 2.1, P = 0.02), and HAS (3.3 to 2.1, P = 0.01) decreased significantly. However, this was followed by increasing values for MRI scores (1.2 to 1.4, P = 0.08), skin activity (1.2 to 1.7, P = 0.11), osteitis activity (1.9 to 2.7, P = 0.01), and HAS (2.2 to 3.3, P = 0.02) from W16 to W28. The comparison of the scores in W1 and W28 in these 12 patients showed no significant differences. Conclusions For the period of application, the antibiotic therapy seems to have controlled

Antibiotics during childhood and inflammatory bowel disease?

PubMed

2014-10-01

Four epidemiological studies, including two large cohort studies in children aged 17 years or under, have studied the link between antibiotic therapy and inflammatory bowel disease. The risk of inflammatory bowel disease appeared to be twice as high in children exposed to an antibiotic as in unexposed children. The risk appeared higher following exposure during the first year of life, with beta-lactam antibiotics, and with repeated antibiotic courses. One postulated mechanism is through destruction of the anaerobic intestinal flora by antibiotics. In practice, these data provide yet another reason to avoid unnecessarily exposing children to antibiotics.

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

PubMed

Wu, Xiang-Dong; Xu, Wei; Liu, Meng-Meng; Hu, Ke-Jia; Sun, Ya-Ying; Yang, Xue-Fei; Zhu, Gui-Qi; Wang, Zi-Wei; Huang, Wei

2018-03-24

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended. © 2018 Wiley Periodicals, Inc.

Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study.

PubMed

Stocker, Martin; Hop, Wim C J; van Rossum, Annemarie M C

2010-12-08

Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis. The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%. Benefit of the study is a possible limitation of unnecessary

Development of a patient-centred intervention to improve knowledge and understanding of antibiotic therapy in secondary care.

PubMed

Rawson, Timothy M; Moore, Luke S P; Castro-Sanchez, Enrique; Charani, Esmita; Hernandez, Bernard; Alividza, Vivian; Husson, Fran; Toumazou, Christofer; Ahmad, Raheelah; Georgiou, Pantelis; Holmes, Alison H

2018-01-01

We developed a personalised antimicrobial information module co-designed with patients. This study aimed to evaluate the potential impact of this patient-centred intervention on short-term knowledge and understanding of antimicrobial therapy in secondary care. Thirty previous patients who had received antibiotics in hospital within 12 months were recruited to co-design an intervention to promote patient engagement with infection management. Two workshops, containing five focus-groups were held. These were audio-recorded. Data were analysed using a thematic framework developed deductively based on previous work. Line-by-line coding was performed with new themes added to the framework by two researchers. This was used to inform the development of a patient information module, embedded within an electronic decision support tool (CDSS).The intervention was piloted over a four-week period at Imperial College Healthcare NHS Trust on 30 in-patients. Pre- and post-intervention questionnaires were developed and implemented to assess short term changes in patient knowledge and understanding and provide feedback on the intervention. Data were analysed using SPSS and NVIVO software. Within the workshops, there was consistency in identified themes. The participants agreed upon and co-designed a personalised PDF document that could be integrated into an electronic CDSS to be used by healthcare professionals at the point-of-care. Their aim for the tool was to provide individualised practical information, signpost to reputable information sources, and enhance communication between patients and healthcare professionals.Eighteen out of thirty in-patients consented to participant in the pilot evaluation with 15/18(83%) completing the study. Median (range) age was 66(22-85) years. The majority were male (10/15;66%). Pre-intervention, patients reported desiring further information regarding their infections and antibiotic therapy, including side effects of treatment. Deployment of the

Sonographic Differentiation of Complicated From Uncomplicated Appendicitis: Implications for Antibiotics-First Therapy.

PubMed

Xu, Yingding; Jeffrey, R Brooke; Chang, Stephanie T; DiMaio, Michael A; Olcott, Eric W

2017-02-01

To evaluate sonographic findings as indicators of complicated versus uncomplicated appendicitis in the setting of known appendicitis, a necessary distinction in deciding whether to proceed with antibiotic therapy or with appendectomy. With Institutional Review Board approval and Health Insurance Portability and Accountability Act compliance, appendiceal sonograms of 119 patients with histopathologically proven appendicitis were retrospectively blindly reviewed to determine the presence or absence of the normally echogenic submucosal layer, the presence of mural hyperemia, periappendiceal fluid, appendicoliths, and hyperechoic periappendiceal fat and to determine the maximum outside diameter. Results were compared with the presence of complicated versus uncomplicated appendicitis on histopathologic examination and assessed by both univariate and mulitvariate logistic regression; confidence intervals (CIs) of proportions were assessed by the exact binomial test. Thirty-two (26.9%) of the 119 patients had complicated appendicitis, including 11 with gangrenous appendicitis without perforation and 21 with gangrenous appendicitis and perforation. Loss of the submucosal layer was the only independent significant indicator of complicated appendicitis in multivariate regression (P < .001) and provided sensitivity and specificity values of 100.0% (95% CI, 89.1%-100.0%) and 92.0% (95% CI, 84.1%-96.7%), respectively. Loss of the normally echogenic submucosal layer was the most useful sonographic finding for discriminating complicated from uncomplicated appendicitis, being the only finding independently and significantly associated with complicated appendicitis and, additionally, providing both high sensitivity and high specificity. This information may help a physician decide whether to proceed with antibiotic therapy or with appendectomy when treating a patient with appendicitis. © 2016 by the American Institute of Ultrasound in Medicine.

Role of antibiotic therapy for bacterial vaginosis and intermediate flora in pregnancy.

PubMed

Ugwumadu, Austin

2007-06-01

Bacterial vaginosis and intermediate flora are associated with late miscarriage and preterm delivery. The mechanisms involved are not yet fully understood. Clinical trials of antibiotic therapy to reduce these complications have yielded conflicting results. These trials, however, were conducted in mixed populations of pregnant women with variable risk profiles for preterm delivery. Furthermore, investigators used different criteria for diagnosis, treated with different antibiotics at different doses and via different routes, and initiated treatment at different gestational ages. Over 80% of pregnant women with abnormal vaginal flora have a good outcome, and in some populations the presence of bacterial vaginosis is not associated with preterm delivery, suggesting that other host factors may modify the risk. Recent studies have examined the roles of genetic regulation of host immune response, bacterial pathogenic factors, and enzymes in the vagina, and how these factors interact to drive a given outcome. These markers have the potential to better define the women at maximal risk and therefore guide future interventions. This chapter aims to appraise the current state of treatment of abnormal vaginal flora in pregnancy and suggest appropriate management based on the available evidence.

Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) in Reducing Aggression of Individuals at the Juvenile Correction and Rehabilitation Center.

PubMed

Milani, Atefeh; Nikmanesh, Zahra; Farnam, Ali

2013-12-01

In the present era, delinquency in children and adolescents is undoubtedly a difficult and upsetting issue attracting the attention of many experts such as psychologists, sociologists, and criminologists. These experts often try to answer why a number of children and adolescents engage in various crimes such as aggressive and anti-social crimes. They also try to find out how these crimes can be prevented. The present study investigates the effectiveness of mindfulness-based cognitive therapy training (MBCT) in reducing aggression in a juvenile correction and rehabilitation center of Zahedan province during years 1991 to 1992. This experimental study included an experimental and a control group with a pretest, posttest, and follow-up approach. The Buss and Perry aggression questionnaire (1992) was used for data collection. The sample group included 22 (10 experimental and 12 control groups) adolescent males in a juvenile correction and rehabilitation center of Zahedan province who were selected through a census method. Using a matching method based on the pre-test scores of the aggression questionnaire, they were then divided into two equivalent categories and were randomly assigned to the two groups. Mindfulness-based cognitive training took the group training in 8 sessions administered on experimental group. The follow-up test was conducted two weeks after the end of the posttest sessions. The results were analyzed using ANCOVA. The results of ANCOVA showed that mindfulness-based cognitive training could significantly reduce aggression during posttest and follow-up test phases in the experimental group, compared to the control group (P < 0.01). Moreover, the results indicated the effectiveness of this method in significantly reducing anger, physical aggression, and hostility during posttest and follow-up test phases (P < 0.05). However, no significant reduction was observed in the verbal aggression subscale. According to the results of the present study

[Pharmaceutical use and antibiotic therapy in intensive care units].

PubMed

Gauzit, R

2000-05-01

The present study has involved a sample of 750 medical or medical/surgical intensive care units. The aim was to identify the variations of antibiotic (AB) use, measured in monetary terms, and to sort out explicative variables accounting for the corresponding expense. Activity and expense data have been recorded for 1997. "Second intention" antibiotics have been defined as follows: imipenem, ceftazidime, cefpirome, cefepime, piperacillin/tazobactam, amikacin, isepamicin, vancomycin and teicoplanin. Only 60 evaluable sheets have been sent back. They include data about 28,000 admissions and 183,960 hospital days. The results are presented as means +/- standard deviation (SD) and the variability has been considered to be important if the ratio SD/mean was > 1. Nosocomial infections (NI) surveillance, antibiotic advisory board and restriction of use for some molecules were present in 95%, 67% and 78% of units, respectively. The units usually had 10 beds (range: 6-24) and the mean activity was 468 +/- 184 admissions/year and 3,066 +/- 1,454 hospital days/year. Mean duration of hospitalisation (MDH) was 6.9 +/- 2.7 days and mean omega score 114 +/- 61. Mean age of patients was 56.5 years, IGS II score 35.7 +/- 7; 29 +/- 16% of patients were mechanically ventilated for more than 48 hours and mortality rate was 17 +/- 7%. The mean number of bacterial isolates per unit was 369 +/- 323: Staphylococcus sp. 30% [including 25% of meticillin-resistant Staphylococcus aureus (MRSA)]; enterobacteria 30% (including 14% of cefotaxime-resistant isolates); Pseudomonas sp. 14% (including 40% of ticarcillin R isolates); other 26%. Pharmaceutical expense was 834 +/- 364 FF per day of hospitalisation, including 536 +/- 273 FF for drugs. Antibiotics accounted for 32% of the expense and second intention molecules for nearly 50% of antibiotic expense. More than 80% of antibiotic expense was accounted for by only 10 molecules. The mean cost/hospital day for the most expensive antibiotic

[Antibiotics: present and future].

PubMed

Bérdy, János

2013-04-14

The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

Antibiotic therapy in preterm premature rupture of the membranes.

PubMed

Yudin, Mark H; van Schalkwyk, Julie; Eyk, Nancy Van

2009-09-01

To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. 1. Following PPROM at < or = 32 weeks' gestation, antibiotics should be administered to women who are not in labour in order to prolong pregnancy and to decrease maternal and neonatal morbidity. (I

Antibiotic stewardship and empirical antibiotic treatment: How can they get along?

PubMed

Zuccaro, Valentina; Columpsi, Paola; Sacchi, Paolo; Lucà, Maria Grazia; Fagiuoli, Stefano; Bruno, Raffaele

2017-06-01

The aim of this review is to focus on the recent knowledge on antibiotic stewardship and empiric antibiotic treatment in cirrhotic patients. The application of antimicrobial stewardship (AMS) rules appears to be the most appropriate strategy to globally manage cirrhotic patients with infectious complications: indeed they represent a unique way to provide both early diagnosis and appropriate therapy in order to avoid not only antibiotic over-prescription but, more importantly, selection and spread of antimicrobial resistance. Moreover, cirrhotic patients must be considered "frail" and susceptible to healthcare associated infections: applying AMS policies would assure a cost reduction and thus contribute to the improvement of public health strategies. Copyright © 2017. Published by Elsevier Ltd.

[Pharmacokinetic/pharmacodynamic analysis of antibiotic therapy in dentistry and stomatology].

PubMed

Isla, Arantxazu; Canut, Andrés; Rodríguez-Gascón, Alicia; Labora, Alicia; Ardanza-Trevijano, Bruno; Solinís, María Angeles; Pedraz, José Luis

2005-03-01

This study evaluates the efficacy of various antimicrobial treatments for orofacial infections on the basis of pharmacokinetic/pharmacodynamic (PK/PD) criteria. A complete a literature search was undertaken to establish the MIC90 values of the five microorganisms most frequently isolated in odontogenic infections and the pharmacokinetic parameters of 13 antibiotics used in these infections. Pharmacokinetic simulations were then carried out with mean population parameters and efficacy indexes were calculated for the 47 treatment regimens analyzed. For drugs showing time-dependent antibacterial killing, the time above MIC (t > MIC) was calculated. For drugs with concentration-dependent bactericidal activity, the AUC/MIC was calculated. Amoxicillin-clavulanic (500 mg/8 h or 1000 mg/12 h) and clindamycin (300 mg/6 h) in the time-dependent killing group and moxifloxacin (400 mg/24 h) in the concentration-dependent group showed adequate efficacy indexes against the five pathogens considered to be the most commonly implicated in odontogenic infections. The spiramycin plus metronidazole combination, present in the commercial formulation Rhodogyl, did not reach satisfactory PK/PD indexes. PK/PD indexes, which are useful predictors of the potential efficacy of antibacterial therapy, were used with ontogenic infections in the present study. The PK/PD simulations showed that amoxicillin-clavulanic, clindamycin and moxifloxacin were the most suitable antibiotics for this kind of infection. Clinical trials are required to confirm that this methodology is useful in these pathologic processes.

An empirical broad spectrum antibiotic therapy in health-care-associated infections improves survival in patients with cirrhosis: A randomized trial.

PubMed

Merli, Manuela; Lucidi, Cristina; Di Gregorio, Vincenza; Lattanzi, Barbara; Giannelli, Valerio; Giusto, Michela; Farcomeni, Alessio; Ceccarelli, Giancarlo; Falcone, Marco; Riggio, Oliviero; Venditti, Mario

2016-05-01

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial because of their high morbidity and mortality. Multidrug-resistant (MDR) infections are on the increase in health care settings. Health-care-associated (HCA) infections are still frequently treated as community-acquired with a detrimental effect on survival. We aimed to prospectively evaluate in a randomized trial the effectiveness of a broad spectrum antibiotic treatment in patients with cirrhosis with HCA infections. Consecutive patients with cirrhosis hospitalized with HCA infections were enrolled. After culture sampling, patients were promptly randomized to receive a standard or a broad spectrum antibiotic treatment (NCT01820026). The primary endpoint was in-hospital mortality. Efficacy, side effects, and the length of hospitalization were considered. Treatment failure was followed by a change in antibiotic therapy. Ninety-six patients were randomized and 94 were included. The two groups were similar for demographic, clinical, and microbiological characteristics. The prevalence of MDR pathogens was 40% in the standard versus 46% in the broad spectrum group. In-hospital mortality showed a substantial reduction in the broad spectrum versus standard group (6% vs. 25%; P = 0.01). In a post-hoc analysis, reduction of mortality was more evident in patients with sepsis. The broad spectrum showed a lower rate of treatment failure than the standard therapy (18% vs. 51%; P = 0.001). Length of hospitalization was shorter in the broad spectrum (12.3 ± 7 days) versus standard group (18 ± 15 days; P = 0.03). Five patients in each group developed a second infection during hospitalization with a similar prevalence of MDR (50% broad spectrum vs. 60% standard). A broad spectrum antibiotic therapy as empirical treatment in HCA infections improves survival in cirrhosis. This treatment was significantly effective, safe, and cost saving. © 2015 by the American Association for the

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients

PubMed Central

Lucidi, Cristina; Di Gregorio, Vincenza; Ceccarelli, Giancarlo; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

2017-01-01

Background Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. Methods This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. Results We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (−37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days (p<0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Conclusion Our study supports the idea that the use of a broad

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients.

PubMed

Lucidi, Cristina; Di Gregorio, Vincenza; Ceccarelli, Giancarlo; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

2017-01-01

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (-37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days ( p <0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Our study supports the idea that the use of a broad-spectrum empirical treatment for HCA

A catheter-related bloodstream infection caused by Chryseobacterium indologenes successfully treated with antibiotic-lock rescue therapy.

PubMed

Corbella, Marta; Brandolini, Micaela; Cambieri, Patrizia; Decembrino, Nunzia; Pagani, Michele; Bottazzi, Andrea; Muzzi, Alba; Zecca, Marco; Mariani, Bianca; Marone, Piero

2017-07-01

We report the case of a catheter-related bloodstream infection caused by Chryseobacterium indologenes, an uncommon and multi-resistant pathogen, in a pediatric patient with a long-term vascular access device placed for chemotherapy treatment. The infection was successfully treated with ciprofloxacin antibiotic-lock therapy. This is the first report on successful salvage of a long-term device colonized by multi-resistant Chryseobacterium indologenes.

Aggressive and acute periodontal diseases.

PubMed

Albandar, Jasim M

2014-06-01

genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alternatives to antibiotics-a pipeline portfolio review.

PubMed

Czaplewski, Lloyd; Bax, Richard; Clokie, Martha; Dawson, Mike; Fairhead, Heather; Fischetti, Vincent A; Foster, Simon; Gilmore, Brendan F; Hancock, Robert E W; Harper, David; Henderson, Ian R; Hilpert, Kai; Jones, Brian V; Kadioglu, Aras; Knowles, David; Ólafsdóttir, Sigríður; Payne, David; Projan, Steve; Shaunak, Sunil; Silverman, Jared; Thomas, Christopher M; Trust, Trevor J; Warn, Peter; Rex, John H

2016-02-01

Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Highly Aggressive Women in a Forensic Psychiatric Hospital.

