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Cefuroxime Axetil tablet  

Center for Drug Evaluation (CDER)

Text Version... Contains Nonbinding Recommendations Draft Guidance on Cefuroxime Axetil ... Active ingredient: Cefuroxime Axetil Form/Route: Tablet/Oral ... More results from


Cefuroxime induced lymphomatoid hypersensitivity reaction  

PubMed Central

An 84 year old women developed erythematous blotchy erythema and purpuric rashes over the lower limbs three days after being started on intravenous cefuroxime for acute diverticulitis. A skin biopsy specimen showed a mixed infiltrate of lymphoid cells and eosinophils; many of the lymphocytes were large, pleomorphic, and showed a raised mitotic rate. Immunohistochemistry showed the infiltrate to be T cell rich, with all the large cells being CD30 positive. Typical mycosis fungoides cells, marked epidermotropism, and Pautrier's abscesses were not seen. The rash disappeared 10 days after cessation of cefuroxime and the patient remained asymptomatic 15 months later. This apparent cutaneous T cell lymphoma-like reaction is best described as lymphomatoid vascular reaction. The drug induced immune response with an atypical cutaneous lymphoid infiltrate mimics a cutaneous pseudolymphoma.???Keywords: cefuroxime; atypical cutaneous lymphomatoid infiltrate; cutaneous T cell lymphoma

Saeed, S; Bazza, M; Zaman, M; Ryatt, K



Pharmacokinetics and tissue concentrations of cefuroxime  

Microsoft Academic Search

Cefuroxime is well-absorbed and distributed over the human body. This review gives a general summary of published information on tissue concentrations of cefuroxime after an intravenous or intramuscular dose of 750 or 1,500 mg of cefuroxime. Tissue concentrations are given for blister fluid, meninges, eyes, respiratory tract, sputum and bronchi, abdominal and urogenital tract, uterine, ovarian and fallopian tube tissue,

T. B. Vree; Y. A. Hekster



Determination of cefuroxime axetil in tablets and biological fluids using liquid chromatography and flow injection analysis  

Microsoft Academic Search

Cefuroxime axetil is the pro-drug of cephalosporin cefuroxime that is used in the treatment of common community-acquired infections. A simple and precise liquid chromatographic method for the determination of cefuroxime axetil in pharmaceutical tablets, human serum and urine has been developed and validated. Cefuroxime axetil and indapamide (internal standard) were separated by a reversed phase column (Supelco Hypersil 5?m, 150mm×4.6mm

Nafiz Ö. Can; Göksel Altiokka; Hassan Y. Aboul-Enein



Randomized comparison of aztreonam and cefuroxime in gram-negative upper urinary tract infections  

Microsoft Academic Search

Summary In order to evaluate the efficacy and safety of aztreonam in hospitalized patients with upper urinary tract infections (UTI), a comparative clinical study with cefuroxime was performed. 62\\/60% (aztreonam\\/cefuroxime) of the patients had a complicating factor, mostly obstructive uropathy. I.v. bolus injections were used at a dose of 1 g aztreonam or 1.5 g cefuroxime t.i.d., for a mean

G. Friman; O. Cars; I. Odenholt-Tornqvist; C. Rydén; E. Bäck; H. Fredlund; H. Beckman; R. Neringer; M. Carlsson; J. Forssell; R. Svensson



Preparation, quality control and stability of 99m Tc-cefuroxime axetil  

Microsoft Academic Search

Cefuroxime axetil, a cephalosporin antibiotic used to treat bacterial infections, was investigated to label with 99mTc. Radiolabeling of cefuroxime axetil was carried out by using stannous chloride method. Effects of pH and stannous chloride\\u000a amount on the radiolabeling yield were investigated. The radiochemical purity of 99mTc-cefuroxime axetil was determined by thin layer radio chromatography (TLRC), electrophoresis and high performance liquid

F. Yurt Lambrecht; K. Durkan; P. Unak



Stability of cefuroxime following gamma-irradiation in the solid state  

NASA Astrophysics Data System (ADS)

The effect of ?-irradiation on cefuroxime, a member of the second generation of cephalosporins, has been assessed by different spectroscopic, HPLC, chemical and microbiological analytical methods. According to the results obtained, the chemical changes in irradiated cefuroxime have relatively low yield. The microbiological assay carried out using B. subtilis test strain reveal that the activity of irradiated cefuroxime did not decrease even for radiation doses as high as 85 kGy. The remarkable radiation stability of cefuroxime irradiated in the solid state supports its suitability for radiation sterilization.

Zegota, Henryk; Koprowski, Marek; Zegota, Alicja



Measurements of cefuroxime concentration in bone in dogs and man.  


Measurements of Cefuroxime levels performed in dogs show a decrease against time in well perfused tissue similar to that in serum, while in bradytrophic tissue--such as bone and articular capsule--there is a distinct rise of these values in the time scale assessed. In similar investigations in man the higher levels in bradytrophic tissue are attributable to delayed elimination from the compact and spongy bone as compared to the serum. The effect on osteomyelitis, to be derived from this, is discussed. PMID:485788

Jung, H H; Mischkowsky, T



Comparative Study of the In Vitro Antibacterial Activity of Cefoxitin, Cefuroxime, and Cephaloridine  

PubMed Central

The in vitro antibacterial effects of cefoxitin, a semisynthetic cephamycin, cefuroxime, a new cephalosporin antibiotic, and cephaloridine were compared. With gram-positive bacteria, marked differences were found only in the effects against Streptococcus faecalis, where cephaloridine and cefuroxime were superior to cefoxitin. With gram-negative aerobic bacteria, cefoxitin, which is known to be more resistant to beta-lactamases from gram-negative bacteria than any cephalosporin, was found to be more effective than cefuroxime and cephaloridine against ampicillin-resistant strains of Escherichia coli and indole-positive strains of Proteus. Haemophilus influenzae was found to be more susceptible to cefuroxime than to cefoxitin and cephaloridine. When ampicillin-resistant strains of H. influenzae were tested, markedly higher minimal inhibitory concentration values were obtained with cephaloridine in comparison to those obtained with ampicillin-susceptible strains. These increases in the minimal inhibitory concentration values were not observed with cefoxitin and cefuroxime, probably due to the resistance of these two compounds to beta-lactamases. Strains of Bacteroides fragilis were found to be much more susceptible to cefoxitin than to cefuroxime, which in turn was superior to cephaloridine. The results obtained indicate that cefoxitin and cefuroxime both are superior in their antibacterial spectra to the cephalosporins that are now in clinical use.

Norrby, Ragnar; Brorsson, John-Erik; Seeberg, Staffan



Meropenem versus Cefuroxime plus Gentamicin for Treatment of Serious Infections in Elderly Patients  

PubMed Central

In this multicenter study, the efficacy of and tolerability for meropenem were compared with those for the combination of cefuroxime-gentamicin (±metronidazole) for the treatment of serious bacterial infections in patients ?65 years of age. A total of 79 patients were randomized; thirty-nine received meropenem (1 g/8 h), and 40 received cefuroxime (1.5 g/8 h) plus gentamicin (4 mg/kg of body weight daily) for 5 to 10 days. Metronidazole (500 mg/6 h) could be added to the cefuroxime-gentamicin regimen for the treatment of intra-abdominal infections (n = 10). Seventy patients were evaluable for clinical efficacy; the primary diagnoses were as follows: pneumonia in 41 patients (20 treated with meropenem, 21 treated with cefuroxime-gentamicin), intra-abdominal infection in 10 patients (7 meropenem, 3 cefuroxime-gentamicin-metronidazole), urinary tract infection (UTI) in 11 patients (6 meropenem, 5 cefuroxime-gentamicin), sepsis syndrome in 7 patients (4 meropenem, 3 cefuroxime-gentamicin), and “other” in 1 patient (cefuroxime-gentamicin). The pathogens isolated from 18 patients with bacteremia were as follows: Staphylococcus spp. (n = 2), Streptococcus spp. (n = 2), members of the family Enterobacteriaceae (n = 11), and Bacteroides spp. (n = 3). A satisfactory clinical response at the end of therapy was achieved in 26 of 37 (70%) and 24 of 33 (73%) evaluable patients treated with meropenem and combination therapy, respectively. Clinical success was achieved in 23 of 31 (74%) and 21 of 28 (75%) evaluable patients with infections other than UTIs, respectively. A satisfactory microbiological response occurred in 15 of 22 (68%) patients in the meropenem group compared with 12 of 19 (63%) treated with combination therapy. Renal failure occurred during therapy in 2 of 39 (5%) meropenem recipients compared with 5 of 40 (13%) of those treated with combination therapy. The findings in this small study indicate that meropenem is as efficacious for and as well tolerated by elderly patients as the combination of cefuroxime-gentamicin (±metronidazole).

Jaspers, C. A. J. J.; Kieft, H.; Speelberg, B.; Buiting, A.; van Marwijk Kooij, M.; Ruys, G. J. H. M.; Vincent, H. H.; Vermeulen, M. C. A.; Olink, A. G.; Hoepelman, I. M.



[Antibiotic prophylaxis in cardiovascular surgery: comparison of sulbactam-ampicillin and cefuroxime].  


A total of 200 patients (131 males and 69 females), scheduled for cardiovascular surgery were randomly assigned to receive either sulbactam/ampicillin 1 g IV of cefuroxime 2 g IV before the surgical incision and then, postoperatively, 8-hourly x 3 days. There were five failure of prophylaxis (all in the cefuroxime group): 3 sternal incision abscesses (1 Pseudomonas aeruginosa and 2 Staphylococcus epidermidis), one urinary tract infection (Staphylococcus aureus) and one Micrococcus pneumoniae. Tolerance to both antibiotics was excellent. In our sample of patients, the efficacy and safety of sulbactam/ampicillin were not different from those of cefuroxime in prophylaxis in cardiovascular surgery. PMID:8159835

Girotto, M; Comoglio, C; Donegani, E; Di Summa, M


Unexpected death due to cefuroxime-induced disulfiram-like reaction  

PubMed Central

Cefuoxime, a second-generation cephalosporin, is used in the treatment of Gram-positive infections. Here, we report a case cefuroxime-induced disulfiram-like reaction which led to sudden death of the patient.

Dong, Hongmei; Zhang, Ji; Ren, Liang; Liu, Qian; Zhu, Shaohua



Comparative clinical efficacy of single oral doses of cefuroxime axetil and amoxicillin in uncomplicated gonococcal infections.  


Cefuroxime axetil (1.5 g) was compared with amoxicillin (3 g), both given as a single oral dose combined with probenecid (1 g) for the treatment of uncomplicated gonorrhea. Of 60 evaluable patients receiving amoxicillin, 55 (91.7%) were cured, whereas 55 (96.5%) of the 57 patients receiving cefuroxime axetil were cured (P greater than 0.1). Both drugs were well tolerated. PMID:3094443

Fong, I W; Linton, W; Simbul, M; Hinton, N A



Penetration of cefetamet pivoxil and cefuroxime axetil into the maxillary sinus mucosa at steady state.  

PubMed Central

The penetration of cefetamet and cefuroxime into the maxillary sinus mucosa after the administration of cefetamet pivoxil and cefuroxime axetil was investigated in patients undergoing elective surgery of the maxillary sinus. A total of 27 patients, 13 for cefetamet pivoxil and 14 for cefuroxime axetil, ranging from 15 to 70 years of age participated in this study. Each patient received three oral doses of either one tablet of cefetamet pivoxil (500 mg of GLOBOCEF) or two film tablets of cefuroxime axetil (125 and 250 mg of ZINAT) every 12 h. Sinus mucosa tissue samples were removed during surgery at times ranging from 2 to 4.5 h after the last oral administration. Blood samples were collected before drug administration, 2 h after the first and third doses, and concomitantly with tissue sample collection during surgery. All samples were analyzed by high-performance liquid chromatography. The concentrations of cefetamet and cefuroxime in plasma samples measured concomitantly with those in tissue samples ranged between 0.83 and 4.5 micrograms/ml for cefetamet and 0.59 and 3 micrograms/ml for cefuroxime. The mean tissue-to-plasma ratios calculated with reference to total (bound plus unbound) plasma drug concentrations were 0.60 (range, 0.52 to 0.77) for cefetamet (n = 4) and 0.38 (range, 0.28 to 0.44) for cefuroxime (n = 6). Both drugs seem to penetrate freely and easily into the sinus mucosa. The antibacterial activities of cefetamet pivoxil and cefuroxime axetil in cases of sinusitis therefore depend mainly on their achieved active plasma drug concentrations and their intrinsic activities in inhibiting the causative organism(s).

Stoeckel, K; Harell, M; Dan, M



Iontophoresis of amoxicillin and cefuroxime: rapid therapeutic concentrations in skin.  


Abstract Context: Amoxicillin (AMX) and cefuroxime (CFX) are antibiotics used often to treat skin bacterial infections. Typically, high oral doses are required to achieve minimum inhibitory concentration (MIC) at the site of infection that may affect only a very small area of skin. Objectives: To lower side effects and increase therapeutic effectiveness, the percutaneous absorption and retention of AMX and CFX administered by iontophoresis was investigated in a rabbit model by measuring dermis concentrations via microdialysis. Methods: Iontophoresis was performed using a stainless steel electrode and a non-woven polypropylene pad. The cartridge pad was soaked with a solution of AMX in glycerin or of CFX in glycerin/water (60:40). Constant current density of 0, 100, 200 or 300?µA/cm(2) was applied for 60?min. Results: For AMX, therapeutically effective skin concentrations were detected immediately after the application of electrical current for any of the current density tested and remained above it for at least 2?h from the end of iontophoresis. For CFX, skin concentrations rose above MIC only at the higher current densities and fell below the MIC by the end of the experiment. Conclusion: Iontophoresis is a promising method to obtain a fast and sustained concentration of AMX and CFX in skin. PMID:23350692

Mannem, Vamshi; Nanjarapalle, Charan; Stagni, Grazia



HPTLC determination of cefuroxime axetil and ornidazole in combined tablet dosage form.  


A new simple high-performance thin layer chromatographic method for determination of cefuroxime axetil and ornidazole in combined tablet dosage form is developed and validated. Cefuroxime axetil is second-generation cephalosporin used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. Ornidazole is used to cure protozoan infections. The separation is carried out on Merck precoated silica gel aluminium plate 60 F(254) using toluene-n-butanol-triethylamine (8.5:2:0.5, v/v/v) as mobile phase. Quantitative determination of drugs is carried out by densitometric scanning of plates at 285 nm. The retention factor for ornidazole and cefuroxime axetil is found to be 0.51 +/- 0.007 and 0.67 +/- 0.009, respectively. The method is validated with respect to linearity, accuracy, precision, and robustness. Response found to be linear in the concentration range of 100-500 ng/band for both cefuroxime axetil and ornidazole. The method has been successfully applied for the analysis of drugs in pharmaceutical formulation. The % assay is found to be 102.36 +/- 0.775 and 101.00 +/- 1.192 for cefuroxime axetil and ornidazole, respectively. PMID:20056032

Ranjane, Poonam N; Gandhi, Santosh V; Kadukar, Sayali S; Bothara, Kailash G



Sputum and blood concentrations of cefuroxime in lower respiratory tract infection.  

PubMed Central

A detailed pharmacokinetic study of cefuroxime has been carried out. Levels of cefuroxime were determined in the blood, sputum, saliva, and urine of 23 patients receiving parenteral cefuroxime eight hourly for chest infections. Profiles were obtained after the first dose and on the final (fifth) day of treatment. Antibiotic levels in the sputum reached 0.8 mg/l within one hour of the first injection, and were maintained close to this value for six hours. There was a build-up by the fifth day, mean cefuroxime concentrations at this time reaching 1.8 mg/l. This concentration was maintained for a prolonged period. Salivary concentrations were detectable but low (maximum mean value was 0.6 mg/l). Concentrations of antibiotic were significantly higher in the serum than those observed after the same doses in volunteers. In the patients there was no build-up in serum levels between the first and fifth days. The data obtained explain the clinical efficacy of cefuroxime in the treatment of lower respiratory infections, and suggest that a 12-hour schedule may be feasible.

Havard, C W; Bax, R P; Samanta, T C; Pearson, R M; Brumfitt, W; Hamilton-Miller, J M; Dash, C H



Are cefuroxime and vancomycin really safe on the corneal endothelial cells?  

Microsoft Academic Search

Purpose  To investigate the biochemical changes of the oxidant\\/antioxidant balance in corneal tissue, and determine the relative corneal\\u000a endothelial toxicities of the following intracameral antibiotic agents: cefuroxime and vancomycin.\\u000a \\u000a \\u000a \\u000a Methods  The experiment was conducted using New Zealand rabbits. The rabbits were randomly divided into three experimental groups as\\u000a follows: cefuroxime group (n?=?10), vancomycin group (n?=?10), and control group (n?=?10). Only the right

Tök Y. Özlem; Demir M. Necati; Yilmaz M. Fatma; Yilmaz Gülsen; Nurözler B. Ay?e; Örnek Firdevs



Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.  


This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0?t, AUC0??, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0?t, AUC0?? and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent. PMID:21888870

Asiri, Y A; Al-Hadiya, B M; Kadi, A A; Al-Khamis, K I; Mowafy, H A; El-Sayed, Y M



Efficacy of levofloxacin versus cefuroxime in treating acute exacerbations of chronic obstructive pulmonary disease  

PubMed Central

Background Antibiotic treatment is one of the major pharmacologic treatments for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the choice of antibiotic depends on the local resistance pattern. A multicenter, randomized, controlled trial was done in patients with AECOPD to compare the efficacy of levofloxacin with that of cefuroxime axetil. Methods Patients with AECOPD and without radiographic evidence of pneumonia were enrolled and randomized to either levofloxacin 500 mg daily or cefuroxime 250 mg twice daily in the mildmoderate exacerbation group, or 500 mg twice daily in the severe exacerbation group, for seven days. Clinical efficacy and microbiologic response were evaluated 5–7 days after the last dose. Results Treatment was clinically successful in 90.4% of patients in the levofloxacin group, and in 90.6% of patients in the cefuroxime group (95% confidence interval ?9.40 to 10.91), within a noninferiority margin of 10%. The microbiologic response appeared to be higher in the levofloxacin group, but the difference was not statistically significant. The safety profile was similar in both groups. Conclusion Levofloxacin is not inferior to cefuroxime with regard to clinical efficacy in treating AECOPD.

Yoon, Ho II; Lee, Chang-Hoon; Kim, Deog Kyeom; Park, Geun Min; Lee, Sang-Min; Yim, Jae-Joon; Kim, Jae-Yeol; Lee, Jae Ho; Lee, Choon-Taek; Chung, Hee Soon; Kim, Young Whan; Han, Sung Koo; Yoo, Chul-Gyu



Antibiotic use after cefuroxime prophylaxis in hip and knee joint replacement  

Microsoft Academic Search

The amount of additional antibiotics measured by defined daily dose (DDD) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses (1502\\/1511 patients) of cefuroxime. No differences were observed between the two regimens with respect to total amount, type, indication, and duration of additional antibiotics. The incidence of joint sepsis did not differ

Ate B Wymenga; Yechiel A Hekster; Ad Theeuwes; Harrie L Muytjens; Jim R van Horn; Tom J J H Slooff



Improvement in Dissolution Rate of Cefuroxime Axetil by using Poloxamer 188 and Neusilin US2.  


A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ?G (0) tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil. PMID:23901163

Sruti, J; Patra, Ch N; Swain, S K; Beg, S; Palatasingh, H R; Dinda, S C; Rao, M E Bhanoji



Single-Dose Intrapulmonary Pharmacokinetics of Azithromycin, Clarithromycin, Ciprofloxacin, and Cefuroxime in Volunteer Subjects  

Microsoft Academic Search

The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithromycin (0.5 g), cipro- floxacin(0.5g),orcefuroxime(0.5g).Insubgroupsoffoursubjectseach,thesubjectsunderwentbronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alve- olar cells (ACs) by high-pressure liquid chromatography.




Evaluation of 99m Tc-Cefuroxime axetil for imaging of inflammation  

Microsoft Academic Search

Localizing and distinguishing the “infection” in body sites are very important and life saving processes. Scintigraphic detections\\u000a may help to determine the sites of inflammation and infection. At this point, nuclear medical imaging may proceed one step\\u000a further and be helpful to localize and distinguish the inflammation. The radiolabeled antibiotic 99mTc-Cefuroxime axetil was assessed as an infection imaging agent in

F. Yurt Lambrecht; O. Yilmaz; P. Unak; B. Seyitoglu; K. Durkan; H. Baskan



Clinical Comparison of Cefuroxime Axetil, Cephalexin and Cefadroxil in the Treatment of Patients with Primary Infections of the Skin or Skin Structures  

Microsoft Academic Search

This study was designed to compare the clinical and bacteriological efficacy of three oral cephalosporins, cefuroxime axetil, cephalexin and cefadroxil, in the treatment of patients with mild to moderate infections of the skin or skin structures. A total of 330 patients were enrolled at 10 centers and were randomly assigned to receive cefuroxime axetil 250 mg (n = 107), cephalexin

W. M. Gooch III; L. Kaminester; G. W. Cole; R. Binder; M. R. Morman; J. M. Swinehart; M. Wisniewski; H. M. Yilmaz; J. J. Collins



Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans.  

PubMed Central

A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Luger, S W; Paparone, P; Wormser, G P; Nadelman, R B; Grunwaldt, E; Gomez, G; Wisniewski, M; Collins, J J



Thrombotic thrombocytopenic purpura after prophylactic cefuroxime axetil administered in relation to a liposuction procedure.  


Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is characterized by platelet and von Willebrand factor (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen vascular disease, cancer, bone marrow transplantation, and drugs (including cephalosporins). Postoperative TTP has been reported after vascular surgery, renal and liver transplantations, and orthopedic, urologic, and abdominal surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the mortality rates, but sometimes patients may have to receive immunosuppressive drugs including vincristine (VCR). This report describes a 42-year-old woman with TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction procedure who was treated successfully with plasma exchange and VCR. The patient fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP still is in remission after 6 months of follow-up evaluation. To the authors' knowledge, this is the first report in the literature describing a patient with TTP after cefuroxime axetil administered in relation to a surgical procedure who was treated successfully with TPE and VCR. PMID:21853406

Eskazan, Ahmet Emre; Salihoglu, Ayse; Gulturk, Emine; Ongoren, Seniz; Soysal, Teoman



Bioequivalence evaluation of two brands of cefuroxime 500 mg tablets (Cefuzime? and Zinnat?) in healthy human volunteers  

Microsoft Academic Search

A bioequivalence study of two oral formulations of 500 mg cefuroxime axetil was carried out in 24 healthy volunteers following a single dose, standard two-treatment cross-over design at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, working jointly with King Khalid University Hospital. The two formulations used were Cefuzime® (Julphar, United Arab Emirates) as the test and Zinnat®

Mansour S. Al-Said; Khalil I. Al-Khamis; Esmail M. Niazy; Yousry M. El-Sayed; Khalid A. Al-Rashood; Sulaiman Al-Bella; Mohd A Al-Yamani; Tawfeeq A Al-Najjar; Syed M Alam; Ruwayda Dham; Q Zaman Qumaruzaman



Effects of test conditions on the susceptibility of staphylococci in vitro to cephradine, cephaloridine, cephalexin, and cefuroxime  

Microsoft Academic Search

Methicillin-resistant staphylococci were tested for susceptibility to cephradine, cephaloridine, cephalexin, and cefuroxime and 30 degree C and 37 degree C on ordinary media and on media of enhanced osmotic strength. The coagulase-negative strains were divided into Staphylococcus epidermis and Staphylococcus hominis. Generally the number of susceptible strains decreased with low incubation temperature and osmotic support. When Staphylococcus aureus was tested

R Bayston; J Swinden



Liquid antisolvent preparation of amorphous cefuroxime axetil nanoparticles in a tube-in-tube microchannel reactor.  


This article presents the preparation of nanoparticles of amorphous cefuroxime axetil (CFA) in a microporous tube-in-tube microchannel reactor (MTMCR). The experimental results indicated that CFA particle with a tunable size of 400-1400 nm could be achieved under a high throughput in the range of 1.5-6L/min. The average particle size decreased with increasing overall volumetric flow rate and decreasing CFA concentration, micropore size, and annular channel width. The produced CFA nanoparticles were characterized by SEM, XRD, FT-IR, DSC and a dissolution test, which indicated that the nanosized CFA was amorphous and exhibited higher dissolution rate compared to the raw CFA. The MTMCR might offer a general and facile pathway for mass production of the nanoparticles of hydrophobic pharmaceuticals thanks to its high throughput capacity and excellent micromixing performance. PMID:20493936

Zhu, Wen-Zhen; Wang, Jie-Xin; Shao, Lei; Zhang, Hai-xia; Zhang, Qian-xia; Chen, Jian-Feng



IV Penicillin G Is as Effective as IV Cefuroxime in Treating Community-Acquired Pneumonia in Children.  


Overuse of broad-spectrum antimicrobials has resulted in bacterial resistance and increasing use of relatively expensive antibiotics for community-acquired pneumonia (CAP). We hypothesized that CAP requiring parenteral medication is still curable with narrow-spectrum and inexpensive penicillin G. A prospective, randomized study was performed on 58 children aged 3 months to 15 years with CAP. Children were randomly assigned to receive low-dose penicillin G, high penicillin G, or cefuroxime intravenously for 4-7 days. The course of illness was monitored clinically and with predetermined laboratory and radiological indices for 30 days. The children recovered at the same rate with no significant differences in time to defervescence or duration of hospitalization. Observed differences in leukocyte counts and C-reactive protein at discharge were of questionable clinical significance. Penicillin G is as effective and safe as cefuroxime for CAP in otherwise healthy children, even in moderate doses. PMID:22407197

Amarilyo, Gil; Glatstein, Miguel; Alper, Arik; Scolnik, Dennis; Lavie, Moran; Schneebaum, Nira; Grisaru-Soen, Galia; Assia, Ayala; Ben-Sira, Liat; Reif, Shimon



Simultaneous determination of cefuroxime axetil and ornidazole in tablet dosage form using reversed-phase high performance liquid chromatography.  