PubMed

Beck, Niels C; Hammer, Joseph H; Robbins, Sharon; Tubbesing, Tara; Menditto, Anthony; Pardee, Alicia

2017-03-01

In this study, we compared three groups of women admitted to a public forensic inpatient facility over the course of a two-year period. Detailed and systematic examination of social and psychiatric histories revealed that the group with the most persistent levels of aggression differed from the other two groups with respect to frequency of self-harming behavior, intellectual impairment, hypothyroidism, a childhood diagnosis of attention deficit-hyperactivity disorder (ADHD), and age of onset of psychiatric and behavioral symptoms. The high-aggression group also had the highest rate of childhood physical and sexual abuse, but the difference between that group and the two lower aggression groups did not achieve statistical significance. From the standpoint of childhood adversity, 94 percent of those in the high-aggression group had been placed outside of the original home by age 11. Eighty-nine percent were intellectually impaired. At admission, physical examinations revealed that 50 percent had a history of hypothyroidism and two-thirds were obese. Before admission, most had manifested severe aggression and emotional dysregulation, as evinced by high levels of self-harm, suicide attempts, and aggressive behavior in previous institutional settings that was both frequent and intense. Patients who share these characteristics are currently placed on a ward at the hospital with a milieu and individual therapy programs that are based on a dialectical behavior therapy approach that targets key symptoms of emotional and behavioral dysregulation. © 2017 American Academy of Psychiatry and the Law.

Effectiveness and safety of procalcitonin-guided antibiotic therapy in lower respiratory tract infections in "real life": an international, multicenter poststudy survey (ProREAL).

PubMed

Albrich, Werner C; Dusemund, Frank; Bucher, Birgit; Meyer, Stefan; Thomann, Robert; Kühn, Felix; Bassetti, Stefano; Sprenger, Martin; Bachli, Esther; Sigrist, Thomas; Schwietert, Martin; Amin, Devendra; Hausfater, Pierre; Carre, Eric; Gaillat, Jacques; Schuetz, Philipp; Regez, Katharina; Bossart, Rita; Schild, Ursula; Mueller, Beat

2012-05-14

In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P < .001), outpatients (86.1%) and inpatients (65.9%) (P < .001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P < .001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P < .001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P < .001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07). This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in

Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

PubMed

Brogan, David M; Mossialos, Elias

2016-02-01

Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development. Copyright © 2016. Published by Elsevier Ltd.

[Endoprosthesis Infections - Guidelines for Antibiotic Therapy Common Guidelines of the Czech Society for Orthopaedics and Traumatology and the Society for Infectious Diseases of the Czech Medical Association of J. E. Purkyně].

PubMed

Musil, D; Balejová, M; Horníková, M; Chrdle, A; Mallátová, N; Nyč, O; Chmelík, V; Gallo, J; Jahoda, D; Stehlík, J

2017-01-01

PURPOSE OF THE STUDY This study aims to articulate regional guidelines for curative and suppressive antibiotic therapy of total joint replacement infections. MATERIAL AND METHODS When developing the standard, used as source materials were the published foreign guidelines for antibiotic therapy of prosthetic joint infections, the analysis of resistance of bacterial strains conducted in the Hospital in České Budějovice, a.s. and the assessment of strain resistance for the Czech Republic published by the European Antimicrobial Resistance Surveillance Network (EARS-Net). Considered was also the availability of individual antibiotics in the Czech Republic and restricted prescription according to the Summary of Product Characteristics as specified in the State Institute for Drug Control marketing authorisation. The expert group composed of orthopaedists, microbiologists and infectious disease specialists elaborated the basic antibiotic guideline for choosing an appropriate antibiotic/antifungal drug based on the usual susceptibility, its dose and dosage interval for initial and continuation therapy. The comments of individual specialists were gradually incorporated therein and in case of doubts majority rule was applied. The drafted document was sent for peer reviews to clinical orthopaedic, infectious disease and microbiological centres, whose comments were also incorporated and the finalised document was submitted for evaluation to specialised medical societies. RESULTS The outcome is the submitted guideline for antibiotic curative and suppressive therapy suitable for managing the prosthetic joint infections, which was approved by the committee of the Czech Society for Orthopaedics and Traumatology andthe Society for Infectious Diseases of the Czech Medical Association of J. E. Purkyně. DISCUSION Curative therapy of total joint replacement infections consists primarily in surgical treatment and has to be accompanied by adequate antibiotic therapy administered

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®).

PubMed

Busetto, Gian Maria; Giovannone, Riccardo; Ferro, Matteo; Tricarico, Stefano; Del Giudice, Francesco; Matei, Deliu Victor; De Cobelli, Ottavio; Gentile, Vincenzo; De Berardinis, Ettore

2014-07-19

Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. NCT02130713. Date of trial Registration: 30/04/2014.

Live intramacrophagic Staphylococcus aureus as a potential cause of antibiotic therapy failure: observations in an in vivo mouse model of prosthetic vascular material infections.

PubMed

Boudjemaa, Rym; Steenkeste, Karine; Jacqueline, Cédric; Briandet, Romain; Caillon, Jocelyne; Boutoille, David; Le Mabecque, Virginie; Tattevin, Pierre; Fontaine-Aupart, Marie-Pierre; Revest, Matthieu

2018-06-12

To evaluate the significant role played by biofilms during prosthetic vascular material infections (PVMIs). We developed an in vivo mouse model of Staphylococcus aureus PVMI allowing its direct observation by confocal microscopy to describe: (i) the structure of biofilms developed on Dacron® vascular material; (ii) the localization and effect of antibiotics on these biostructures; and (iii) the interaction between bacteria and host tissues and cells during PVMI. In this model we demonstrated that the biofilm structures are correlated to the activity of antibiotics. Furthermore, live S. aureus bacteria were visualized inside the macrophages present at the biofilm sites, which is significant as antibiotics do not penetrate these immune cells. This intracellular situation may explain the limited effect of antibiotics and also why PVMIs can relapse after antibiotic therapy.

Antibiotics for treating lower urinary tract infection in children.

PubMed

Fitzgerald, Anita; Mori, Rintaro; Lakhanpaul, Monica; Tullus, Kjell

2012-08-15

Urinary tract infection (UTI) is one of the most common bacterial infections in infants and children. Lower UTI is the most commonly presenting and in the majority of cases can be easily treated with a course of antibiotic therapy with no further complications. A number of antimicrobials have been used to treat children with lower UTIs; however is it unclear what are the specific benefits and harms of such treatments. This review aims to summarise the benefits and harms of antibiotics for treating lower UTI in children. We searched the Renal Group's Specialised Register (April 2012), CENTRAL (The Cochrane Library 2012, Issue 5), MEDLINE OVID SP (from 1966), and EMBASE OVID SP (from 1988) without language restriction. Date of last search: May 2012. Randomised controlled trials (RCTs) and quasi-RCTs in which antibiotic therapy was used to treat bacteriologically proven, symptomatic, lower UTI in children aged zero to 18 years in primary and community healthcare settings were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratios (RR) with 95% confidence intervals (CI). Sixteen RCTs, analysing 1,116 children were included. Conventional 10-day antibiotic treatment significantly increased the number of children free of persistent bacteriuria compared to single-dose therapy (6 studies, 228 children: RR 2.01, 95%CI 1.06 to 3.80). No heterogeneity was observed. Persistent bacteriuria at the end of treatment was reported in 24% of children receiving single-dose therapy compared to 10% of children who were randomised to 10-day therapy. There were no significant differences between groups for persistent symptoms, recurrence following treatment, or re-infection following treatment. There was insufficient data to analyse the effect of antibiotics on renal parenchymal damage, compliance, development of resistant organisms or adverse events. Despite

Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

PubMed

Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

2016-06-01

Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P < .001). Ten-day sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p < .001) and 10-day standard therapy (RR = 1.179; 95% CI = 1.074-1.295; P = .001), but had lower eradication rates compared to 14-day standard therapy (RR = 0.926; 95% CI = 0.811-1.059; P = .261). The use of sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration. © The Author(s) 2015.

[Clinical effect of different sequences of debridement-antibiotic therapy in treatment of severe chronic periodontitis].

PubMed

Li, Yi; Xu, Li; Lu, Rui-fang; An, Yue-bang; Wang, Xian-e; Song, Wen-li; Meng, Huan-xi

2015-02-18

To evaluate the feasibility of full-mouth debridement (subgingival scaling and root planning, SRP) by 2 times within 1 week and compare the clinical effects of different sequences of debridement-antibiotic usage in patients with severe chronic periodontitis (CP). A double-blinded, placebo-controlled, randomized clinical trial was conducted in 30 severe CP patients (14 males and 16 females, 40.5 ± 8.4 years old on average from 35 to 60) receiving 3 different sequences of debridement-antibiotictherapy: Group A, antibiotic usage (metronidazole, MTZ, 0.2 g, tid, 7 d; amoxicillin, AMX 0.5 g, tid, 7 d) was started together with SRP (completed by 2 times in 7 d); Group B, antibiotic usage (MTZ 0.2 g, tid, 7 d; AMX 0.5 g, tid, 7 d) was started 1 d after SRP(completed by 2 times in 7 d); Group C, SRP alone[probing depth (PD), bleeding index (BI) and tooth mobility] was examined. The average full-mouth probing depth, the average full-mouth proximal probing depth (pPD), the percentage of sites with PD>5 mm (PD>5 mm%), the percentage of sites with proximal PD>5 mm (pPD>5 mm%), the average bleeding index (BI) and the percentage of sites with bleeding on probing (BOP%) were calculated. Clinical examinations were performed at baseline and 2 months post therapy. (1) Compared with baseline conditions, all the subjects showed clinical improvements in all the parameters evaluated 2 months post therapy, P<0.05. (2) Significant difference were observed in the average PD changes between Group A [(2.15 ± 0.42) mm], Group B [(1.76 ± 0.29) mm] and Group C [(1.57 ± 0.33) mm], P<0.05. No significant difference was observed in the average PD changes between Group B and Group C, P=0.354. Significant differences were observed in the average pPD changes between Group A [(2.45 ± 0.43)mm] and Group C[(1.90 ± 0.48) mm], P<0.05. No significant difference was observed in BI and BOP% changes between Group A,Group B and Group C. For patients with severe chronic periodontitis, it is safe and

Origins and Evolution of Antibiotic Resistance

PubMed Central

Davies, Julian; Davies, Dorothy

2010-01-01

Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

A prospective randomized cohort study evaluating 3 weeks vs 6 weeks of oral antibiotic treatment in the setting of "maximal medical therapy" for chronic rhinosinusitis.

PubMed

Sreenath, Satyan B; Taylor, Robert J; Miller, Justin D; Ambrose, Emily C; Rawal, Rounak B; Ebert, Charles S; Senior, Brent A; Zanation, Adam M

2015-09-01

Surprisingly, little literature exists evaluating the optimal duration of antibiotic treatment in "maximal medical therapy" for chronic rhinosinusitis (CRS). As such, we investigated whether 3 weeks vs 6 weeks of antibiotic therapy resulted in significant differences in clinical response. A prospective, randomized cohort study was performed with patients assigned to 3-week or 6-week cohorts. Our primary outcome was failure of "maximal medical therapy" and surgical recommendation. Secondary outcomes included changes in pretherapy and posttherapy scores for the Rhinosinusitis Disability Index (RSDI), Chronic Sinusitis Survey (CSS), and computed tomography (CT)-based Lund-Mackay (LM) evaluation. Analyses were substratified based on presence of nasal polyps. Forty patients were randomized to the 3-week or 6-week treatment cohorts, with near-complete clinical follow-up achieved. No significant difference was found between the proportion of patients who failed medical therapy and were deemed surgical candidates between the 2 cohorts (71% vs 68%, p = 1.000). No significant difference was found in the change of RSDI or CSS scores in the 3 vs 6 weeks of treatment groups (mean ± standard error of the mean [SEM]; RSDI: 9.62 ± 4.14 vs 1.53 ± 4.01, p = 0.868; CSS: 5.75 ± 4.36 vs 9.65 ± 5.34, p = 0.573). Last, no significant difference was found in the change of LM scores (3.35 ± 1.11 vs 1.53 ± 0.81, p = 0.829). Based on this data, there is little difference in clinical outcomes between 3 weeks vs 6 weeks of antibiotic treatment as part of "maximal medical therapy" for CRS. Increased duration of antibiotic treatment theoretically may increase risk from side effects and creates higher healthcare costs. © 2015 ARS-AAOA, LLC.

Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

PubMed Central

Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

2005-01-01

Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p<0.05). In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p<0.05). Based upon these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n=54) had their blood drawn six hours after CLP and then were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

Pseudomonas aeruginosa Bacteremia among Immunocompetent and Immunocompromised Patients: Relation to Initial Antibiotic Therapy and Survival.

PubMed

Migiyama, Yohei; Yanagihara, Katsunori; Kaku, Norihito; Harada, Yosuke; Yamada, Koichi; Nagaoka, Kentaro; Morinaga, Yoshitomo; Akamatsu, Norihiko; Matsuda, Junichi; Izumikawa, Koichi; Kohrogi, Hirotsugu; Kohno, Shigeru

2016-01-01

Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P < 0.01; 30-day mortality, 23% vs. 39%, P = 0.053). Multivariate analysis showed that a higher sequential organ failure assessment score (hazard ratio [HR]: 1.27, P < 0.01) and underlying malignancies (HR: 3.33, P < 0.01) were independently associated with 30-day mortality. Initial antibiotic therapy (HR: 0.21, P < 0.01) and patients' immune status (HR: 0.29, P = 0.02) also had a significant impact on survival. However, there was a significant interaction between these 2 variables (P = 0.03 for interaction). A subgroup analysis showed that in immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

PubMed

Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

2017-09-01

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy.

PubMed

Cheng, Chi-Hui; Tsai, Ming-Horng; Huang, Yhu-Chering; Su, Lin-Hui; Tsau, Yong-Kwei; Lin, Chi-Jen; Chiu, Cheng-Hsun; Lin, Tzou-Yien

2008-12-01

The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum beta-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum beta-lactamase-producing bacteria or multidrug-resistant uropathogens

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

PubMed Central

Uppu, Divakara S. S. M.; Konai, Mohini M.; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C. M.; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R.; Franco, Octávio L.

2017-01-01

Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections. PMID:28837596

[Paths to the professional and responsible use of antibiotics].

PubMed

Abele-Horn, Marianne; Pantke, Ellen; Eckmanns, Tim

2018-05-01

Germany's position on prescribing antibiotics is among the lower third in Europe. There are some countries that prescribe remarkably fewer antibiotics. In Germany, the number of out-patient antibiotic prescriptions is too high for patients with low-grade infections and non-bacterial infections. Often, broad-spectrum antibiotics are prescribed instead of narrow-spectrum antibiotics. For in-patients, perioperative prophylaxis is given for too long.In this article, different ways to reduce antibiotic prescriptions are introduced. Recommendations are given to improve the quality of therapy, implementation of diagnostics and scores, as well as information for physicians and patients.In this regard, an unsystematic literature search was done.To optimise the quality of prescribing, antibiotic checklists should be used. The important initial questions are if there is a bacterial infection and if antibiotic therapy is necessary. To apply diagnostics correctly is essential. Antibiotic use can be shortened or in some cases totally omitted if point-of-care tests (POCTs) are applied correctly. Species identification and resistance testing are essential for quality assurance. S3-guidelines are central for modern evidence-based medicine. Another key factor is good communication within the team and with patients. All measurements, like the application of POCTs, back-up prescribing, and prescribing an antibiotic, have to be communicated in a clear and sensitive way.

Inhaled Antibiotics for Ventilator-Associated Infections.

PubMed

Palmer, Lucy B

2017-09-01

Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

PubMed

Porpaczy, Edit; Tripolt, Sabrina; Hoelbl-Kovacic, Andrea; Gisslinger, Bettina; Bago-Horvath, Zsuzsanna; Casanova-Hevia, Emilio; Clappier, Emmanuelle; Decker, Thomas; Fajmann, Sabine; Fux, Daniela A; Greiner, Georg; Gueltekin, Sinan; Heller, Gerwin; Herkner, Harald; Hoermann, Gregor; Kiladjian, Jean-Jacques; Kolbe, Thomas; Kornauth, Christoph; Krauth, Maria-Theresa; Kralovics, Robert; Muellauer, Leonhard; Mueller, Mathias; Prchal-Murphy, Michaela; Putz, Eva Maria; Raffoux, Emmanuel; Schiefer, Ana-Iris; Schmetterer, Klaus; Schneckenleithner, Christine; Simonitsch-Klupp, Ingrid; Skrabs, Cathrin; Sperr, Wolfgang R; Staber, Philipp Bernhard; Strobl, Birgit; Valent, Peter; Jaeger, Ulrich; Gisslinger, Heinz; Sexl, Veronika

2018-06-14

Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 MPN patients. Considering primary myelofibrosis only (N=216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) versus 1/185 controls (0.54%). Lymphomas were of aggressive B-cell type, extra-nodal or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a pre-existing B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1 -/- mice: 16/24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a pre-existing B-cell clone may identify individuals at risk. Copyright © 2018 American Society of Hematology.

Non-absorbed Antibiotics for IBS

DTIC Science & Technology

2012-03-16

absorbed antibiotic rifaximin for nonconstipated irritable bowel syndrome (IBS). This effort adds to the body of literature from other, smaller studies that...have demonstrated clinical efficacy for IBS with rifaximin . Non-absorbed antibiotics have been endorsed by the American College of Gastroenterology... rifaximin 400 mg three times daily for 10 days or placebo. During the initial 2 weeks of therapy and the subsequent 10 weeks of follow-up rifaximin

[Peripherally inserted central catheter antibiotic therapy for cystic fibrosis patients].

PubMed

Betegnie, A-L; Cracowski, C; Bedouch, P; Segond, C; Robein-Dobremez, M-J; Pin, I; Allenet, B

2014-11-01

Peripherally inserted central catheters (PICC) are more and more used for intravenous antibiotic infusions in cystic fibrosis (CF) patients in the Grenoble area (France). The aim of this study was to assess the use of this technique in this indication. 1. Retrospective evaluation of 102 consecutive PICC insertions over 3years and the incidence of adverse events during the therapy. 2. Prospective evaluation of 12 patient's satisfaction and their nurses over a 3-month period. 3. Comparative analysis of single domiciliary treatment costs using PICC versus peripheral catheter (PC). 102 PICC insertions were attempted in 31 patients. Seven failures and 7 complications occurred during the treatment requiring removal of the PICC, i.e. an overall success rate of 86.2% (88/102). Pain during PICC introduction was 4.2/10 (visual analogical scale). Mean satisfaction levels during therapy were 9.3/10 for patients and 8.7/10 for nurses. Compared with PC, all the patients said that PICC was "more comfortable". Differential costs of treatment with PC and with PICC at home were estimated at 57.15€ and 590.16€ respectively. PICC is an alternative to CP for intravenous antibiotherapy in CF patients, providing better safety and comfort. PICC use should be promoted in this indication. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Approach to osteomyelitis treatment with antibiotic loaded PMMA.

PubMed

Wentao, Zhang; Lei, Guangyu; Liu, Yang; Wang, Wei; Song, Tao; Fan, Jinzhu

2017-01-01

To reduce the incidence of osteomyelitis infection, local antibiotic impregnated delivery systems are commonly used as a promising and effective approach to deliver high antibiotic concentrations at the infection site. The objective of this review was to provide a literature review regarding approach to osteomyelitis treatment with antibiotic loaded PMMA. Literature study regarding osteomyelitis treatment with antibiotic loaded carriers using key terms Antibiotic, osteomyelitis, biodegradable PMMA through published articles. Hands searching of bibliographies of identified articles were also undertaken. We concluded that Antibiotic-impregnated PMMA beads are useful options for the treatment of osteomyelitis for prolonged drug therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Short-course antibiotics for acute otitis media.

PubMed

Kozyrskyj, Anita; Klassen, Terry P; Moffatt, Michael; Harvey, Krystal

2010-09-08

Acute otitis media (AOM) is a common illness during childhood, for which antibiotics are frequently prescribed. To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a long course of antibiotics (seven days or greater) for the treatment of AOM in children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CINAHL, BIOSIS Previews, OCLC Papers First and Proceedings First, Proquest Dissertations and Theses (inception to November 2009); International Pharmaceutical Abstracts, the NLM Gateway, ClinicalTrials.gov and Current Controlled Trials (inception to August 2008). Trials were included if they met the following criteria: participants aged one month to 18 years; clinical diagnosis of ear infection; no previous antimicrobial therapy; and randomisation to treatment with less than seven days versus seven days or more of antibiotics. The primary outcome of treatment failure was defined as the absence of clinical resolution, relapse or recurrence of AOM during one month following initiation of therapy. Treatment outcomes were extracted from individual studies and combined in the form of a summary odds ratio (OR). A summary OR of 1.0 indicates that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of treatment. This update included 49 trials containing 12,045 participants. Risk of treatment failure was higher with short courses of antibiotics (OR 1.34, 95% CI 1.15 to 1.55) at one month after initiation of therapy (21% failure with short-course treatment and 18% with long-course; absolute difference of 3% between groups). There were no differences found when examining treatment with ceftriaxone for less than seven days (30% failure

Natural solution to antibiotic resistance: bacteriophages 'The Living Drugs'.

PubMed

Jassim, Sabah A A; Limoges, Richard G

2014-08-01

Antibiotics have been a panacea in animal husbandry as well as in human therapy for decades. The huge amount of antibiotics used to induce the growth and protect the health of farm animals has lead to the evolution of bacteria that are resistant to the drug's effects. Today, many researchers are working with bacteriophages (phages) as an alternative to antibiotics in the control of pathogens for human therapy as well as prevention, biocontrol, and therapy in animal agriculture. Phage therapy and biocontrol have yet to fulfill their promise or potential, largely due to several key obstacles to their performance. Several suggestions are shared in order to point a direction for overcoming common obstacles in applied phage technology. The key to successful use of phages in modern scientific, farm, food processing and clinical applications is to understand the common obstacles as well as best practices and to develop answers that work in harmony with nature.

Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

PubMed

Vyas, Dinesh; Javadi, Pardis; Dipasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P < 0.05). In mice with IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P < 0.05). On the basis of these results, we examined whether targeted antibody therapy could improve survival in mice with elevated IL-6 levels. A different cohort of mice (n = 54) had blood drawn 6 h after CLP, and then they were randomized to receive either monoclonal anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

Antibiotic use in acute cholecystitis: practice patterns in the absence of evidence-based guidelines.

PubMed

Kanafani, Zeina A; Khalifé, Nadine; Kanj, Souha S; Araj, George F; Khalifeh, Mohammad; Sharara, Ala I

2005-08-01

Antibiotics are frequently administered in acute cholecystitis for preoperative prophylaxis or postoperative treatment. The optimal timing, choice, and duration of antibiotics are unclear. We conducted a retrospective review of all cases of acute cholecystitis between 1996 and 2001 at the American University of Beirut Medical Centre. A survey among general surgeons was also performed to describe the pattern of antibiotic prescribing in uncomplicated acute cholecystitis. A MEDLINE search for guidelines for antibiotic use in acute cholecystitis was conducted. The number of cases of acute cholecystitis was 79. The mean duration of postoperative antibiotic therapy was 5 days. There was no correlation between the severity of symptoms, gallbladder description, or positive gallbladder culture and the use of antibiotics postoperatively. Sixty five percent of interviewed surgeons would continue antibiotic therapy postoperatively for 3 or more days. Search of the medical literature failed to provide clear guidelines for antibiotic use in acute cholecystitis. The use of antibiotics in patients with acute cholecystitis is erratic and costly. Prospective studies are needed to better study the effectiveness of a short course of antibiotics in uncomplicated cases. The role of gallbladder culture in guiding antibiotic therapy should be defined as routine cultures add to the cost without evident benefit.

[Antibiotic-resistant bacteria and new directions of antimicrobial chemotherapy].

PubMed

Tateda, Kazuhiro

2012-05-01

The emergence and spread of antibiotic-resistant organisms are becoming more and more serious and are a worldwide problem. Recent trends in new antibiotic-resistant organisms include multiple-drug resistant Pseudomonas aeruginosa (MDRP), MDR-Acinetobacter baumannii (MDR-AB) and New Deli metallo beta-lactamase-1 (NDM-1) -producing bacteria. Antibiotic combination therapy is an option to overcome these MDR organisms. A breakpoint checkerboard plate was created to measure antibiotic combination effects at breakpoint concentrations, making it possible to evaluate the synergy of antibiotic combination within 24 hours. In this article, recent topics regarding antibiotic-resistant organisms are briefly reviewed and the directions of antibiotic chemotherapy against these organisms are discussed.

Antibiotics for preventing recurrent sore throat.

PubMed

Ng, Gareth J Y; Tan, Stephanie; Vu, Anh N; Del Mar, Chris B; van Driel, Mieke L

2015-07-14

Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. To assess the effects of antibiotics in patients with recurrent sore throat. The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

The history and evolution of outpatient parenteral antibiotic therapy (OPAT).

PubMed

Williams, David N; Baker, Cristina A; Kind, Allan C; Sannes, Mark R

2015-09-01

Outpatient parenteral antibiotic therapy (OPAT) is now a widely accepted and safe therapeutic option for carefully selected patients. Benefits include cost savings and improved patient satisfaction; risks include failure to adhere to care, unexpected changes in the underlying infection, and adverse drug and intravenous access events. We report on our 40-year experience with OPAT in a single healthcare system in the USA and highlight OPAT developments in several countries. We compared data on patients treated in our programme over two time periods: Period 1 from 1978 to 1990; and Period 2, calendar year 2014. In Period 2 paediatric patients were excluded. Between Periods 1 and 2, changes included an almost three-fold increase in the number of patients treated per year (80 vs. 229), treatment of more patients with severe orthopaedic-related infections (20% vs. 38%), a marked increase in the use of peripherally inserted central catheters to administer antibiotics (20% vs. 98%), a shorter duration of inpatient stay and a longer duration of OPAT (13 days vs. 24 days). Other changes in Period 2 included treatment of 20% of patients without antecedent hospitalisation, and use of carbapenems rather than cephalosporins as the most frequently administered agents. OPAT was safe, with rehospitalisation rates of 6% and 1% in Periods 1 and 2, respectively. We recommend increased access to structured OPAT teams and the development of standard definitions and criteria for important outcome measures (e.g. clinical 'cure' and unplanned hospital re-admissions). These steps are critical for patient safety and financial stewardship of resources. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Listeria monocytogenes: antibiotic resistance in food production.

PubMed

Lungu, Bwalya; O'Bryan, Corliss A; Muthaiyan, Arunachalam; Milillo, Sara R; Johnson, Michael G; Crandall, Philip G; Ricke, Steven C

2011-05-01

Listeria monocytogenes is an opportunistic human pathogen that causes listeriosis, a disease that mainly affects the immunocompromised, the elderly, infants, and pregnant women. Listeriosis has become increasingly common in the last 25 years since the first foodborne outbreak was noted. Treatment for listeriosis currently consists primarily of supportive therapy in conjunction with the use of intravenous antibiotics. Antibiotics have been commercially available for over 60 years for treatment of a myriad of clinical diseases. Bacteria resistant to antibiotics have been developing over this same period. This review seeks to elucidate the extent of antibiotic resistance in L. monocytogenes, the possible transmission mechanisms, and contributing factors to distribution of antibiotic resistance among Listeria species, and possible control strategies.

Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections and Rationale for Empirical Antibiotic Therapy.

PubMed

Gökçe, İbrahim; Çiçek, Neslihan; Güven, Serçin; Altuntaş, Ülger; Bıyıklı, Neşe; Yıldız, Nurdan; Alpay, Harika

2017-09-29

The causative agent spectrum and resistance patterns of urinary tract infections in children are affected by many factors. To demonstrate antibiotic resistance in urinary tract infections and changing ratio in antibiotic resistance by years. Retrospective cross-sectional study. We analysed antibiotic resistance patterns of isolated Gram (-) bacteria during the years 2011-2014 (study period 2) in children with urinary tract infections. We compared these findings with data collected in the same centre in 2001-2003 (study period 1). Four hundred and sixty-five uncomplicated community-acquired Gram (-) urinary tract infections were analysed from 2001-2003 and 400 from 2011-2014. Sixty-one percent of patients were female (1.5 girls : 1 boy). The mean age of children included in the study was 3 years and 9 months. Escherichia coli was the predominant bacteria isolated during both periods of the study (60% in study period 1 and 73% in study period 2). Bacteria other than E. coli demonstrated a higher level of resistance to all of the antimicrobials except trimethoprim-sulfamethoxazole than E. coli bacteria during the years 2011-2014. In our study, we found increasing resistance trends of urinary pathogens for cefixime (from 1% to 15%, p<0.05), amikacin (from 0% to 4%, p<0.05) and ciprofloxacin (from 0% to 3%, p<0.05) between the two periods. Urinary pathogens showed a decreasing trend for nitrofurantoin (from 17% to 7%, p=0.0001). No significant trends were detected for ampicillin (from 69% to 71%), amoxicillin-clavulanate (from 44% to 43%), cefazolin (from 39% to 32%), trimethoprim-sulfamethoxazole (from 32% to 31%), cefuroxime (from 21% to 18%) and ceftriaxone (from 10% to 14%) between the two periods (p>0.05). In childhood urinary tract infections, antibiotic resistance should be evaluated periodically and empiric antimicrobial therapy should be decided according to antibiotic sensitivity results.

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma.

PubMed

Jain, Michael D; Bachmeier, Christina A; Phuoc, Vania H; Chavez, Julio C

2018-01-01

Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis.

Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tseng, Yolanda D., E-mail: ydt2@uw.edu; Chen, Yu-Hui; Catalano, Paul J.

Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treatedmore » with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a

Role of biomarkers in the management of antibiotic therapy: an expert panel review: I – currently available biomarkers for clinical use in acute infections

PubMed Central

2013-01-01

In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics. PMID:23837559

VB-CHEP chemotherapy regimen for aggressive non-Hodgkin's lymphomas.

PubMed

Yalçin, S; Kars, A; Ozişik, Y; Tekuzman, G; Ozyilkan, O; Celik, I; Barişta, I; Güllü, I; Güler, N; Baltali, E; Firat, D

1998-10-01

Despite intensive search for the optimal combination chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), the CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) regimen is still the standard therapy. We investigated the clinical efficacy of a new combination regimen consisting of vincristine, bleomycin-cyclophosphamide, adriamycin, etoposide and prednisolone (VB-CHEP) in patients with aggressive NHL. A total of 29 patients with aggressive NHL was enrolled into the protocol. Eight patients were consolidated with cisplatin and cytarabine and 5 patients received radiotherapy for bulky disease. Objective response was achieved in 82.8% of the patients. Complete remission (CR) and partial remission rates were 72.4%, and 10.3%, respectively. CR rate was significantly lower in patients with advanced stage, extranodal disease and bone marrow involvement. Median follow-up time is 34+ months; 17 patients are disease-free while 12 died and only 2 patients with CR have relapsed so far. Median response duration is 29+ months and the median survival is 48+ months. The survival rate is 69% in the first year and 66% in the second year. A total of 152 cycles were evaluated for toxicity. Major hematological toxicity was myelosuppression and neutropenia, detected in 50.65%, was mostly grades 1-2. Neutropenic fever occurred in only 11 cycles. The side effects of the consolidation therapy were also acceptable. We conclude that the VB-CHEP regimen with consolidation therapy for high-risk patients may be an effective treatment for advanced stage aggressive NHL.

Antibiotics and inflammatory bowel diseases.

PubMed

Scribano, Maria Lia; Prantera, Cosimo

2013-01-01

Inflammatory bowel diseases are characterized by an altered composition of gut microbiota (dysbiosis) that may contribute to their development. Antibiotics can alter the bacterial flora, and a link between antibiotic use and onset of Crohn's disease (CD), but not ulcerative colitis, has been reported. The hypothesis that Mycobacterium avium subspecies paratuberculosis (MAP) could be an etiologic agent of CD has not been confirmed by a large study on patients treated by an association of antibiotics active against MAP. The observations supporting a role of intestinal microbiota in CD pathogenesis provide the rationale for a therapeutic manipulation of the intestinal flora through the employment of antibiotics. However, current data do not strongly support a therapeutic benefit from antibiotics, and there is still controversy regarding their use as primary therapy for treatment of acute flares of CD, and for postoperative recurrence prevention. Nevertheless, clinical practice and some studies suggest that a subgroup of patients with colonic involvement, early disease, and abnormal laboratory test of inflammation may respond better to antibiotic treatment. Since their long-term use is frequently complicated by a high rate of side effects, the use of antibiotics that work locally appears to be promising.

Risk factors associated with bacteriological cure, new infection, and incidence of clinical mastitis after dry cow therapy with three different antibiotics.

PubMed

Gundelach, Yasmin; Kalscheuer, Elke; Hamann, Henning; Hoedemaker, Martina

2011-09-01

Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status.

Risk factors associated with bacteriological cure, new infection, and incidence of clinical mastitis after dry cow therapy with three different antibiotics

PubMed Central

Gundelach, Yasmin; Kalscheuer, Elke; Hamann, Henning

2011-01-01

Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status. PMID:21897095

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®)

PubMed Central

2014-01-01

Background Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. Methods 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. Results Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram – (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. Conclusions Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. Trial registration NCT02130713 Date of trial

Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns).

PubMed

Stocker, Martin; van Herk, Wendy; El Helou, Salhab; Dutta, Sourabh; Fontana, Matteo S; Schuerman, Frank A B A; van den Tooren-de Groot, Rita K; Wieringa, Jantien W; Janota, Jan; van der Meer-Kappelle, Laura H; Moonen, Rob; Sie, Sintha D; de Vries, Esther; Donker, Albertine E; Zimmerman, Urs; Schlapbach, Luregn J; de Mol, Amerik C; Hoffman-Haringsma, Angelique; Roy, Madan; Tomaske, Maren; Kornelisse, René F; van Gijsel, Juliette; Visser, Eline G; Willemsen, Sten P; van Rossum, Annemarie M C

2017-08-26

Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844

The relationship between antibiotic therapy in early childhood and the symptoms of allergy in children aged 6-8 years - the questionnaire study results.

PubMed

Raciborski, Filip; Tomaszewska, Aneta; Komorowski, Jarosław; Samel-Kowalik, Piotr; Białoszewski, Artur Z; Walkiewicz, Artur; Lusawa, Adam; Szymański, Jakub; Opoczyńska, Dagmara; Drużba, Michał; Borowicz, Jacek; Lipiec, Agnieszka; Kapalczynski, Wojciech J; Samoliński, Bolesław

2012-09-01

Studies based on the ISAAC questionnaire suggest a correlation between the use of antibiotics and the prevalence of asthma and allergy in children aged 6-7 years. The number of courses of antibiotic therapy is an important factor. To investigate the relationship between the use of antibiotics during the first years of life and the prevalence of allergy and asthma among children (aged 6-8 years) in the urban population of Poland. A survey-based study with a self-completed questionnaire. The respondents were parents of children aged 6-8 years living in Warszawa, Poland. 1461 completed questionnaires were collected. Asthma was declared in 4.3% of the children. Wheezing and/or sibilant rhonchi within 12 months before the study was observed in 13.5% of the cases. Asthma medication was taken by 21.8% of the children. Allergic rhinitis was declared in 18.7% of the children. Problems with sneezing, rhinorrhea, and nasal congestion not associated with cold or fever were observed in 40.7% of the children. The analysis of the odds ratios between the use of antibiotics and the symptoms of allergic diseases revealed a clear correlation. The highest odds ratio was observed between the completion of over three courses of antibiotic therapy prior to the age of 12 months and the declaration of one of the following: asthma (OR = 5.59, 95% CI: 2.6-12.01), wheezing and/or sibilant rhonchi (OR = 4.68, 95% CI: 3.01-7.27) and taking medicines for breathlessness (OR = 5.12, 95% CI: 3.42-7.68). There is a direct relationship between antibiotic use in the first 3 years of life and asthma and allergy symptoms in children aged 6-8 years old.