A simple, accurate and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) method for the simultaneous determination of cefuroxime axetil and ornidazole in combined tablet dosage form has been developed. The method was performed with a HiQ-SiL C18 column (250 mm x 4.6 mm) and photodiode array (PDA) detector, using 0.01 mol/L potassium dihydrogen orthophosphate-methanol (56 : 44, v/v) as the mobile phase and tinidazole as the internal standard. Beer's law obeys in the concentration ranges of 5 - 25 microg/mL and 10 - 50 microg/mL for cefuroxime axetil and ornidazole, respectively. The method has been successfully validated statistically and applied for the analysis of the drugs in pharmaceutical formulation. PMID:19253561

Ranjane, Poonam N; Gandhi, Santosh V; Kadukar, Sayali S; Ranher, Sandeep S



Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens  

Microsoft Academic Search

Summary In conjugational crosses, threeKlebsiella pneumoniae strains and oneSerratia marcescens strain have been demonstrated to transfer resistance determinants to newer types of cephalosporins. WhileKlebsiella strains donated cefotaxime, cefamandole and cefuroxime resistance toEscherichia coli K-12 recipients, the genetic analysis of exconjugants after the transfer of plasmids fromSerratia strains toProteus orSalmonella recipients showed that the cefoxitin resistance determinant was also co-transferred. In

H. Knothe; P. Shah; V. Krcmery; M. Antal; S. Mitsuhashi



Simultaneous determination of cefoxitin, cefuroxime, cephalexin and cephaloridine in plasma using HPLC and a column-switching technique  

Microsoft Academic Search

A new high performance liquid chromatographic method was developed using a column-switching technique for the simultaneous determination of cephalexin, cefuroxime, cefoxitin and cephaloridine in plasma. The plasma samples were injected onto a precolumn packed with Corasil RP C18 (37–50 ?m) after simple dilution with an internal standard solution in 0.01 M acetate buffer (pH 3.5). Polar plasma components were washed

Y. J. Lee; H. S. Lee



Optimization and validation of spectrofluorimetric method for determination of cefadroxile and cefuroxime sodium in pharmaceutical formulations.  


A simple, accurate, precise and validated spectrofluorimetric method is proposed for the determination of two cephalosporins, namely, cefadroxile (cefa) and cefuroxime sodium (cefu) in pharmaceutical formulations. The method is based on a reaction between cephalosporins with 1,2-naphthoquinone-4-sulfonate in alkaline medium, to form fluorescent derivatives that are extracted with chloroform and subsequently measured at 610 and 605 nm after excitation at 470 and 460 nm for cefa and cefu respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over the concentrations of 20-70 ng/mL and 15-40 ng/mL for cefa and cefu, respectively. The detection limits were 4.46 ng/mL and 3.02 ng/mL with a linear regression correlation coefficient of 0.9984 and 0.998, and recoveries ranging 97.50-109.96% and 95.73-98.89% for cefa and cefu, respectively. The effects of pH, temperature, reaction time, 1,2-naphthoquinone-4-sulfonic concentration and extraction solvent on the determination of cefa and cefu, have been examined. The proposed method can be applied for the determination of cefa and cefu in pharmaceutical formulations in quality control laboratories. PMID:23345111

Elbashir, Abdalla A; Ahmed, Shazalia M A; Aboul-Enein, Hassan Y



Effects of amlodipine on the oral bioavailability of cephalexin and cefuroxime axetil in healthy volunteers.  


In this study, the authors compared the effects of amlodipine (AML) on the bioavailability of cephalexin (LEX) and cefuroxime axetil (CXM). Twenty-four healthy men were randomized to 4 treatments according to a crossover design with a 14-day washout. After an overnight fast, they were administered orally LEX 500 mg alone, LEX 500 mg 2 hours after oral administration of AML 5 mg, CXM 500 mg alone, and CXM 500 mg 2 hours after oral administration of AML 5 mg. All participants completed the whole study without side effects being observed. Pharmacokinetic data were analyzed by noncompartmental modeling with WinNonlin software. The geometric mean (GM) ratios were 1.38 (90% confidence interval [CI], 1.32-1.45) for the area under the concentration-time curve (AUC) for LEX and 1.27 (1.18-1.36) for the maximum concentration of drug in serum (C(max)) for LEX followed by AML versus alone. In contrast, no significant differences were found in the pharmacokinetic parameters of CXM between treatments (P < .05). They authors conclude that AML possesses an enhancement effect in ?-lactam antibiotic bioavailability (in this case, LEX), and this interaction may be specific to the peptidomimetic ?-lactam antibiotics. PMID:23400747

Ding, Yi; Liu, WenXing; Jia, YanYan; Lu, ChengTao; Jin, Xin; Yang, Jing; Zhu, YanRong; Yang, Lin; Song, Ying; Ding, LiKun; Wen, AiDong



Antibiotic use after cefuroxime prophylaxis in hip and knee joint replacement.  


The amount of additional antibiotics measured by defined daily dose (DDD) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses (1502/1511 patients) of cefuroxime. No differences were observed between the two regimens with respect to total amount, type, indication, and duration of additional antibiotics. The incidence of joint sepsis did not differ significantly between the two trial arms, but the sample was too small for definite conclusions. There were 11.4 DDD/100 bed days of additional antibiotics used in 21% of patients after hip replacement and 15.7 DDD/100 bed days in 31% after knee replacement. For wound problems, 3.8 and 6.9 DDD/100 bed days were given in the hip- and knee-replacement groups. For distant infection, 6.5 DDD/100 bed days was administered in both groups. Duration of therapy varied only in relation to indication. Prescribed were penicillins (43% to 50%), sulfonamides (18%), cephalosporins (10% to 16%), and nitrofurantoin (8% to 13%); drug use was related to the type of infection. PMID:1868681

Wymenga, A B; Hekster, Y A; Theeuwes, A; Muytjens, H L; van Horn, J R; Slooff, T J



A fast, sensitive, and high throughput method for the determination of cefuroxime lysine in dog plasma by UPLC-MS/MS.  


In order to investigate the preclinical pharmacokinetics of cefuroxime lysine, a fast, sensitive and high throughput UPLC-ESI-MS/MS method has been developed and validated for the quantitative determination of cefuroxime in dog plasma. Cefuroxime and IS phenacetin were extracted from plasma samples by PPT or LLE procedure, and then separated on an ACQUITY UPLC™ BEH C(18) column with an isocratic elution of acetonitrile-0.1% formic acid in 10mM ammonium acetate (40:60, v/v). MRM using the fragmentation transitions of m/z 442 ? 364 and 180 ? 110 in positive ESI mode was performed to quantify cefuroxime and IS, respectively. The calibration curves were linear over the concentration range of 2-400 ?g/ml for PPT and 0.01-5 ?g/ml for LLE. The LLOQ was 0.01 ?g/ml. The intra- and inter-day precisions in all samples were no more than 8.1%, while the accuracy was within ± 6.2% of nominal values. The method was successfully applied to the evaluation of pharmacokinetic parameters of cefuroxime lysine in beagle dogs. PMID:22284463

Zhao, Longshan; Zhao, Yunli; Li, Qing; Chen, Xiaohui; Xiao, Feng; He, Bosai; Wang, Jie; Bi, Kaishun



Levofloxacin 500 mg once daily versus cefuroxime 250 mg twice daily in patients with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and exacerbation-free interval.  


The long-term outcome time to relapse determined as the exacerbation-free interval (EFI) has been proposed as a standard measure for comparing the efficacy of antimicrobial therapies in acute exacerbation of chronic obstructive bronchitis (AECOB). In this 6-month, randomised, open-label study, the efficacy of 10 days of oral levofloxacin 500 mg once daily or cefuroxime 250 mg twice daily was evaluated in 689 well-defined patients experiencing AECOB episodes. In the clinically evaluable per-protocol (PPc) population and the modified intent-to-treat population, the clinical cure rates at test of cure were, respectively, 94.6% for levofloxacin versus 93.8% for cefuroxime (0.8% difference, 95% confidence interval (CI) -3.2 to 4.8) and 94.5% for levofloxacin versus 92.2% for cefuroxime (2.3% difference, 95% CI -1.8 to 6.2), whilst the probability that 25% of patients would relapse during follow-up was reached within 93 days for levofloxacin compared with 81 days for cefuroxime in the PPc population (P=0.756). A multivariate analysis revealed that only congestive heart failure and number of AECOB episodes in the previous 12 months were predictive of relapse. Safety was comparable in the two treatment groups, with possibly related treatment-emergent adverse events occurring in 5.0% and 2.9% of subjects in the levofloxacin and cefuroxime groups, respectively. In addition to demonstrating the non-inferiority of levofloxacin compared with cefuroxime in AECOB, the data from this study raise the question of whether EFI is a useful discriminative endpoint for comparing antimicrobial therapies. PMID:17512704

Petitpretz, Patrick; Choné, Claudie; Trémolières, François



Comparison of the efficacy and safety of faropenem daloxate and cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in adults  

Microsoft Academic Search

In this multicentre, multinational, comparative, double-blind clinical trial, outpatients with both clinical signs and symptoms and radiographic evidence of acute sinusitis were randomly assigned to receive for 7 days either a twice-daily oral regimen of faropenem daloxate (300 mg) or a twice daily oral regimen of cefuroxime axetil (250 mg). Among 452 patients considered valid for clinical efficacy, faropenem daloxate

Ralf Siegert; Olof Berg; Pierre Gehanno; Alberto Leiberman; Jonas Laimutis Martinkenas; Paul Nikolaidis; Pierre Arvis; Melody Alefelder; Peter Reimnitz



Levofloxacin versus cefuroxime axetil in the treatment of acute exacerbation of chronic bronchitis: results of a randomized, double-blind study.  


A randomized, double-blind, double-dummy, three-arm parallel design, multicentre study was conducted among adult patients with acute exacerbation of chronic bronchitis (AECB) in order to compare the efficacy and safety of two different doses of levofloxacin with cefuroxime axetil. A total of 832 patients were randomized to receive oral levofloxacin (250 mg od or 500 mg od) or oral cefuroxime axetil (250 mg bd) for 7-10 days. The primary efficacy analysis was based on the clinical response in patients with bacteriologically confirmed AECB, determined 5-14 days after the end of therapy (per-protocol population). Of 839 patients enrolled (at 71 centres in 14 countries), seven were not treated, giving an intention-to-treat (ITT) population of 832. In total, 281 patients received levofloxacin 250 mg, 280 received levofloxacin 500 mg and 271 received cefuroxime axetil. The cure rates in the ITT population were: levofloxacin 250 mg, 70% (196/281); levofloxacin 500 mg, 70% (195/280); cefuroxime axetil, 61% (166/271); those in the per-protocol population were: 78% (121/156), 79% (108/137) and 66% (88/134), respectively. Both doses of levofloxacin were at least as effective as cefuroxime axetil and were active against the main pathogens of clinical relevance (Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis). All three treatment regimens were equally well tolerated. In conclusion, the results show that levofloxacin (250 mg and 500 mg) od is effective and well tolerated in the treatment of AECB in adult patients. PMID:10350383

Shah, P M; Maesen, F P; Dolmann, A; Vetter, N; Fiss, E; Wesch, R



[Determination of cefuroxime in liver-injured rat plasma by ultra fast liquid chromatography-tandem mass spectrometry via acidified protein precipitation].  


In order to investigate the pharmacokinetic profiles of cefuroxime lysine, a new second generation cephalosporins, in liver-injured rat model, an ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the determination of cefuroxime in liver-injured rat plasma was developed and validated. The plasma sample was pretreated by protein precipitation with acidified acetonitrile. The analytes were separated on a Shim-pack XR-ODS column (75 mm x 3.0 mm, 2.2 microm) with acetonitrile-0. 1% formic acid aqueous solution (40:60, v/v) as the mobile phase at a flow rate of 400 microL/min. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode with a negative electrospray ionization (ESI) interface. The precursor to product ion transitions of m/z 423.2 --> 206.8 and m/z 454.1 --> 238.4 were selected to determine cefuroxime and cefotaxime (internal standard, IS), respectively. The linearities ranged from 0.01 to 1 mg/L and 1 to 400 mg/L (r > 0.99), and the limit of quantification of cefuroxime was 0.01 mg/L. The relative standard deviations (RSDs) of intra- and inter-day precisions were both less than 11.5%, and the accuracy (relative error) was between -7.1% and 2.2%. The mean extraction recovery was more than 83.5%. The total run time was 3.0 min per sample. The method is simple and fast for the preliminary pharmacokinetic study of cefuroxime lysine in liver-injured rats. PMID:23189666

Zhao, Longshan; Li, Qing; Yang, Wei; He, Bosai; Wei, Binbin; Liu, Ran; Liu, Jingjing; Chen, Xiaohui; Bi, Kaishun



A Multicenter, Randomized Study Comparing the Efficacy and Safety of Intravenous and\\/or Oral Levofloxacin versus Ceftriaxone and\\/or Cefuroxime Axetil in Treatment of Adults with Community-Acquired Pneumonia  

Microsoft Academic Search

posttherapy was superior for the levofloxacin group (96%) compared with the ceftriaxone and\\/or cefuroxime axetil group (90%) (95% confidence interval (CI) of 210.7 to 21.3). Among patients with typical respira- tory pathogens who were evaluable for microbiological efficacy, the overall bacteriologic eradication rates were superior for levofloxacin (98%) compared with the ceftriaxone and\\/or cefuroxime axetil group (85%) (95% CI of




A comparison of the safety and efficacy of moxifloxacin (BAY 12-8039) and cefuroxime axetil in the treatment of acute bacterial sinusitis in adults  

Microsoft Academic Search

The aim of this multicentre, randomized study was to compare the efficacy and safety of moxifloxacin (BAY 12-8039), a new 8-methoxy fluoroquinolone, with that of cefuroxime axetil for the treatment of acute bacterial sinusitis in adults. Diagnosis was made on a range of clinical signs and symptoms combined with radiology and microbiology.A 400 mg dose of moxifloxacin was administered once




Single dose cefotaxime plus metronidazole versus three dose cefuroxime plus metronidazole as prophylaxis against wound infection in colorectal surgery: multicentre prospective randomised study  

Microsoft Academic Search

OBJECTIVE--To establish whether a single preoperative dose of cefotaxime plus metronidazole was as effective as a standard three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery. DESIGN--Prospective randomised allocation to one of two prophylactic antibiotic regimens in a parallel group trial. Group sequential analyses of each 250 patients were performed. SETTING--14 District general and teaching

D C Rowe-Jones; A L Peel; R D Kingston; J F Shaw; C Teasdale; D S Cole



Preformulation studies for direct compression suitability of cefuroxime axetil and paracetamol: a graphical representation using SeDeM diagram.  


The direct compression suitability of active pharmaceutical ingredients could be studied by SeDeM diagram method. Cefuroxime axetil (CfA) and paracetamol (PCM) were employed for SeDeM studies as these powders are well-characterized and known to be particularly difficult with respect to flowability and compactibility. Twelve different selected pharmacotechnical parameters were determined experimentally and were treated mathematically for being expressed in graphic representation as SeDeM diagram. Parameter index, parameter profile index and good compression index were calculated for both the selected drugs. Good compression index was found to be 2.19 and 1.36 for CfA and PCM, respectively, indicating poor direct compression characteristics of the selected drugs. The results from this SeDeM diagram method are in line with the previously reported studies where it was established as a reliable method for preformulation studies and as a quality control tool for studying batch-to-batch reproducibility of API's. Furthermore, it once again established the notion that blending poorly compressible drugs with suitable ingredients followed by SeDeM studies could be used as method for identifying best excipient and calculating maximum amount of excipient required for direct compression of API. PMID:22574511

Singh, Inderbir; Kumar, Pradeep


Preparation and evaluation of 99mTc-cefuroxime, a potential infection specific imaging agent: a reliable thin layer chromatographic system to delineate impurities from the 99mTc-antibiotic.  


Technetium-99m labelled cefuroxime, a second-generation cephalosporin antibiotic and potential bacteria specific infection imaging agent was evaluated. A good radiochemical purity (95%) of the labelled product was obtained after filtering the reaction mixture through a 0.22 ?m filter. Scintigraphy study of the purified product showed uptake in infectious lesions 45 min after injection and abscess-to-muscle ratios were found to be 1.80, 1.85 and 1.88 at 45 min, 1.5 hr and 3 hr, respectively. A versatile and reliable chromatographic technique to assess the radiochemical purity of (99m)Tc-cefuroxime has also been described. PMID:22871442

Chattopadhyay, Sankha; Ghosh, Mayuri; Sett, Sucharita; Das, Malay Kanti; Chandra, Susmita; De, Kakali; Mishra, Mridula; Sinha, Samarendu; Ranjan Sarkar, Bharat; Ganguly, Shantanu



[Fractures with loss of substance of the middle and upper third of the face: nosographic classification, surgical indications and the prevention of meningeal infections with the new antibiotic, cefuroxime].  


Reference is made to considerable personal experience acquired in the treatment of craniofacial fractures, particularly those affecting the upper third of the face. An account is given of the anatomical and surgical features of the naso-ethmoid-frontal and temporo-orbito-sphenoid areas--now recognised as within the domain of maxillofacial surgery--and their symptomatologies. Particular attention is directed to the question of liquorrhoea and the possibility of ascendent infections of the meninges. Reduction is favoured with respect to the former, since forward and upward repositioning often leads to the regression of ethmoidal liquorrhoea. Exclusion of the frontal sinus is regarded as a "categorical imperative" as far as meningeal infection is concerned, and support is also given for its prevention with antibiotics. A personal preference is expressed for cefuroxim, a new antibiotic with particular potency and marked diffusibility within the cerebrospinal fluid. PMID:6935507

Torrielli, F; Camurati, R; Cervar, M F; Tel, A


Effects of Amino Acid Alterations in Penicillin-Binding Proteins (PBPs) 1a, 2b, and 2x on PBP Affinities of Penicillin, Ampicillin, Amoxicillin, Cefditoren, Cefuroxime, Cefprozil, and Cefaclor in 18 Clinical Isolates of Penicillin-Susceptible, Intermediate, and Resistant Pneumococci  

Microsoft Academic Search

Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin- binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-suscep- tible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing

Kensuke Nagai; Todd A. Davies; Michael R. Jacobs; Peter C. Appelbaum



Discontinued Drug: Kefurox (cefuroxime for injection USP) ...  

Center for Drug Evaluation (CDER)

... Although no generic version of cefamandole is available, there are multiple therapeutic alternatives that provide a similar spectrum of activity ... More results from


Cost Effectiveness of Azithromycin Versus Cefuroxime, with/without Erythromycin, in Hospitalized Patients with Community Acquired Pneumonia.  

National Technical Information Service (NTIS)

The purpose of this report is to assess the cost-effectiveness of azithromycin monotherapy for hospitalized patients with community acquired pneumonia against the current practice of a second generation cephalosporin with/without erythromycin. A pharmacoe...

L. D. Gudgel



In vitro and in vivo release of cefuroxime axetil from bioactive glass as an implantable delivery system in experimental osteomyelitis  

Microsoft Academic Search

The aim of this study was to evaluate the characterisation, in vitro and in vivo biocompatibility and antimicrobial activity of bioactive glass (BG) impregnated with an antibiotic. The BG was prepared by normal glass melting procedures as a controlled release device to treat experimental osteomyelitis. The study design was for prospective in vivo experimental study. Two sets of porous bioactive

Samit K. Nandi; Biswanath Kundu; Prasenjit Mukherjee; Tapan K. Mandal; Someswar Datta; Dipak K. De; Debabrata Basu



List of Drugs Manufactured at the Dewas and Paonta Sahib ...  

Center for Drug Evaluation (CDER)

... Proxetil Cefprozil Cefuroxime Axetil Cephalexin Ciprofloxacin HCl Clarithromycin Fenofibrate Fluconazole Fosinopril Sodium Fosinopril Sodium ... More results from


In vitro activity of BAY v 3522, a new cephalosporin for oral administration.  

PubMed Central

The activity of BAY v 3522 was tested against over 500 clinical bacterial isolates and compared with the activities of ampicillin, amoxicillin-clavulanate, cefaclor, cefixime, cefuroxime, cephalexin, and/or ciprofloxacin, erythromycin, and metronidazole. BAY v 3522 activity against staphylococci and streptococci equaled or exceeded those of the other agents. BAY v 3522 exhibited no significant advantage over cefaclor, cefuroxime, or cephalexin against gram-negative bacilli.

Hodges, T L; Eliopoulos, G M; Klimm, K; Moellering, R C



Neue Entwicklungen bei den Cephalosporin-Antibiotika  

Microsoft Academic Search

Zusammenfassung Cephalosporine sind bakterizide ß-Laktamring-Antibiotika mit einem breiten antibakteriellen Spektrum. Ihre molekularbiologische Wirkung beruht auf der Hemmung der Biosynthese der Bakterienzellwand. Die neuentwickelten Cephalosporine (Cefamandol, Cefoxitin, Cefuroxim) zeichnen sich durch eine verbesserte und verbreiterte Wirkung gegenüberEnterobacteriaceae aus. Bei den klinisch häufigsten gramnegativen Keimen ist Cefamandol die aktivste Substanz, Cefuroxim ist nur unwesentlich weniger aktiv. Cefoxitin bietet Vorteile bei indolpositivenProteus-Spezies,Serratia und

H. Lode; B. Baruch; P. Koeppe; S. Lehmann-Brauns



Endophthalmitis prophylaxis in cataract surgery: overview of current practice patterns in 9 European countries.  


Data on practice patterns for prophylaxis against infectious postoperative endophthalmitis (IPOE) during cataract surgery in 9 European countries were searched in national registers and reviews of published surveys. Summary reports assessed each nation's IPOE rates, nonantibiotic prophylactic routines, topical and intracameral antibiotic use, and coherence to the European Society of Cataract & Refractive Surgeons (ESCRS) 2007 guidelines. Although the reliability and completeness of available data vary between countries, the results show that IPOE rates differ significantly. Asepsis routines with povidone-iodine and postoperative topical antibiotics are generally adopted. Use of preoperative and perioperative topical antibiotics as well as intracameral cefuroxime varies widely between and within countries. Five years after publication of the ESCRS guidelines, there is no consensus on intracameral cefuroxime use. Major obstacles include legal barriers or persisting controversy about the scientific rationale for systematic intracameral cefuroxime use in some countries and, until recently, lack of a commercially available preparation. PMID:23988244

Behndig, Anders; Cochener, Beatrice; Güell, José Luis; Kodjikian, Laurent; Mencucci, Rita; Nuijts, Rudy M M A; Pleyer, Uwe; Rosen, Paul; Szaflik, Jacek P; Tassignon, Marie-José



Comparative in vitro activity of 1-oxa-beta-lactam (LY127935) and cefoperazone with other beta-lactam antibiotics against anaerobic bacteria.  

PubMed Central

The in vitro activity of 1-oxa-beta-lactam (LY127935), cefoperazone (T-1551), cefuroxime, cefsulodin, cefaclor, cefotaxime, and cefoxitin on 85 anaerobic clinical isolates (30 Bacteroides, 30 Clostridium, 25 Peptococcaceae) was simultaneously determined by the agar dilution test in two different media, Brucella Agar (Difco Laboratories) and Wilkins-Chalgren agar. In Wilkins-Chalgren agar, 90% of Bacteroides were inhibited by (micrograms per milliliter): LY127935, 0.5; T-1551, 64; cefoxitin or cefuroxime, 8; cefsulodin or cefotaxime, 32; and cefaclor, 128. All Clostridia were inhibited in Wilkins-Chalgren by (micrograms per milliliter): LY127935, 4; T-1551, 2; cefoxitin, 6; cefuroxime, 0.12; cefsulodin, 0.5; cefaclor, 1; and cefotaxime, 8. All Peptococccaceae were inhibited by T-1551, cefsulodin or cefotaxime at 4 microgram/ml and by cefoxitin or cefuroxime at 1 to 2 microgram/ml. With cefaclor at 8 microgram/ml, 92% of strains were inhibited, and LY127935 at 16 microgram/ml only inhibited 64% of strains. LY127935 was the most active of the antibiotics tested against Bacteroides, showing good activity against Clostridia and poor activity on Peptococcaceae, whereas T-1551 was more active against Peptococccaceae and had similar activity against Clostridia and poor activity on Bacteroides. There are no significant differences between minimal inhibitory concentrations obtained in Brucella Agar and those obtained in Wilkins-Chalgren.

Borobio, M V; Aznar, J; Jimenez, R; Garcia, F; Perea, E J



Prolong antibiotics release by encapsulating PLGA for hip prosthesis  

Microsoft Academic Search

In this study, encapsulating antibiotic loaded titanium alloy by polylactide-co-polyglycolide copolymer (PLGA) for preventing burst releasing and extending antibiotic releasing time will be make for potential future hip prosthesis with deep infection prevention ability. Antibiotics, vancomycin and cefuroxime, were used to measure their temporal release from titanium disc. The result by elution test showed non PLGA coated of antibiotic loaded

K. H. Chen; G. A. Lai; S. D. Chen; J. C. Shiu; M. L. Yeh



Perspectives on antibiotics for postoperative endophthalmitis prophylaxis: potential role of moxifloxacin.  