Identification and treatment of aggressive thyroid cancers. Part 1: subtypes.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-03-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radioiodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article describes in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2, which will appear in next month's issue, covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and the value of treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

[INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

PubMed

Kuzovlev, A N; Moroz, V V; Golubev, A M

2015-01-01

Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia.

Marine bacteria: potential sources for compounds to overcome antibiotic resistance.

PubMed

Eom, Sung-Hwan; Kim, Young-Mog; Kim, Se-Kwon

2013-06-01

Methicillin-resistant Staphylococcus aureus (MRSA) is the most problematic Gram-positive bacterium in the context of public health due to its resistance against almost all available antibiotics except vancomycin and teicoplanin. Moreover, glycopeptide-resistant S. aureus have been emerging with the increasing use of glycopeptides. Recently, resistant strains against linezolid and daptomycin, which are alternative drugs to treat MRSA infection, have also been reported. Thus, the development of new drugs or alternative therapies is clearly a matter of urgency. In response to the antibiotic resistance, many researchers have studied for alternative antibiotics and therapies. In this review, anti-MRSA substances isolated from marine bacteria, with their potential antibacterial effect against MRSA as potential anti-MRSA agents, are discussed and several strategies for overcoming the antibiotic resistance are also introduced. Our objective was to highlight marine bacteria that have potential to lead in developing novel antibiotics or clinically useful alternative therapeutic treatments.

Use of antibiotic beads to salvage infected breast implants.

PubMed

Sherif, Rami D; Ingargiola, Michael; Sanati-Mehrizy, Paymon; Torina, Philip J; Harmaty, Marco A

2017-10-01

When an implant becomes infected, implant salvage is often performed where the implant is removed, capsulectomy is performed, and a new implant is inserted. The patient is discharged with a PICC line and 6-8 weeks of intravenous (IV) antibiotics. This method has variable success and subjects the patient to long-term systemic antibiotics. In the 1960s, the use of antibiotic-impregnated beads for the treatment of chronic osteomyelitis was described. These beads deliver antibiotic directly to the site of the infection, thereby eliminating the complications of systemic IV antibiotics. This study aimed to present a case series illustrating the use of STIMULAN calcium sulfate beads loaded with vancomycin and tobramycin to increase the rate of salvage of the infected implant and forgo IV antibiotics. A retrospective analysis was performed of patients who were treated at Mount Sinai Hospital for implant infection with salvage and antibiotic beads. Twelve patients were identified, 10 of whom had breast cancer. Comorbidities included hypertension, smoking, and immunocompromised status. Infections were noted anywhere from 5 days to 8 years postoperatively. Salvage was successful in 9 out of the 12 infected implants using antibiotic bead therapy without home IV antibiotics. The use of antibiotic beads is promising for salvaging infected breast implants without IV antibiotics. Seventy-five percent of the implants were successfully salvaged. Of the three patients who had unsalvageable implants, one was infected with antibiotic-resistant Rhodococcus that was refractory to bead therapy and one was noncompliant with postoperative instructions. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Synthetic membrane-targeted antibiotics.

PubMed

Vooturi, S K; Firestine, S M

2010-01-01

Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

Parenteral and oral antibiotic duration for treatment of pediatric osteomyelitis: a systematic review protocol

PubMed Central

2013-01-01

Background Pediatric osteomyelitis is a bacterial infection of bones requiring prolonged antibiotic treatment using parenteral followed by enteral agents. Major complications of pediatric osteomyelitis include transition to chronic osteomyelitis, formation of subperiosteal abscesses, extension of infection into the joint, and permanent bony deformity or limb shortening. Historically, osteomyelitis has been treated with long durations of antibiotics to avoid these complications. However, with improvements in management and antibiotic treatment, standard of care is moving towards short durations of intravenous antibiotics prior to enteral antibiotics. Methods/Design The authors will perform a systematic review based on PRISMA guidelines in order to evaluate the literature, looking for evidence to support the optimal duration of parenteral and enteral therapy. The main goals are to see if literature supports shorter durations of either parenteral antibiotics and/or enteral antibiotics. Multiple databases will be investigated using a thorough search strategy. Databases include Medline, Cochrane, EMBASE, SCOPUS, Dissertation Abstracts, CINAHL, Web of Science, African Index Medicus and LILACS. Search stream will include medical subject heading for pediatric patients with osteomyelitis and antibiotic therapy. We will search for published or unpublished randomized and quasi-randomized controlled trials. Two authors will independently select articles, extract data and assess risk of bias by standard Cochrane methodologies. We will analyze comparisons between dichotomous outcomes using risk ratios and continuous outcomes using mean differences. 95% confidence intervals will be computed. Discussion One of the major dilemmas of management of this disease is the duration of parenteral therapy. Long parenteral therapy has increased risk of serious complications and the necessity for long therapy has been called into question. Our study aims to review the currently available

A New Approach for the Discovery of Antibiotics by Targeting Non-Multiplying Bacteria: A Novel Topical Antibiotic for Staphylococcal Infections

PubMed Central

Hu, Yanmin; Shamaei-Tousi, Alireza; Liu, Yingjun; Coates, Anthony

2010-01-01

In a clinical infection, multiplying and non-multiplying bacteria co-exist. Antibiotics kill multiplying bacteria, but they are very inefficient at killing non-multipliers which leads to slow or partial death of the total target population of microbes in an infected tissue. This prolongs the duration of therapy, increases the emergence of resistance and so contributes to the short life span of antibiotics after they reach the market. Targeting non-multiplying bacteria from the onset of an antibiotic development program is a new concept. This paper describes the proof of principle for this concept, which has resulted in the development of the first antibiotic using this approach. The antibiotic, called HT61, is a small quinolone-derived compound with a molecular mass of about 400 Daltons, and is active against non-multiplying bacteria, including methicillin sensitive and resistant, as well as Panton-Valentine leukocidin-carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The mechanism of action of the drug is depolarisation of the cell membrane and destruction of the cell wall. The speed of kill is within two hours. In comparison to the conventional antibiotics, HT61 kills non-multiplying cells more effectively, 6 logs versus less than one log for major marketed antibiotics. HT61 kills methicillin sensitive and resistant S. aureus in the murine skin bacterial colonization and infection models. No resistant phenotype was produced during 50 serial cultures over a one year period. The antibiotic caused no adverse affects after application to the skin of minipigs. Targeting non-multiplying bacteria using this method should be able to yield many new classes of antibiotic. These antibiotics may be able to reduce the rate of emergence of resistance, shorten the duration of therapy, and reduce relapse rates. PMID:20676403

Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

PubMed

Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

2016-01-01

Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

PubMed

Scheer, Christian S; Fuchs, Christian; Gründling, Matthias; Vollmer, Marcus; Bast, Juliane; Bohnert, Jürgen A; Zimmermann, Kathrin; Hahnenkamp, Klaus; Rehberg, Sebastian; Kuhn, Sven-Olaf

2018-06-04

Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known how antibiotic treatment prior to sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn prior to and under antibiotic therapy. Prospective clinical cohort study of septic patients. Adult ICU patients with 2 or 3 blood culture (BC) sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samplings obtained prior to antibiotic therapy were compared to patients with samplings under antibiotic therapy. Blood culture positivity, defined as microbiological pathogen finding, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analyzed. BC positivity was 50.6% (78/154) among septic patients who did not receive antibiotics and only 27.7% (112/405) in those who were already under antibiotics (P<0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (Odds ratio 0.4; 95%CI 0.3-0.6). Gram-positive pathogens (28.3%(111/392) vs. 11.9%(116/972);P<0.001) and also gram-negative pathogens (16.3%(64/392) vs. 9.3%(90/972);P<0.001) were more frequent in BC sets drawn prior to antibiotic therapy compared to sets under antibiotics. Obtaining blood cultures under antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures prior to antibiotic administration in patients with sepsis. Copyright © 2018. Published by Elsevier Ltd.

KNOWLEDGE, ATTITUDE AND PERCEPTION REGARDING ANTIBIOTICS AMONG POLISH PATIENTS.

PubMed

2015-01-01

Antibiotics are drugs often used. This drugs used without legitimate indications or incorrectly may cause not satisfactory clinical results. It is therefore important for the society members to be aware of what is an antibiotic and which benefits and risks its use may bring. The survey was conducted in 2010. Objective of the study was to obtain information on the current knowledge and beliefs about antibiotic therapy of Poles. The research material consisted of 609 questionnaires and interviews, conducted among the adult population residing in the Lublin voivodeship. The study shows that rural inhabitants don't know the term herbal medicine or antibiotic more often than inhabitants in the city. Similarly, they more often don't know the action of antibiotics as well as use them less frequently. Poles treat them as an emergency exit if they are not helped by home treatments. There was a problem of overuse of antibiotics, related to young people, which were busy and have no time for illness. Self-medication in the antibiotic therapy also occurs and is caused, among others, by undisciplined patients. The respondents admited that they have antibiotics from the previous treatment, from pharmacy, or from family or friends. However, residents of rural areas using an antibiotic most frequently, cited a pharmacy as the source of this drug. Other issues dealt within this study generally doesn't differ for rural inhabitants from the data obtained among the urban population.

Evaluation of the efficiency of hospital antibiotic policy applied Dr Jan Biziel University Hospital No 2 in Bydgoszcz in 2009-2013.

PubMed

Kuziemski, Arkadiusz; Frankowska, Krystyna; Gonia, Ewa; Czerniak, Beata; Bakhurynska, Olena; Sobociński, Zbigniew

2015-01-01

The Hospital Infection Control Team (HICT) of Dr Jan Biziel University Hospital No 2 in Bydgoszcz developed and implemented the principles of a rational antibiotic therapy in 2008. A behavior algorithm has worked since 01.10.2008. Implementation of the principles of a rational antibiotic therapy was part of the hospital antibiotic policy. is to evaluate either introductory principles of the rational antibiotic therapy, after five-year experience lived up to expectations in the range specified by the authors. Hospital microbiological maps, comparisons of antibiotic cost, specification of microbiological tests made before and after introduction of the principles of a rational antibiotic therapy have been analyzed. Annual antibiotic consumption has been counted according to the defined daily dose (DDD) index created by the WHO. After 6 years of implementation of the rational antibiotic therapy principles, the decrease in number of isolated strains which are resistant to Klebsiella pneumoniae ESBL and Acinetobacter baumanii (resistant to carbapenems) has been indicated. The number of the Pseudomonas aeruginosa isolates has increased approximately three times, and the number of resistant isolates to carbapenem has grown six times. The cost of antibiotics has been gradually decreased in 2012 in order to represent 9,66% of all drug budget (without drug programs). Detailed analysis of antibiotic consumption has showed that after the implementation of rational antibiotic therapy principles the consumption of meropenem has increased twice in comparison to the all drugs. The number of microbiological tests grew from 0,20 to 0,29 per one patient, which means material to microbiological tests has been taken from every third patient. Annual DDD index calculated on 100 person-days has been reduced from 59,552 in 2007 to 39,90 in 2009, and it is 47,88 in 2013. The principles of rational antibiotic therapy in comparison with the other elements of antibiotic policy in hospital have

Prospective evaluation of antibiotic treatment for urological procedure in patients presenting with neurogenic bladder.

PubMed

Weglinski, L; Rouzaud, C; Even, A; Bouchand, F; Davido, B; Duran, C; Salomon, J; Perronne, C; Denys, P; Chartier-Kastler, E; Dinh, A

2016-09-01

Patients presenting with neurogenic bladder often require urological procedures (urodynamic testing and botulinum toxin injections) and a preventive antibiotic therapy. We aimed to assess the efficacy of this little known strategy in a cohort of patients. All patients presenting with neurogenic bladder who underwent urological procedure were included in the study. They received an antibiotic therapy in accordance with the urine cytobacteriological examination results. The antibiotic therapy was initiated two days before the procedure and prolonged up until two days after the procedure if the culture was positive. Patients were treated with a single dose of fosfomycin-trometamol in case of a negative culture. The main study outcome was the occurrence of urinary tract infection (UTI), defined by a positive urine culture and symptoms, up until 14 days after the procedure. A total of 80 urological procedures were performed. Mean patient age was 47±13.1 years (sex ratio 1.22); 59 (73.8%) presented with asymptomatic bacteriuria before the procedure. Nine (11.1%) UTIs were recorded on Day 14, of which one (1.2%) was febrile. Two patients required an additional curative antibiotic therapy. No patient was hospitalized. Overall, 77.8% of UTIs were cured without antibiotic therapy. Screening and treating asymptomatic bacteriuria before urological procedures seems unnecessary and vainly exposes this population at high risk of infectious diseases to antibiotic therapies. This data should be confirmed by a randomized clinical trial. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use

PubMed Central

Decloe, Melissa; Gill, Suzanne; Ho, Grace; McCready, Janine; Powis, Jeff

2017-01-01

Background The success of antimicrobial stewardship is dependent on how often it is completed and which antimicrobials are targeted. We evaluated the impact of an antimicrobial stewardship program (ASP) in three non-ICU settings where all systemic antibiotics, regardless of spectrum, were targeted on the first weekday after initiation. Methods Prospective audit and feedback (PAAF) was initiated on the surgical, respiratory, and medical wards of a community hospital on July 1, 2010, October 1, 2010, and April 1, 2012, respectively. We evaluated rates of total antibiotic use, measured in days on therapy (DOTs), among all patients admitted to the wards before and after PAAF initiation using an interrupted time series analysis. Changes in antibiotic costs, rates of C. difficile infection (CDI), mortality, readmission, and length of stay were evaluated using univariate analyses. Results Time series modelling demonstrated that total antibiotic use decreased (± standard error) by 100 ± 51 DOTs/1,000 patient-days on the surgical wards (p = 0.049), 100 ± 46 DOTs/1,000 patient-days on the respiratory ward (p = 0.029), and 91 ± 33 DOTs/1,000 patient-days on the medical wards (p = 0.006) immediately following PAAF initiation. Reductions in antibiotic use were sustained up to 50 months after intervention initiation, and were accompanied by decreases in antibiotic costs. There were no significant changes to patient outcomes on the surgical and respiratory wards following intervention initiation. On the medical wards, however, readmission increased from 4.6 to 5.6 per 1,000 patient-days (p = 0.043), while mortality decreased from 7.4 to 5.0 per 1,000 patient-days (p = 0.001). CDI rates showed a non-significant declining trend after PAAF initiation. Conclusions ASPs can lead to cost-effective, sustained reductions in total antibiotic use when interventions are conducted early in the course of therapy and target all antibiotics. Shifting to such a model may help strengthen the

Every antibiotic, every day: Maximizing the impact of prospective audit and feedback on total antibiotic use.

PubMed

Campbell, Tonya J; Decloe, Melissa; Gill, Suzanne; Ho, Grace; McCready, Janine; Powis, Jeff

2017-01-01

The success of antimicrobial stewardship is dependent on how often it is completed and which antimicrobials are targeted. We evaluated the impact of an antimicrobial stewardship program (ASP) in three non-ICU settings where all systemic antibiotics, regardless of spectrum, were targeted on the first weekday after initiation. Prospective audit and feedback (PAAF) was initiated on the surgical, respiratory, and medical wards of a community hospital on July 1, 2010, October 1, 2010, and April 1, 2012, respectively. We evaluated rates of total antibiotic use, measured in days on therapy (DOTs), among all patients admitted to the wards before and after PAAF initiation using an interrupted time series analysis. Changes in antibiotic costs, rates of C. difficile infection (CDI), mortality, readmission, and length of stay were evaluated using univariate analyses. Time series modelling demonstrated that total antibiotic use decreased (± standard error) by 100 ± 51 DOTs/1,000 patient-days on the surgical wards (p = 0.049), 100 ± 46 DOTs/1,000 patient-days on the respiratory ward (p = 0.029), and 91 ± 33 DOTs/1,000 patient-days on the medical wards (p = 0.006) immediately following PAAF initiation. Reductions in antibiotic use were sustained up to 50 months after intervention initiation, and were accompanied by decreases in antibiotic costs. There were no significant changes to patient outcomes on the surgical and respiratory wards following intervention initiation. On the medical wards, however, readmission increased from 4.6 to 5.6 per 1,000 patient-days (p = 0.043), while mortality decreased from 7.4 to 5.0 per 1,000 patient-days (p = 0.001). CDI rates showed a non-significant declining trend after PAAF initiation. ASPs can lead to cost-effective, sustained reductions in total antibiotic use when interventions are conducted early in the course of therapy and target all antibiotics. Shifting to such a model may help strengthen the effectiveness of ASPs in non

Attitudes of pharmacists and physicians to antibiotic policies in hospitals.

PubMed

Adu, A; Simpson, J M; Armour, C L

1999-06-01

Antibiotic therapy in hospitals has substantial impact on patient outcome and the pharmacy drug budget. Antibiotic policies have been implemented by some hospitals to improve the quality of patient outcome and cost of antibiotic therapy. Antibiotic policies impose certain requirements on pharmacists and physicians. Pharmacists' and physicians' attitudes to and opinions about antibiotic policies are likely to affect the usefulness of such policies. To determine the attitudes of pharmacists and physicians to antibiotic policies in New South Wales (NSW) hospitals. Pharmacists and physicians in NSW public hospitals were surveyed to determine their attitudes to and opinions on antibiotic policies. A simple one-stage cluster sample of 241 pharmacists and a two-stage cluster sample of 701 physicians were obtained. Factor analysis was used to identify the attitudinal dimensions. General linear modelling was used to investigate the effects of predictor variables on outcome variables. The response rates were 91% and 77% for pharmacists and physicians, respectively. Factor analysis identified three dimensions of attitude to antibiotic policies: that they encourage rational antibiotic use; that they improve the quality of antibiotic prescribing and that they are associated with some problems. The reliability of these factors (Cronbach's alpha) ranged from 0.71 to 0.74, and was 0.90 for the overall attitude scale. Pharmacists and physicians had a positive overall attitude to antibiotic policies. Whereas physicians recognize that antibiotic policies improve the quality of prescribing, this was highly correlated with identification of problems (alpha = 0.71). In urban hospitals, pharmacists were more likely than physicians to associate antibiotics with problems. There was a positive overall attitude to hospital antibiotic policies expressed by pharmacists and physicians.

Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

PubMed

Lima, Stella Sala Soares; Nobre, Vandack; de Castro Romanelli, Roberta Maia; Clemente, Wanessa Trindade; da Silva Bittencourt, Henrique Neves; Melo, Ana Catarina Mourão; Salomão, Luciana Caetano Botelho; Serufo, José Carlos

2016-06-01

Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.

Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.

PubMed

Lewis, James D; Chen, Eric Z; Baldassano, Robert N; Otley, Anthony R; Griffiths, Anne M; Lee, Dale; Bittinger, Kyle; Bailey, Aubrey; Friedman, Elliot S; Hoffmann, Christian; Albenberg, Lindsey; Sinha, Rohini; Compher, Charlene; Gilroy, Erin; Nessel, Lisa; Grant, Amy; Chehoud, Christel; Li, Hongzhe; Wu, Gary D; Bushman, Frederic D

2015-10-14

Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

PubMed

Kroll, Amanda L; Corrigan, Patricia A; Patel, Shejal; Hawks, Kelly G

2016-10-01

Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications. © The Author(s) 2015.

Antibiotics and Antibiotic Resistance

MedlinePlus

... Medicine Safely Antibiotics and Antibiotic Resistance Antibiotics and Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... throughout the world are becoming resistant to antibiotics. Antibiotic resistance has been called one of the world's most ...

Continuous infusion of antibiotics in critically ill patients.

PubMed

Smuszkiewicz, Piotr; Szałek, Edyta; Tomczak, Hanna; Grześkowiak, Edmund

2013-02-01

Antibiotics are the most commonly used drugs in intensive care unit patients and their supply should be based on pharmacokinetic/pharmacodynamic rules. The changes that occur in septic patients who are critically ill may be responsible for subtherapeutic antibiotic concentrations leading to poorer clinical outcomes. Evolving in time the disturbed pathophysiology in severe sepsis (high cardiac output, glomerular hyperfiltration) and therapeutic interventions (e.g. haemodynamically active drugs, mechanical ventilation, renal replacement therapy) alters antibiotic pharmacokinetics mainly through an increase in the volume of distribution and altered drug clearance. The lack of new and efficacious drugs and increased bacterial resistance are current problems of contemporary antibiotic therapy. Although intermittent administration is a standard clinical practice, alternative methods of antibiotic administration are sought, which may potentialise effects and reduce toxicity as well as contribute to inhibition of bacterial resistance. A wide range of studies prove that the application of continuous infusion of time-dependent antibiotics (beta-lactams, glycopeptides) is more rational than standard intermittent administration. However, there are also studies which do not confirm the advantage of one method over the other. In spite of controversy the continuous administration of this group of antibiotics is common practice, because the results of both studies point to the higher efficacy of this method in critically ill patients. Authors reviewed the literature to determine whether any clinical benefits exist for administration of time-dependent antibiotics by continuous infusion. Definite specification of the clinical advantage of administration this way over standard dosage requires a large-scale multi-centre randomised controlled trial.

Suspected postpartum endometritis: a controlled clinical trial of single-agent antibiotic therapy with Amox-CA (Augmentin) vs. ampicillin-metronidazole +/- aminoglycoside.

PubMed

Fernandez, H; Claquin, C; Guibert, M; Papiernik, E

1990-01-01

Endometritis is the commonest postpartum complication and is one of the leading causes of maternal morbidity, if not mortality. The object of the present clinical trial was to assess the efficiency of single-agent therapy with Amox-CA (Augmentin) (formulation which includes a beta-lactamase inhibitor), against standard treatment which necessarily combines two or three antibiotics depending on the clinical severity of the case. 101 patients were evaluated in this comparative prospective randomized study. The mild forms were defined by a temperature between 37.9 and 38.4 degrees C and the severe forms by a temperature of more than 38.5 degrees C (which alone required treatment with three antibiotics). The time until the return of apyrexia and the clinical cure rate, as well as duration of treatment, were identical in both groups. Tolerance was good: no side effect requiring discontinuation of treatment occurred. In the population value, the use of a single-agent therapy with amoxycillin/clavulanic acid is not significantly different from a double or triple-agent regimen, and the convenience is increase.

Cefoxitin-based antibiotic therapy for extended-spectrum β-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot study.

PubMed

Demonchy, Elisa; Courjon, Johan; Ughetto, Estelle; Durand, Matthieu; Risso, Karine; Garraffo, Rodolphe; Roger, Pierre-Marie

2018-06-01

The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Introduction of a PCT-based algorithm to guide antibiotic prescription in COPD exacerbation.

PubMed

Picart, J; Moiton, M P; Gaüzère, B-A; Gazaille, V; Combes, X; DiBernardo, S

2016-12-01

Prescribing antibiotics for COPD exacerbations is not easy. Procalcitonin (PCT) is a useful biomarker that helps reduce the rate of antibiotic therapies. However, its proper cut-off levels are often unknown. We aimed to assess the impact of a PCT-based algorithm to guide antibiotic therapy prescription in COPD exacerbations. We conducted an observational, retrospective, and before/after study. We reviewed physician practices regarding PCT test and antibiotic therapy prescription to all patients hospitalized for COPD exacerbation. We then analyzed the rate of antibiotic prescriptions and the number of PCT tests prescribed before and after the introduction of a protocol validated by previous high-power studies. The primary endpoint was the rate of antibiotic prescriptions. A total of 124 patients before protocol and 121 patients after protocol were included. Antibiotic prescriptions decreased by 41% after protocol introduction (59% vs. 35%, P<0.001), with no increase in morbidity and mortality at Day 30. Compliance with protocol was complete in 60% of cases and partial (no PCT guidance to discontinue antibiotics) in 8% of cases. Both antibiotic duration (8.3 days vs. 8.7 days) and length of hospital stay (8.5 days vs. 8.3 days, P=0.78) did not change. Hospital physicians are already using PCT-based algorithm to guide antibiotic prescription in COPD exacerbations. Disseminating information on the appropriate PCT cut-off level to use to decide whether or not to initiate antibiotics is effective. Its proper use should be clarified to reduce antibiotic prescriptions to these overexposed patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Focus on aggressive behaviour in mental illness.

PubMed

Pompili, Enrico; Carlone, Cristiano; Silvestrini, Cristiana; Nicolò, Giuseppe

2017-01-01

Aggression is a behaviour with evolutionary origins, but in today’s society it is often both destructive and maladaptive. Increase of aggressive behaviour has been observed in a number of serious mental illnesses, and it represents a clinical challenge for mental healthcare provider. These phenomena can lead to harmful behaviours, including violence, thus representing a serious public health concern. Aggression is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Moreover, it has an effect on healthcare use and costs in terms of longer length of stay, more readmissions and higher drug use. In this review, based on a selective search of 2010-2016 pertinent literature on PubMed, we analyze and summarize information from original articles, reviews, and book chapters about aggression and psychiatric disorders, discussing neurobiological basis and therapy of aggressive behaviour. A great challenge has been revealed regarding the neurobiology of aggression, and an integration of this body of knowledge will ultimately improve clinical diagnostics and therapeutic interventions. The great heterogeneity of aggressive behaviour still hampers our understanding of its causal mechanisms. Still, over the past years, the identification of specific subtypes of aggression has released possibilities for new and individualized treatment approaches. Neuroimaging studies may help to further elucidate the interrelationship between neurocognitive functioning, personality traits, and antisocial and violent behaviour. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. These combined approaches could improve treatment efficacy. As current pharmacological and therapeutic interventions are

Examination of a novel, specified local antibiotic therapy through polymethylmethacrylate capsules in a rabbit osteomyelitis model.

PubMed

Börzsei, László; Mintál, Tibor; Koós, Zoltán; Kocsis, Béla; Helyes, Zsuzsanna; Kereskai, László; Nyárády, József

2006-01-01

Chronic bone and soft tissue suppurations have become more frequent recently due to the increasing number of high-energy injuries. There are certain antibiotic beads available for local administration, but they cannot always be applied specifically against the pyogenic microorganisms. In the present study, a new technique of local antibiotic therapy for the treatment of infections is described. Polymethylmethacrylate (PMMA) capsules were produced and filled with 0.1 ml Tazocin (0.02 g piperacillin sodium + 0.005 g tazobactam). The efficacy of these Tazocin-filled capsules was examined in vivo using a rabbit osteomyelitis model. Chronic osteomyelitis was induced in rabbit tibia by local injection of Staphylococcus aureus. The treatment included surgical debridement and implantation of Tazocin-containing PMMA capsules into the medullar cavity (n = 12). Simple surgical debridement with no antibiotic implantation was performed in control animals (n = 7). Results were evaluated using microbiological, radiological and histological methods 14 weeks after induction of osteomyelitis. Eight weeks after the implantation of PMMA capsules, complete physical, radiological and histological healing was achieved in 7 animals, initiation of the reparative phase was observed histologically in 3 cases and no reparative signs were detected in 2 rabbits. In the control group, no significant sign of reparation could be seen in any of the cases. Copyright 2006 S. Karger AG, Basel.

Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Dippel, Diederik W J; Dijkgraaf, Marcel G W; van der Poll, Tom; Prins, Jan M; Vermeij, Frederique H; Roos, Yvo B W E M; Brouwer, Matthijs C; Zwinderman, Aeilko H; van de Beek, Diederik; Nederkoorn, Paul J

2014-10-01

Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia.

PubMed

Thønnings, S; Knudsen, J D; Schønheyder, H C; Søgaard, M; Arpi, M; Gradel, K O; Østergaard, C

2016-08-01

Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment. The rareness of the infection makes it difficult to improve antibiotic treatment through randomized clinical trials. This observational study investigated clinical features and outcome of invasive L. monocytogenes infections including the efficacy of empiric and definitive antibiotic therapies. Demographic, clinical and biochemical findings, antibiotic treatment and 30-day mortality for all episodes of L. monocytogenes bacteraemia and/or meningitis were collected by retrospective medical record review in the North Denmark Region and the Capital Region of Denmark (17 hospitals) from 1997 to 2012. Risk factors for 30-day all-cause mortality were assessed by logistic regression. The study comprised 229 patients (median age: 71 years), 172 patients had bacteraemia, 24 patients had meningitis and 33 patients had both. Significant risk factors for 30-day mortality were septic shock (OR 3.0, 95% CI 1.4-6.4), altered mental state (OR 3.6, 95% CI 1.7-7.6) and inadequate empiric antibiotic therapy (OR 3.8, 95% CI 1.8-8.1). Cephalosporins accounted for 90% of inadequately treated cases. Adequate definitive antibiotic treatment was administered to 195 patients who survived the early period (benzylpenicillin 72, aminopenicillin 84, meropenem 28, sulfamethoxazole/trimethoprim 6, and piperacillin/tazobactam 5). Definitive antibiotic treatment with benzylpenicillin or aminopenicillin resulted in a lower 30-day mortality in an adjusted analysis compared with meropenem (OR 0.3; 95% CI 0.1-0.8). In conclusion, inadequate empiric antibiotic therapy and definitive therapy with meropenem were both associated with significantly higher 30-day mortality. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma

PubMed Central

Jain, Michael D; Bachmeier, Christina A; Phuoc, Vania H; Chavez, Julio C

2018-01-01

Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin’s lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis. PMID:29910620

Antibiotic stewardship in community-acquired pneumonia.

PubMed

Viasus, Diego; Vecino-Moreno, Milly; De La Hoz, Juan M; Carratalà, Jordi

2017-04-01

Community-acquired pneumonia (CAP) continues to be associated with significant mortality and morbidity. As with other infectious diseases, in recent years there has been a marked increase in resistance to the antibiotics commonly used against the pathogens that cause CAP. Antimicrobial stewardship denotes coordinated interventions to improve and measure the appropriate use of antibiotics by encouraging the selection of optimal drug regimens. Areas covered: Several elements can be applied to antibiotic stewardship strategies for CAP in order to maintain or improve patient outcomes. In this regard, antibiotic de-escalation, duration of antibiotic treatment, adherence to CAP guidelines recommendations about empirical treatment, and switching from intravenous to oral antibiotic therapy may each be relevant in this context. Antimicrobial stewardship strategies, such as prospective audit with intervention and feedback, clinical pathways, and dedicated multidisciplinary teams, that have included some of these elements have demonstrated improvements in antimicrobial use for CAP without negatively affecting clinical outcomes. Expert commentary: Although there are a limited number of randomized clinical studies addressing antimicrobial stewardship strategies in CAP, there is evidence that antibiotic stewardship initiatives can be securely applied, providing benefits to both healthcare systems and patients.

Antibiotics and probiotics in treatment of inflammatory bowel disease

PubMed Central

Gionchetti, Paolo; Rizzello, Fernando; Lammers, Karen M; Morselli, Claudia; Sollazzi, Lucia; Davies, Samuel; Tambasco, Rosy; Calabrese, Carlo; Campieri, Massimo

2006-01-01

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn’s disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy. PMID:16733845

Oral anti-pseudomonal antibiotics for cystic fibrosis.

PubMed

Remmington, Tracey; Jahnke, Nikki; Harkensee, Christian

2016-07-14

Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review. To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016. Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment. Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information. We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the

Generalized aggressive periodontitis: microbiological composition and clinical parameters in non-surgical therapy.

PubMed

Usin, María M; Tabares, Sandra M; Menso, Julieta; de Albera, Estela R; Sembaj, Adela

2016-12-01

The aim of this study was to determine the variations in periodontal parameters and microbiological composition in periodontal pockets at the baseline and 3 and 6 months post treatmentin patients with Generalized Aggressive Periodontitis(GAP) undergoing non surgical periodontal treatment combined with chlorhexidine and systemic antibiotics. Medical and dental history was taken from 10 subjects, average age 30.6±2.7 years, diagnosed with GAP. A non surgical periodontal treatment combined with 0.12% chlorhexidine, 875 mg amoxicillin and 500 mg metronidazole every 12 hours for ten days was conducted. At each visit, the following measurements wererecorded: bacterial plaque (BP), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), hypermobility, and furcation lesions, and a sample of subgingivalplaque was taken from the site of the deepest probing depth of each sextant to identify Porphyromonas gingivalis, Treponemadenticola, Tannerella forsythia, Prevotella intermedia and Aggregatibacter actinomycetemcomitans using molecular biology techniques. After 6 months, the Wilcoxon test showed an increase of 0.97 mm in CAL (p=0.0047) and 2.54 mm in PD(p=0.009). A healthy site was defined as having a PD <5 mm, negative BOP and no pathogenic bacteria detected at 6 months, indicating significant improvement (p=0.008), with OR (95%CI) =4.7 (1.102220.11).With the treatment protocol used in this study, 6 months after treatment, patients had an approximately 4- fold higher possibility of presenting PD <5 mm and periodontal pockets without periodontal pathogenic bacteria. Sociedad Argentina de Investigación Odontológica.

Antibiotic susceptibility, heteroresistance, and updated treatment strategies in Helicobacter pylori infection.

PubMed

Mascellino, Maria Teresa; Porowska, Barbara; De Angelis, Massimiliano; Oliva, Alessandra

2017-01-01

In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori ( Hp ) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests. We also examined literature data regarding eradication success rates of culture-guided and empiric therapies. The empiric therapy and the one based on susceptibility testing, in Hp eradication, may depend on several factors such as concomitant diseases, the number of previous antibiotic treatments, differences in bacterial virulence in individuals with positive or negative cultures, together with local antibiotic resistance patterns in real-world settings. Updated treatment strategies in Hp infection presented in the guidelines of the Toronto Consensus Group (2016) are reported. These suggest to prolong eradication therapy up to 14 days, replacing the old triple therapy with a quadruple therapy based on proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline for most of the patients, or as an alternative quadruple therapy without bismuth, based on the use of PPI, amoxicillin, metronidazole, and clarithromycin. The new drug vonoprazan, a first-in-class potassium-competitive acid blocker recently approved in Japan, is also considered to be a promising solution for Hp eradication, even for clarithromycin-resistant strains. Furthermore, there is growing interest in finding new therapeutic strategies, such as the development of vaccines or the use of natural resources, including

Identifying aggressive prostate cancer foci using a DNA methylation classifier.

PubMed

Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

2017-01-12

Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

Rapid Improvement of thyroid storm-related hemodynamic collapse by aggressive anti-thyroid therapy including steroid pulse: A case report.

PubMed

Kiriyama, Hiroyuki; Amiya, Eisuke; Hatano, Masaru; Hosoya, Yumiko; Maki, Hisataka; Nitta, Daisuke; Saito, Akihito; Shiraishi, Yasuyuki; Minatsuki, Shun; Sato, Tatsuyuki; Murakami, Haruka; Uehara, Masae; Manaka, Katsunori; Makita, Noriko; Watanabe, Masafumi; Komuro, Issei

2017-06-01

Heart failure is relatively common in patients with hyperthyroidism, but thyrotoxic cardiomyopathy with poor left ventricular (LV) systolic function is very rare. We experienced a representative case of a patient who presented with severe LV dysfunction related to thyroid storm and needed extracorporeal membrane oxygenation (ECMO) temporally. Thyrotoxic cardiomyopathy. Aggressive antithyroid therapy, including steroid pulse to hyperthyroidism, leads to the dramatic improvement of cardiac function and she was successfully weaned from ECMO. The most outstanding feature of the current case was the rapid decrease of cardiac injury and improvement of cardiac function by strengthening antithyroid therapy, including steroid pulse, without thyroid hormone level normalization. In thyroid storm, various systemic inflammatory reactions have different time courses and among them, the cardiac phenotype emerges in most striking and critical ways.