To aid the cataract surgeon's understanding of rational approaches to antimicrobial prophylaxis and place the European Society of Cataract & Refractive Surgeons (ESCRS) postoperative endophthalmitis study in perspective, a review was conducted of published and unpublished data on intracameral antibiotic use during cataract surgery and the antimicrobial efficacy, pharmacodynamics, ocular penetration, and safety of moxifloxacin. The ESCRS-sponsored study of postoperative endophthalmitis prophylaxis reported rates of presumed infectious postoperative endophthalmitis of 0.07% with intracameral cefuroxime treatment and 0.34% in control groups. Postoperative endophthalmitis after cefuroxime use was mostly due to cefuroxime-resistant gram-positive bacteria. Intracameral cefuroxime also requires extemporaneous compounding, has short-term stability, and carries a risk for hypersensitivity. Moxifloxacin, a fourth-generation fluoroquinolone, has potent and rapid bactericidal activity against the most common gram-positive postoperative endophthalmitis pathogens, has excellent ocular penetration after topical administration, and is available in a self-preserved ophthalmic formulation that has been shown safe and effective in preventing endophthalmitis when administered intracamerally in an animal model. Available data suggest that the optimum antibiotic regimen and route of delivery for cataract surgery antimicrobial prophylaxis require further study. Moxifloxacin offers many theoretical advantages that make it an attractive first-line choice for topical use and of interest for intracameral administration. PMID:17889778

O'Brien, Terrence P; Arshinoff, Steve A; Mah, Francis S



Multidrug resistant Escherichia coli isolates of poultry origin in Abeokuta, South Western Nigeria  

Microsoft Academic Search

resistant patterns to Nitrofurantoin (100 µg), Cefuroxime (20 µg), Norfloxacin (10 µg), Cotrimoxazole (50 µg), Ciprofloxacin (5 µg), Nalidicic acid (30 µg), Chloramphenicol (10 µg), Ampicillin (10 µg, 25 µg), Ofloxacin (5 µg), Penicillin G (5 i.u), Amoxylin (20 µg), and Cloxacilin (5 µg, 10 µg) discs that were tested.

Akinlabi Oladele Ogunleye; Mufutau Atanda Oyekunle; Adekayode Olanrewaju Sonibare



Prospective randomized comparison of two different sized percutaneous endoscopically placed gastrostomy tubes  

Microsoft Academic Search

We performed a prospective randomised study of two different sized percutaneous endoscopicgastrostomy (PEG) tubes to determine if tube size influenced the incidence of PEG-related complications. Patients were given prophylactic cefuroxime, if not already on antibiotics at the time of PEG insertion. Fifty-two PEGs were successfully placed, 26 in each group. Most patients who required a PEG had suffered a cerebrovascular

H. D. Duncan; M. J. Bray; S. A. Kapadia; T. E. Bowling; S. J. Cole; S. M. Gabe; E. R. Walters; D. B. A. Silk



Eradication of endotracheal tube biofilm by nebulised gentamicin  

Microsoft Academic Search

Objective: To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm. Setting: General intensive care units in two university teaching hospitals. Design: The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations

C. Adair; S. Gorman; L. Byers; D. Jones; B. Feron; M. Crowe; H. Webb; G. McCarthy; K. Milligan



In Vivo Correlates forStreptococcus pneumoniaePenicillin Resistance in Acute Otitis Media  

Microsoft Academic Search

Eighty-four children suffering from acute otitis media caused by Streptococcus pneumoniae were treated prospectively with cefuroxime axetil suspension (30 mg\\/kg of body weight twice daily for 8 days). The high incidence of isolates with decreased susceptibilities to penicillin (42 of 84 isolates) allowed us to establish a relationship between clinical success and the penicillin MICs for pneumococcal isolates. It was




Prodrugs for masking bitter taste of antibacterial drugs--a computational approach.  


DFT calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. Further, it was established that when the amine leaving group was a secondary amine, acyclovir or cefuroxime moiety the tetrahedral intermediate formation was the rate-limiting step such as in the cases of acyclovir ProD 1- ProD 4 and cefuroxime ProD 1- ProD 4. In addition, the linear correlation between the calculated and experimental rates provided a credible basis for designing prodrugs for masking bitter taste of the corresponding parental drugs which have the potential to release the parent drug in a sustained release fashion. For example, based on the DFT calculated rates the predicted t?/? (a time needed for 50 % of the reactant to be hydrolyzed to products) for cefuroxime prodrugs, cefuroxime ProD 1- ProD 4, were 12 min, 18 min, 200 min and 123 min, respectively. PMID:23420399

Karaman, Rafik



Lactamases of Kluyvera ascorbata, Probable Progenitors of Some Plasmid-Encoded CTX-M Types  

Microsoft Academic Search

Kluyvera ascorbata produces a -lactamase that results in an atypical susceptibility pattern, including low- level resistance to penicillins, cephalothin, and cefuroxime, but this resistance is reversed by clavulanate. Ten nucleotide sequences of the corresponding gene, blaKLUA, were obtained and were found to have minor vari- ations (96 to 100%). Otherwise, blaKLUA was found to be similar (95 to 100%) to

Christel Humeniuk; Guillaume Arlet; Valerie Gautier; Patrick Grimont; Roger Labia; Alain Philippon



Chemotherapeutic principles of difficult-to-treat infections in surgery: II. Bone and joint infections  

Microsoft Academic Search

Summary The surgical principles applied in the treatment of bone and joint infections are presented. The antimicrobial chemotherapy of these infections depends on sufficient bone concentrations of the antibiotic. The problems of antibiotic bone level determination are presented. The results of bone level determinations with cefuroxime, cefoxitin, cephalexin, cefotaxime, oxacillin, azlocillin, mezlocillin, piperacillin and fosfomycin are given. The problem of

D. H. Wittmann



Die Resistenz methicillinresistenter Staphylokokken gegenüber neuen Cephalosporin-Antibiotika  

Microsoft Academic Search

Zusammenfassung An einem Kollektiv von 60 Koagulase-positiven staphylokokkenstämmen mit Methicillin-resistenz wurde die Aktivität neuer Cephalosporine geprüft und mit der von Cefalotin, Methicillin und Oxacillin verglichen. Dabei ergab sich, daß das Cefamandol als aktivste Substanz der neuen Cephalosporine in seiner Aktivität dem Cefalotin gleichkommt, Cefoxitin dem Oxacillin und Methicillin gleichzusetzen ist und Cefuroxim, Cefoperazon, Cefotaxim sowie das Moxalactam gegen Staphylokokken mit

F. H. Kayser



Die antibakterielle Effektivität von Cefamandol im Vergleich mit anderen Antibiotika  

Microsoft Academic Search

Zusammenfassung Die antibakterielle Aktivität von Cefamandol wurde mit der Wirksamkeit von Cefuroxim, Cefoxitin, Cephalotin, Ampicillin, Mezlocillin, Azlocillin, Ticarcillin und Tobramycin bei 450 gramnegativen Bakterien sowie bei 150 grampositiven Kokken verglichen. Bei den grampositiven Bakterien wurde zusätzlich die Wirksamkeit von Penicillin und Oxacillin geprüft. Bestimmt wurden die minimalen Hemmkonzentrationen und minimalen bakteriziden Konzentrationen (partielle und totale) mittels Reihenverdünnungstest in Mueller-Hinton-Bouillon (Difco).

H.-H. Schassan



Campylobacteriosis des Menschen durch die Subspezies intestinalis und fetus unter Berücksichtigung sechs neuer Erkrankungen  

Microsoft Academic Search

Zusammenfassung Campylobacter fetus Subspeziesintestinalis und Subspeziesfetus sind beim Menschen opportunistische Krankheitserreger. Weltweit wurden bisher etwa 200 Erkrankungen beschrieben. Sechs neue Erkrankungen werden kurz vorgestellt. Am häufigsten ist die Sepsis, gefolgt von Meningitis. Wirksame Antibiotika sind Ticarcillin, Erythromycin, Clindamycin und Tetracyclin; weitgehende Resistenz besteht gegenüber Cefalotin, Cefazolin, Cefuroxim, Cefoxitin und Cefotaxim, mäßige Empfindlichkeit gegenüber Gentamicin. Die Epidemiologie der Erkrankung ist unklar.

U. Ullmann; Heike Langmaack; Christa Blasius



Experimental infections for the evaluation of beta-lactamase resistance.  

PubMed Central

The antibacterial activity and pharmacokinetics of the beta-lactamase-stable cephalosporin cefuroxime and the gram-negative beta-lactamase-susceptible cephalosporin cefazolin were compared in two contrasting infection models in which Proteus morganii 82, which produces chromosomally mediated beta-lactamase, was the pathogen. In the rat paw model, characterized by high numbers of localized bacteria, cefazolin was destroyed at the site of infection and consequently did not produce a therapeutic response. In the mouse intraperitoneal model cefazolin was also inactive, despite peritoneal concentrations being unaffected by high counts of the beta-lactamase-producing P. morganii in the body cavity. In contrast the pharmacokinetics of cefuroxime was unaffected by the presence of the beta-lactamase-producing P. morganii, and good therapeutic responses were seen in both models.

Xerri, L; Orsolini, P; Erani, E; Broggio, R



Neisseria lactamica and Neisseria polysaccharea as possible sources of meningococcal beta-lactam resistance by genetic transformation.  

PubMed Central

We studied the susceptibilities of relatively penicillin G-resistant and -susceptible strains of Neisseria meningitidis, as well as Neisseria lactamica and Neisseria polysaccharea, to penicillin, ampicillin, and several cephalosporins. The MICs of penicillin, ampicillin, cephalothin, and cefuroxime for moderately resistant meningococci have increased two- to sixfold in relation to MICs for susceptible strains. For these strains of meningococci, N. lactamica, and N. polysaccharea, penicillin, ampicillin, cephalothin, and cefuroxime MICs for 50 and 90% of strains were similar. By genetic transformation of a penicillin-susceptible strain of N. meningitidis to low-level penicillin resistance with DNA from penicillin-resistant strains of N. meningitidis, N. lactamica, N. polysaccharea, and N. gonorrhoeae, isogenic strains with the same pattern of resistance to beta-lactams were obtained, suggesting that these commensal Neisseria spp. could be the source of meningococcal resistance genes.

Saez-Nieto, J A; Lujan, R; Martinez-Suarez, J V; Berron, S; Vazquez, J A; Vinas, M; Campos, J



Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.  


Faropenem medoxomil is the first oral penem in a new class of beta-lactam antibiotics. Faropenem medoxomil has excellent in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of treatment with faropenem medoxomil is as clinically and bacteriologically effective as 10 days of treatment with cefuroxime axetil. One study showed faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety profile of faropenem medoxomil is similar to that of most comparators. Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal flora leads to less diarrhea and other adverse events than coamoxicillin-clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little requirement for dosage adjustments in the typical acute rhinosinusitis population. PMID:17181408

Hadley, James A; Tillotson, Glenn S; Tosiello, Robert; Echols, Roger M



In vitro activities of cefcanel and some other cephalosporins against Pasteurella multocida.  

PubMed Central

Thirty-five strains of Pasteurella multocida from humans and animals were tested for susceptibility to five cephalosporins by a broth dilution method. Cefcanel showed high activity against all isolates (MIC and MBC, less than or equal to 0.64 micrograms/ml). The corresponding figure for cefaclor and cefuroxime was 2.56 micrograms/ml. Cefadroxil and cephalexin were the least active compounds tested.

Holst, E; Rollof, J; Miorner, H



Study of volatile compounds from the radiosterilization of solid cephalosporins  

NASA Astrophysics Data System (ADS)

The use of ?-rays is a promising method to sterilize thermosensitive drugs. Although radiosterilization does not modify drugs activity, this mode of sterilization produces new radiolytic products. This study is devoted to the analysis of volatile compounds which may induce a modification of odour. The volatile compounds produced by radiolysis of cefotaxime, cefuroxime and ceftazidime, three cephalosporins, were analyzed by gas chromatography with headspace sampling. They were detected and identified by mass and infrared spectrometry. An explanation of their origin is proposed.

Barbarin, N.; Crucq, A. S.; Tilquin, B.



Electron spin resonance studies of some irradiated pharmaceuticals  

NASA Astrophysics Data System (ADS)

Five antibiotics belonging to the cephalosporins and penicillins groups have been irradiated: anhydrous ampicilline acid, amoxicilline acid trihydrate, cefuroxime sodium salt, cloxacilline sodium salt monohydrate and ceftazidime pentahydrate. ESR studies have been carried out, showing the influence of irradiation and storage parameters on the nature and concentration of the free radicals trapped. These results may be used to detect an irradiation treatment on such pharmaceuticals.

Gibella, M.; Crucq, A.-S.; Tilquin, B.; Stocker, P.; Lesgards, G.; Raffi, J.



Detection of potential risk of wastewater effluents for transmission of antibiotic resistance from Vibrio species as a reservoir in a peri-urban community in South Africa  

Microsoft Academic Search

We assessed the antibiogram characteristics of some Vibrio species isolated from wastewater final effluents in a typical peri-urban community of South Africa. Marked resistances were noted against erythromycin (100%), chloramphenicol (100%), nitrofurantoin, cefuroxime and cephalothin (90–95%) in V. parahaemolyticus, V. fluvialis and V. vulnificus, respectively. Fourteen antibiotypes were identified, with multiresistance to 8–10 antibiotics being common. The antibiotypes AMP, PEN,

Etinosa O. Igbinosa; Larry C. Obi; Mvuyo Tom; Anthony I. Okoh



Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 Oral Antimicrobial Agents Based on Pharmacodynamic Parameters: 1997 U.S. Surveillance Study  

Microsoft Academic Search

Virtually all H. influenzae strains were susceptible to amoxicillin-clavulanate (98%), cefixime (100%), and ciprofloxacin (100%), while 78% were susceptible to cefuroxime, 57% were susceptible to amoxicillin, 14% were susceptible to cefprozil, 9% were susceptible to loracarbef, 2% were susceptible to cefaclor, and 0% were susceptible to azithromycin and clarithromycin. Among S. pneumoniae isolates, 49.6% were penicillin suscep- tible, 17.9% were




Outbreak of OXY-2-Producing Klebsiella oxytoca in a Renal Transplant Unit?  

PubMed Central

We describe a Klebsiella oxytoca infection outbreak in a renal transplant unit that involved seven patients. All strains belonged to a single pulsed-field gel electrophoresis pattern and were resistant to amoxicillin-clavulanate, cefuroxime, piperacillin-tazobactam, and aztreonam but susceptible to ceftriaxone, ceftazidime, cefepime, and imipenem. Chromosomal ?-lactamase hyperproduction was caused by a point mutation in the blaOXY-2 gene promoter region.

Zarate, Mariela Soledad; Gales, Ana C.; Picao, Renata C.; Pujol, Gervasio Soler; Lanza, Alejandra; Smayevsky, Jorgelina



Prevalence of serotype 19A Streptococcus pneumoniae among isolates from U.S. children in 2005-2006 and activity of faropenem.  


Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC(90) of faropenem against serotype 19A isolates was 1 mug/ml, compared to > or =8 microg/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin. PMID:18443117

Critchley, Ian A; Jacobs, Michael R; Brown, Steven D; Traczewski, Maria M; Tillotson, Glenn S; Janjic, Nebojsa



Prevalence of Serotype 19A Streptococcus pneumoniae among Isolates from U.S. Children in 2005-2006 and Activity of Faropenem?  

PubMed Central

Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC90 of faropenem against serotype 19A isolates was 1 ?g/ml, compared to ?8 ?g/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin.

Critchley, Ian A.; Jacobs, Michael R.; Brown, Steven D.; Traczewski, Maria M.; Tillotson, Glenn S.; Janjic, Nebojsa



Clinical Efficacy of Intravenous followed by Oral Azithromycin Monotherapy in Hospitalized Patients with Community-Acquired Pneumonia  

Microsoft Academic Search

The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteri- ologic and clinical




Antipneumococcal Activity of DK507k, a New Quinolone, Compared with the Activities of 10 Other Agents  

Microsoft Academic Search

Agar dilution MIC determination was used to compare the activity of DK-507k with those of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, sitafloxacin, amoxicillin, cefuroxime, erythromycin, azithromycin, and clarithromycin against 113 penicillin-susceptible, 81 penicillin-intermediate, and 67 penicillin-resistant pneu- mococci (all quinolone susceptible). DK-507k and sitafloxacin had the lowest MICs of all quinolones against quinolone-susceptible strains (MIC at which 50% of isolates were inhibited

Frederick A. Browne; Bulent Bozdogan; Catherine Clark; Linda M. Kelly; Lois Ednie; Klaudia Kosowska; Bonifacio Dewasse; Michael R. Jacobs; Peter C. Appelbaum



Usefulness of teicoplanin for preventing methicillin-resistant Staphylococcus aureus infections in orthopedic surgery  

Microsoft Academic Search

In order to gather more data on the use of teicoplanin for reducing MRSA infections in high-risk populations, the present\\u000a study was conducted. At a hospital in Barcelona, Spain, there was a high prevalence of MRSA infections among patients who\\u000a underwent surgery for femoral neck fracture during the first 5 months of 2002 (period A) when cefuroxime was the antibiotic\\u000a prophylaxis.

A. Soriano; D. Popescu; S. García; G. Bori; J. A. Martínez; V. Balasso; F. Marco; M. Almela; J. Mensa



Prospective study of epidemiology and prognostic factors in community-acquired pneumonia  

Microsoft Academic Search

Of 342 patients with community-acquired pneumonia, 100 were diagnosed etiologically. In these patients, disease epidemiology, prognostic factors, and influence of antibiotic treatment were analyzed prospectively. Fifty-two patients were treated with a broad-spectrum antibiotic (ceftriaxone), and 48 received a medium-spectrum antibiotic (cefuroxime); some patients in each group also received erythromycin.Streptococcus pneumoniae was the most frequently isolated microorganism (43%), followed byChlamydia pneumoniae

J. Ruiz Gdrnez; V. Baños; J. Ruiz Gómez; M. C. Soto; L. Muñoz; M. L. Nuñez; M. Canteras; M. Valdés



Erregerspektrum und Antibiotikaresistenz beim Harnwegsinfekt und Konsequenzen für die Antibiotikatherapie  

Microsoft Academic Search

Zusammenfassung In den Jahren 1994-2001 wurden alle Uropathogene von stationären, urologischen Patienten identifiziert und die Empfindlichkeit gegenüber 14 Antibiotika (Trimethoprim (TMP)\\/Sulfamethoxazol (SMZ), Ciprofloxacin, Ampicillin, Mezlocillin, Ampicillin\\/Sulbactam, Piperacillin\\/Tazobaktam, Cefuroxim, Cefpodoxim, Cefotaxim, Ceftazidim, Gentamicin, Penicillin, Oxacillin und Vancomycin) getestet. Erregerduplikate wurden eliminiert. Dabei fanden sich folgende Ergebnisse: 1. Während des Beobachtungszeitraumes gab es keinen generellen Trend einer Resistenzzunahme, außer bei E. coli

F. Wagenlehner; A. Niemetz; K. Naber



In-vitro-Vergleich neuer Beta-Laktam-Antibiotika bei Gentamicin-resistenten Erregern und Darstellung der Cefoxitin-Regressionsgeraden  

Microsoft Academic Search

Zusammenfassung Durch MHK-Bestimmungen im Agar-Dilutionstest wurde gezeigt, daß Gentamicin-resistente Enterobakterien auch weitgehend resistent sind gegenüber Ampicillin, Carbenicillin, Ticarcillin, Mezlocillin und Cephalothin. Cefoxitin, Cefuroxim und z. T. auch Cefamandol erfassen einen hohen Prozentsatz dieser Bakterien. Regressionsanalysen mit Cefoxitin auf Mueller-Hinton-, DST- und Iso-Sensitest-Agar ergaben in allen Fällen eine sehr gute Korrelation von Hemmhofdurchmesser und MHK für das Gesamtkollektiv von 300 Kulturen

H. Grimm



Detection of plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis  

Microsoft Academic Search

Aims:This study investigated the prevalence of plasmid-mediated AmpC production in selected clinical isolates of Escherichia coli, Klebsiella species and Proteus mirabilis, and compared the results of boronic acid disc screening with conventional susceptibility testing for the detection of AmpC-positive isolates.Methods:E coli, Klebsiella species and P mirabilis with reduced susceptibility to amoxycillin-clavulanate, cefuroxime and cephalexin, but without phenotypic evidence of extended-spectrum

T Y Tan; S Y Ng; L Teo; Y Koh; C H Teok



Effects of some antibiotics on human erythrocyte glutathione reductase: an in vitro study.  


Inhibitory effects of some antibiotics on purified human erythrocyte glutathione reductase were investigated. Human erythrocyte glutathione reductase was purified 2800-fold (29% yield) at 4 degrees C using 2', 5'-ADP Sepharose 4B affinity gel and Sephadex G-200 gel filtration chromatography. SDS polyacrylamide gel electrophoresis showed a single band for the enzyme. Imipenem, rifamycin, sulfanylacetamide, ceftazidime, chloramphenicol, seftriaxon, vancomycin, cefuroxime and ornidazole exhibited inhibitory effects but clindamycin, lincomycin, amoxicillin, amikacin exhibited activatory effects on the enzyme in vitro. The IC(50) values of imipenem, rifamycin, sulfanylacetamide, ceftazidime, chloramphenicol, seftriaxon, vancomycin, cefuroxime and ornidazole were 0.030, 0.146, 0.59, 2.476, 2.36, 2.88, 4.83, 15.43 and 19.632 mM, respectively, and the K(i) constants were 0.06 +/- 0.01, 0.275 +/- 0.10, 0.85 +/- 0.05, 3.59 +/- 0.51, 3.85 +/- 0.40, 3.71 +/- 0.60, 15.11 +/- 2.50, 23.50 +/- 2.94 and 28.49 +/- 6.50 mM, respectively. While imipenem, rifamycin, sulfanylacetamide, ceftazidime, chloramphenicol and seftriaxon cefuroxime and ornidazole showed competitive inhibition, vankomycine displayed noncompetitive inhibition. PMID:18341267

Senturk, Murat; Kufrevioglu, O Irfan; Ciftci, Mehmet



Analysis of the role of Bacillus subtilis ?(M) in ?-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis.  


The Bacillus subtilis extracytoplasmic function (ECF) ? factor ?(M) is inducible by, and confers resistance to, several cell envelope-acting antibiotics. Here, we demonstrate that ?(M) is responsible for intrinsic ?-lactam resistance, with ?(X) playing a secondary role. Activation of ?(M) upregulates several cell wall biosynthetic enzymes including one, PBP1, shown here to be a target for the beta-lactam cefuroxime. However, ?(M) still plays a major role in cefuroxime resistance even in cells lacking PBP1. To better define the role of ?(M) in ?-lactam resistance, we characterized suppressor mutations that restore cefuroxime resistance to a sigM null mutant. The most frequent suppressors inactivated gdpP (yybT) which encodes a cyclic-di-AMP phosphodiesterase (PDE). Intriguingly, ?(M) is a known activator of disA encoding one of three paralogous diadenylate cyclases (DAC). Overproduction of the GdpP PDE greatly sensitized cells to ?-lactam antibiotics. Conversely, genetic studies indicate that at least one DAC is required for growth with depletion leading to cell lysis. These findings support a model in which c-di-AMP is an essential signal molecule required for cell wall homeostasis. Other suppressors highlight the roles of ECF ? factors in counteracting the deleterious effects of autolysins and reactive oxygen species in ?-lactam-treated cells. PMID:22211522

Luo, Yun; Helmann, John D



Pattern of urinary tract infection in Kashmir and antimicrobial susceptibility.  


Antibiotic resistance of urinary tract pathogens has increased worldwide. The purpose of this study is to provide information regarding the causative agents of urinary tract infection in Kashmiri patients, identify the uropathogens responsible for the infection and study the antibiotic susceptibility patterns of the uropathogens. Clean voided mid-stream urine samples were collected from 2190 patients. The specimens were cultured and the isolates were identified using standard microbiological techniques. The antibiotic susceptibilities of the isolates were also determined. Of 2190 specimens, 591 (27%) showed significant growth upon culture. Approximately 84.1% (497/591) of the 591 patients with UTI were females, most of which belonged to the 21-30 age group (206). The males accounted for 15.9% (94/591) UTI cases. Most of the male patients belonged to the 21-30 age group (34). The lowest incidence of urinary tract infections was seen among the 13-20 years age group. Throughout this study males accounted for only 16% of all UTI cases. Escherichia coli was the most predominant isolate, 53.8% followed by Klebsiella pneumoniae 22.4% and Pseudomonas aeruginosa 7.6%. All isolates were fully sensitive to ofloxacin, and more than 94% were sensitive to cefuroxime. Apart from group D Streptococcus, the overall response to ampicillin by all isolates was less than 15%. The prevalence of multi-resistant Pseudomonas aeruginosa in community-acquired urinary tract infections is increasing. All Pseudomonas aeruginosa isolates were fully susceptible to cefuroxime and ofloxacin. It is recommended that cefuroxime and ofloxacin or both are used in the blind treatment of urinary tract infection while awaiting the culture and sensitivity results. Concurrent with the necessary shift in the prescription pattern, attention should be paid to restriction of antibiotic abuse in the community to retard development of further drug resistance. PMID:23540181

Ahmad, S



Development of a Long-Term Ascending Urinary Tract Infection Mouse Model for Antibiotic Treatment Studies  

PubMed Central

A model of ascending unobstructed urinary tract infection (UTI) in mice was developed to study the significance of the antibiotic concentration in urine, serum, and kidney tissue for efficacy of treatment of UTI in general and pyelonephritis in particular. Outbred Ssc-CF1 female mice were used throughout the study, and Escherichia coli was used as the pathogen. The virulence of 11 uropathogenic E. coli isolates and 1 nonpathogenic laboratory E. coli strain was examined. Strain C175-94 achieved the highest counts in the kidneys, and this strain was subsequently used as the infecting organism. The model gave reproducible bladder infections, i.e., bacteria were recovered from 22 of 23 control mice after 3 days, and histological examination of kidney tissue showed that of 14 infected kidneys, 7 (50%) showed major histological changes, whereas 3 of 36 uninfected kidneys showed major histological changes (P = 0.018). Once the model was established, the efficacies of different doses of cefuroxime and gentamicin, corresponding to active concentrations in urine only or in urine, serum, and kidney tissue simultaneously, were examined. All cefuroxime doses resulted in significantly lower counts in urine than control treatments, but the dose which produced concentrations of cefuroxime only in urine and not in serum or kidney tissue had no effect on kidney infection. Even low doses of gentamicin (0.05 mg/mouse) resulted in concentrations in renal tissue for prolonged times due to accumulation. All gentamicin doses had a significant effect (compared to the effect of the control treatment) on bacterial counts in urine and kidneys. The antibiotic effect on bacterial counts in bladders was negligible for unknown reasons. Use of the mouse UTI model is feasible for study of the effect of an antibiotic in the urinary system, although the missing antibacterial effect in the bladder needs further evaluation.