Duration of intravenous antibiotic therapy for children with acute osteomyelitis or septic arthritis: a feasibility study.

PubMed

de Graaf, Hans; Sukhtankar, Priya; Arch, Barbara; Ahmad, Nusreen; Lees, Amanda; Bennett, Abigail; Spowart, Catherine; Hickey, Helen; Jeanes, Annmarie; Armon, Kate; Riordan, Andrew; Herberg, Jethro; Hackett, Scott; Gamble, Carrol; Shingadia, Delane; Pallett, Ann; Clarke, Stuart C; Henman, Philip; Emonts, Marieke; Sharland, Mike; Finn, Adam; Pollard, Andrew J; Powell, Colin; Marsh, Peter; Ballinger, Claire; Williamson, Paula R; Clarke, Nicholas Mp; Faust, Saul N

2017-09-01

There is little current consensus regarding the route or duration of antibiotic treatment for acute osteomyelitis (OM) and septic arthritis (SA) in children. To assess the overall feasibility and inform the design of a future randomised controlled trial (RCT) to reduce the duration of intravenous (i.v.) antibiotic use in paediatric OM and SA. (1) A prospective service evaluation (cohort study) to determine the current disease spectrum and UK clinical practice in paediatric OM/SA; (2) a prospective cohort substudy to assess the use of targeted polymerase chain reaction (PCR) in diagnosing paediatric OM/SA; (3) a qualitative study to explore families' views and experiences of OM/SA; and (4) the development of a core outcome set via a systematic review of literature, Delphi clinician survey and stakeholder consensus meeting. Forty-four UK secondary and tertiary UK centres (service evaluation). Children with OM/SA. PCR diagnostics were compared with culture as standard of care. Semistructured interviews were used in the qualitative study. Data were obtained on 313 cases of OM/SA, of which 218 (61.2%) were defined as simple disease and 95 (26.7%) were defined as complex disease. The epidemiology of paediatric OM/SA in this study was consistent with existing European data. Children who met oral switch criteria less than 7 days from starting i.v. antibiotics were less likely to experience treatment failure (9.6%) than children who met oral switch criteria after 7 days of i.v. therapy (16.1% when switch was between 1 and 2 weeks; 18.2% when switch was > 2 weeks). In 24 out of 32 simple cases (75%) and 8 out of 12 complex cases (67%) in which the targeted PCR was used, a pathogen was detected. The qualitative study demonstrated the importance to parents and children of consideration of short- and long-term outcomes meaningful to families themselves. The consensus meeting agreed on the following outcomes: rehospitalisation or recurrence of symptoms while on oral

Use and prescription of antibiotics in primary health care settings in China.

PubMed

Wang, Jin; Wang, Pan; Wang, Xinghe; Zheng, Yingdong; Xiao, Yonghong

2014-12-01

Appropriate antibiotic use is a key strategy to control antibacterial resistance. The first step in achieving this is to identify the major problems in antibiotic prescription in health care facilities, especially in primary health care settings, which is where most patients receive medical care. To identify current patterns of antibiotic use and explore the reasons for inappropriate prescription in primary health care settings in China. A total of 48 primary health care facilities in China were randomly selected from 6 provinces at various levels of economic development. Data for the years 2009 through 2011 from 39 qualifying facilities (23 city and 16 rural primary health care centers) were analyzed retrospectively. The study sample consisted of prescription records for 7311 outpatient visits and 2888 inpatient hospitalizations. General health center information, drug usage, disease diagnoses, and antibiotic use by outpatients and inpatients were surveyed. Cases of inappropriate antibiotic prescription were identified. Most staff in the primary health care facilities had less than a college degree, and the medical staff consisted primarily of physician assistants, assistant pharmacists, nurses, and nursing assistants. The median (range) governmental contribution to each facility was 34.0% (3.6%-92.5%) of total revenue. The facilities prescribed a median (range) of 28 (8-111) types of antibiotics, including 34 (10-115) individual agents. Antibiotics were included in 52.9% of the outpatient visit prescription records: of these, only 39.4% were prescribed properly. Of the inpatients, 77.5% received antibiotic therapy: of these, only 24.6% were prescribed properly. Antibiotics were prescribed for 78.0% of colds and 93.5% of cases of acute bronchitis. Of the antibiotic prescriptions, 28.0% contained cephalosporins and 15.7% fluoroquinolones. A total of 55.0% of the antibiotic prescriptions were for antibiotic combination therapy with 2 or more agents. In nonsurgical

Analysis of preoperative antibiotic prophylaxis in stented, distal hypospadias repair.

PubMed

Smith, Jacob; Patel, Ashay; Zamilpa, Ismael; Bai, Shasha; Alliston, Jeffrey; Canon, Stephen

2017-04-01

Surgical site infection [SSI] is a risk for any surgical procedure, including hypospadias repair. Prophylactic antibiotic therapy for patients having surgery is often effective in preventing SSIs, but with increasing rates of antibiotic resistance, this practice has been questioned. The objectives of this study are 1) to assess the incidence of SSIs in patients following stented, distal hypospadias repair and 2) to observe for any potential difference in the incidence of SSIs for patients with and without preoperative antibiotic utilization in this setting. We retrospectively reviewed consecutive patients treated with stented, distal hypospadias repair from 2011 to 2014 by three surgeons and compared two groups: patients who received preoperative antibiotics and patients who did not. Patients with a history of previous hypospadias repair were excluded from the study. Two hundred twenty-four subjects were identified. Group 1 (135) received preoperative antibiotic and Group 2 (89) did not receive preoperative antibiotics. There was no statistically significant difference in SSI prevalence with 0 patients in Group 1 and 1 patient in Group 2 having a SSI. Although prophylactic antibiotics prior to hypospadias repair are most often used by pediatric urologists, this study demonstrates further evidence that antibiotics prior to this procedure do not appear to lower the rate of SSI. This study is limited by its retrospective nature and disparate mean follow up in the two cohorts. Surgical site infection does not appear to be decreased by prophylactic antibiotic therapy before distal hypospadias repair.

Basis for selecting optimum antibiotic regimens for secondary peritonitis.

PubMed

Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

2016-01-01

Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

Antibiotics for acute bronchitis.

PubMed

Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

2014-03-01

The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and assess adverse effects of antibiotic therapy for patients with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to January 2014). Randomised controlled trials (RCTs) comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in patients without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. Seventeen trials with 3936 participants were included in the primary analysis. The quality of trials was generally good. There was limited evidence to support the use of antibiotics in acute bronchitis. At follow-up, there was no difference in participants described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15; number needed to treat for an additional beneficial outcome (NNTB) 22. Participants given antibiotics were less likely to have a cough (four studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a shorter mean cough duration (seven studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated patients were more likely to be unimproved according to clinician's global assessment (six studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB

Antibiotics for treating septic abortion.

PubMed

Udoh, Atim; Effa, Emmanuel E; Oduwole, Olabisi; Okusanya, Babasola O; Okafo, Obiamaka

2016-07-01

A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion. This review aimed to bridge this gap in knowledge to inform policy and practice. To review the effectiveness of various individual antibiotics or antibiotic regimens in the treatment of septic abortion. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and POPLINE using the following keywords: 'Abortion', 'septic abortion', 'Antibiotics', 'Infected abortion', 'postabortion infection'. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 19 April, 2016. We considered for inclusion randomised controlled trials (RCTs) and non-RCTs that compared antibiotic(s) to another antibiotic(s), irrespective of route of administration, dosage, and duration as well as studies comparing antibiotics alone with antibiotics in combination with other interventions such as dilation and curettage (D&C). Two review authors independently extracted data from included trials. We resolved disagreements through consultation with a third author. One review author entered extracted data into Review Manager 5.3, and a second review author cross-checked the entry for accuracy. We included 3 small RCTs involving 233 women that were conducted over 3 decades ago.Clindamycin did not differ significantly from penicillin plus chloramphenicol in reducing fever in all women (mean difference (MD) -12.30, 95% confidence interval (CI) -25.12 to 0.52; women = 77; studies = 1

Decision-support models for empiric antibiotic selection in Gram-negative bloodstream infections.

PubMed

MacFadden, D R; Coburn, B; Shah, N; Robicsek, A; Savage, R; Elligsen, M; Daneman, N

2018-04-25

Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia. We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%). A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68-0.89, optimism-corrected AUCs 0.63-0.85) and pathogen-guided (12 models, AUCs 0.75-0.98, optimism-corrected AUCs 0.64-0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy. Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires

Comparative study of the efficacy of topical steroid and antibiotic combination therapy versus oral antibiotic alone when treating acute rhinosinusitis.

PubMed

El-Hennawi, D M; Ahmed, M R; Farid, A M; Al Murtadah, A M

2015-05-01

Acute rhinosinusitis arises as a consequence of viral rhinitis, and bacterial infection can subsequently occur. Intranasal antibiotics as an adjunct to corticosteroids usually demonstrate the greatest symptom relief. We wanted to clinically evaluate the effects of a topical antibiotic and steroid combination administered intranasally, versus an oral antibiotic alone when treating acute rhinosinusitis. Forty patients with acute bacterial rhinosinusitis were divided into two groups. Group A received an antibiotic and steroid combination (ofloxacin 0.26 per cent and dexamethasone 0.053 per cent nasal drops) for 10 days, administered intranasally (5 drops in each nostril/8 hours). Group B, the control group, received an oral antibiotic alone (amoxicillin 90 mg/kg). Eight hours after commencing treatment, facial pain was more severe in group B and nasal obstruction was reduced in both groups. Ten days after commencing treatment, anterior nasal discharge was 0.15 per cent in group A and absent in group B. The application of a topical antibiotic and steroid combination into the nasal cavity is an effective way of treating uncomplicated, acute bacterial rhinosinusitis with the theoretical advantages of easy administration, high local drug concentration and minimal systemic adverse effects.

Antibiotic-impregnated calcium phosphate cement as part of a comprehensive treatment for patients with established orthopaedic infection.

PubMed

Niikura, Takahiro; Lee, Sang Yang; Iwakura, Takashi; Sakai, Yoshitada; Kuroda, Ryosuke; Kurosaka, Masahiro

2016-07-01

The treatment of established orthopaedic infection is challenging. While the main focus of treatment is wide surgical debridement, systemic and local antibiotic administration are important adjuvant therapies. Several reports have described the clinical use of antibiotic-impregnated calcium phosphate cement (CPC) to provide local antibiotic therapy for bone infections. However, these were all individual case reports, and no case series have been reported. We report a case series treated by a single surgeon using antibiotic-impregnated CPC as part of a comprehensive treatment plan in patients with established orthopaedic infection. We enrolled 13 consecutive patients with osteomyelitis (n = 6) or infected non-union (n = 7). Implantation of antibiotic-impregnated CPC was performed to provide local antibiotic therapy as part of a comprehensive treatment plan that also included wide surgical debridement, systemic antibiotic therapy, and subsequent second-stage reconstruction surgery. We investigated the rate of successful infection eradication and systemic/local complications. The concentration of antibiotics in the surgical drainage fluids, blood, and recovered CPC (via elution into a phosphate-buffered saline bath) were measured. The mean follow-up period after surgery was 50.4 (range, 27-73) months. There were no cases of infection recurrence during follow-up. No systemic toxicity or local complications from the implantation of antibiotic-impregnated CPC were observed. The vancomycin concentration in the fluid from surgical drainage (n = 6) was 527.1 ± 363.9 μg/mL on postoperative day 1 and 224.5 ± 198.4 μg/mL on postoperative day 2. In patients who did not receive systemic vancomycin therapy (n = 3), the maximum serum vancomycin level was <0.8 μg/mL. In vitro vancomycin elution was observed from the CPC that was surgically retrieved (n = 2). Implantation of antibiotic-impregnated CPC is an option to provide local antibiotic therapy as part of

Antibiotics for acute bronchitis.

PubMed

Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

2017-06-19

The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017. Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies

Costs, quality of life and treatment compliance associated with antibiotic therapies in patients with cystic fibrosis: a review of the literature.

PubMed

Weiner, Jennifer R; Toy, Edmond L; Sacco, Patricia; Duh, Mei Sheng

2008-04-01

Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients. This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients. A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007. Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

[A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases].

PubMed

Ikegaya, Satoshi; Iwasaki, Hiromichi; Kinoshita, Keiichi; Urasaki, Yoshimasa; Tsutani, Hiroshi; Ueda, Takanori

2004-03-01

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

Efficacy of Antibiotic Suppressive Therapy in Patients with a Prosthetic Joint Infection.

PubMed

Wouthuyzen-Bakker, Marjan; Nijman, Jasperina M; Kampinga, Greetje A; van Assen, Sander; Jutte, Paul C

2017-01-01

Introduction: For chronic prosthetic joint infections (PJI), complete removal of the infected prosthesis is necessary in order to cure the infection. Unfortunately, a subgroup of patients is not able to undergo a revision surgery due to high surgical risk. Alternatively, these patients can be treated with antibiotic suppressive therapy (AST) to suppress the infection. Aim: To evaluate the efficacy and tolerability of AST. Methods: We retrospectively collected data (period 2009-2015) from patients with a PJI (of hip, knee or shoulder) who were treated with AST at the University Medical Center Groningen, the Netherlands. AST was defined as antibiotic treatment for PJI that was started after the usual 3 months of antibiotic treatment. The time of follow-up was defined from the time point AST was started. Treatment was considered as failed, when the patient still experienced joint pain, when surgical intervention (debridement, removal, arthrodesis or amputation) was needed to control the infection and/or when death occurred due to the infection. Results: We included 21 patients with a median age of 67 years (range 21 - 88) and with a median follow-up of 21 months (range 3 - 81). Coagulase negative staphylococci (CNS) (n=6), S. aureus (n=6) and polymicrobial flora (n=4) were the most frequently found causative pathogens. Most patients with CNS and S. aureus were treated with minocycline (67%) and clindamycin (83%) as AST, respectively. Overall, treatment was successful in 67% of patients. Failure was due to persistent joint pain (n=1), surgical intervention because of an uncontrolled infection (n=3), and death due the infection (n=3). We observed a treatment success of 90% in patients with a 'standard' prosthesis (n=11), compared to only 50% in patients with a tumor-prosthesis (n=10). Also, treatment was successful in 83% of patients with a CNS as causative microorganism for the infection, compared to 50% in patients with a S. aureus . Patients who failed on AST had a

Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

PubMed Central

Shah, Dhara; Dang, Minh-Duc; Hasbun, Rodrigo; Koo, Hoonmo L; Jiang, Zhi-Dong; DuPont, Herbert L; Garey, Kevin W

2010-01-01

Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. PMID:20455684

When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition.

PubMed

Pena-Miller, Rafael; Laehnemann, David; Jansen, Gunther; Fuentes-Hernandez, Ayari; Rosenstiel, Philip; Schulenburg, Hinrich; Beardmore, Robert

2013-01-01

Conventional wisdom holds that the best way to treat infection with antibiotics is to 'hit early and hit hard'. A favoured strategy is to deploy two antibiotics that produce a stronger effect in combination than if either drug were used alone. But are such synergistic combinations necessarily optimal? We combine mathematical modelling, evolution experiments, whole genome sequencing and genetic manipulation of a resistance mechanism to demonstrate that deploying synergistic antibiotics can, in practice, be the worst strategy if bacterial clearance is not achieved after the first treatment phase. As treatment proceeds, it is only to be expected that the strength of antibiotic synergy will diminish as the frequency of drug-resistant bacteria increases. Indeed, antibiotic efficacy decays exponentially in our five-day evolution experiments. However, as the theory of competitive release predicts, drug-resistant bacteria replicate fastest when their drug-susceptible competitors are eliminated by overly-aggressive treatment. Here, synergy exerts such strong selection for resistance that an antagonism consistently emerges by day 1 and the initially most aggressive treatment produces the greatest bacterial load, a fortiori greater than if just one drug were given. Whole genome sequencing reveals that such rapid evolution is the result of the amplification of a genomic region containing four drug-resistance mechanisms, including the acrAB efflux operon. When this operon is deleted in genetically manipulated mutants and the evolution experiment repeated, antagonism fails to emerge in five days and antibiotic synergy is maintained for longer. We therefore conclude that unless super-inhibitory doses are achieved and maintained until the pathogen is successfully cleared, synergistic antibiotics can have the opposite effect to that intended by helping to increase pathogen load where, and when, the drugs are found at sub-inhibitory concentrations.

Response of first-line antibiotic therapy in patients with febrile neutropenia during treatment of hematological disorders.

PubMed

Taj, M; Qureshi, R N; Farzana, T; Shamsi, T S; Ahmed, S S

2015-06-01

Patients with hematological disorders develop febrile neutropenia (FN); most of these events remain undetermined in origin. We performed a prospective study to determine the microbiological characteristics of infections and their response to the first-line antibiotic therapy in FN. The study was conducted at National Institute of Blood Disease and Bone Marrow Transplant. Two-hundred episodes of FN were assessed for the bacterial growth, antimicrobial susceptibility pattern and response to the first-line treatment of FN. All patients were given Ceftazidime and Amikacin Bosch Pharmaceutical (Pvt. Ltd), as first-line antibiotic in FN. Out of 200 episodes we had 108 clinically and microbiologically documented infections. The isolated frequencies for gram negative and gram positive organisms were n = 52 and 49 (48 and 45 %) respectively. Among gram negative micro-organisms, Escherichia coli (E. coli) was isolated in 15 (28.8 %), Klebsiella pneumonae in 4 (7.6 %) and Pseudomonas aeruginosa in 10 (19.2 %) were in highest frequencies. Methicillin sensitive staphylococci emerged as the frequently isolated gram-positive bacteria. Eight-one episodes (45.3 %) responded to the first-line treatment and death reported in 20 cases (10 %). Our study showed almost equal trend of gram positive and gram negative bacteria isolated from patients suffering from neutropenic fever. Empirical use of Ceftazidime and Amikacin as first-line antibiotics was able to cover the infection only in 45.3 % of episodes suffering from FN.