Hvidberg, Hanne; Struve, Carsten; Krogfelt, Karen A.; Christensen, Nils; Rasmussen, S?ren N.; Frimodt-M?ller, Niels



Implementation of a short course of prophylactic antibiotic treatment for prevention of postoperative infections in clean orthopaedic surgeries  

PubMed Central

Background & objectives: Perioperative antimicrobial prophylaxis constitutes the bulk of antimicrobial consumption in any hospital. This study was conducted at a level 1 Trauma Centre of a tertiary care hospital of India to assess the efficacy of a short (24 h) course of perioperative antibiotic prophylactic regimen in preventing surgical site infections (SSI) in open reduction and internal fixation (ORIF) of closed fractures of limbs and to assess if the same can be implemented as a general policy. Methods: Patients of either sex, aged 18 yr or more, who were scheduled for ORIF and were willing and able to give informed consent, were included in the study. Patients were randomly allocated into two groups. Group 1 (n=100) received 3 doses of 1 g i.v. cefuroxime perioperatively spaced 12 h apart and group 2 (n=97) received the conventional existing regimen [5 days of i.v. antibiotics (cefuroxime 1 g twice daily along with amikacin 15 mg/kg in 2 divided doses), followed by oral cefuroxime, 500 mg twice daily till suture removal]. Results: Of the 197 patients, four patients developed a surgical site infection (three with methicillin resistant Staphylococcus aureus and one Acinetobacter baumanii). Of these, two patients were in group 1 and the remaining two in group 2. These patients were treated with i.v. antibiotics based on the culture and antimicrobial sensitivity reports. The cost of the short course treatment was 150 per patient as compared to 1,900 per patient for conventional regimen. Interpretation & conclusions: There was no significant difference in rates of SSI among the two groups in our study. Cost evaluation revealed that shorter course was less expensive than conventional long course regimen. Implementation of a short course perioperative regimen will go a long way in reducing antimicrobial resistance, cost and adverse reactions to antimicrobials.

Mathur, Purva; Trikha, Vivek; Farooque, Kamran; Sharma, Vijay; Jain, Neetu; Bhardwaj, Nidhi; Sharma, Satyapriya; Misra, M.C.



Microbiologically active Mannich bases derived from 1,2,4-triazoles. The effect of C-5 substituent on antibacterial activity.  


Our research proved that chemical character of the C-5 substituent significantly determines the antibacterial activity of the Mannich bases derived from 4,5-disubstituted 1,2,4-triazole-3-thiones. This activity was considerably increased by an introduction of a chlorine atom to the phenyl ring. The obtained compounds were particularly active against opportunistic bacteria (Bacillus subtilis and Bacillus cereus). The antibacterial activity of some Mannich bases was similar or higher than the activity of commonly used antibiotics such as ampicillin and cefuroxime. PMID:23543889

Plech, Tomasz; Wujec, Monika; Majewska, Magdalena; Kosikowska, Urszula; Malm, Anna



Minimum inhibitory concentrations for 25 selected antimicrobial agents against Dichelobacter nodosus and Fusobacterium strains isolated from footrot in sheep of Portugal and Spain.  


The agar dilution method was used to determine the inhibitory activity of 25 antimicrobial agents against 69 strains of Dichelobacter nodosus and 108 strains of the genus Fusobacterium, all of which were isolated from 90 clinical cases of ovine footrot between October 1998 and November 2000. In the case of the micro-organisms belonging to the genus Fusobacterium, the six beta-lactams studied (benzyl penicillin, ampicillin, cloxacillin, cefadroxil, cefuroxime and cephalexine) proved to be, in general, the most effective antimicrobial agents. Chloramphenicol, clindamycin and doxycycline were also quite active against Fusobacterium spp. With regard to the 69 strains of D. nodosus tested, the levels of resistance remain low. PMID:15330985

Jiménez, R; Píriz, S; Mateos, E; Vadillo, S



Antiinfective agents affecting cognition: a review.  


The adverse effects of antimicrobial, antiviral and anthelmintic agents on cognitive function have attracted substantial research interest in the last three decades. There are sporadic individual reports of negative effects on cognition by penicillin, amoxycillin, cloxacillin, cephalothin, cephazolin, cefuroxime, ceftazidime, tobramycin, doxycycline, chloramphenicol, lomefloxacin, pefloxacin, isoniazid, amphotericin B, acyclovir, chloroquine, clioquinol, metronidazole, sulfasalazine among other antimicrobial agents. Antimicrobial and antiprotozoal agents reported to affect consciousness in particular are amoxycillin, cloxacillin, ticarcillin, cephalothin, cephazolin, ceftazidime, cefuroxime, tobramycin, lomefloxacin, pefloxacin, amphotericin B, acyclovir, chloroquine, clioquinol, and metronidazole. The relationship between some other antimicrobial, antiviral and anthelmintic agents and cognition is yet to be clearly established due to the existence of controversial reports. Few antimicrobial, antiviral or anthelmintic agents have been found to be devoid of any effect on memory. A few others may enhance cognitive performance. This review focuses on this issue, summarizing the published clinical and experimental studies relevant to this area of research and discussing its clinical implications. Suggested mechanisms responsible for the adverse effects of different antimicrobial, antiviral, and anthelmintic agents on cognitive function are reported. Future recommendations point to immense research opportunities to investigate the cognitive profile of newly discovered antimicrobial agents. PMID:18230542

Khalifa, A E



In vitro selective antibiotic concentrations of beta-lactams for penicillin-resistant Streptococcus pneumoniae populations.  

PubMed Central

Therapeutic regimens containing beta-lactam antibiotics are selecting penicillin-resistant Streptococcus pneumoniae populations all over the world. The selective pressure after 4 h of exposure to different concentrations of amoxicillin, cefixime, cefuroxime, and cefotaxime for low-level or high-level penicillin-resistant S. pneumoniae was evaluated in an in vitro model with mixed populations with penicillin susceptibilities of 0.015, 0.5, 1, and 2 micrograms/ml. The antibiotic concentration selecting for low-level resistance strongly reduced the susceptible population. Increasing antibiotic concentrations tended to decrease the total proportion of penicillin-resistant bacteria because of reduced numbers of the low-level-resistant population. The antibiotic concentration selecting for high-level resistance produced fewer resistant populations, but most of the organisms selected represented high-level resistance. In general, amoxicillin was a good selector for the low-level-resistant population and a poor selector for high-level resistance; cefuroxime and cefotaxime were poor selectors for low-level resistance and better selectors than amoxicillin for high-level penicillin resistance. Cefixime was the best selector of low-level penicillin resistance. When only resistant populations were mixed, the strains with high-level resistance were selected even at low antibiotic concentrations. Determination of the effects of selective antibiotic concentrations on mixed cultures of bacteria expressing different antibiotic resistance levels may help researchers to understand the ecology and epidemiology of penicillin-resistant S. pneumoniae populations.

Negri, M C; Morosini, M I; Loza, E; Baquero, F



Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development.  


New drug deployment strategies are imperative to address the problem of drug resistance, which is limiting the management of infectious diseases and cancers. We evolved resistance in Escherichia coli toward 23 drugs used clinically for treating bacterial infections and mapped the resulting collateral sensitivity and resistance profiles, revealing a complex collateral sensitivity network. On the basis of these data, we propose a new treatment framework-collateral sensitivity cycling-in which drugs with compatible collateral sensitivity profiles are used sequentially to treat infection and select against drug resistance development. We identified hundreds of such drug sets and demonstrated that the antibiotics gentamicin and cefuroxime can be deployed cyclically such that the treatment regimen selected against resistance to either drug. We then validated our findings with related bacterial pathogens. These results provide proof of principle for collateral sensitivity cycling as a sustainable treatment paradigm that may be generally applicable to infectious diseases and cancer. PMID:24068739

Imamovic, Lejla; Sommer, Morten O A



In Vitro Activities of Antibiotics against Plasmodium falciparum Are Inhibited by Iron  

PubMed Central

The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated on Plasmodium falciparum clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro activity against P. falciparum, which increased after a prolonged exposure (96 or 144 h). In the presence of iron (FeCl3), only the activities of tetracyclines and norfloxacin were decreased. Their in vitro activity against intraerythrocytic stages of multidrug-resistant P. falciparum and their efficacy in vivo favor the use of antibiotics as antimalarial drugs. However, due to their slow antimalarial action and to the fact that they act better after prolonged contact, they probably need to be administered in conjunction with a rapidly acting antimalarial drug, such as a short course of chloroquine or quinine.

Pradines, Bruno; Rogier, Christophe; Fusai, Thierry; Mosnier, Joel; Daries, William; Barret, Eric; Parzy, Daniel



Molecular and biochemical characterization of a novel class A beta-lactamase (HER-1) from Escherichia hermannii.  


Escherichia hermannii showed a low level of resistance to amoxicillin and ticarcillin, reversed by clavulanate, and a moderate susceptibility to piperacillin but was susceptible to all cephalosporins. A bla gene was cloned and encoded a typical class A beta-lactamase (HER-1, pI 7.5), which shares 45, 44, 41, and 40% amino acid identity with other beta-lactamases, AER-1 from Aeromonas hydrophila, MAL-1/Cko-1 from Citrobacter koseri, and TEM-1 and LEN-1, respectively. No ampR gene was detected. Only penicillins were efficiently hydrolyzed, and no hydrolysis was observed for cefuroxime and broad-spectrum cephalosporins. Sequencing of the bla gene in 12 other strains showed 98 to 100% identity with bla(HER-1). PMID:12878539

Beauchef-Havard, Anne; Arlet, Guillaume; Gautier, Valerie; Labia, Roger; Grimont, Patrick; Philippon, Alain



Molecular and Biochemical Characterization of a Novel Class A ?-Lactamase (HER-1) from Escherichia hermannii  

PubMed Central

Escherichia hermannii showed a low level of resistance to amoxicillin and ticarcillin, reversed by clavulanate, and a moderate susceptibility to piperacillin but was susceptible to all cephalosporins. A bla gene was cloned and encoded a typical class A ?-lactamase (HER-1, pI 7.5), which shares 45, 44, 41, and 40% amino acid identity with other ?-lactamases, AER-1 from Aeromonas hydrophila, MAL-1/Cko-1 from Citrobacter koseri, and TEM-1 and LEN-1, respectively. No ampR gene was detected. Only penicillins were efficiently hydrolyzed, and no hydrolysis was observed for cefuroxime and broad-spectrum cephalosporins. Sequencing of the bla gene in 12 other strains showed 98 to 100% identity with blaHER-1.

Beauchef-Havard, Anne; Arlet, Guillaume; Gautier, Valerie; Labia, Roger; Grimont, Patrick; Philippon, Alain



Antibiotic sensitivity of Salmonella strains from food-handlers in the period 1980-1988 in Italy.  


Throughout the past nine years, between 1980 and 1988, we tested 1,205,257 food-handlers as Salmonella carriers in Milan. We isolated 20,286 Salmonella strains with annual average prevalence of 1.68%, fairly costant in recent years. The serotype isolated confirm the prevalence of minor Salmonella, such as S. thypimurium, S. panama, S. anatum, S. london, S. derby, S. infantis, S. heidelberg, S. bredeney, S. braenderup. The frequency of new strains decreased from 15 in 1980 to 1 in 1988 and these were infrequent serogroups. Salmonella strains isolated were generally sensitive to aminoglycoside antibiotics (tobramycin, netilmicin), while they were often resistant to rifampicin, aztreonam, and sometimes to cefuroxime and tetracycline with multiple-resistance. PMID:12041794

Gelosa, L



[Pharmacological aspects of Lyme borreliosis].  


Clinical signs of Lyme boreliosis in humans are versatile and in their whole scope they finally affect the nervous system, heart, and joints. The therapeutic effect of antibiotics is maximal in the first acute stage of the disease when doxycycline and amoxiciline are administered. These antibiotics possess a comparable in vitro effect, tissue penetration, pharmacokinetics, and therapeutic effect. The treatment of disseminated infections in the second stage, such as neuroborreliosis, carditis, and iritis, is difficult and with relative success they are treated with large doses of penicillin G, or cefriaxon, and doxycycline. The treatment of the third stage of borreliosis aims at chronic inflammatory changes in the affected organs. Antibiotics, however, are successfully effective only in 50% of cases. Administration of antibiotics, such as tetracycline, cefuroxim, doxycycline, or large doses of penicillin is a long-term one, coming up to four weeks. A special therapeutic regimen is used in pregnant women and children. PMID:15369225

Dvoráková, J; Celer, V



Predicting evolutionary potential: in vitro evolution accurately reproduces natural evolution of the tem beta-lactamase.  

PubMed Central

To evaluate the validity of our in vitro evolution method as a model for natural evolutionary processes, the TEM-1 beta-lactamase gene was evolved in vitro and was selected for increased resistance to cefotaxime, cefuroxime, ceftazadime, and aztreonam, i.e., the "extended-spectrum" phenotype. The amino acid substitutions recovered in 10 independent in vitro evolvants were compared with the amino acid substitutions in the naturally occurring extended-spectrum TEM alleles. Of the nine substitutions that have arisen multiple times in naturally occurring extended-spectrum TEM alleles, seven were recovered multiple times in vitro. We take this result as evidence that our in vitro evolution technique accurately mimics natural evolution and can therefore be used to predict the results of natural evolutionary processes. Additionally, our results predict that a phenotype not yet observed among TEM beta-lactamases in nature-resistance to cefepime-is likely to arise in nature.

Barlow, Miriam; Hall, Barry G



Biochemical Characterization of the FEZ-1 Metallo-?-Lactamase of Legionella gormanii ATCC 33297T Produced in Escherichia coli  

PubMed Central

The blaFEZ-1 gene coding for the metallo-?-lactamase of Legionella (Fluoribacter) gormanii ATCC 33297T was overexpressed via a T7 expression system in Escherichia coli BL21(DE3)(pLysS). The product was purified to homogeneity in two steps with a yield of 53%. The FEZ-1 metallo-?-lactamase exhibited a broad-spectrum activity profile, with a preference for cephalosporins such as cephalothin, cefuroxime, and cefotaxime. Monobactams were not hydrolyzed. The ?-lactamase was inhibited by metal chelators. FEZ-1 is a monomeric enzyme with a molecular mass of 29,440 Da which possesses two zinc-binding sites. Its zinc content did not vary in the pH range of 5 to 9, but the presence of zinc ions modified the catalytic efficiency of the enzyme. A model of the FEZ-1 three-dimensional structure was built.

Mercuri, Paola Sandra; Bouillenne, Fabrice; Boschi, Letizia; Lamotte-Brasseur, Josette; Amicosante, Gianfranco; Devreese, Bart; van Beeumen, Jozef; Frere, Jean-Marie; Rossolini, Gian Maria; Galleni, Moreno



Increase resistant rates and ESBL production between E. coli isolates causing urinary tract infection in young patients from Iran  

PubMed Central

Emerging antimicrobial resistance rates and Extended-spectrum beta-lactamase producing Escherichia coli recovered from urinary tract infections (UTI) is an increasing problem in specific regions, limiting therapeutic options. One hundred E. coli isolates causing UTI in patients with age from 2 months to 12 years admitted at CMC in the period of April 2009 to March 2010 were tested for antibiotic susceptibility using the disk diffusion method. Surprisingly high resistance rates were recorded for E. coli against TMP/SMX (84%), cefalotin (66%), cefuroxime (50%), cefixime (50%) and ceftriaxone (45%). Antimicrobial susceptibility of E. coli isolates was followed by meropenem (98%), amikacin (95%), nitrofurantoin (91%) and gentamicin (68%). Extended spectrum beta-lactamase production, was observed in 32% of community and 42% of nosocomial isolates. The results of this study and numerous observations regarding the increasing resistance to these antibiotics, in several countries, emphasize the need for local population-specific surveillance for guiding empirical therapy for UTI in children.

Pourakbari, Babak; Ferdosian, Farzad; Mahmoudi, Shima; Teymuri, Mostafa; Sabouni, Farah; Heydari, Hossein; Ashtiani, Mohammad Taghi Haghi; Mamishi, Setareh



Determination of ticarcillin levels in serum by high-pressure liquid chromatography.  

PubMed Central

A high-pressure liquid chromatographic method for determining the concentrations of ticarcillin in serum was developed and compared, with 93 patient sera, to a standard agar well diffusion bioassay. For analysis, serum plus temocillin, the internal standard, were extracted with chloroform-n-amyl alcohol and back extracted into phosphate buffer. A reverse-phase C18 column and an ammonium acetate-methanol mobile phase were used with detection at 242 nm. Reproducibility studies yielded coefficients of variation ranging from 2.4 to 4.7% for low, mid, and high controls. Although cefoxitin, cephalothin, and cefuroxime exhibited retention similar to that of ticarcillin, a wide range of commonly administered antibiotics and other drugs did not interfere. The high-pressure liquid chromatographic assay is an accurate, reproducible method for determining the concentration of ticarcillin in serum during multiple antibiotic therapy or when rapid results are required.

Shull, V H; Dick, J D



Novel plasmid-mediated beta-lactamase from Escherichia coli that inactivates oxyimino-cephalosporins.  

PubMed Central

A highly cephem-resistant Escherichia coli strain, FP1546, isolated from the fecal flora of laboratory dogs previously administered beta-lactam antibiotics was found to produce a beta-lactamase, FEC-1, of 48-kilodalton size and pI 8.2. FEC-1 hydrolyzed cefuroxime, cefotaxime, cefmenoxime, and ceftriaxone, as well as the enzymatically less-stable antibiotics cephaloridine, cefotiam, and cefpiramide. Of the oxyimino-cephalosporins, ceftizoxime was fairly stable to FEC-1. FEC-1 differed notably from chromosomal E. coli cephalosporinase, especially in its broad-spectrum substrate profile and its high inhibition by clavulanic acid, sulbactam, and imipenem. A conjugation study revealed that FEC-1 was encoded by a 74-megadalton plasmid, pFCX1. This may be the first instance of a plasmid-mediated oxyimino-cephalosporinase from E. coli.

Matsumoto, Y; Ikeda, F; Kamimura, T; Yokota, Y; Mine, Y



Susceptibilities of beta-lactamase-positive and -negative strains of Campylobacter coli to beta-lactam agents.  

PubMed Central

The percentages of susceptibility of 28 strains of Campylobacter coli to beta-lactam agents were 96% for amoxicillin and ampicillin, 57% for ticarcillin, 4% for cefoxitin and cefuroxime, 61% for cefotaxime, and 11% for ceftazidime. None of the strains were susceptible to penicillin G, piperacillin, cefazolin, cephalothin, cefamandole, and cefoperazone. All strains were susceptible to imipenem and ciprofloxacin, and 21% were susceptible to erythromycin. A beta-lactamase was detected in 68% of the strains by cefinase disks and by the nitrocefin method. The beta-lactamase-positive strains were significantly less susceptible to amoxicillin, ampicillin, and ticarcillin than the beta-lactamase-negative strains (P < or = 0.003). Clavulanic acid (0.25 microgram/ml) but not sulbactam and tazobactam (2 micrograms/ml) lowered to susceptible levels the amoxicillin and ampicillin MICs of the only strain of C. coli resistant to amoxicillin, ampicillin, and ticarcillin.

Lachance, N; Gaudreau, C; Lamothe, F; Turgeon, F



Comparative efficacy of gemifloxacin in experimental models of pyelonephritis and wound infection.  


Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than gemifloxacin (P < 0.01). No comparator agent had greater activity than gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection. PMID:10824038

Berry, V; Page, R; Satterfield, J; Singley, C; Straub, R; Woodnutt, G



Comparative in vivo activity of gemifloxacin in a rat model of respiratory tract infection.  


The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of significant benefit in the treatment of RTI. PMID:10824037

Berry, V; Page, R; Satterfield, J; Singley, C; Straub, R; Woodnutt, G



Effects of Gender and Seasonal Variation on the Prevalence of Bacterial Septicemia Among Young Children in Benin City, Nigeria  

PubMed Central

Aim To determine the effects of gender and seasonal variations on the prevalence of bacterial septicaemia among children 5 years and younger, and to identify the bacterial agents responsible for septicaemia and their antibiotic susceptibility profiles. Methods Blood was collected from 1,724 children (967 males and 757 females) aged 1 day to 5 years with clinical signs and symptoms of septicaemia. This study was carried out from 1 January to 31 December 2007 at the University of Benin Teaching Hospital, Benin City, Nigeria. The blood samples were processed to diagnose bacterial septicaemia. Bacterial isolates were identified and susceptibility test was performed using standard techniques. Results An overall prevalence of 22.10% of confirmed bacterial septicaemia was observed in this study. Generally, gender and seasonal variations did not significantly affect the prevalence of bacterial septicaemia, though females (50.57%) during the dry season had significantly (p < 0.001) higher prevalence than their male counterparts (19.91%). Staphylococcus aureus was the predominant bacterial isolate causing septicaemia in both seasons, while Citrobacter freundii was the least frequent. Pseudomonas aeruginosa was not recovered during the dry season. Most isolates were susceptible to gentamicin and cefuroxime, but only 1.44% of Staphylococcus aureus strains were susceptible to ceftriaxone. Conclusion Bacterial septicaemia was observed in 22.1% of children 5 years and younger with clinical signs and symptoms of septicaemia. Seasonal variation did not affect the prevalence. Effect of gender was only noticed in the dry season, where females had a higher prevalence than males. Gentamicin and cefuroxime were the most active antibacterial agents. Rational use of antibiotics is advocated.

Omoregie, R; Egbe, CA; Ogefere, HO; Igbarumah, I; Omijie, RE



Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study  

PubMed Central

Background: Although fluoroquinolones are sometimes associated with mild, transient elevations in aminotransferase levels, serious acute liver injury is uncommon. Regulatory warnings have identified moxifloxacin as presenting a particular risk of hepatotoxicity. Thus, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents. Methods: We conducted a population-based, nested, case–control study using health care data from Ontario for the period April 2002 to March 2011. We identified cases as outpatients aged 66 years or older with no history of liver disease, and who were admitted to hospital for acute liver injury within 30 days of receiving a prescription for 1 of 5 broad-spectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, we selected up to 10 age- and sex-matched controls from among patients who had received a study antibiotic, but who were not admitted to hospital for acute liver injury. We calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference. Results: A total of 144 patients were admitted to hospital for acute liver injury within 30 days of receiving a prescription for one of the identified drugs. Of these patients, 88 (61.1%) died while in hospital. After multivariable adjustment, use of either moxifloxacin (adjusted OR 2.20, 95% confidence interval [CI] 1.21–3.98) or levofloxacin (adjusted OR 1.85, 95% CI 1.01–3.39) was associated with an increase in risk of acute liver injury relative to the use of clarithromycin. We saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil. Interpretation: Among older outpatients with no evidence of liver disease, moxifloxacin and levofloxacin were associated with an increased risk of acute liver injury relative to clarithromycin.

Paterson, J. Michael; Mamdani, Muhammad M.; Manno, Michael; Juurlink, David N.



Intracellular activity of antibiotics against Staphylococcus aureus in a mouse peritonitis model.  


Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response to therapy and the high frequency of infection recurrence. The intracellular persistence of staphylococci has been recognized and could offer a good explanation for these treatment difficulties. Knowledge of the interplay between intracellular antibiotic activity and the overall outcome of infection is therefore important. Several intracellular in vitro models have been developed, but few experimental animal models have been published. The mouse peritonitis/sepsis model was used as the basic in vivo model exploring a quantitative ex vivo extra- and intracellular differentiation assay. The intracellular presence of S. aureus was documented by electron microscopy. Five antibiotics, dicloxacillin, cefuroxime, gentamicin, azithromycin, and rifampin (rifampicin), were tested in the new in vivo model; and the model was able to distinguish between their extra- and intracellular effects. The intracellular effects of the five antibiotics could be ranked as follows as the mean change in the log(10) number of CFU/ml (Delta log(10) CFU/ml) between treated and untreated mice after 4 h of treatment: dicloxacillin (3.70 Delta log(10) CFU/ml) > cefuroxime (3.56 Delta log(10) CFU/ml) > rifampin (1.86 Delta log(10) CFU/ml) > gentamicin (0.61 Delta log(10) CFU/ml) > azithromycin (0.21 Delta log(10) CFU/ml). We could also show that the important factors during testing of intracellular activity in vivo are the size, number, and frequency of doses; the time of exposure; and the timing between the start of infection and treatment. A poor correlation between the intracellular accumulation of the antibiotics and the actual intracellular effect was found. This stresses the importance of performing experimental studies, like those with the new in vivo model described here, to measure actual intracellular activity instead of making predictions based on cellular pharmacokinetic and MICs. PMID:19223616

Sandberg, Anne; Hessler, Jonas H R; Skov, Robert L; Blom, Jens; Frimodt-Møller, Niels



Susceptibilities of 228 penicillin- and erythromycin-susceptible and -resistant pneumococci to RU 64004, a new ketolide, compared with susceptibilities to 16 other agents.  

PubMed Central

The susceptibilities of 228 penicillin- and erythromycin-susceptible and -resistant pneumococci to RU 64004, a new ketolide, were tested by agar dilution, and the results were compared with those for penicillin G, erythromycin, azithromycin, clarithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. RU 64004 was very active against all strains tested, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.016 microg/ml for erythromycin-susceptible strains (MIC, < or = 0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MIC, > or = 0.5 microg/ml). All other macrolides had MIC90s of 0.03 to 0.25 and > or = 128 microg/ml for erythromycin-susceptible and -resistant strains, respectively. Among erythromycin-resistant strains, clindamycin MICs for 28 of 91 (30.7%) were < or = 0.125 microg/ml. Pristinamycin MICs for all strains were < or = 1.0 microg/ml. MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.25 microg/ml, respectively, and were unaffected by susceptibility to penicillin or erythromycin. Vancomycin and imipenem inhibited all strains at < or = 0.5 and < or = 0.25 microg/ml, respectively. MICs of cefuroxime and cefotaxime rose with those of penicillin G. MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher for penicillin- and erythromycin-resistant strains. RU 64004 is the first member of the macrolide group which has low MICs for erythromycin-resistant pneumococci.

Ednie, L M; Spangler, S K; Jacobs, M R; Appelbaum, P C



Activity of telithromycin and comparators against bacterial pathogens isolated from 1,336 patients with clinically diagnosed acute sinusitis  

PubMed Central

Background Increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections has the potential to limit the effectiveness of antibiotics available to treat these infections. Since there are regional differences in the susceptibility patterns observed and treatment is frequently empirical, the selection of antibiotic therapy may be challenging. PROTEKT, a global, longitudinal multicentre surveillance study, tracks the activity of telithromycin and comparator antibacterial agents against key respiratory tract pathogens. Methods In this analysis, we examine the prevalence of antibacterial resistance in 1,336 bacterial pathogens, isolated from adult and paediatric patients clinically diagnosed with acute bacterial sinusitis (ABS). Results and discussion In total, 58.0%, 66.1%, and 55.8% of S. pneumoniae isolates were susceptible to penicillin, cefuroxime, and clarithromycin respectively. Combined macrolide resistance and reduced susceptibility to penicillin was present in 200/640 (31.3 %) of S. pneumoniae isolates (128 isolates were resistant to penicillin [MIC >= 2 mg/L], 72 intermediate [MIC 0.12–1 mg/L]) while 99.5% and 95.5% of isolates were susceptible to telithromycin and amoxicillin-clavulanate, respectively. In total, 88.2%, 87.5%, 99.4%, 100%, and 100% of H. influenzae isolates were susceptible to ampicillin, clarithromycin, cefuroxime, telithromycin, and amoxicillin-clavulanate, respectively. In vitro, telithromycin demonstrated the highest activity against M. catarrhalis (MIC50 = 0.06 mg/L, MIC90 = 0.12 mg/L). Conclusion The high in vitro activity of against pathogens commonly isolated in ABS, together with a once daily dosing regimen and clinical efficacy with 5-day course of therapy, suggest that telithromycin may play a role in the empiric treatment of ABS.

Dohar, Joseph; Canton, Rafael; Cohen, Robert; Farrell, David John; Felmingham, David



Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics.  


This study examines the role of the penicillin-binding proteins (PBPs) of Bacteroides fragilis in the mechanism of resistance to different beta-lactam antibiotics. Six of the eight strains used were beta-lactamase-positive by the nitrocefin assay. These strains displayed reduced susceptibility to imipenem (MIC, 2-16 mg l(-1)) and some of them were resistant to the actions of ampicillin, cefuroxime, cephalexin, cefoxitin and piperacillin. When studying specific enzymic activity, the capacity to degrade cefuroxime was only detected in strains AK-4, R212 and 0423 and the capacity to degrade cephalexin was only detected in strains R212 and 2013E; no specific activity was detected on imipenem. Metallo-beta-lactamase activity was only detected in strains AK-2 and 119, despite the fact that the cfiA gene was identified in four strains (AK-2, 2013E, 119 and 7160). The cepA gene was detected in six of the eight strains studied. Three high-molecular-mass PBPs were detected in all strains; however, in some cases, PBP2Bfr and/or PBP3Bfr appeared as a faint band. PBP4Bfr and PBP5Bfr were detected in six strains. PBP6Bfr only was detected in B. fragilis strains AK-2, 0423, 119 and 7160. By analysis of the sequence of B. fragilis chromosomal DNA and comparison with genes that are known to encode PBPs in Escherichia coli, six genes that encode PBP-like proteins were detected in the former organism. The gene that encodes the PBP2 orthologue of E. coli (pbpABfr, PBP3Bfr) was sequenced in six of the eight strains and its implications for resistance were examined. Differences in the PBP3Bfr amino acid sequences of strains AK-2 and 119 and their production of beta-lactamases indicate that these differences are not involved in the mechanism of resistance to imipenem and/or cephalexin. PMID:14970246

Píriz, Segundo; Vadillo, Santiago; Quesada, Alberto; Criado, Jerónimo; Cerrato, Rosario; Ayala, Juan



NagZ-dependent and NagZ-independent mechanisms for ?-lactamase expression in Stenotrophomonas maltophilia.  


?-N-Acetylglucosaminidase (NagZ), encoded by the nagZ gene, is a critical enzyme for basal-level ampC derepression (ampC expression in the absence of ?-lactam challenge) in ampD and dacB mutants of Pseudomonas aeruginosa. Three mutants with a phenotype of basal-level L1 and L2 ?-lactamase derepression in Stenotrophomonas maltophilia have been reported, including KJ?DI (ampD(I) mutant), KJ?mrcA (mrcA mutant), and KJ?DI?mrcA (ampD(I) and mrcA double mutant). In this study, nagZ of S. maltophilia was characterized, and its roles in basal-level ?-lactamase derepression, induced ?-lactamase activities, and ?-lactam resistance of KJ?DI, KJ?mrcA, and KJ?DI?mrcA were evaluated. Expression of the nagZ gene was constitutive and not regulated by AmpR, AmpD(I), AmpN, AmpG, PBP1a, and NagZ. Introduction of ?nagZ into KJ?DI nearly abolished basal-level derepressed ?-lactamase activity; conversely, introduction of ?nagZ into KJ?mrcA did not affect it. At least two activator ligands (ALs) are thus considered responsible for ?-lactamase expression in the S. maltophilia system, specifically, the NagZ-dependent (AL1) and NagZ-independent (AL2) ligands responsible for the basal-level derepressed ?-lactamase activities of KJ?DI and KJ?mrcA, respectively. The contributions of AL1 and AL2 to the induced ?-lactamase activities may vary with the types of ?-lactams. nagZ inactivation did not affect aztreonam-, cefoxitin-, and carbenicillin-induced ?-lactamase activities, but it attenuated cefuroxime- and piperacillin-induced ?-lactamase activities. Introduction of ?nagZ into KJ, KJ?DI, KJ?mrcA, and KJ?DI?mrcA did not significantly change the MICs of the ?-lactams tested except that the MICs of cefuroxime and piperacillin moderately decreased in strains KJ?Z and KJ?DI?Z (nagZ mutants). PMID:22252801

Huang, Yi-Wei; Hu, Rouh-Mei; Lin, Cheng-Wen; Chung, Tung-Ching; Yang, Tsuey-Ching



NagZ-Dependent and NagZ-Independent Mechanisms for ?-Lactamase Expression in Stenotrophomonas maltophilia  

PubMed Central

?-N-Acetylglucosaminidase (NagZ), encoded by the nagZ gene, is a critical enzyme for basal-level ampC derepression (ampC expression in the absence of ?-lactam challenge) in ampD and dacB mutants of Pseudomonas aeruginosa. Three mutants with a phenotype of basal-level L1 and L2 ?-lactamase derepression in Stenotrophomonas maltophilia have been reported, including KJ?DI (ampDI mutant), KJ?mrcA (mrcA mutant), and KJ?DI?mrcA (ampDI and mrcA double mutant). In this study, nagZ of S. maltophilia was characterized, and its roles in basal-level ?-lactamase derepression, induced ?-lactamase activities, and ?-lactam resistance of KJ?DI, KJ?mrcA, and KJ?DI?mrcA were evaluated. Expression of the nagZ gene was constitutive and not regulated by AmpR, AmpDI, AmpN, AmpG, PBP1a, and NagZ. Introduction of ?nagZ into KJ?DI nearly abolished basal-level derepressed ?-lactamase activity; conversely, introduction of ?nagZ into KJ?mrcA did not affect it. At least two activator ligands (ALs) are thus considered responsible for ?-lactamase expression in the S. maltophilia system, specifically, the NagZ-dependent (AL1) and NagZ-independent (AL2) ligands responsible for the basal-level derepressed ?-lactamase activities of KJ?DI and KJ?mrcA, respectively. The contributions of AL1 and AL2 to the induced ?-lactamase activities may vary with the types of ?-lactams. nagZ inactivation did not affect aztreonam-, cefoxitin-, and carbenicillin-induced ?-lactamase activities, but it attenuated cefuroxime- and piperacillin-induced ?-lactamase activities. Introduction of ?nagZ into KJ, KJ?DI, KJ?mrcA, and KJ?DI?mrcA did not significantly change the MICs of the ?-lactams tested except that the MICs of cefuroxime and piperacillin moderately decreased in strains KJ?Z and KJ?DI?Z (nagZ mutants).

Huang, Yi-Wei; Hu, Rouh-Mei; Lin, Cheng-Wen; Chung, Tung-Ching



Restoration of Susceptibility of Intracellular Methicillin-Resistant Staphylococcus aureus to ?-Lactams: Comparison of Strains, Cells, and Antibiotics? †  

PubMed Central

Staphylococcus aureus invades eukaryotic cells. When methicillin-resistant S. aureus (MRSA) ATCC 33591 is phagocytized by human THP-1 macrophages, complete restoration of susceptibility to cloxacillin and meropenem is shown and the strain becomes indistinguishable from MSSA ATCC 25923 due to the acid pH prevailing in phagolysosomes (S. Lemaire et al., Antimicrob. Agents Chemother. 51:1627-1632, 2007). We examined whether this observation can be extended to (i) strains of current clinical and epidemiological interest (three hospital-acquired MRSA [HA-MRSA] strains, two community-acquired MRSA [CA-MRSA] strains, two HA-MRSA strains with the vancomycin-intermediate phenotype, one HA-MRSA strain with the vancomycin-resistant phenotype, and one animal [porcine] MRSA strain), (ii) activated THP-1 cells and nonprofessional phagocytes (keratinocytes, Calu-3 bronchial epithelial cells), and (iii) other ?-lactams (imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked reduction in MICs in broth at pH 5.5 compared with the MIC at pH 7.4 and (ii) sigmoidal dose-response curves with cloxacillin (0.01× to 100× MIC, 24 h of incubation) after phagocytosis by THP-1 macrophages that were indistinguishable from each other and from the dose-response curve for methicillin-susceptible S. aureus (MSSA) ATCC 25923 (relative potency [50% effect], 6.09× MIC [95% confidence interval {CI}, 4.50 to 8.25]; relative efficacy [change in bacterial counts over the original inoculum for an infinitely large cloxacillin concentration, or maximal effect], ?0.69 log CFU [95% CI, ?0.79 to ?0.58]). Similar dose-response curves for cloxacillin were also observed with MSSA ATCC 25923 and MRSA ATCC 33591 after phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By contrast, there was a lower level of restoration of susceptibility of MRSA ATCC 33591 to cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when the data were normalized for differences in MICs. We conclude that the restoration of MRSA susceptibility to ?-lactams after phagocytosis is independent of the strain and the types of cells but varies between ?-lactams.

Lemaire, Sandrine; Olivier, Aurelie; Van Bambeke, Francoise; Tulkens, Paul M.; Appelbaum, Peter C.; Glupczynski, Youri



Ultrasound-assisted matrix solid phase dispersive extraction for the simultaneous analysis of ?-lactams (four penicillins and eight cephalosporins) in milk by high performance liquid chromatography with photodiode array detection.  


The application of ultrasound-assisted matrix solid phase dispersive extraction for the confirmatory analysis of 12 ?-lactam antibiotics in milk by high performance liquid chromatography with photodiode array detection has been proposed herein. Four penicillins (cloxacillin, dicloxacillin, oxacillin, and amoxicillin) and eight cephalosporins (cefaclor, cefadroxil, ceftiofur, cefuroxime, cefoperazone, cefazolin, cephalexin, and cefotaxime) are effectively extracted using a mixed sorbent of Quick Easy Cheap Effective Rugged Safe technique and OASIS HLB providing a matrix free from any endogenous interference. Examined analytes were well resolved on an Inertsil ODS-3 analytical column with a mobile phase of CH(3)COONH(4) (0.05 M) and acetonitrile delivered under a gradient program. 1,7-Dimethyl-xanthine was used as internal standard. The method was validated meeting the European Legislation determining linearity, selectivity, stability, decision limit, detection capability, accuracy, precision, and ruggedness according to the Youden approach. Recoveries of all antibiotics rated from 85.0 to 115.7%, while RSD values were <12.7%. Finally, the method was successfully applied to milk samples purchased from local market. PMID:22941669

Karageorgou, Eftichia G; Samanidou, Victoria F; Papadoyannis, Ioannis N



High antibiotic susceptibility among bacterial pathogens in Swedish ICUs. Report from a nation-wide surveillance program using TA90 as a novel index of susceptibility.  


Local infection control measures, antibiotic consumption and patient demographics from 1999-2000 together with bacteriological analyses were investigated in 29 ICUs participating in the ICU-STRAMA programme. The median antibiotic consumption per ICU was 1147 (range 605-2143) daily doses per 1000 occupied bed d (DDD1000). Antibiotics to which > 90% of isolates of an organism were susceptible were defined as treatment alternatives (TA90). The mean number of TA90 was low (1-2 per organism) for Enterococcus faecium (vancomycin:VAN), coagulase negative staphylococci (VAN), Pseudomonas aeruginosa (ceftazidime:CTZ, netilmicin: NET) and Stenotrophomonas maltophilia (CTZ, trimethoprim-sulfamethoxazole: TSU), but higher (3-7) for Acinetobacter spp. (imipenem:IMI, NET, TSU), Enterococcus faecalis (ampicillin:AMP, IMI, VAN), Serratia spp. (ciprofloxacin:CIP, IMI, NET), Enterobacter spp. (CIP, IMI, NET, TSU), E. coli (cefuroxime:CXM, cefotaxime/eftazidime:CTX/CTZ, CIP, IMI, NET, piperacillin-tazobactam:PTZ, TSU), Klebsiella spp. (CTX/CTZ CIP, IMI, NET, PTZ, TSU) and Staphylococcus aureus (clindamycin, fusidic acid, NET, oxacillin, rifampicin, VAN). Of S. aureus isolates 2% were MRSA. Facilities for alcohol hand disinfection at each bed were available in 96% of the ICUs. The numbers of TA90 available were apparently higher than in ICUs in southern Europe and the US, despite a relatively high antibiotic consumption. This may be due to a moderate ecological impact of the used agents and the infection control routines in Swedish ICUs. PMID:15000555

Hanberger, Håkan; Erlandsson, Marcus; Burman, Lars G; Cars, Otto; Gill, Hans; Lindgren, Sune; Nilsson, Lennart E; Olsson-Liljequist, Barbro; Walther, Sten



Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift.  


Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to certain cephalosporins in penicillin-allergic patients is smaller than previously postulated. Medline and EMBASE databases were searched using the following keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 to 2005. Among 219 articles retrieved, 106 served as source material for this review. A significant increase in allergic reactions to cephalothin, cephaloridine, cephalexin, cefazolin, and cefamandole was observed in penicillin-allergic patients; no increase was observed with cefprozil, cefuroxime, ceftazidime, or ceftriaxone. Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins. First-generation cephalosporins have a modest cross-allergy with penicillins, but cross-allergy is negligible with 2nd- and 3rd-generation cephalosporins. Particular emphasis is placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents. PMID:17349459

Pichichero, Michael E



Antibiotics-why so many and when should we use them?  


Antibiotic prophylaxis in vascular surgery has been proven beneficial to reduce surgical site infections after reconstruction of the aorta, procedures on the leg that involve a groin incision, any procedure that implants a vascular prosthesis or endoluminal stent, and lower extremity amputation for ischemia. Bactericidal antibiotics administered before induction-cefazolin or cefuroxime for 1 to 2 days alone or in combination with vancomycin if a hospital wound surveillance program indicates a high incidence of methicillin-resistant Staphylococcus aureus infection-is recommended. If a patient is felt to be at increased risk for infection and require prosthetic grafting, the use of a rifampin-soaked (1 mg/mL) gelatin- or collagen-impregnated graft may decrease the incidence of wound and graft infection. Antibiotic treatment of established vascular graft infections should begin with broad-spectrum coverage for expected pathogens (S aureus, Staphylococcus epidermidis, Gram-negative bacteria) followed by culture-specific therapy based on antibiotic susceptibility testing. Specific antibiotic usage involves a decision regarding efficacy to expected or isolated pathogens versus its potential side effects and the drug costs. New applications for antibiotics in vascular surgery include the use of specific tetracyclines (doxycycline, azithromycin) as an inhibitor of matrix metalloproteinases to retard aortic aneurysm growth or for their antiinflammatory properties to retard atherogenesis related to Chylamydia pneumoniae. PMID:12478501

Bandyk, Dennis F



[Pharyngeal A-streptococcal infection encountered in the practical work of an internal medicine specialist].  


The problem of pharyngeal infections caused by beta-hemolytic streptococci of group A (BHSA) remains a challenge for both health providers and general medicine. The present paper was designed to provide the data suggesting the "reappearance" of a highly virulent BHSA infection and a rise in the frequency of its complications (such as acute rheumatic fever and toxic shock syndrome) and to substantiate the necessity of rational antibacterial therapy for the management of this pathology. The agents of choice for the treatment of acute forms of BHSA (tonsillitis and pharyngitis) include penicillins (amoxicillin, benzathine-penicillin, phenoxymethyl penicillin) and cephalosporins of the first generation (cephadroxyl) as well as macrolids (spiramycin, azithromycin, roxithromycin, midecamycin, josamycin) for the patients who do not tolerate beta-lactam antibiotics. Inhibitor-protected penicillins (amoxicillin, clavulanate) or cephalosporins of the second generations (cefuroxime-axetil) should be prescribed to the patients presenting with chronic recurring BHSA characterized by the rather high probability of colonization of the site of infection by beta-lactamase producing microorganisms. Lincosamine-derived antibiotics, such as lincomycin and clindamycin, are reserved for the patients with acute and chronic BHSA (tonsillitis and pharyngitis). PMID:23887373

Belov, B S



[Beta lactam resistance and molecular markers of 157 Haemophilus influenzae isolates from infants in Tunis].  


The aim of this study was to precise the capsular type of Haemophilus influenzae, to determine its susceptibility to beta-lactam agents, and to search for an eventual clonality between the clinical strains of the pathogen. Polymerase chain reaction was carried out to confirm the capsular type and to determine the beta-lactamase type. Minimum inhibitory concentrations (MICs) of beta-lactam agents for H. influenzae were determined by the agar dilution method on Haemophilus test medium, and the strains were analyzed by pulsed-field gel electrophoresis after SmaI restriction. Among 157 strains of H. influenzae studied, 12.1% was of serotype b. Sixty-seven strains (42.7%) were resistant to amoxicillin, among which 51 were resistant through production of TEM-type beta-lactamase while 16 showed high MICs for amoxicillin, amoxicillin + clavulanic acid, and cefuroxim, which suggested a resistance by modification of penicillin-binding proteins. Among the latter strains, five were producing TEM-type beta-lactamase. Cefotaxim, cefixim, and cefpodoxim had low MICs in all cases. The pulsed-field gel electrophoresis revealed 110 pulsotypes. All H. influenzae strains, including noncapsulated strains and serotype-b encapsulated strains, had a high level of heterogeneity, with diversity indices of respectively 0.67 and 0.94. PMID:19483779

Oueslati, S; Smaoui, H; Joubert, G; Dabernat, H; Kechrid, A



Comparison of agar disk diffusion, microdilution broth, and agar dilution for testing antimicrobial susceptibility of coagulase-negative staphylococci.  

PubMed Central

A collection of 120 oxacillin-susceptible and 120 oxacillin-resistant coagulase-negative staphylococci (CNS) from six tertiary care hospital laboratories were tested by agar disk diffusion, three microdilution broth systems (Sensititre, Dynatech, and Alpkem), and the Vitek AutoMicrobic system for comparison with reference agar dilution results. The antimicrobial agents tested were oxacillin, cefazolin, cefotaxime, cefuroxime, cefamandole, fusidic acid, rifampin, and vancomycin. Incubation was at 30 or 35 degrees C for 24, 48, and 72 h. The broth media were supplemented with 2% NaCl for some antimicrobial agents, and the agar dilution method was used with and without the addition of 4% NaCl. The CNS were identified to species by the method of Kloos and Schleifer. The results showed a lack of concordance between two hospitals with respect to oxacillin susceptibility testing by agar dilution with no NaCl supplement. The reasons are not clear but may be related to variations in media. The 4% NaCl supplement or extended incubation to 48 h eliminated this difference. The cefazolin and cefotaxime susceptibility results in the agar disk diffusion test were unreliable if accepted at face value. Cefamandole testing correlated well with the reference method regardless of the method used, and salt supplementation is not recommended. Most of the oxacillin-resistant CNS were resistant to the other beta-lactam drugs except cefamandole. Of 22 CNS resistant to cefamandole, 21 were S. haemolyticus.

Smith, J A; Henry, D A; Bourgault, A M; Bryan, L; Harding, G J; Hoban, D J; Horsman, G B; Marrie, T; Turgeon, P



Characterization of two plasmid-encoded cefotaximases found in clinical Escherichia coli isolates: CTX-M-65 and a novel enzyme, CTX-M-87.  


Three clinical strains of Escherichia coli (p168, p517 and p667) were collected in 2006 from three hospitals in Anhui Province (China). PCR and DNA sequencing revealed that E. coli p168 carried a novel extended-spectrum beta-lactamase (ESBL), which was designated CTX-M-87. The extended-spectrum beta-lactamase which was carried by E. coli p517 and E. coli p667 was previously named CTX-M-65. The deduced amino acid sequence of CTX-M-87, with pI 9.1, differed from that of CTX-M-14 by the substitutions Ala77-->Val and Pro167-->Leu. Like CTX-M-14, CTX-M-87 had a more potent hydrolytic activity against cefotaxime than against ceftazidime and had high affinity for cefuroxime and cefotaxime. These data show that mutations at position 167 in CTX-M do not always affect catalytic activity and substrate preference. PMID:19429759

Yin, Jun; Cheng, Jun; Sun, Zhen; Ye, Ying; Gao, Yu-Feng; Li, Jia-Bin; Zhang, Xue-Jun



In Vitro Analysis of ISEcp1B-Mediated Mobilization of Naturally Occurring ?-Lactamase Gene blaCTX-M of Kluyvera ascorbata  

PubMed Central

ISEcp1B has been reported to be associated with and to mobilize the emerging expanded-spectrum ?-lactamase blaCTX-M genes in Enterobacteriaceae. Thus, the ability of this insertion sequence to mobilize the blaCTX-M-2 gene was tested from its progenitor, Kluyvera ascorbata. Insertions of ISEcp1B upstream of the blaCTX-M-2 gene in K. ascorbata reference strain CIP7953 were first selected with cefotaxime (0.5 and 2 ?g/ml). In those cases, ISEcp1B brought promoter sequences enhancing blaCTX-M-2 expression in K. ascorbata. Then, ISEcp1B-mediated mobilization of the blaCTX-M-2 gene from K. ascorbata to Escherichia coli J53 was attempted. The transposition frequency of ISEcp1B-blaCTX-M-2 occurred at (6.4 ± 0.5) × 10?7 in E. coli. Cefotaxime, ceftazidime, and piperacillin enhanced transposition, whereas amoxicillin, cefuroxime, and nalidixic acid did not. Transposition was also enhanced when studied at 40°C.

Lartigue, Marie-Frederique; Poirel, Laurent; Aubert, Daniel; Nordmann, Patrice



In vitro analysis of ISEcp1B-mediated mobilization of naturally occurring beta-lactamase gene blaCTX-M of Kluyvera ascorbata.  


ISEcp1B has been reported to be associated with and to mobilize the emerging expanded-spectrum beta-lactamase blaCTX-M genes in Enterobacteriaceae. Thus, the ability of this insertion sequence to mobilize the blaCTX-M-2 gene was tested from its progenitor, Kluyvera ascorbata. Insertions of ISEcp1B upstream of the blaCTX-M-2 gene in K. ascorbata reference strain CIP7953 were first selected with cefotaxime (0.5 and 2 microg/ml). In those cases, ISEcp1B brought promoter sequences enhancing blaCTX-M-2 expression in K. ascorbata. Then, ISEcp1B-mediated mobilization of the blaCTX-M-2 gene from K. ascorbata to Escherichia coli J53 was attempted. The transposition frequency of ISEcp1B-blaCTX-M-2 occurred at (6.4+/-0.5)x10(-7) in E. coli. Cefotaxime, ceftazidime, and piperacillin enhanced transposition, whereas amoxicillin, cefuroxime, and nalidixic acid did not. Transposition was also enhanced when studied at 40 degrees C. PMID:16569841

Lartigue, Marie-Frédérique; Poirel, Laurent; Aubert, Daniel; Nordmann, Patrice



Resistance to antimicrobial drugs in Ghana  

PubMed Central

Background Antimicrobial drug resistance is a global issue that affects health, economic, and social development. The problem has been attributed to misuse of antimicrobial agents. Purpose To identify the agents of bacterial infection in Ghana, determine their antibiogram, and the possibility of setting up a surveillance program. Patients and methods A prospective quantitative study set in various hospitals including two teaching hospitals, seven regional hospitals, and two district hospitals in Ghana. A total of 5099 bacterial isolates from various clinical specimens were collected over a period of 1 year, including data related to the patients. Susceptibility of the isolates was determined by the Kirby–Bauer method. In addition, the minimum inhibitory concentration (MIC) of multidrug-resistant isolates of epidemiological significance was also determined using the E-test. Results A wide range of bacterial isolates were identified in both teaching and regional hospitals. High percentage of resistance was observed for tetracycline (82%), cotrimoxazole (73%), ampicillin (76%), and chloramphenicol (75%). Multidrug resistance was observed to a combination of ampicillin, tetracycline, chloramphenicol, and cotrimoxazole. On the other hand, a lower percentage of resistance was observed for ceftriaxone (6.3%), ciprofloxacin (11%), and amikacin (9.9%). Conclusion Generally, the prevalence of multidrug resistance was widespread among the various isolates. Some multidrug-resistant strains of Staphylococcus aureus, Salmonella typhi, and non-typhoidal Salmonella (NTS) had high MIC to cefuroxime (>256), gentamicin (>256), and ciprofloxacin (>32).

Newman, Mercy J; Frimpong, Enoch; Donkor, Eric S; Opintan, Japheth A; Asamoah-Adu, Alex



Clinical trial design for mild-to-moderate community-acquired pneumonia--an industry perspective.  