Identification and treatment of aggressive thyroid cancers. Part 2: risk assessment and treatment.

PubMed

Sturgeon, Cord; Angelos, Peter

2006-04-01

Most thyroid cancers are slow-growing, easily treatable tumors with an excellent prognosis after surgical resection and targeted medical therapy. Unfortunately, 10% to 15% of thyroid cancers exhibit aggressive behavior and do not follow an indolent course. Approximately one-third of patients with differentiated thyroid cancers will have tumor recurrences. Distant metastases are present in about 20% of patients with recurrent cancer. Approximately half of patients with distant metastases die within 5 years. The loss of the ability to concentrate radio-iodine and produce thyroglobulin is a sign of dedifferentiation, which occurs in about 30% of patients with persistent or recurrent thyroid cancer. Dedifferentiation is associated with poorer responses to conventional therapy and difficulty monitoring tumor burden. Clinicians must identify tumors with more aggressive biology and treat them accordingly with more aggressive regimens. Part 1 of this two-part article, which appeared in March, described in detail the distinct types of thyroid cancer, as well as risk factors, outcomes, treatment, and prognostic factors, with a focus on thyroid cancers of follicular cell origin. Part 2 covers risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.

Antibiotics May be Safely Discontinued Within One Week of Percutaneous Cholecystostomy.

PubMed

Loftus, Tyler J; Brakenridge, Scott C; Dessaigne, Camille G; Sarosi, George A; Zingarelli, William J; Moore, Frederick A; Jordan, Janeen R; Croft, Chasen A; Smith, R Stephen; Efron, Phillip A; Mohr, Alicia M

2017-05-01

For patients with acute cholecystitis managed with percutaneous cholecystostomy (PC), the optimal duration of post-procedural antibiotic therapy is unknown. Our objective was to compare short versus long courses of antibiotics with the hypothesis that patients with persistent signs of systemic inflammation 72 h following PC would receive prolonged antibiotic therapy and that antibiotic duration would not affect outcomes. We performed a retrospective cohort analysis of 81 patients who underwent PC for acute cholecystitis at two hospitals during a 41-month period ending November 2014. Patients who received short (≤7 day) courses of post-procedural antibiotics were compared to patients who received long (>7 day) courses. Treatment response to PC was evaluated by systemic inflammatory response syndrome (SIRS) criteria. Logistic and linear regressions were used to evaluate associations between antibiotic duration and outcomes. Patients who received short (n = 30) and long courses (n = 51) of antibiotics had similar age, comorbidities, severity of cholecystitis, pre-procedural vital signs, treatment response, and culture results. There were no differences in recurrent cholecystitis (13 vs. 12%), requirement for open/converted to open cholecystectomy (23 vs. 22%), or 1-year mortality (20 vs. 18%). On logistic and linear regressions, antibiotic duration as a continuous variable was not predictive of any salient outcomes. Patients who received short and long courses of post-PC antibiotics had similar baseline characteristics and outcomes. Antibiotic duration did not predict recurrent cholecystitis, interval open cholecystectomy, or mortality. These findings suggest that antibiotics may be safely discontinued within one week of uncomplicated PC.

Changes in endogenous microflora among febrile granulocytopenic patients receiving empiric antibiotic therapy: implications for fungal superinfection.

PubMed Central

Bow, E J; Louie, T J

1987-01-01

The ecologic effect of empiric systemic antibiotic therapy on the endogenous microflora was evaluated in 83 febrile granulocytopenic patients with cancer who were randomly allocated to receive moxalactam plus ticarcillin (45 patients) or tobramycin plus ticarcillin (38 patients) for suspected infection. Serial surveillance cultures of the nasal passages, oropharynx and feces performed twice a week showed that patients who received the former regimen had higher elimination rates and significantly lower acquisition rates (p = 0.027) for aerobic gram-negative bacilli than did patients who received the latter regimen. However, therapy with moxalactam plus ticarcillin also resulted in significantly higher acquisition rates for yeasts (p = 0.004). This was associated with a significantly higher fungal superinfection rate among these patients than among those who received tobramycin plus ticarcillin (40% v. 16%) (p less than 0.05). Moxalactam plus ticarcillin therapy created a greater microbial ecologic vacuum by the elimination of intestinal anaerobes, which, in turn, permitted fungal colonization and an increased risk of superinfection. Our results support the recommendation that an antipseudomonal penicillin plus an aminoglycoside be selected as empiric therapy for suspected infection in febrile granulocytopenic patients with cancer. Such a regimen would spare the anaerobic intestinal microflora, thereby reducing the risk of fungal colonization and infection. PMID:3304600

Outcome of coronary plaque burden: a 10-year follow-up of aggressive medical management.

PubMed

Goh, Victor K; Lau, Chu-Pak; Mohlenkamp, Stefan; Rumberger, John A; Achenbach, Stephan; Budoff, Matthew J

2010-03-12

The effect of aggressive medical therapy on quantitative coronary plaque burden is not generally known, especially in ethnic Chinese. We reasoned that Cardiac CT could conveniently quantify early coronary atherosclerosis in our patient population, and hypothesized that serial observation could differentiate the efficacy of aggressive medical therapy regarding progression and regression of the atherosclerotic process, as well as evaluating the additional impact of life-style modification and the relative effects of the application of statin therapy. We employed a standardized Cardiac CT protocol to serially scan 113 westernized Hong Kong Chinese individuals (64 men and 49 women) with Chest Pain and positive coronary risk factors. In all cases included for this serial investigation, subsequent evaluation showed no significantly-obstructive coronary disease by functional studies and angiography. After stringent risk factor modification, including aggressive statin therapy to achieve LDL-cholesterol lowering conforming to N.C.E.P. ATP III guidelines, serial CT scans were performed 1-12 years apart for changes in coronary artery calcification (CAC), using the Agatston Score (AS) for quantification. At baseline, the mean AS was 1413.6 for males (mean age 54.4 years) and 2293.3 for females (mean age 62.4 years). The average increase of AS in the entire study population was 24% per year, contrasting with 16.4% per year on strict risk factor modification plus statin therapy, as opposed to 33.2% per year for historical control patients (p < 0.001). Additionally, 20.4% of the 113 patients demonstrated decreasing calcium scores. Medical therapy also yielded a remarkably low adverse event rate during the follow-up period --- 2 deaths, 2 strokes and only 1 case requiring PCI. This study revealed that aggressive medical therapy can positively influence coronary plaque aiding in serial regression of calcium scores.

Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

PubMed Central

Gill, Erin E; Franco, Octavio L; Hancock, Robert E W

2015-01-01

The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era. PMID:25393203

Need for "counter-detailing" antibiotics.

PubMed

Hendeles, L

1976-09-01

Selected antibiotic advertisements in medical journals are discussed to illustrate the misleading information that is often disseminated to physicians by the pharmaceutical industry. Laboratory and clinical data are presented to question the validity of selected advertisements which (1) encourage the use of Keflex for severe respiratory infections in children, (2) recommend the use of Keflex for the treatment of bacterial bronchitis, (3) suggest that high tissue penetration is a unique property of Vibramycin, (4) present pooled susceptability data which do not reflect microbial resistance patterns in the patient's hospital, (5) recommend twice-daily administration of Ancef for urinary tract infections but do not clearly state the potential danger of this regimen for other infections, (6) suggest that gentamicin should be given to adults in only two dosage sizes for the treatment of serious Gram-negative infections, and (7) lead the reader to assume that only women need to be treated for Trichomonas infections. It is suggested that as antibiotics are marketed, hospital therapeutics committees should evaluate their advantages and permit formulary additions for only those agents demonstrating increased efficacy, decreased toxicity or decreased cost. Pharmacists who monitor drug therapy can provide information to the physician which will increase his awareness of optimal antibiotic therapy.

Aggressive behaviour in adolescent psychiatric settings: what are risk factors, possible interventions and implications for nursing practice? A literature review.

PubMed

Hage, S; Van Meijel, B; Fluttert, F; Berden, G F M G

2009-09-01

This study was aimed to identify the risk factors of aggressive behaviour in adolescents (1318 years), and to describe available intervention strategies. The findings are evaluated on the basis of their implications for nursing practice. Aggressive behaviour in adolescent psychiatric settings is a neglected research area. The consequences of aggressive behaviour on nurses, other patients and the therapeutic environment can be profound. For the development and implementation of innovative intervention strategies aimed at preventing aggressive behaviour in adolescent psychiatric patients, knowledge of risk factors and evidence-based interventions for aggressive behaviour are of the utmost importance. A systematic search of PubMed, Cinahl, PsychINFO and Cochrane Systematic Reviews (19912007) was employed. The risk factors for aggressive behaviour comprise personal and environmental risk factors. Some risk factors can be influenced by nursing intervention strategies. Available intervention programmes range from interpersonal skills training to massage therapy, parent management training, functional family therapy and multi-systemic therapy. The most effective programmes combine interpersonal skills training with parent management training. No specific nursing intervention programmes were found for dealing with aggressive behaviour in adolescent patients. Nursing staff can assist in achieving a systematic improvement in the treatment outcomes of existing intervention programmes for the prevention of aggression. There is a need for specific nursing intervention programmes to deal with aggressive behaviour in adolescent psychiatric settings.

Application of a Silicone Sheet in Negative-Pressure Wound Therapy to Treat an Abdominal Wall Defect after Necrotizing Fasciitis.

PubMed

Shin, Jin Su; Choi, Hwan Jun

2017-01-01

Necrotizing fasciitis (NF) is an aggressive soft-tissue infection involving the deep fascia and is characterized by extensive deterioration of the surrounding tissue. Immediate diagnosis and intensive treatment, including debridement and systemic antibiotics, represent the most important factors influencing the survival of NF patients. In this report, we present a case of NF in the abdomen due to an infection caused by a perforated small bowel after abdominal liposuction. It was successfully treated using negative-pressure wound therapy, in which a silicone sheet functioned as a barrier between the sponge and internal organs to protect the small bowel.

Antibiotics and bioactive natural products in treatment of methicillin resistant Staphylococcus aureus: A brief review

PubMed Central

Kali, Arunava

2015-01-01

Infections caused by Staphylococcus aureus strains with Methicillin resistance are associated with increased mortality and morbidity, aggressive course, multiple drug resistance and hospital outbreaks. Several first and second line antibiotics are rapidly becoming ineffective for treatment due to emergence of resistance. Extracts of medicinal plants are rich source of unique phytochemicals. Plants used in traditional medicine have been reported to have significant anti-MRSA activity. The objective of this review is to provide a brief overview of antibiotics as well as anti-MRSA natural products and their future prospect. PMID:26009690

Antibiotics and bioactive natural products in treatment of methicillin resistant Staphylococcus aureus: A brief review.

PubMed

Kali, Arunava

2015-01-01

Infections caused by Staphylococcus aureus strains with Methicillin resistance are associated with increased mortality and morbidity, aggressive course, multiple drug resistance and hospital outbreaks. Several first and second line antibiotics are rapidly becoming ineffective for treatment due to emergence of resistance. Extracts of medicinal plants are rich source of unique phytochemicals. Plants used in traditional medicine have been reported to have significant anti-MRSA activity. The objective of this review is to provide a brief overview of antibiotics as well as anti-MRSA natural products and their future prospect.

Nonuremic calciphylaxis precipitated by teriparatide [rhPTH(1-34)] therapy in the setting of chronic warfarin and glucocorticoid treatment.

PubMed

Spanakis, E K; Sellmeyer, D E

2014-04-01

Calciphylaxis occurs rarely in the absence of end stage renal disease. Predisposing factors for nonuremic calciphylaxis (NUC) include hyperparathyroidism, coagulopathies, connective tissue disease, liver disease, glucocorticoid use, and malignancy. Warfarin can facilitate vascular calcification by reducing vitamin K-dependent carboxylation of matrix-Gla proteins. An 86-year-old Caucasian woman with a history of polymyalgia rheumatica, two spontaneous deep venous thromboses (DVTs) and multiple fractures was treated with calcium, vitamin D, prednisone, and warfarin. The patient's low bone density was treated initially with estrogen, then oral bisphosphonate, which was discontinued due to upper gastrointestinal symptoms. Nasal calcitonin was initiated. After 10 years of calcitonin treatment, she was changed to teriparatide. Two months after initiating teriparatide, she developed lower extremity edema and painful erythematous nodular lesions on her calves bilaterally, that progressed to necrotic ulcers despite antibiotic therapy. Biopsy of the lesions showed calcification in the media of small blood vessels and subcutaneous fat with fat necrosis, consistent with calciphylaxis. Teriparatide was discontinued. Aggressive wound care, antibiotics, and intravenous zoledronic acid were initiated. With cessation of teriparatide therapy and intensive wound care, the patient's lesions resolved over 8 months. We report the first case of NUC precipitated by teriparatide therapy. Our patient had multiple underlying predisposing factors including a connective tissue disorder, glucocorticoid therapy, warfarin use, and possible underlying coagulopathy given her history of multiple DVTs. In such patients, alternative osteoporosis therapies may be preferred.

Bacteriuria and antibiotic resistance in catheter urine specimens following radical prostatectomy.

PubMed

Banks, Jessica A; McGuire, Barry B; Loeb, Stacy; Shrestha, Sanjina; Helfand, Brian T; Catalona, William J

2013-10-01

There are increasing reports of infectious complications following prostate biopsy due to fluoroquinolone resistance. To determine infectious complications at catheter removal following radical prostatectomy (RP), another setting in daily urological practice where fluoroquinolone prophylaxis is frequently used. We prospectively examined urine culture results collected from 334 RP patients immediately prior to catheter removal. Patients received prophylactic antibiotics 1 day before, the day of, and for 5 days after catheter removal. Culture results were reviewed for bacterial species and antimicrobial susceptibilities. Patients with positive urine cultures resistant to the prophylactic antibiotic were switched to culture-specific antibiotic therapy and underwent follow-up culture. The frequency of urinary tract infection (UTI), complications, additional antibiotic therapy, and repeat urine cultures was determined within 60 days. Of the 334 patients identified, 203 (61%) had cultures with no bacterial growth, and 48 (14%) had colony counts of <1,000 bacteria or Candida albicans and received no further antibiotics. The remaining 83 (25%) had positive culture results, of which 7% were resistant to ciprofloxacin. Twenty-four bacterial species were identified, with Pseudomonas aeruginosa (5%) Escherichia coli (4%), and Staphylococcus epidermidis (3%) being the most frequent. Only two (0.6%) men developed clinical symptoms consistent with UTI (i.e., suprapubic pain, fever) prior to catheter removal, and no serious complications occurred. A substantial proportion of RP patients have positive urine cultures at the time of catheter removal, despite the administration of prophylactic fluoroquinolone antibiotics. Potentially virulent organisms are commonly cultured, and ciprofloxacin resistance is frequent. However, outcomes are favorable when culture-specific oral antibiotic therapy is initiated. Copyright © 2013 Elsevier Inc. All rights reserved.

Parents’ Aggressive Influences and Children's Aggressive Problem Solutions with Peers

PubMed Central

Duman, Sarah; Margolin, Gayla

2009-01-01

This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents’ responses to similar hypothetical social scenarios and parents’ actual marital aggression. The study included 118 9−10 year old children, and their mothers and fathers. Children's aggressive solutions correlated with same-sex parents’ actual marital aggression. For children with mothers who exhibit low actual marital aggression, mothers’ aggressive solutions to hypothetical situations corresponded with children's tendencies to propose aggressive but not assertive solutions. In a 3-way interaction, fathers’ aggressive solutions to peer scenarios and marital aggression, combined, exacerbated girls’ aggressive problem solving, but had the opposite effect for boys. Discussion addresses the complexity, particularly with respect to parent and child gender combinations, in understanding parents’ aggressive influences on children's peer relationships. PMID:17206880

Resistance Elasticity of Antibiotic Demand in Intensive Care.

PubMed

Heister, Thomas; Hagist, Christian; Kaier, Klaus

2017-07-01

The emergence and spread of antimicrobial resistance (AMR) is still an unresolved problem worldwide. In intensive care units (ICUs), first-line antibiotic therapy is highly standardized and widely empiric while treatment failure because of AMR often has severe consequences. Simultaneously, there is a limited number of reserve antibiotics, whose prices and/or side effects are substantially higher than first-line therapy. This paper explores the implications of resistance-induced substitution effects in ICUs. The extent of such substitution effects is shown in a dynamic fixed effect regression analysis using a panel of 66 German ICUs with monthly antibiotic use and resistance data between 2001 and 2012. Our findings support the hypothesis that demand for reserve antibiotics substantially increases when resistance towards first-line agents rises. For some analyses the lagged effect of resistance is also significant, supporting the conjecture that part of the substitution effect is caused by physicians changing antibiotic choices in empiric treatment by adapting their resistance expectation to new information on resistance prevalence. The available information about resistance rates allows physicians to efficiently balance the trade-off between exacerbating resistance and ensuring treatment success. However, resistance-induced substitution effects are not free of charge. These effects should be considered an indirect burden of AMR. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Pattern of Antibiotic Prescribing by Dental Practitioners in Zagreb, Croatia.