The use of noninferiority clinical trials is problematic unless one can establish the benefit of the active control versus no treatment. In community-acquired pneumonia, there are no placebo-controlled clinical trials establishing the benefit of antibiotic treatment, because the observed benefit of sulfapyridine and, subsequently, penicillin was established before the advent of randomized clinical studies. Historical data and observational cohort studies have established the marked decrease in mortality resulting from antimicrobial therapy; however, mortality is not a suitable end point for contemporary clinical trials for mild-to-moderate community-acquired pneumonia that is treated with oral antimicrobial drugs in ambulatory patients. There are historical clinical data that describe the timing of spontaneous recovery in patients with documented pneumonia caused by Streptococcus pneumoniae. In addition, there is one contemporary clinical trial that demonstrated superiority in clinical response of levofloxacin versus a cephalosporin regimen of ceftriaxone and/or cefuroxime for treatment of mild-to-moderate community-acquired pneumonia. Using either the historical data or the superiority study of levofloxacin, one can justify a noninferiority margin of 10% for the per-protocol population and 15% for the microbiologically evaluable population for future noninferiority clinical trials for mild-to-moderate community-acquired pneumonia. PMID:18986284

Echols, Roger M; Tillotson, Glenn S; Song, James X; Tosiello, Robert L



Swedish guidelines for diagnosis and treatment of infective endocarditis.  


Swedish guidelines for diagnosis and treatment of infective endocarditis (IE) by consensus of experts are based on clinical experience and reports from the literature. Recommendations are evidence based. For diagnosis 3 blood cultures should be drawn; chest X-ray, electrocardiogram, and echocardiography preferably transoesophageal should be carried out. Blood cultures should be kept for 5 d and precede intravenous antibiotic therapy. In patients with native valves and suspicion of staphylococcal aetiology, cloxacillin and gentamicin should be given as empirical treatment. If non-staphylococcal etiology is most probable, penicillin G and gentamicin treatment should be started. In patients with prosthetic valves treatment with vancomycin, gentamicin and rifampicin is recommended. Patients with blood culture negative IE are recommended penicillin G (changed to cefuroxime in treatment failure) and gentamicin for native valve IE and vancomycin, gentamicin and rifampicin for prosthetic valve IE, respectively. Isolates of viridans group streptococci and enterococci should be subtyped and MIC should be determined for penicillin G and aminoglycosides. Antibiotic treatment should be chosen according to sensitivity pattern given 2-6 weeks intravenously. Cardiac valve surgery should be considered early, especially in patients with left-sided IE and/or prosthetic heart valves. Absolute indications for surgery are severe heart failure, paravalvular abscess, lack of response to antibiotic therapy, unstable prosthesis and multiple embolies. Follow-up echocardiography should be performed on clinical indications. PMID:18027277

Westling, Katarina; Aufwerber, Ewa; Ekdahl, Christer; Friman, Göran; Gårdlund, Bengt; Julander, Inger; Olaison, Lars; Olesund, Christina; Rundström, Hanna; Snygg-Martin, Ulrika; Thalme, Anders; Werner, Maria; Hogevik, Harriet



Bacterial etiology and serotypes of acute otitis media in Mexican children.  


Streptococcus pneumoniae and Haemophilus influenzae have been consistently reported to be the two major bacterial pathogens responsible for acute otitis media (AOM), mainly from studies in the US and Europe. However, data on bacterial pathogens causing AOM in Latin America are limited. Understanding the relative importance of these pathogens in a specific setting, the serotype distribution, and their antibiotic susceptibility levels is important to provide local vaccine and treatment recommendations. We therefore conducted a prospective, multi-center, tympanocentesis-based epidemiological study of Mexican children three months to less than five years of age. Fifty percent of episodes were in children who had received at least one dose of PCV7. Overall, 64% of samples were culture positive for bacterial pathogens. H. influenzae and S. pneumoniae were the leading causes of bacterial AOM, detected in 34% and 29% of AOM episodes, respectively. The most commonly isolated S. pneumoniae serotypes were 19A, 19F and 23F. All H. influenzae isolates were identified as non-typeable. Seventy-four percent of S. pneumoniae were susceptible to penicillin, while 97% were susceptible to amoxicillin/clavulanate. All H. influenzae samples were susceptible to amoxicillin/clavulanate and cefotaxime, 95% to cefuroxime and 75% to ampicillin. Both S. pneumoniae and non-typable H. influenzae represent important targets for vaccination strategies to reduce AOM in Mexican children. PMID:21596081

Parra, Mercedes Macias; Aguilar, Gerardo Martinez; Echaniz-Aviles, Gabriela; Rionda, Romulo Galo; Estrada, Maria de Los Angeles Meza; Cervantes, Yolanda; Pirçon, Jean-Yves; Van Dyke, Melissa K; Colindres, Romulo E; Hausdorff, William P



Influence of carbon dioxide on growth and antibiotic susceptibility of coagulase-negative staphylococci cultured in human peritoneal dialysate.  

PubMed Central

Used peritoneal dialysis fluid was collected from patients undergoing continuous ambulatory peritoneal dialysis, and its pH and composition were assessed after incubation in either air or air with 5% CO2. Precipitation of calcium, magnesium, phosphate, and proteins occurred in the dialysis fluid incubated in air at 37 degrees C and was associated with a mean pH increase of 1.23 U. Incubation of dialysis fluid in air with 5% CO2 prevented precipitation and maintained pCO2 and pH levels at those found physiologically. Coagulase-negative staphylococcal strains isolated from patients with peritonitis tended to grow less well in dialysis fluid incubated in air than in dialysis fluid incubated in the carbon dioxide-enriched atmosphere. MICs of cefuroxime, ciprofloxacin, and vancomycin for seven strains of coagulase-negative staphylococci in dialysis fluid were markedly affected by atmosphere type (16 of 21 MICs). Of these 16 atmosphere-dependent MICs, 14 were at least fourfold higher in air than in air with 5% CO2. Images

Wilcox, M H; Smith, D G; Evans, J A; Denyer, S P; Finch, R G; Williams, P



Patterns of antibiotic susceptibility of gonococci isolated in Hong Kong, 1987-1990.  


Among the 14,528 strains of Neisseria gonorrhoeae isolated from the Government Social Hygiene Sexually Transmitted Disease (STD) Clinics in Hong Kong between 1987 and 1990, there has been a trend toward a decrease in the percentage of penicillin resistant strains in both penicillinase-producing and nonpenicillinase producing N. gonorrhoeae (PPNG and non-PPNG) and an increase in moderate resistant strains, whereas the proportion of sensitive strains has remained stable, except for a small increase in 1990. Presently, PPNG still accounts for 31% of all isolates. In early 1991, 100 consecutive isolates were tested for minimum inhibitory concentrations (MIC) against 6 commonly used antibiotics. Although ofloxacin has been used as the first-line treatment for gonorrhea for the last 5 years, there is still no sign of in vitro resistance. Two isolates with high-level tetracycline resistance (MIC greater than 16 mg/l) were detected that have not been seen before. Sensitivity to spectinomycin, cefuroxime, and ceftriaxone has also been maintained, and these drugs can probably be recommended as alternative treatments in noncompliant cases. Analysis of location of contact shows an increasing proportion of cases of gonorrhea from overseas, particularly from parts of China. Comparison with the limited information published in the region shows that the population sampled can be very heterogeneous. With the continued flux of international travel, one should be extremely careful when trying to get an accurate assessment of epidemiologic data. PMID:1411845

Kam, K M; Lai, C F; Egglestone, S; Chan, C B


Antibiotic therapy in pyogenic meningitis in paediatric patients.  


Objective: To isolate and identify the causative pathogen, antibiotic sensitivity testing and success rate of empirical antibiotic therapy in pyogenic meningitis. Study Design: Analytical study. Place and Duration of Study: The Children's Hospital and Institute of Child Health, Lahore, Pakistan, from March to July 2012. Methodology: The study was performed on 72 culture positive meningitis cases in children less than 15 years of age. This therapy was evaluated by monitoring the patient's clinical picture for 14 - 21 days. The collected data was analyzed by Chi-square test. Results: Seventeen different bacteria were isolated. The most commonly occurring bacteria were coagulase negative Staphylococci (25%), E. coli (12.5%), Klebsiella pneumoniae (8.3%), Streptococcus pneumoniae (8.3%) and Pseudomonas aeruginosa (8.3%). All the bacteria were sensitive to vancomycin (96.7%), meropenem (76.7%), amikacin (75%), ciprofloxacin (65.3%), chloramphenicol (46.5%), ceftazidime (44.2%), cefepime (41.9%), co-amoxiclav (38.0%), oxacillin (34.8%), cefotaxime (21.4%), penicillin (20.7%), ceftriaxone (18.6%), cefuroxime (14%) and ampicillin (6.9%). The combination of sulbactam and cefoperazone showed antimicrobial sensitivity of 81.4%. The success rate of empirical antibiotic therapy was 91.7%. Conclusion: It was found that Gram negative bacteria were the major cause of pyogenic meningitis. Mostly there were resistant strains against all commonly used antibiotics except vancomycin. All empirical antibiotic therapies were found to be most successful. PMID:24112254

Tajdin, Fauzia; Rasheed, Muhammad Adil; Ashraf, Muhammad; Rasheed, Huma; Ejaz, Hasan; Khan, Ghulam Jilany



Rapid assessment of antibiotic effects on Escherichia coli by bis-(1,3-dibutylbarbituric acid) trimethine oxonol and flow cytometry.  

PubMed Central

The effects of selected antibiotics on Escherichia coli were studied by flow cytometry with the fluorescent anionic membrane potential probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)]. The actions of azithromycin, cefuroxime, and ciprofloxacin at five times the MIC on E. coli were compared by the traditional CFU assay and flow cytometry. Changes in viable counts of bacteria determined with DiBAC4(3) and by flow cytometry following treatment with the antibiotics showed trends similar to those found by the CFU assays. However, viable counts determined by flow cytometry following antibiotic treatment were 1 to 2 logs higher than those determined by the corresponding CFU assays. All the results obtained by flow cytometry were provided within 10 min after sampling, whereas the conventional CFU assay results took at least 18 h. The results indicated that flow cytometry is a sensitive analytical technique that can rapidly monitor the physiological changes of individual microorganisms following antibiotic action and can provide information on the mode of action of a drug. The membrane potential probe DiBAC4(3) provides a robust flow cytometric indicator for bacterial cell viability.

Jepras, R I; Paul, F E; Pearson, S C; Wilkinson, M J



Spectrophotometric complexation of cephalosporins with palladium (II) chloride in aqueous and non-aqueous solvents  

NASA Astrophysics Data System (ADS)

The complexation reaction of cephalosporins namely cefotaxime (CTX), cefuroxime (CRX), and cefazolin (CEFAZ) with palladium (II) ions have been studied in water and DMF in 25 °C by the spectrophotometric methods. The method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulfate (SLS) as surfactant. The complexation process was optimized in terms of pH, temperature and contact time. The stoichiometry of all the complexes was found to be 2:1 (metal ion/ligand) for CTX, CRX, and 1:2 for CEFAZ. The stoichiometry of palladium (II)-cephalosporins was estimated by mole ratio and continuous variation methods and emphasized by the KINFIT program. These drugs could be determined by measuring the absorbance of each complex at its specific ?max. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms.

Bagheri Gh., A.; Yosefi rad, A.; Rezvani, M.; Roshanzamir, S.



The effect of amphotericin B, aztreonam, imipenem and cephalosporins on the bone marrow progenitor cell activity.  


The effects of certain antibiotics on the colony forming activity of human bone marrow cells in semisolid methylcellulose medium in vitro and on murine BM cells in spleen colony forming units (cfu-s) in vivo were evaluated. Amikacin, gentamicin, piperacillin, co-trimoxazole and pentamidine had little or no effect on human bone marrow progenitor cell function; amphotericin B, aztreonam, ceftazidime and imipenem caused significant suppression of human colony forming unit-erythroid (cfu-e), burst forming unit-erythroid (bfu-e) and colony forming unit-granulocyte macrophage (cfu-gm) at both peak and trough serum concentrations. At molar equivalent concentrations ceftazidime, cefotaxime and cefoperazone caused significant decreases in human cfu-e, bfu-e and cfu-gm in vitro (P less than 0.01) and murine cfu-s in vivo (P less than 0.05); cefoxitin, cefuroxime, ceftizoxime and ceftriaxone did not suppress human bone marrow progenitor cell activity. Gentamicin, piperacillin and ceftriaxone had no effect on murine cfu-s formation. Further studies to evaluate the effect of these antibiotics on human bone marrow in vivo are suggested. PMID:2050599

Charak, B S; Louie, R; Malloy, B; Twomey, P; Mazumder, A



Epidemiological characteristics and molecular typing of Salmonella enterica serovar Typhi during a waterborne outbreak in Eastern Anatolia.  


In this study, we aimed to study the molecular and epidemiological characteristics of Salmonella enterica serovar Typhi (S. Typhi) outbreak in Eastern Anatolia. Six hundred and thirty-seven patients from the same county with clinical diagnosis of typhoid fever were investigated with conventional methods from stool, urine and blood specimens. Antibiotic susceptibility tests and identifications were performed for positive specimens. Clonal relationships between the isolates were investigated using pulsed field gel electrophoresis (PFGE) method. A questionnaire was completed for the water consumption habits of patients. Of 91 culture positive specimens, 76 were blood, 13 were stool and 2 were urine. The isolates were resistant to ampicillin, ampicillin/sulbactam, chloramphenicol, cefuroxime, amikacin, gentamicin and trimethoprim-sulfamethoxazole. Although there was a single band difference in some isolates, PFGE results indicated that this was an outbreak caused by single strain according to the Tenover criteria. This outbreak thought to be associated with the consumption of tap water contaminated with sewage represents a breakdown of the basic public health and civil engineering infrastructure. Appropriate public health measures should be taken in order to avoid such outbreaks in the future. PMID:21929877

Bayram, Y; Güdücüo?lu, H; Otlu, B; Aypak, C; Gürsoy, N C; Uluç, H; Berkta?, M



[Pathogen and resistance spectrum in intraoral infections of the jaw-facial area with special reference to anaerobic bacteria].  


The aim of the study was to obtain more knowledge about the aerobic and anaerobic species causing maxillofacial infections and their resistance patterns today. Samples of pus or infectious tissue obtained from 110 patients of maxillofacial surgery were investigated microbiologically by means of aerobic and anaerobic cultivation. After incubation, the cultivated species were isolated and identified. The resistance patterns of all bacteria to penicillin, doxycyclin, and clindamycin were determined. Additionally, the resistance of aerobic species to cefuroxim was documented, and the MICs of cefoxitin and metronidazole to the anaerobic species were assessed. The most frequent disease was periodontitis apicalis (70 patients). Aerobic species alone were found in 23% of the samples, 14% of the infections harbored only anaerobes, but 63% were mixed infections caused by aerobic and anaerobic bacteria. In case of detection of aerobic species, streptococci were always identified. Five patients were infected by Staphylococcus aureus and gram-negative aerobic rods were found in eight patients. Most of the anaerobic species were black pigmented prevotella species (62), nonpigmented prevotellae (56), and fusobacteria (37). Metronidazole and clindamycin were highly efficient to gram-negative anaerobic rods. Most of the oral species were resistant to penicillin and doxycyclin. The indication for applying antibiotics should always be noticed and these drugs should only be used after determination of the pathogenic microorganisms and their susceptibility to the antimicrobials. PMID:10994323

Eick, S; Pfister, W; Korn-Stemme, S; Mägdefessel-Schmutzer, U; Straube, E



Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.  


In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC?0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance. PMID:23537749

Yap, Polly Soo Xi; Lim, Swee Hua Erin; Hu, Cai Ping; Yiap, Beow Chin



Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.  


The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta-lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase-negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%. PMID:1416851

Clendennen, T E; Echeverria, P; Saengeur, S; Kees, E S; Boslego, J W; Wignall, F S



Post-operative wound infection in salvage laryngectomy: does antibiotic prophylaxis have an impact?  


Salvage laryngectomy carries a high risk of post-operative infection with reported rates of 40-61%. The purpose of this study was to analyse infections in our own patients and review the potential impact of our current antibiotic prophylaxis (AP). A retrospective analysis of infection in 26 consecutive patients between 2000 and 2010 undergoing salvage total laryngectomy (SL) following recurrent laryngeal cancer after failed radiotherapy or chemo-radiation was undertaken. The antibiotic prophylaxis was intravenous teicoplanin, cefuroxime and metronidazole at induction and for the following 24 h. Infection was defined by Tabet and Johnson's grade 5, categorized as pharyngocutaneous fistula. Fifteen patients (58%) developed a post-operative wound infection, which occurred on average at 12 days after surgery. Univariate analysis demonstrated three risk variables that had a significant correlation with infection: alcohol consumption (p = 0.01), cN stage of tumour (p < 0.01), and pre-operative albumin levels <3.2 g/L (p = 0.012). There was a trend, though not significant, for increased infection in patients with high or low BMIs. The most common organisms isolated from clinical samples from infected patients were methicillin-resistant Staphylococcus aureus MRSA (43%), Pseudomonas aeruginosa (36%), Serratia marcescens, Proteus mirabilis and Enterococcus faecalis (7% each). All these organisms are typical hospital-acquired pathogens. Pseudomonas and Serratia were not covered by the prophylactic regime we used. The current antibiotic regime following SL is inadequate as the rate of infection is high. It would therefore seem logical to trial a separate antibiotic protocol of AP for patients undergoing SL that would include an extended course of antibiotics after the standard prophylaxis. In addition, infection rates may also be reduced by improving the metabolic state of patients pre-operatively by multi-disciplinary action. Steps should also be taken to reduce cross-infection with nosocomial pathogens in these patients. Other aspects of surgical management should be also taken in consideration. PMID:22274693

Scotton, William; Cobb, Richard; Pang, Leo; Nixon, Iain; Joshi, Anil; Jeannon, Jeanne-Pierre; Oakley, Richard; French, Gary; Hemsley, Carolyn; Simo, Ricard



Drug risk factors associated with a sustained outbreak of Clostridium difficile diarrhea in a teaching hospital.  


A case-control study was undertaken to identify and quantify antimicrobial and nonantimicrobial drug risk factors associated with a sustained outbreak of Clostridium difficile diarrhea on two medical (teaching and nonteaching) units and an oncology unit. In total, 80 cases associated with an endemic clone of toxigenic C difficile were compared with controls. Eighty controls were selected from a group of 290 controls randomly chosen from the outbreak period. The controls were matched to cases according to age, admitting diagnosis and unit of admission. Seventy (88%) patients in the case group received at least one antibiotic before diarrhea, compared with 37 (46%) patients in the control group. Major risk factors implicated in the development of C difficile diarrhea in hospitalized patients were the following antimicrobial agents: ceftazidime (adjusted odds ratio [aor]=26.01, 95% ci 5.67 to 119.19, P=0.0001); cefuroxime (aor=5.17, ci 1.86 to 14.36, P=0.005); ciprofloxacin (aor=3.81, ci 1.05 to 13.79, P=0.04); and clindamycin (aor=15.16, ci 2.93 to 78.44, P=0.004). This is the first time that the use of ciprofloxacin has been linked to the development of C difficile diarrhea. Use of gastrointestinal drugs (ranitidine, famotidine, cimetidine, omeprazole and sucralfate) was also an added risk (aor=3.20, ci 1.39 to 7.34, P=0.01); however, antineoplastic therapy was not significant (P<0.53). Recognition of the specific high risk drugs may spur more restricted use of these agents, which may help in controlling C difficile diarrhea in hospitalized patients. PMID:22346513

Nath, S K; Salama, S; Persaud, D; Thornley, J H; Smith, I; Foster, G; Rotstein, C



[A rare cause of pneumonia: Shewanella putrefaciens].  


Shewanella putrefaciens is a gram-negative, non-fermentative, oxidase positive, motile bacillus that produces hydrogen sulphide. It is found widely in the nature especially in marine environments. Although it is accepted as saprophytic, different clinical syndromes, most commonly skin or soft tissue infections, have been associated with S.putrefaciens, mainly in immunocompromised cases and patients with underlying diseases. However, pneumonia cases due to S.putrefaciens are quite limited in the literature. In this report, a case of pneumonia caused by S.putrefaciens was presented. A 43-year-old female patient was admitted to our hospital with the complaints of fever, cough, sputum and weakness. The patient has had brochiectasis since childhood and has used periodical antibiotic therapies due to pneumoniae episodes. She was diagnosed to have pneumonia based on the clinical, radiological and laboratory findings, and empirical antibiotic treatment with ciprofloxacin and ceftazidime combination was initiated. Gram-stained smear of sputum yielded abundant leucocytes and gram-negative bacteria, and the isolate grown in the sputum culture was identified as S.putrefaciens by conventional methods and API 20 NE (BioMerieux, France) system. The isolate was found susceptible to ceftriaxone, ceftazidime, cefepime, ciprofloxacin, piperacillin-tazobactam, cephoperazon-sulbactam, imipenem, amikacin, gentamicin and trimethoprime-sulphametoxazole; whereas resistant to ampicillin, amoxycillin-clavulanate, cefazolin and cefuroxime, by Kirby-Bauer disk diffusion method. According to the antibiogram results, the therapy was changed to ceftriaxone (1 x 2 g, intravenous). The patient was discharged with complete cure after 14 days of therapy. In conclusion, S.putrefaciens should be considered in patients with predisposing factors as an unusual cause of pneumonia and the characteristics such as H2S production and sensitivity to third generation cephalosporins and penicillins should be used to differentiate it from Pseudomonas aeruginosa and prevent the unnecessary use of antipseudomonal antibiotics. PMID:22399180

Durdu, Bülent; Durdu, Yasemin; Güleç, Nuray; Islim, Filiz; Biçer, Mualla



Pharmacodynamic modelling of intravenous antibiotic prophylaxis in elective colorectal surgery.  


Surgical-site infections are the leading cause of post-operative morbidity and mortality as well as increased costs following colorectal surgery. The purpose of this study was to evaluate different ?-lactam antimicrobial dosing regimens currently used for prophylaxis in elective colorectal procedures with the aim of identifying optimal antibiotics and dosing regimens. Serum pharmacokinetic (PK) parameters specific to each drug for use in pharmacodynamic (PD) modelling were obtained from the published literature. Susceptibility data for Escherichia coli, Bacteroides fragilis and Staphylococcus aureus for use in modelling simulations were obtained from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Monte Carlo simulation was used to evaluate the influence of dose and dosing frequency of tested antibiotics to achieve a prophylaxis target fT>MIC (time during which the free drug concentration exceeds the pathogen minimum inhibitory concentration) of 100% for up to 4h. Ertapenem 1g, cefuroxime 1.5 g and cefazolin 2 g were the only antibiotic regimens that consistently yielded target fT>MIC of 100% for the entire 4-h post-dose interval and against all targeted organisms more than 90% of the time. In contrast, cefoxitin, cefotetan and ampicillin/sulbactam yielded very poor predicted PK/PD performances. In conclusion, this study demonstrates the value of, and need for, applied PD research in the area of surgical prophylaxis. Whether cefoxitin, cefotetan or ampicillin/sulbactam should continue to be advocated as first-line agents for prophylaxis during elective colorectal surgery, particularly at the standard doses currently being used, is debatable. PMID:23182539

Moine, P; Fish, D N



How suitable are available pharmaceuticals for the treatment of sexually transmitted diseases? 1: Conditions presenting as genital discharges  

PubMed Central

The relative prevalence of sexually transmitted diseases and the agents available for the treatment of these diseases commonly presenting as genital discharges—namely, gonorrhoea, candidosis, trichomoniasis, and non-specific genital infection—are reviewed. The many agents that are active against gonorrhoea are listed, but none is ideal. Penicillin, in spite of its allergic side effects, has remained the drug of choice for 25 years because it is cheap, easily obtained, lacks toxicity even in pregnancy, and is effective. Its use is now threatened by the emergence of some strains that are able to produce penicillinase. At present the policy is to obtain the best results from penicillin while these are acceptable, but the clinician in some countries is badly served by the availability of procaine penicillin in aqueous suspension. There is a need for an effective penicillin or cephalosporin that is penicillinase resistant and cheap. Cefuroxime offers considerable hope but it is likely to be expensive in the immediate future. There are many preparations for the local treatment of candidosis. The confidence expressed by the manufacturers in recommending a three-day treatment is, it is hoped, based on a superior product. Nevertheless there is a need for a safe systemically absorbed fungicide which could be used orally, or some substance that could render the vagina an inhospitable environment for the organism. In the treatment of trichomoniasis the pharmaceutical industry in providing substances more than 90% effective in a single dose has done all that can be expected. Any further advances lie in the field of human behaviour rather than pharmaceutical research. In the treatment of non-specific genital infection the needs are more of research than of therapy. More knowledge is required of the cause of the condition and the relative role of contending pathogens, and of the results of treatment of patients and contacts in which Chlamydia or other suspect pathogens have been isolated.

Willcox, R. R.



Deep neck abscess: an analysis of microbial etiology and the effectiveness of antibiotics  

PubMed Central

The objective was to demonstrate the aerobic and anaerobic microbiology of deep neck space abscess and to analyze the coverage rate of different empiric antimicrobial agents. A retrospective review of hospitalized patients with deep neck abscess diagnosed at a tertiary-care, general hospital between April 2001 and October 2006. The study enrolled 100 patients. The bacterial cultures of 89 patients yielded positive results (89%). The predominant aerobes were viridans streptococci, Klebsiella pneumoniae, and Staphylococcus aureus. The predominant anaerobes included species of Prevotella, Peptostreptococcus, and Bacteroides. Five different combinations of empiric antibiotics, namely regimen 1: penicillin G and clindamycin and gentamicin, regimen 2: ceftriaxone and clindamycin, regimen 3: ceftriaxone and metronidazole, regimen 4: cefuroxime and clindamycin, and regimen 5: penicillin and metronidazole, were compared using the antimicrobial susceptibility of 89 cases. The coverage rates of regimens 1, 2, 3, 4, and 5 were 67.4%, 76.4%, 70.8%, 61.8%, and 16.9%, respectively. The coverage of regimen 5 was considerably worse than that of the other four regimens (p < 0.001). Regimen 2 was significantly better than regimen 4 (p < 0.001). Regimen 2 had better coverage than regimens 1 (p = 0.096) and 3 (p = 0.302), but the difference was not statistically significant. This study demonstrates the bacteriology of deep neck abscess and analyzes the coverage rate of different empiric antimicrobial agents. Regimens 1, 2, and 3 could be good candidates for empiric antibiotics. Pathogen-directed antimicrobial therapy should be adjusted after the culture results are obtained.

Yang, Shih-Wei; Lee, Ming-Hsun; See, Lai-Chu; Huang, Shu-Huan; Chen, Tsung-Ming; Chen, Tai-An



Natural antibiotic susceptibility of Klebsiella pneumoniae, K. oxytoca, K. planticola, K. ornithinolytica and K. terrigena strains.  


The natural susceptibility of 221 Klebsiella strains to 71 antibiotics was examined. The strains were isolated from clinical specimens and the environment, and belonged to K. pneumoniae subsp. pneumoniae (n = 40), K. pneumoniae subsp. ozaenae (37), K. pneumoniae subsp. rhinoscleromatis (10), K. oxytoca (44), K. planticola (40), K. ornithinolytica (25) and K. terrigena (25). MIC values were determined by a microdilution procedure in IsoSensitest broth according to the German standard (DIN). All Klebsiella spp. were naturally resistant or intermediate to amoxicillin, ticarcillin and to antibiotics to which other Enterobacteriaceae are also intrinsically resistant. Klebsiella spp. were naturally sensitive or intermediate to several penicillins, all tested cephalosporins, aminoglycosides, quinolones, tetracyclines, trimethoprim, cotrimoxazole, chloramphenicol and nitrofurantoin. K. pneumoniae subsp. ozaenae and subsp. rhinoscleromatis strains were generally more susceptible to antibiotics than strains of other Klebsiella taxa. K pneumoniae subsp. rhinoscleromatis was the most susceptible taxon, being highly susceptible to cefuroxime, anti-folates and naturally intermediate to erythromycin and clarithromycin. K. pneumoniae subsp. ozaenae was most susceptible to glycopeptides. K. oxytoca and K. terrigena strains were least susceptible to cefazoline, cefoperazone and fosfomycin, respectively. The results of the present study describe a database of the natural antimicrobial susceptibility of Klebsiella spp., which can be used for the validation of antibiotic susceptibility results of these bacteria. MIC patterns to beta-lactams indicate the expression of chromosomally encoded class A gamma-lactamases in all the species, including the subspecies of K. pneumoniae. Similar natural susceptibility patterns of K. planticola and K. ornithinolytica to all tested antibiotics support the status of K. ornithinolytica as a biovar of K. planticola. PMID:11339246

Stock, I; Wiedemann, B



Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe.  


Consecutive klebsiellae were collected from ICU patients at 35 centres in Western and Southern Europe. Of 966 isolates obtained, 716 were Klebsiella pneumoniae, 248 were Klebsiella oxytoca and two were Klebsiella ozaenae. Most were from Belgium, France, Germany, Holland, Italy, Portugal, Spain, Turkey and a few from Greece and the UK. Production of extended-spectrum beta-lactamases (ESBLs) was inferred in 220 isolates on the basis of synergy between ceftazidime and clavulanate. Putative ESBL producers were received from 23 centres, including 20 of the 27 that contributed more than 10 klebsiellae. Over 88% of putative ESBL producers were resistant to ceftazidime 2 mg/L, ceftriaxone 1 mg/L and aztreonam 1 mg/L, whereas, amongst ESBL-negative isolates, more than 98% of K. pneumoniae and 87% of K. oxytoca were susceptible to these concentrations. Putative ESBL producers wre also more resistant to cefuroxime and cefoxitin than non-producers, but not to biapenem. MIC distributions of ciprofloxacin, piperacillin/tazobactam and aminoglycosides were bimodal for ESBL producers, with some isolates highly sensitive and others very resistant. For example, 70% of putative ESBL producers were susceptible to piperacillin/tazobactam 16 + 4 mg/L, but 30% were resistant, some highly so. Resistance to this combination, and to ciprofloxacin, was clustered in certain centres. Two other groups of cephalosporin-resistant isolates were identified besides ESBL producers, viz. (i) nine isolates, from three centres, with AmpC beta-lactamases and (ii) 20 K. oxytoca, from 15 centres, that hyperproduced K1 enzyme. Examination of the hospitals' own susceptibility data indicated that up to 33% of putative ESBL producers had been reported susceptible to third-generation cephalosporins or monobactams. This is disturbing, since ESBLs have been associated with clinical failure even when only low-level resistance was apparent in vitro. PMID:8889716

Livermore, D M; Yuan, M



Diversity and Evolution of the Class A Chromosomal Beta-Lactamase Gene in Klebsiella pneumoniae  

PubMed Central

We investigated the diversity of the chromosomal class A beta-lactamase gene in Klebsiella pneumoniae in order to study the evolution of the gene. A 789-bp portion was sequenced in a panel of 28 strains, representative of three phylogenetic groups, KpI, KpII, and KpIII, recently identified in K. pneumoniae and of different chromosomal beta-lactamase variants previously identified. Three groups of sequences were found, two of them corresponding to the families SHV (pI 7.6) and LEN (pI 7.1), respectively, and one, more heterogeneous, corresponding to a new family that we named OKP (for other K. pneumoniae beta-lactamase). Levels of susceptibility to ampicillin, cefuroxime, cefotaxime, ceftazidime, and aztreonam and inhibition by clavulanic acid were similar in the three groups. One new SHV variant, seven new LEN variants, and four OKP variants were identified. The OKP variants formed two subgroups based on nucleotide sequences, one with pIs of 7.8 and 8.1 and the other with pIs of 6.5 and 7.0. The nucleotide sequences of the housekeeping genes gyrA, coding for subunit A of gyrase, and mdh, coding for malate dehydrogenase, were also determined. Phylogenetic analysis of the three genes studied revealed parallel evolution, with the SHV, OKP, and LEN beta-lactamase families corresponding to the phylogenetic groups KpI, KpII, and KpIII, respectively. This correspondence was fully confirmed for 34 additional strains in PCR assays specific for the three beta-lactamase families. We estimated the time since divergence of the phylogenetic groups KpI and KpIII at between 6 and 28 million years, confirming the ancient presence of the beta-lactamase gene in the genome of K. pneumoniae.

Haeggman, S.; Lofdahl, S.; Paauw, A.; Verhoef, J.; Brisse, S.



Antimicrobial resistance status and prevalence rates of extended spectrum beta-lactamase (ESBL) producers isolated from a mixed human population.  


Owing to the increasing epidemiological and therapeutic challenges associated with infections due to ESBL producers, ESBL prevalence rate among some bacteria isolates from healthy and non-healthy human population in a metropolitan Nigerian setting was evaluated. A total of one hundred and forty-five (145) bacteria strains were isolated from a total of four hundred and sixty (460) samples collected from urine, wound, throat and anal swabs of 220 healthy volunteers in the community and from 240 patients in 2 secondary and 2 tertiary hospitals (altogether, 4) in Enugu metropolis. The presumptive confirmatory test used for ESBL detection was the Double Disc Synergy Test (DDST) method. Conjugation and plasmid curing studies were also done for resistance factor determination. Of the 145 isolates, 20 were ESBL producers with 35% of these ESBL producers being of community origin and 65% from hospitals. This translates to 4.8% and 9% incidences (comparably higher than established prevalence of 4.4% and 7.5 respectively) for community and hospital infections respectively. The ESBL isolates showed high resistance to tetracycline, gentamicin, pefloxacin, ceftriaxone, cefuroxime, ciprofloxacin and Augmentin(®) (Amoxicilin and clavulanic acid combination). Conjugation studies for Resistance plasmid transfer showed non-transference of resistance determinants between the ESBL transconjugants and recipient strains. Correspondingly, the plasmid curing studies revealed that the acridine orange could not effect a cure on the isolates as they still retained high resistance to the antibiotics after the treatment. This study confirms the growing incidences/pool of ESBL strains in Nigeria and call for widespread and continuous monitoring towards an effective management of the potential therapeutic hurdle posed by this trend. PMID:21619555

Afunwa, Ruth A; Odimegwu, Damian C; Iroha, Romanus I; Esimone, Charles O



Antibiotic susceptibility pattern of urinary tract pathogens in Ibadan, Nigeria.  


Urinary tract infections (UTI) affect all age groups and occur in both hospitalized and non-hospitalized individuals and have serious impact on the socioeconomic life of the individual and the society, and also account for a large proportion of antibacterial drug consumption. Treatment failure has been attributed to increasing resistance to common antibiotics, but there is paucity of data from this part of Nigeria. This prospective study was carried out to determine the prevalence and antibiotic susceptibility pattern of uropathogens in Ibadan using standard microbiological diagnostic methods. Statistical analysis was by simple percentages among related variables. Four hundred and nine urinary isolates, 239 (58.4%) and 170 (41.6%) from hospitalized and non-hospitalized patients respectively were studied. Frequency of occurrence of urinary pathogens were Klebsiella spp 171 (41.8%), Pseudomonas species (including Pseudomonas aeruginosa) 81 (19.8%), Escherichia coli 78 (19.1%), Staphylococcus aureus 31 (7.6%) and Proteus mirabilis 31 (7.6%). Resistance to commonly used antibiotics such as ampicillin 97%, tetracycline 93%, cotrimoxazole 98%, and amoxycillin 89% was observed among most uropathogens. Seventy-five to 100% Pseudomonas spp. were resistant to the common antibiotics and also 87.1% and 82.4% were resistant to nalidixic acid and cefuroxime respectively. However, appreciable susceptibility by all uropathogens was found with amikacin 75%, ciprofloxacin 72.2%, ceftriaxone 68.4%, and pefloxacin 64.9%. Isolates from the community showed more susceptibility to tested drugs. In conclusion, widespread resistance to most antibiotics including cephalosporins and quinolones was found among all uropathogens. PMID:21416786

Dada-Adegbola, H O; Muili, K A



Bacteriological efficacy of 5-day therapy with telithromycin in acute maxillary sinusitis.  


Increasing resistance among the key pathogens responsible for community-acquired respiratory tract infections, namely Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, has the potential to limit the effectiveness of the antibacterial agents available to treat these infections. Moreover, there are regional differences in the susceptibility patterns observed and, as treatment is usually empirical, choosing an effective treatment can be challenging. Telithromycin, the first ketolide to be approved for clinical use, offers an activity profile that covers the key respiratory pathogens including penicillin- and macrolide-resistant S. pneumoniae as well as beta-lactamase-producing H. influenzae and M. catarrhalis. In a pooled analysis of three large controlled clinical trials involving patients with acute maxillary sinusitis, the bacteriological efficacy of 5- or 10-day treatment with telithromycin and 10-day treatment with comparators was evaluated. Telithromycin administered as a once-daily 800 mg dose for 5 days achieved eradication rates of 91.8, 87.5 and 92.9% for S. pneumoniae, H. influenzae and M. catarrhalis, respectively. Bacteriological eradication of 8/10 and 12/14 isolates of S. pneumoniae resistant to penicillin and erythromycin, respectively, was also reported following 5-day treatment with telithromycin. The clinical efficacy of this regimen was equivalent to that of a 10-day regimen of telithromycin or standard 10-day courses of amoxicillin-clavulanic acid or cefuroxime axetil. Telithromycin 800mg given for 5 days was well tolerated, with the majority of adverse events being of mild or moderate intensity. These data suggest that telithromycin provides effective first-line therapy for use in patients with acute maxillary sinusitis in a short and convenient once-daily dosage regimen. PMID:15737519

Buchanan, P; Roos, K; Tellier, G; Rangaraju, M; Leroy, B



Cephalosporins in surgical prophylaxis.  


Controlled clinical trials have shown that antimicrobial prophylaxis can lower the incidence of infection after certain operations, thus reducing morbidity, hospital stay, antibiotic usage and mortality due to sepsis. An effective prophylactic regimen should be directed against the most likely infecting organisms, but need not be active against every potential pathogen. Infection can be prevented when effective concentrations are present in the blood and the tissue during and shortly after the procedure. Therefore, antimicrobial prophylaxis should begin just before the operation: beginning earlier is unnecessary and potentially dangerous, beginning later is less effective. A single-dose prophylaxis after the induction of anesthesia is sufficient. If surgery is delayed or prolonged, a second dose is advisable if an antimicrobial drug with a short half-life is used. Postoperative administration is unnecessary and is harmful. Cephalosporins are considered to be the drug of choice, because they offer fewer allergic reactions. From the first generation cephalosporins, cefazolin has been widely recommended with success. From the second generation cephalosporins, cefuroxime, cefamandole and cefoxitin are increasingly recommended. Their antistaphylococcal activity is somewhat less strong but their activity against gram-negative bacteria is stronger. In addition, cefoxitin has good activity against anaerobes. Third generation cephalosporins, such as cefotaxime, cefoperazone, ceftriaxone, ceftazidime or ceftizoxime are generally not recommended for surgical prophylaxis. Despite these recommendations, they have been accepted by the medical community and are today in use in many countries as the most common drugs in surgical prophylaxis. Ceftriaxone in particular, is far exceeding the sales of any other drug for prophylaxis. Contra-indications, limitations, additional or other drugs and practical recommendations for specific procedures are discussed and the results of several prospective randomized studies are presented. PMID:11936371

Geroulanos, S; Marathias, K; Kriaras, J; Kadas, B



Pharmacokinetic/Pharmacodynamic (PK/PD) Indices of Antibiotics Predicted by a Semimechanistic PKPD Model: a Step toward Model-Based Dose Optimization?  

PubMed Central

A pharmacokinetic-pharmacodynamic (PKPD) model that characterizes the full time course of in vitro time-kill curve experiments of antibacterial drugs was here evaluated in its capacity to predict the previously determined PK/PD indices. Six drugs (benzylpenicillin, cefuroxime, erythromycin, gentamicin, moxifloxacin, and vancomycin), representing a broad selection of mechanisms of action and PK and PD characteristics, were investigated. For each drug, a dose fractionation study was simulated, using a wide range of total daily doses given as intermittent doses (dosing intervals of 4, 8, 12, or 24 h) or as a constant drug exposure. The time course of the drug concentration (PK model) as well as the bacterial response to drug exposure (in vitro PKPD model) was predicted. Nonlinear least-squares regression analyses determined the PK/PD index (the maximal unbound drug concentration [fCmax]/MIC, the area under the unbound drug concentration-time curve [fAUC]/MIC, or the percentage of a 24-h time period that the unbound drug concentration exceeds the MIC [fT>MIC]) that was most predictive of the effect. The in silico predictions based on the in vitro PKPD model identified the previously determined PK/PD indices, with fT>MIC being the best predictor of the effect for ?-lactams and fAUC/MIC being the best predictor for the four remaining evaluated drugs. The selection and magnitude of the PK/PD index were, however, shown to be sensitive to differences in PK in subpopulations, uncertainty in MICs, and investigated dosing intervals. In comparison with the use of the PK/PD indices, a model-based approach, where the full time course of effect can be predicted, has a lower sensitivity to study design and allows for PK differences in subpopulations to be considered directly. This study supports the use of PKPD models built from in vitro time-kill curves in the development of optimal dosing regimens for antibacterial drugs.

Nielsen, Elisabet I.; Cars, Otto; Friberg, Lena E.



Antipneumococcal Activity of DK-507k, a New Quinolone, Compared with the Activities of 10 Other Agents  

PubMed Central

Agar dilution MIC determination was used to compare the activity of DK-507k with those of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, sitafloxacin, amoxicillin, cefuroxime, erythromycin, azithromycin, and clarithromycin against 113 penicillin-susceptible, 81 penicillin-intermediate, and 67 penicillin-resistant pneumococci (all quinolone susceptible). DK-507k and sitafloxacin had the lowest MICs of all quinolones against quinolone-susceptible strains (MIC at which 50% of isolates were inhibited [MIC50] and MIC90 of both, 0.06 and 0.125 ?g/ml, respectively), followed by moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. MICs of ?-lactams and macrolides rose with those of penicillin G. Against 26 quinolone-resistant pneumococci with known resistance mechanisms, DK-507k and sitafloxacin were also the most active quinolones (MICs, 0.125 to 1.0 ?g/ml), followed by moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Mutations in quinolone resistance-determining regions of quinolone-resistant strains were in the usual regions of the parC and gyrA genes. Time-kill testing showed that both DK-507k and sitafloxacin were bactericidal against all 12 quinolone-susceptible and -resistant strains tested at twice the MIC at 24 h. Serial broth passages in subinhibitory concentrations of 10 strains for a minimum of 14 days showed that development of resistant mutants (fourfold or greater increase in the original MIC) occurred most rapidly for ciprofloxacin, followed by moxifloxacin, DK-507k, gatifloxacin, sitafloxacin, and levofloxacin. All parent strains demonstrated a fourfold or greater increase in initial MIC in <50 days. MICs of DK-507k against resistant mutants were lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. Four strains were subcultured in subinhibitory concentrations of each drug for 50 days: MICs of DK-507k against resistant mutants were lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Exposure to DK-507k and sitafloxacin resulted in mutations, mostly in gyrA.

Browne, Frederick A.; Bozdogan, Bulent; Clark, Catherine; Kelly, Linda M.; Ednie, Lois; Kosowska, Klaudia; Dewasse, Bonifacio; Jacobs, Michael R.; Appelbaum, Peter C.



Multiply resistant nontyphoidal Salmonella gastroenteritis in children.  


From January, 1990, to December 31, 1990, 75 children with multiply resistant Salmonella gastroenteritis were studied at the Children's Hospital "Ricardo Gutierrez" of Buenos Aires. These children ranged from 1 month to 15 years of age. Infection was community-acquired in 20 (26.6%), nosocomially acquired in 50 (66.7%) and undetermined in 5. Thirty-nine (52%) had grossly bloody stools. Fever occurred at some point in the clinical course in 61 children (81.3%) with a duration of 1 to 33 days (mean, 6.7 days). The duration of diarrhea (1 to 69 days) was longer in those who developed complications (P < 0.001). Six (8%) developed enterocolitis (2 with bowel perforation), 1 had a pulmonary abscess and 8 (11.4%) had bacteremia; 4 children died (5.3%). Salmonella typhimurium was the most common serovar (85.3%). Ninety percent minimum inhibitory concentration studies demonstrated that all strains were resistant to ampicillin (> 128 micrograms/ml), cephalothin (> 128 micrograms/ml), cefuroxime (> 128 micrograms/ml), nalidixic acid (> 256 micrograms/ml), rifampin (> 256 micrograms/ml), gentamicin (> 256 micrograms/ml) and tobramycin (256 micrograms/ml); 77.3% of strains were resistant to ceftazidime (32 micrograms/ml), 97.6% to netilmicin (> 256 micrograms/ml), 92.8% to amikacin (256 micrograms/ml), 24.4% to isepamicin (32 micrograms/ml), 5.3% to chloramphenicol (4 micrograms/ml) and 2.7% to cefoxitin (2 micrograms/ml). The 90% minimum inhibitory concentration of cefotaxime and ceftazidime was reduced by the addition of clavulanate. Aggressive multiply resistant Salmonella strains are a major pediatric problem in Buenos Aires. PMID:8426772

Maiorini, E; Lopez, E L; Morrow, A L; Ramirez, F; Procopio, A; Furmanski, S; Woloj, G M; Miller, G; Cleary, T G



Phenotypic Description and Antimicrobial Susceptibilities of Aerococcus sanguinicola Isolates from Human Clinical Samples  

PubMed Central

This report describes the clinical sources and phenotypic characterization of 16 isolates of Aerococcus sanguinicola. Sixteen conventional tests were used to describe and differentiate the 16 isolates of A. sanguinicola from 30 strains of Aerococcus viridans, 27 strains of Aerococcus urinae, and a single strain each of Aerococcus christensenii and Aerococcus urinaehominis. The phenotypic characterizations of the type strains for each species and 14 A. sanguinicola isolates were also compared in the two reference laboratories. A. sanguinicola are catalase-negative, vancomycin-susceptible, gram-positive cocci arranged in clusters and tetrads, as are all Aerococcus species except A. christensenii (which is arranged in short chains). All 16 isolates of A. sanguinicola were leucine aminopeptidase and pyrrolidonylarylamidase positive, which is unique to this species among the aerococci. All A. sanguinicola isolates grew in broth containing 6.5% NaCl, hydrolyzed hippurate, and were variable in the bile-esculin test. None of the isolates deaminated arginine or were Voges-Proskauer positive. The type strain of A. sanguinicola was isolated from a blood culture of a patient living in Denmark. Seven additional isolates were from patients living in Canada, all with urinary tract infections (six were female). Eight isolates were from patients living in five different states in the United States; five were from patients with urinary tract infections, and three were from blood cultures of one patient each with pneumonia, suspected endocarditis, and unknown clinical conditions. The antimicrobial susceptibility patterns were unremarkable; all isolates tested were susceptible to penicillin, amoxicillin, cefotaxime, cefuroxime, erythromycin, chloramphenicol, vancomycin, quinupristin-dalfopristin (Synercid), rifampin, linezolid, and tetracycline. Six of the 15 cultures were resistant to ciprofloxacin and levofloxacin, but all 15 strains were susceptible to sparfloxacin. High-level resistance was detected for meropenem (2 strains) and trimethoprim-sulfamethonazole (1 strain). Intermediate resistance was detected for trimethoprim-sulfamethoxazole (10 strains) and clindamycin (3 strains).

Facklam, Richard; Lovgren, Marguerite; Shewmaker, Patricia Lynn; Tyrrell, Gregory



Impact of regular attendance by infectious disease specialists on the management of hospitalised adults with community-acquired febrile syndromes.  


The impact of attendance by infectious disease specialists (IDS) on hospitalised adults with community-acquired infection was assessed by studying 402 consecutive febrile adults who were admitted randomly to either of two internal medicine wards over a 4-month period and given intravenous antibiotics. In ward 1, patients were attended by IDS, whereas those in ward 2 were attended by physicians from other specialties. In total, 160 patients were treated in ward 1 and 242 in ward 2 (median age 66 years; 49% male). The case-mix was comparable. Only 39% of ward 2 patients underwent minimal fever diagnostic tests compared to 82% in ward 1 (p < 0.001). Ward 1 and 2 patients received 188 and 315 antibiotic courses, respectively, of which 32% and 20% required approval from IDS (p 0.003). Patients in ward 1 were more likely to receive ceftriaxone (7.5% vs. 2%; p 0.002), erythromycin (7% vs. 1.5%; p 0.002) and cefuroxime (48% vs. 26%; p < 0.0001), but were less likely to receive amoxycillin-clavulanate (8% vs. 28%; p < 0.0001). The mean durations of therapy were 3.6 and 3.2 days (not significant), and therapy was deemed to be completely appropriate in 55.5% and 43% of cases, respectively (p 0.012). The crude mortality rates were 6.3% and 7.9%, respectively (not significant), while the medication costs were US dollars 27.4 and US dollars 26.4/patient/antibiotic day, respectively. Regular attendance by IDS resulted in significantly higher rates of accurate diagnosis and appropriate therapy. IDS prescribed more restricted (and expensive) agents, but preferred less expensive agents among unrestricted drugs, thereby offsetting the overall medication costs. PMID:15373886

Borer, A; Gilad, J; Meydan, N; Schlaeffer, P; Riesenberg, K; Schlaeffer, F



Diagnosis, treatment, and prevention of Lyme disease in children.  


The approaches to diagnosing and treating Lyme disease (LD) have been improved and refined as a result of basic and clinical research, and considerable practical experience. In addition, there have been recent studies that have allowed improvements in the ability to prevent infection with Borrelia burgdorferi. This paper will review the relevant literature and address recent developments in the diagnosis, treatment, and prevention of LD. Issues specifically related to the management of children will be identified. Controversies regarding treatment approaches will be examined in some detail. Understanding the clinical manifestations, or stage, of LD is crucial when approaching both diagnosis and treatment. Early localized disease is best diagnosed by recognizing the characteristic skin lesion, erythema migrans. Early disease will frequently, but not always, be accompanied by a detectable antibody response, particularly IgM antibody to the spirochete. Late disease, chiefly arthritis, is generally associated with high levels of IgG antibody. Western blot technology allows confirmation of enzyme immunoassay results and is especially useful when the latter is in the low or equivocal range. Early localized disease responds well to oral antibacterial therapy. Early disseminated disease, often associated with neurologic findings, may require parenteral therapy. The arthritis associated with LD frequently responds to oral antibacterials, but some refractory cases may require intravenous therapy, and occasionally surgery. Doxycycline is the oral antibacterial of choice, while amoxicillin and cefuroxime axetil are alternatives that may be preferred in young children. Owing to its long half-life and once daily dose administration, intravenous ceftriaxone has become the accepted standard for parenteral therapy. Tick avoidance has long been the mainstay for preventing LD. Antibacterial prophylaxis, using doxycycline, for tick bites has been shown to be an effective approach to prevention, but its relevance to pediatrics is uncertain. Vaccines designed to prevent infection have also been developed. PMID:12765486

Eppes, Stephen C



The phenotypic and genotypic characteristics of antibiotic resistance in Escherichia coli populations isolated from farm animals with different exposure to antimicrobial agents.  