PubMed

Perić, Marina; Perković, Ivana; Romić, Martina; Simeon, Paris; Matijević, Jurica; Mehičić, Goranka Prpić; Krmek, Silvana Jukić

2015-06-01

Bacterial resistance is considered a consequence of misuse or overuse of antibiotics. Dentistry significantly contributes to this increasing public health problem. The aim of this cross-sectional study was to examine the pattern of antibiotics prescribed by Croatian dentists in Zagreb area. Out of 220 Doctors of Dental Medicine (DMDs) from Zagreb 110 responded to survey. Prior to the research an ethical approval was obtained. Participants were directly contacted. The questionnaire consisted of two parts: general data on DMDs and the part concerning indications, duration, type and dosage of antibiotic therapy. Data were processed using MS Excel and SPSS for Windows, Version 17.0. Statistical significance was tested by Fisher's exact test, chi-square test, Mann-Whitney U test and Spearman's rank correlation at the level of statistical significance p<0.05. During the period of two months, the doctors prescribed antibiotics to 1,500 patients, 690 (46%) were men and 810 (54%) women. The most often prescribed antibiotics were penicillin (72.5% of patients), represented mostly by amoxicillin in combination with clavulanic acid (57.6%). The most common indication for the prescribed antibiotics was periapical or periodontal abscess (44%). Definite clinical indication (71.2%) was stated as the most common reason for antibiotic prescription. Antibiotic therapy usually lasted 7 days (62.9%). The doctors prescribed daily doses of antibiotics according to the instructions for the use of specific drugs. The examined subjects prescribe antibiotics according to the curriculum taught at the School of Dental Medicine for majority of types, doses and duration of the treatments, although antibiotics over-prescription in cases without medical indication was observed. The national guidelines on antibiotic regimens are required in order to reduce unnecessary antibiotic use. Copyright© by the National Institute of Public Health, Prague 2015.

Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

PubMed

Greimel, Felix; Scheuerer, Christine; Gessner, Andre; Simon, Michaela; Kalteis, Thomas; Grifka, Joachim; Benditz, Achim; Springorum, Hans-Robert; Schaumburger, Jens

2017-01-01

The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus , whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.

ANTIBIOTIC THERAPY OF ABSCESS OF THE LUNG AND BRONCHIECTASIS

PubMed Central

Hewitt, William L.

1952-01-01

Since the fusospirochetal group of bacteria are the commonest etiologic agents in abscess of the lung, aqueous crystalline penicillin is the agent of first choice in the majority of cases. Streptomycin is indicated for a small group of cases in which Klebsiella is the etiologic agent. Aureomycin, chloramphenicol or terramycin may produce an excellent therapeutic response either initially or after therapeutic failure with penicillin. Administration of antibiotics by inhalation should be carried out in conjunction with systemic forms of treatment. In the treatment of bronchiectasis, the antibiotics are most useful in the control of acute exacerbations of pulmonary infection which punctuate the course of this disease. PMID:14935877

Role of antibiotics for treatment of inflammatory bowel disease.

PubMed

Nitzan, Orna; Elias, Mazen; Peretz, Avi; Saliba, Walid

2016-01-21

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms

Initial therapy of mantle cell lymphoma

PubMed Central

Witzig, Thomas E.

2011-01-01

Mantle cell lymphoma is a well-recognized distinct clinicopathologic subtype of B-cell non-Hodgkin lymphoma. The current World Health Organization (WHO) classification subdivides this entity into aggressive and other variants. The disease has a predilection for older males, and patients typically present at an advanced stage with frequent splenomegaly and extranodal involvement including bone marrow, peripheral blood, gastrointestinal, and occasional central nervous system involvement. Early studies of therapy outcomes in this disease revealed that while response rates where high, relapse was expected after a limited period of time. Prolonged survival was uncommon, with initial median survival rates typically in the 3–4-year range. Those with a high proliferative rate, blastoid morphology, and selected clinical features were recognized as having a worse prognosis. Therapeutic approaches have diverged into aggressive therapies with high response rates and promising progression free survival rates, which may be applied to younger healthy patients, and less aggressive approaches. Aggressive therapies include intensive chemotherapy alone or chemotherapy followed by autologous stem cell transplant, which has been shown to be most effective when applied in first remission. Whether these more intense therapies result in improved survival as compared with less aggressive therapies is not well established. Allogeneic transplant has also been investigated, although high treatment-related mortality and the risk of chronic graft versus host disease and the relatively advanced age of this patient population have tempered enthusiasm for this approach. A number of less aggressive therapies have been shown to produce promising results. Consolidation and maintenance strategies are an active area of investigation. A number of newer agents have shown promising activity in relapsed disease, and are being investigated in the front-line setting. Overall survival rates are improving in

[Alliance against MDRO: safeguarding antibiotics].

PubMed

Carlet, J; Rambaud, C; Pulcini, C

2012-09-01

Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the 5 next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practitioners, and veterinarians. Copyright © 2012 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Orthodontic Management in Aggressive Periodontitis

PubMed Central

Bhattarai, Bhagabat

2017-01-01

Aggressive periodontitis is a type of periodontitis with early onset and rapid progression and mostly affecting young adults who occupy a large percentage of orthodontic patients. The role of the orthodontist is important in screening the disease, making a provisional diagnosis, and referring it to a periodontist for immediate treatment. The orthodontist should be aware of the disease not only before starting the appliance therapy, but also during and after the active mechanotherapy. The orthodontic treatment plan, biomechanics, and appliance system may need to be modified to deal with the teeth having reduced periodontal support. With proper force application and oral hygiene maintenance, orthodontic tooth movement is possible without any deleterious effect in the tooth with reduced bone support. With proper motivation and interdisciplinary approach, orthodontic treatment is possible in patients with controlled aggressive periodontitis. PMID:28299350

A procalcitonin-based algorithm to guide antibiotic therapy in secondary peritonitis following emergency surgery: a prospective study with propensity score matching analysis.

PubMed

Huang, Ting-Shuo; Huang, Shie-Shian; Shyu, Yu-Chiau; Lee, Chun-Hui; Jwo, Shyh-Chuan; Chen, Pei-Jer; Chen, Huang-Yang

2014-01-01

Procalcitonin (PCT)-based algorithms have been used to guide antibiotic therapy in several clinical settings. However, evidence supporting PCT-based algorithms for secondary peritonitis after emergency surgery is scanty. In this study, we aimed to investigate whether a PCT-based algorithm could safely reduce antibiotic exposure in this population. From April 2012 to March 2013, patients that had secondary peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. PCT levels were obtained pre-operatively, on post-operative days 1, 3, 5, and 7, and on subsequent days if needed. Antibiotics were discontinued if PCT was <1.0 ng/mL or decreased by 80% versus day 1, with resolution of clinical signs. Primary endpoints were time to discontinuation of intravenous antibiotics for the first episode and adverse events. Historical controls were retrieved for propensity score matching. After matching, 30 patients in the PCT group and 60 in the control were included for analysis. The median duration of antibiotic exposure in PCT group was 3.4 days (interquartile range [IQR] 2.2 days), while 6.1 days (IQR 3.2 days) in control (p < 0.001). The PCT algorithm significantly improves time to antibiotic discontinuation (p < 0.001, log-rank test). The rates of adverse events were comparable between 2 groups. Multivariate-adjusted extended Cox model demonstrated that the PCT-based algorithm was significantly associated with a 87% reduction in hazard of antibiotic exposure within 7 days (hazard ratio [HR] 0.13, 95% CI 0.07-0.21, p < 0.001), and a 68% reduction in hazard after 7 days (adjusted HR 0.32, 95% CI 0.11-0.99, p  =  0.047). Advanced age, coexisting pulmonary diseases, and higher severity of illness were significantly associated with longer durations of antibiotic use. The PCT-based algorithm safely reduces antibiotic exposure in this study. Further randomized trials are needed to confirm our findings and incorporate cost

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.

PubMed

Nelson, R

2007-07-18

Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis. The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy. MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial". Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death. Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView. Twelve studies (total of 1157 participants) involving patients with diarrhea who recently received antibiotics for an infection other than C. difficile were included. The definition of diarrhea ranged from at least two loose stools

Adolescents’ Aggression to Parents: Longitudinal Links with Parents’ Physical Aggression

PubMed Central

Margolin, Gayla; Baucom, Brian R.

2014-01-01

Purpose To investigate whether parents’ previous physical aggression (PPA) exhibited during early adolescence is associated with adolescents’ subsequent parent-directed aggression even beyond parents’ concurrent physical aggression (CPA); to investigate whether adolescents’ emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. Methods Adolescents (N = 93) and their parents participated in a prospective, longitudinal study. Adolescents and parents reported at waves 1–3 on four types of parents’ PPA (mother-to-adolescent, father-to-adolescent, mother-to-father, father-to-mother). Wave 3 assessments also included adolescents’ emotion dysregulation, attitudes condoning aggression, and externalizing behaviors. At waves 4 and 5, adolescents and parents reported on adolescents’ parent-directed physical aggression, property damage, and verbal aggression, and on parents’ CPA Results Parents’ PPA emerged as a significant indicator of adolescents’ parent-directed physical aggression (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.0–1.55; p = .047), property damage (OR: 1.29, 95% CI: 1.1–1.5, p = .002), and verbal aggression (OR: 1.35, 95% CI: 1.15–1.6, p < .001) even controlling for adolescents’ sex, externalizing behaviors, and family income. When controlling for parents’ CPA, previous mother-to-adolescent aggression still predicted adolescents’ parent-directed physical aggression (OR: 5.56, 95% CI: 1.82–17.0, p = .003), and father-to-mother aggression predicted adolescents’ parent-directed verbal aggression (OR: 1.86, 95% CI: 1.0–3.3, p = .036). Emotion dysregulation and attitudes condoning aggression did not produce direct or moderated effects. Conclusions Adolescents’ parent-directed aggression deserves greater attention in discourse about lasting, adverse effects of even minor forms of parents’ physical aggression. Future research should investigate parent-directed aggression as

Role of outpatient parenteral antibiotic therapy in the treatment of community acquired skin and soft tissue infections in Singapore.

PubMed

Chan, Monica; Ooi, Chee Kheong; Wong, Joshua; Zhong, Lihua; Lye, David

2017-07-06

Treatment of community acquired skin and soft tissue infections (SSTIs) is a common indication for outpatient parenteral antibiotic therapy (OPAT) in USA, UK and Australasia, however data from Asia are lacking. OPAT is well established within the Singapore healthcare since 2002, however, systematic use of OPAT for the treatment of SSTIs remains infrequent. In this report, we describe the treatment and outcome of patients with SSTIs referred directly from Emergency Department (ED) to OPAT for continuation of intravenous (IV) antibiotics in Singapore, thus avoiding potential hospital admission. This is a single center university hospital retrospective study of patients with SSTIs presenting to ED who were assessed to require IV antibiotics and accepted to the OPAT clinic for continuation of IV treatment. Exclusion criteria were: haemodynamic instability, uncontrolled or serious underlying co-morbidities, necessity for inpatient surgical drainage, facial cellulitis and cephalosporin allergy. Patients returned daily to the hospital’s OPAT clinic for administration of IV antibiotics and review, then switched to oral antibiotics on improvement. From 7 February 2012 to 31 July 2015, 120 patients with SSTIs were treated in OPAT. Median age was 56 years and 63% were male. Lower limbs were affected in 91%. Diabetes was present in 20%. Sixty-seven (56%) had been treated with oral antibiotics for a median duration of 3 days prior to OPAT treatment. Common symptoms were erythema (100%), swelling (96%), pain (88%) and fever (55%). Antibiotics administered were IV cefazolin with oral probenecid (71%) or IV ceftriaxone (29%) for median 3 days then oral cloxacillin (85%) for median 7 days. Clinical improvement occurred in 90%. Twelve patients (10%) were hospitalized for worsening cellulitis, with 4 patients requiring surgical drainage of abscess. Microbiological cultures from 2 patients with drained abscess grew methicillin sensitive Staphylococcus aureus (MSSA) and Klebsiella

Osmotic therapies added to antibiotics for acute bacterial meningitis.

PubMed

Wall, Emma Cb; Ajdukiewicz, Katherine Mb; Bergman, Hanna; Heyderman, Robert S; Garner, Paul

2018-02-06

Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013. To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability. We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015). Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence. We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0

Procalcitonin Testing to Guide Antibiotic Therapy in Acute Upper and Lower Respiratory Tract Infections.

PubMed

Schuetz, Philipp; Wirz, Yannick; Mueller, Beat

2018-03-06

Is the use of procalcitonin for guiding antibiotic decisions in patients with acute upper and lower respiratory tract infections associated with improved clinical outcomes compared with usual care? Among patients with varying types and severity of acute respiratory infection, using procalcitonin to guide decisions about antibiotics is associated with lower rates of antibiotic exposure, antibiotic-related adverse effects, and mortality.

Evaluation of the effects of colostrum replacer supplementation of the milk replacer ration on the occurrence of disease, antibiotic therapy, and performance of pre-weaned dairy calves.

PubMed

Chamorro, Manuel F; Cernicchiaro, Natalia; Haines, Deborah M

2017-02-01

The objective of this study was to evaluate the effects of colostrum supplementation of the milk replacer ration on disease occurrence, antibiotic therapy, and performance of pre-weaned dairy calves with adequate transfer of passive immunity. Two hundred and two 1-d-old Holstein dairy calves were assigned to 1 of 2 groups after arrival to a dairy calf rearing facility. Calves assigned to the control group (n = 100) received milk replacer (28% crude protein and 20% crude fat) without colostrum inclusion twice daily. Calves assigned to the treatment group (n = 102) received 150 g of supplemental colostrum replacer powder added to their milk replacer twice daily for the first 14 d of life. Before group assignment, serum samples were collected from all calves to confirm transfer of passive immunity. Calves were evaluated daily until weaning (56 d of life) for signs of clinical disease as well as any treatment with antibiotics. Presentation of clinical disease and antibiotic treatment was recorded daily by personnel blinded to treatment allocation. Adequate transfer of passive immunity was confirmed in all calves at the start of the study and mean serum IgG values were similar among calves from treatment and control groups. The odds ratios of having abnormal feces and abnormal respiration during the pre-weaning period for calves from the treatment group were 0.15 and 0.46 the odds ratios of calves from the control group, respectively. The odds ratios of receiving antibiotic therapy during the pre-weaning period for calves from the treatment group were 0.09 the odds ratios of calves from the control group. Mean body weight and average daily gain at weaning were not significantly different among calves from the treatment and control groups. Colostrum replacer supplementation of the milk replacer ration was effective in reducing antibiotic therapy and occurrence of disease during the pre-weaning period. Copyright © 2017 American Dairy Science Association. Published by

Antibiotic Resistance and the Biology of History.

PubMed

Landecker, Hannah

2016-12-01

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as 'the biology of history': the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today.

Antibiotic Resistance and the Biology of History

PubMed Central

2015-01-01

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as ‘the biology of history’: the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today. PMID:28458609

Optimal use of modern antibiotics: emerging trends.

PubMed

Polk, R

1999-08-01

Development of new antimicrobial drugs is an essential component in the effort to remain ahead of emerging microbial resistance. However, when new antibiotics are used with unrestrained enthusiasm, a predictable consequence is the further expansion of resistance. This problem is well known to the infectious diseases specialist and is increasingly appreciated by the nonspecialist and the public. A far more sensible strategy is to identify new ways to use these drugs to increase the duration of their usefulness. New methods to optimize antibiotic selection, dose, and duration of therapy are being investigated, and application of some of these strategies has been shown to have a favorable impact on resistance. Much of the classic thinking of how to use antibiotics is changing, and these newer strategies may result in prolongation of the era of the "antibiotic miracle."

[Perspective applications of multi-species probiotics in the prevention of antibiotic-associated diarrhea].

PubMed

Uspenskiĭ, Iu P; Zakharenko, S M; Fominykh, Iu A

2013-01-01

The problem of antibiotic-associated conditions is one of the most actual problems of clinical practice. The antibiotic-associated diarrhea is a multidisciplinary problem. Investigations of the small intestine microecological status and assessment of microflora at the patients receiving antibiotics testifies to dysbiosis existence. In article results of open-label investigation of a multispecies probiotic RioFlora Balance using for antibiotic-associated diarrhea prophylaxis in patients used antibacterial therapy are presented.

Antibiotic Use in Small Community Hospitals.

PubMed

Stenehjem, Edward; Hersh, Adam L; Sheng, Xiaoming; Jones, Peter; Buckel, Whitney R; Lloyd, James F; Howe, Stephen; Evans, R Scott; Greene, Tom; Pavia, Andrew T

2016-11-15

 Antibiotic use and misuse is driving drug resistance. Much of US healthcare takes place in small community hospitals (SCHs); 70% of all US hospitals have <200 beds. Antibiotic use in SCHs is poorly described. We evaluated antibiotic use using data from the National Healthcare and Safety Network antimicrobial use option from the Centers for Disease Control and Prevention.  We used Intermountain Healthcare's monthly antibiotic use reports for 19 hospitals from 2011 to 2013. Hospital care units were categorized as intensive care, medical/surgical, pediatric, or miscellaneous. Antibiotics were categorized based on spectrum of coverage. Antibiotic use rates, expressed as days of therapy per 1000 patient-days (DOT/1000PD), were calculated for each SCH and compared with rates in large community hospitals (LCHs). Negative-binomial regression was used to relate antibiotic use to predictor variables.  Total antibiotic use rates varied widely across the 15 SCHs (median, 436 DOT/1000PD; range, 134-671 DOT/1000PD) and were similar to rates in 4 LCHs (509 DOT/1000PD; 406-597 DOT/1000PD). The proportion of patient-days spent in the respective unit types varied substantially within SCHs and had a large impact on facility-level rates. Broad-spectrum antibiotics accounted for 26% of use in SCHs (range, 8%-36%), similar to the proportion in LCHs (32%; range, 26%-37%). Case mix index, proportion of patient-days in specific unit types, and season were significant predictors of antibiotic use.  There is substantial variation in patterns of antibiotic use among SCHs. Overall usage in SCHs is similar to usage in LCHs. Small hospitals need to become a focus of stewardship efforts. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Prophylactic antibiotics in acute pancreatitis: endless debate.

PubMed

Mourad, M M; Evans, Rpt; Kalidindi, V; Navaratnam, R; Dvorkin, L; Bramhall, S R

2017-02-01

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.