The aim of the study was to determine the influence of the presence or the absence of antibiotic input on the emergence and maintenance of resistance in commensal bacteria from food producing animals. The research material constituted E. coli isolates from two animal species: swine at different age from one conventional pig farm with antibiotic input in young pigs and from beef and dairy cattle originated from organic breeding farm. The sensitivity to 16 antimicrobial agents was tested, and the presence of 15 resistance genes was examined. In E. coli from swine, the most prevalent resistance was resistance to streptomycin (88.3%), co-trimoxazole (78.8%), tetracycline (57.3%) ampicillin (49.3%) and doxycycline (44.9%) with multiple resistance in the majority. The most commonly observed resistance genes were: bla(TEM) (45.2%), tetA (35.8%), aadA1 (35.0%), sul3 (29.5%), dfrA1 (20.4%). Differences in phenotypes and genotypes of E. coli between young swine undergoing prevention program and the older ones without the antibiotic pressure occurred. A disparate resistance was found in E. coli from cattle: cephalothin (36.9%), cefuroxime (18.9%), doxycycline (8.2%), nitrofurantoin (7.7%), and concerned mainly dairy cows. Among isolates from cattle, multidrug resistance was outnumbered by resistance to one or two antibiotics and the only found gene markers were: bla(SHV), (3.4%), tetA (1.29%), bla(TEM) (0.43%) and tetC (0.43%). The presented outcomes provide evidence that antimicrobial pressure contributes to resistance development, and enteric microflora constitutes an essential reservoir of resistance genes. PMID:24053020

Mazurek, Justyna; Pusz, Pawe?; Bok, Ewa; Stosik, Micha?; Baldy-Chudzik, Katarzyna



Purification and Biochemical Characterization of the VIM-1 Metallo-?-Lactamase  

PubMed Central

VIM-1 is a new group 3 metallo-?-lactamase recently detected in carbapenem-resistant nosocomial isolates of Pseudomonas aeruginosa from the Mediterranean area. In this work, VIM-1 was purified from an Escherichia coli strain carrying the cloned blaVIM-1 gene by means of an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme exhibited a molecular mass of 26 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and an acidic pI of 5.1 in analytical isoelectric focusing. Amino-terminal sequencing showed that mature VIM-1 results from the removal of a 26-amino-acid signal peptide from the precursor. VIM-1 hydrolyzes a broad array of ?-lactam compounds, including penicillins, narrow- to expanded-spectrum cephalosporins, carbapenems, and mechanism-based serine-?-lactamase inactivators. Only monobactams escape hydrolysis. The highest catalytic constant/Km ratios (>106 M?1 · s?1) were observed with carbenicillin, azlocillin, some cephalosporins (cephaloridine, cephalothin, cefuroxime, cefepime, and cefpirome), imipenem, and biapenem. Kinetic parameters showed remarkable variability with different ?-lactams and also within the various penam, cephem, and carbapenem compounds, resulting in no clear preference of the enzyme for any of these ?-lactam subfamilies. Significant differences were observed with some substrates between the kinetic parameters of VIM-1 and those of other metallo-?-lactamases. Inactivation assays carried out with various chelating agents (EDTA, 1,10-o-phenanthroline, and pyridine-2,6-dicarboxylic acid) indicated that formation of a ternary enzyme-metal-chelator complex precedes metal removal from the zinc center of the protein and revealed notable differences in the inactivation parameters of VIM-1 with different agents.

Franceschini, Nicola; Caravelli, Berardo; Docquier, Jean-Denis; Galleni, Moreno; Frere, Jean-Marie; Amicosante, Gianfranco; Rossolini, Gian Maria



Antimicrobial susceptibility profiles of human and piglet Clostridium difficile PCR-ribotype 078  

PubMed Central

In the last decade, outbreaks of nosocomial Clostridium difficile infections (CDI) occurred worldwide. A new emerging type, PCR-ribotype 027, was the associated pathogen. Antimicrobial susceptibility profiles of this type were extensively investigated and used to partly explain its spread. In Europe, the incidence of C. difficile PCR-ribotype 078 recently increased in humans and piglets. Using recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory Standards Institute (CLSI) we studied the antimicrobial susceptibility to eight antimicrobials, mechanisms of resistance and the relation with previously prescribed antimicrobials in human (n=49) and porcine (n=50) type 078 isolates. Human and porcine type 078 isolates showed similar antimicrobial susceptibility patterns for the antimicrobials tested. In total, 37% of the isolates were resistant to four or more antimicrobial agents. The majority of the human and porcine isolates were susceptible to amoxicillin (100%), tetracycline (100%) and clindamycin (96%) and resistant to ciprofloxacin (96%). More variation was found for resistance patterns to erythromycin (76% in human and 59% in porcine isolates), imipenem (29% in human and 50% in porcine isolates) and moxifloxacin (16% for both human and porcine isolates). MIC values of cefuroxim were high (MICs >256 mg/L) in 96% of the isolates. Resistance to moxifloxacin and clindamycin was associated with a gyr(A) mutation and the presence of the erm(B) gene, respectively. A large proportion (96%) of the erythromycin resistant isolates did not carry the erm(B) gene. The use of ciprofloxacin (humans) and enrofloxacin (pigs) was significantly associated with isolation of moxifloxacin resistant isolates. Increased fluoroquinolone use could have contributed to the spread of C. difficile type 078.



Prevalence of antimicrobial resistance among gram-negative isolates in an adult intensive care unit at a tertiary care center in Saudi Arabia  

PubMed Central

BACKGROUND AND OBJECTIVES: Patients in the ICU have encountered an increasing emergence and spread of antibiotic-resistant pathogens. We examined patterns of antimicrobial susceptibility in gram-negative isolates to commonly used drugs in an adult ICU at a tertiary care hospital in Riyadh, Saudi Arabia. METHODS: A retrospective study was carried out of gram-negative isolates from the adult ICU of King Fahad National Guard Hospital (KFNGH) between 2004 and 2009. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. RESULTS: The most frequently isolated organism was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pnemoniae, Stenotrophomonas maltophilia, and Enterobacter. Antibiotic susceptibility patterns significantly declined in many organisms, especially A baumannii, E coli, S marcescens, and Enterobacter. A baumannii susceptibility was significantly decreased to imipenem (55% to 10%), meropenem (33% to 10%), ciprofloxacin (22% to 10%), and amikacin (12% to 6%). E coli susceptibility was markedly decreased (from 75% to 50% or less) to cefuroxime, ceftazidime, cefotaxime, and cefepime. S marcescens susceptibility was markedly decreased to cefotaxime (100% to 32%), ceftazidime (100% to 35%), and cefepime (100% to 66%). Enterobacter susceptibility was markedly decreased to ceftazidime (34% to 5%), cefotaxime (34% to 6%), and pipracillin-tazobactam (51% to 35%). Respiratory samples were the most frequently indicative of multidrug-resistant pathogens (63%), followed by urinary samples (57%). CONCLUSION: Antimicrobial resistance is an emerging problem in the KFNGH ICU, justifying new more stringent antibiotic prescription guidelines. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to eliminate major outbreaks in the future.

Al Johani, Sameera M.; Akhter, Javed; Balkhy, Hanan; El-Saed, Ayman; Younan, Mousaad; Memish, Ziad



Geographical Variation in Antibiotic-Resistant Escherichia coli Isolates from Stool, Cow-Dung and Drinking Water  

PubMed Central

Little information is available on relationships between the biophysical environment and antibiotic resistance. This study was conducted to investigate the antibiotic resistance pattern of Escherichia coli isolated from child stool samples, cow-dung and drinking water from the non-coastal (230 households) and coastal (187 households) regions of Odisha, India. Susceptibility testing of E. coli isolates (n = 696) to the following antibiotics: tetracycline, ampicillin/sulbactam, cefuroxime, cefotaxime, cefixime, cotrimoxazole, amikacin, ciprofloxacin, norfloxacin and nalidixic acid was performed by the disk diffusion method. Ciprofloxacin minimum inhibitory concentration (MIC) values were determined for ciprofloxacin-resistant isolates (n = 83). Resistance to at least one antibiotic was detected in 90% or more of the E. coli isolates. Ciprofloxacin MIC values ranged from 8 to 32 µg/mL. The odds ratio (OR) of resistance in E. coli isolates from children’s stool (OR = 3.1, 95% CI 1.18–8.01), cow-dung (OR = 3.6, 95% CI 1.59–8.03, P = 0.002) and drinking water (OR = 3.8, 95% CI 1.00–14.44, P = 0.049) were higher in non-coastal compared to coastal region. Similarly, the co-resistance in cow-dung (OR = 2.5, 95% CI 1.39–4.37, P = 0.002) and drinking water (OR = 3.2, 95% CI 1.36–7.41, P = 0.008) as well as the multi-resistance in cow-dung (OR = 2.2, 95% CI 1.12–4.34, P = 0.022) and drinking water (OR = 2.7, 95% CI 1.06–7.07, P = 0.036) were also higher in the non-coastal compared to the coastal region.

Sahoo, Krushna Chandra; Tamhankar, Ashok J.; Sahoo, Soumyakanta; Sahu, Priyadarshi Soumyaranjan; Klintz, Senia Rosales; Lundborg, Cecilia Stalsby



Persistence of Escherichia coli Clones and Phenotypic and Genotypic Antibiotic Resistance in Recurrent Urinary Tract Infections in Childhood?  

PubMed Central

We assessed the clonality of consecutive Escherichia coli isolates during the course of recurrent urinary tract infections (RUTI) in childhood in order to compare clonality with phenotypic antibiotic resistance patterns, the presence of integrons, and the presence of the sul1, sul2, and sul3 genes. Altogether, 78 urinary E. coli isolates from 27 children, who experienced recurrences during a 1-year follow-up after the first attack of acute pyelonephritis, were investigated. The MICs of sulfamethoxazole, trimethoprim-sulfamethoxazole (SXT), ampicillin, cefuroxime, cefotaxime, and gentamicin and the presence or absence of the intI gene for class 1 integrons and the sulfamethoxazole resistance-encoding genes sul1, sul2, and sul3 were determined. All E. coli strains were genotyped by pulsed-field gel electrophoresis. There were no significant differences in the prevalences of resistance to beta-lactams and SXT between initial and consecutive E. coli isolates (41 versus 45% and 41 versus 29%, respectively). However, the E. coli strains obtained after SXT administration more frequently carried two or more sul genes than the nonexposed strains (9/21 [43%] versus 11/57 [19%], respectively; P = 0.044). In 78% of the patients, the recurrence of unique clonal E. coli strains alone or combined with individual strains was detected. Phenotypic resistance and the occurrence of sul genes were more stable in clonal strains than in individual strains (odds ratios, 8.7 [95% confidence interval {95% CI}, 1.8 to 40.8] and 4.4 [95% CI, 1.1 to 17.7], respectively). Thus, in children with RUTIs, the majority of E. coli strains from consecutive episodes are unique persisting clones, with rare increases in the initially high antimicrobial resistance, the presence of sul genes, and the presence of integrons.

Koljalg, Siiri; Truusalu, Kai; Vainumae, Inga; Stsepetova, Jelena; Sepp, Epp; Mikelsaar, Marika



Lemierre's syndrome due to Klebsiella pneumoniae in a 63-year-old man with diabetes: a case report  

PubMed Central

Introduction Lemierre's syndrome was originally documented to be caused by Fusobacterium necrophorum. It is a very rare condition with a prevalence of one to 14.4 instances per million. Its presentation is varied, not only in composition but also in the infecting organism. Treatment with anticoagulants has been controversial and applied only on a case-by-case basis. Case presentation A 63-year-old Saudi man who had had uncontrolled diabetes mellitus for 47 years presented to our facility with a five-day history of swelling on the right side of his neck and fever. The swelling progressively increased in size and was associated with pain, dysphagia, odynophagia, change of voice ('hot potato voice'), and reduced appetite. Abscess content culture and sensitivity testing revealed Klebsiella pneumoniae. However, blood culture results were repeatedly negative. The abscess was incised and drained without any complication. Our patient was treated with clindamycin and cefuroxime. Warfarin was also administered concurrently for six weeks, for an isolated internal jugular vein thrombosis (IJV), with complete resolution of the thrombus. Normoglycemia was achieved and our patient was discharged after complete wound healing and the return of his biochemical parameters to normal. Conclusions Only two cases of Lemierre's syndrome in patients with diabetes due to K. pneumoniae have been reported previously. A review of the literature suggested that an association exists between deep neck infections due to K. pneumoniae and diabetes mellitus. The reasons for this association are still not clear. This poses a question as to whether diabetes mellitus specifically predisposes these patients to infection with this organism. It is suggested that clinicians should consider infectious agents other than F. necrophorum in the causation of Lemierre's syndrome, especially in patients with diabetes.



Bactericidal activity of oral beta-lactam antibiotics in plasma and urine versus isogenic Escherichia coli strains producing broad- and extended-spectrum beta-lactamases.  


Bacteria harbouring extended-spectrum beta-lactamases (ESBLs), derived by mutation from TEM-1, TEM-2 or SHV-1 beta-lactamases, have been described world-wide. The in vitro activities of these enzymes against beta-lactam antibiotics, including oral cephalosporins, are well recognised. The aim of this investigation was to assess the bactericidal activity of oral beta-lactam antibiotics available in Croatia (amoxicillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten), in biological fluids against isogenic Escherichia coli strains producing broad-spectrum (TEM-1, TEM-2 and SHV-1) and extended-spectrum beta-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12). Bactericidal activity of oral beta-lactams in plasma and urine was tested in time-kill experiments and by determining bactericidal titres at different time intervals post-dose. The killing rate of antibiotics in urine was slower than in plasma, but faster than in Mueller-Hinton broth. High bactericidal titres in urine were only maintained throughout the whole dosing interval by ceftibuten against strains producing broad-, SHV-2 and SHV-3 beta-lactamases. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring TEM-1, TEM-2 and SHV-1 beta-lactamases but a shorter dosing interval is needed. Ceftibuten can be recommended with caution in ESBL producing E. coli except those producing SHV-4, SHV-5 and SHV-12 that confer resistance to it. If these enzymes are produced, fluoroquinolones or carbapenems could be considered. PMID:15894465

Bedenic, Branka; Vranes, Jasmina; Suto, Sandra; Zagar, Zivojin



Clinical breakpoint changes and their impact on surveillance of antimicrobial resistance in Escherichia coli causing bacteraemia.  


Dutch laboratories are currently changing their breakpoint criteria from mostly Clinical Laboratory and Standards Institute (CLSI) breakpoints to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. To evaluate the impact of these changes, we studied antimicrobial resistance trends of Escherichia coli in blood specimens from January 2008 to January 2012 using CLSI and EUCAST breakpoints and compared them with the antimicrobial susceptibility test (AST) interpretations reported by Dutch laboratories participating in the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR). ISIS-AR collects AST interpretations, including underlying minimal inhibitory concentrations (MICs) of routinely cultured bacterial species on a monthly basis from Dutch laboratories. MICs of Etests or automated systems were reinterpreted according to the CLSI 2009 and EUCAST 2010 guidelines. Trends in non-susceptibility (i.e. intermediate resistant and resistant) over time were analysed by the Cochran-Armitage test for trend. The effects of the change from CLSI to EUCAST breakpoints on non-susceptibility were small. There were no differences in non-susceptibility to amoxicillin, amoxicillin/clavulanic acid, cefuroxim, gentamicin and co-trimoxazol and only small differences (1-1.5%) for ciprofloxacin between AST interpretations by CLSI or EUCAST. However, for ceftazidime, and cefotaxime/ceftriaxone the proportion of non-susceptibility was substantially higher when EUCAST breakpoints were used (2-3%). The effects on time trends of the change in guidelines were limited, with only substantial differences for the oxymino-cephalosporins. Our study shows that the implementation of EUCAST breakpoints has a limited effect on the proportion of non-susceptible isolates and time trends in E. coli for most, but not all, antimicrobial agents. PMID:22925456

van der Bij, A K; van Dijk, K; Muilwijk, J; Thijsen, S F T; Notermans, D W; de Greeff, S; van de Sande-Bruinsma, N



Urinary tract infection among symptomatic outpatients visiting a tertiary hospital based in midwestern Nigeria.  


Microbial pathogens implicated in urinary tract infection and their antibiotic susceptibility patterns as prevalent in UTI symptomatic outpatients resident in Benin City, Nigeria was the focus of this study. One hundred (100) midstream urine samples were collected into sterile plastic universal bottles from outpatients who visited the University of Benin Teaching Hospital, Nigeria and who were tentatively diagnosed as manifesting symptoms of UTI. Patients were referred to the Medical Microbiology department by the consulting doctors. Significant bacterial counts and neutrophil (pus cells) counts were carried out on samples by standard methods. Positive samples for both counts were inoculated aseptically on sterile MacConkey agar, Cystine Lactose Electrolyte Deficient (CLED) agar and Sabouraud Dextrose agar plates and incubated appropriately. Microbial isolates were identified and antibiotic sensitivity testing was carried out on isolates by standard methods. Thirty nine (39.0%) and 61 (61.0%) samples recorded significant microbial growth and no growth respectively. Gram negative bacilli constituted 86.1% (of which enterobacteriaceae made up 49.9%) while gram positive cocci made up 13.9%. Strains of uropathogens isolated were Alcaligenes spp (19.4%), Klebsiella aerogenes (16.7%), Escherichia coli (13.9%), Staphylococcus aureus (13.9%), Candida albicans (11.1%), Proteus mirabilis (8.3%), Pseudomonas aeruginosa (5.5%), Enterobacter spp (5.5%) and Providencia spp (5.5%). Occurrence of UTI in male and female patients were 58.3% and 41.7% respectively of which UTI occurred highest in the 25-46, 15-54 and 27-54 age groups in that decreasing order. Alcaligenes spp occurred most in very old female patients. Candida albicans (the only fungal uropathogen) occurred in an 8day old male patient. Other isolates occurred in much older patients. A significantly high microscopic neutrophil count or pyuria was recorded from deposits of UTI positive patients (i.e. < 5/HPF). Eighteen (representing 50.5%) and 15 (47.8%) of total microbial strains isolated were sensitive to nitrofurantoin and ceftriaxone respectively. Antibiotic susceptibility profile also showed 13(41.6%), 13(41.6%), 13(41.6%) for ciprofloxacin, cefuroxime and ofloxacin respectively suggesting moderate sensitivity of the fluoroquinolones and second/third generation cephalosporins. Gentamicin, ampicillin and augmentin recorded over 70.0% resistance level each. A total of nineteen bacterial strains made of E.coli, Enterobacter spp, Proteus mirabilis, Providencia spp, Staph. aureus and Pseudomonas aeruginosa were multi drug resistant as they resisted 3, 3, 4, 4, 5 and 8 antibiotics respectively. PMID:23445708

Otajevwo, F D



Prevalence, Pathogenesis, Antibiotic Susceptibility Profiles, and In-vitro Activity of Selected Medicinal Plants Against Aeromonas Isolates from Stool Samples of Patients in the Venda Region of South Africa  

PubMed Central

The prevalence, pathogenic indices, such as haemolytic and haemagglutinating activities, antibiograms, and in-vitro activities of local medicinal plants against Aeromonas isolates in Vhembe district of Limpopo province, South Africa, were studied using standard microbiological methods. In total, 309 diarrhoeic stool samples were collected from patients attending five health centres in the region during December 2004–May 2005. Aeromonas species were identified using the API 20E system. The haemagglutinating and haemolytic activities of isolates on human, sheep, pig and chicken red blood cells were investigated. Antibiotic susceptibility profiles of the isolates to several antibiotics and in-vitro activity of local medicinal plants were also ascertained using previously-reported schemes. Results showed that 104 (33.6%) of the 309 samples were positive for Aeromonas species, of which 89 (85.6%) were Aeromonas hydrophila, 12 (11.5%) A. sobria, and three (2.9%) A. caviae. All strains of A. hydrophila and A. caviae produced haemolysis on sheep blood, while eight of the 12 A. sobria strains were haemolytic on sheep blood. The haemolytic activities of the isolates were variable on other red blood cells tested. High level of resistance was observed to amoxicillin and ampicillin, followed by cefuroxime (79%), chloramphenicol (74%), and erythromycin (65%). The carbapenems were the most active drugs with only 7% resistance to meropenem and 11% to imipenem. About 12% of the isolates were resistant to ciprofloxacin. The extracts of three of seven medicinal plants tested showed inhibitory activity against all Aeromonas isolates; these included acetone and hexane extracts of Pterocarpus angolensis, Syzygium cordatum, and Zornia milneana. The results suggest a high prevalence of Aeromonas species in the region. The isolates demonstrated multiple resistant profiles to different antibiotics tested. Some local medicinal plants were inhibitory to Aeromonas isolates, indicating a potential role in the management of Aeromonas-related infections. Structural elucidation of the active components may pave the way for the discovery of candidate templates for eventual drug design. Most isolates possessed important virulence characteristics based on their haemolytic and haemagglutinating ability. However, the genetic characterization of the isolates will further confirm their pathogenicity and the origin of multiple antibiotic resistance.

Obi, C.L.; Ramalivhana, J.; Samie, A.; Igumbor, E.O.



Diversity and antibiograms of bacterial organisms isolated from samples of household drinking-water consumed by HIV-positive individuals in rural settings, South Africa.  


Diarrhoea is a hallmark of HIV infections in developing countries, and many diarrhoea-causing agents are often transmitted through water. The objective of the study was to determine the diversity and antibiotic susceptibility profiles of bacterial organisms isolated from samples of household drinking-water consumed by HIV-infected and AIDS patients. In the present study, household water stored for use by HIV-positive patients was tested for microbial quality, and isolated bacterial organisms were analyzed for their susceptibility profiles against 25 different antibiotics. The microbial quality of water was generally poor, and about 58% of water samples (n=270) were contaminated with faecal coliforms, with counts varying from 2 colony-forming unit (CFU)/100 mL to 2.4x10? CFU/100 mL. Values of total coliform counts ranged from 17 CFU/100 mL to 7.9x10?/100 mL. In total, 37 different bacterial species were isolated, and the major isolates included Acinetobacter lwoffii (7.5%), Enterobacter cloacae (7.5%), Shigella spp. (14.2%), Yersinia enterocolitica (6.7%), and Pseudomonas spp. (16.3%). No Vibrio cholerae could be isolated; however, V. fluvialis was isolated from three water samples. The isolated organisms were highly resistant to cefazolin (83.5%), cefoxitin (69.2%), ampicillin (66.4%), and cefuroxime (66.2%). Intermediate resistance was observed against gentamicin (10.6%), cefepime (13.4%), ceftriaxone (27.6%), and cefotaxime (29.9%). Levofloxacin (0.7%), ceftazidime (2.2%), meropenem (3%), and ciprofloxacin (3.7%) were the most active antibiotics against all the microorganisms, with all recording less than 5% resistance. Multiple drug resistance was very common, and 78% of the organisms were resistant to three or more antibiotics. Education on treatment of household water is advised for HIV-positive patients, and measures should be taken to improve point-of-use water treatment as immunosuppressed individuals would be more susceptible to opportunistic infections. PMID:23082625

Samie, A; Mashao, M B; Bessong, P O; NKgau, T F; Momba, M N B; Obi, C L



Bacterial Bloodstream Infections in HIV-infected Adults Attending a Lagos Teaching Hospital  

PubMed Central

An investigation was carried out during October 2005–September 2006 to determine the prevalence of bloodstream infections in patients attending the outpatient department of the HIV/AIDS clinic at the Lagos University Teaching Hospital in Nigeria. Two hundred and one patients—86 males and 115 females—aged 14-65 years were recruited for the study. Serological diagnosis was carried out on them to confirm their HIV status. Their CD4 counts were done using the micromagnetic bead method. Twenty mL of venous blood sample collected from each patient was inoculated into a pair of Oxoid Signal blood culture bottles for 2-14 days. Thereafter, 0.1 mL of the sample was plated in duplicates on MacConkey, blood and chocolate agar media and incubated at 37 °C for 18-24 hours. The CD4+ counts were generally low as 67% of 140 patients sampled had <200 cells/?L of blood. Twenty-six bacterial isolates were obtained from the blood samples and comprised 15 (58%) coagulase-negative staphylococci as follows: Staphylococcus epidermidis (7), S. cohnii cohnii (1), S. cohnii urealyticum (2), S. chromogenes (1), S. warneri (2), S. scuri (1), and S. xylosus (1). Others were 6 (23%) Gram-negative non-typhoid Salmonella spp., S. Typhimurium (4), S. Enteritidis (2); Pseudomonas fluorescens (1), Escherichia coli (1), Ochrobactrum anthropi (1), Moraxella sp. (1), and Chryseobacterium meningosepticum. Results of antimicrobial susceptibility tests showed that coagulase-negative staphylococci had good sensitivities to vancomycin and most other antibiotics screened but were resistant mainly to ampicilin and tetracycline. The Gram-negative organisms isolated also showed resistance to ampicillin, tetracycline, chloramphenicol, and septrin. This study demonstrates that co-agulase-negative staphylococci and non-typhoidal Salmonellae are the most common aetiological agents of bacteraemia among HIV-infected adults attending the Lagos University Teaching Hospital, Nigeria. The organisms were resistant to older-generation antibiotics often prescribed in this environment but were sensitive to vancomycin, cefotaxime, cefuroxime, and other new-generation antibiotics.

Sulaiman, Akanmu A.; Solomon, Bamiro B.; Chinedu, Obosi A.; Victor, Inem A.



Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial  

PubMed Central

Objective Prospective studies show a 10% incidence of sternal wound infection (SWI) after 90?days of follow?up, compared with infection rates of 5% reported by the National Nosocomial Infections Surveillance System after only 30?days of follow?up. This incidence increases 2–3 times in high?risk patients. Design Prospective randomised double?blind controlled clinical trial. Setting Cardiothoracic centre, UK. Patients Patients were eligible if they were undergoing median sternotomy for primary isolated coronary artery bypass grafting, with at least one internal thoracic artery used for coronary grafting and having one or more of the following three risk factors: (1) obesity, defined as body mass index 30?kg/m2; (2) diabetes mellitus; or (3) bilateral internal thoracic artery grafts (ie, the use of the other internal thoracic artery). Interventions The study group received a single dose of gentamicin 2?mg/kg, rifampicin 600?mg and vancomycin 15?mg/kg, with three further doses of 7.5?mg/kg at 12?hour intervals. The control group received cefuroxime 1.5?g at induction and three further doses of 750?mg at 8?hour intervals. Main outcome measures The primary end point was the incidence of SWI at 90?days. The secondary end point was the antibiotic and hospital costs. Results During the study period, 486 patients underwent isolated coronary artery bypass grafting with a 30?day SWI of 7.6%. 186 high?risk patients were recruited and analysed: 87 in the study group and 99 in the control group. 90?day SWI was significantly reduced in 8 patients in the study group (9.2%; 95% CI 3.5% to 15.3%) compared with 25 patients in the control group (25.2%; 95% CI 19.5% to 39.4%; p?=?0.004). The study group had a significantly lower cost of antibiotics (21.2% reduction—US$96/patient; p<0.001), and a significantly lower hospital cost (20.4% reduction in cost—US$3800/patient; p?=?0.04). Conclusions Longer and broader?spectrum antibiotic prophylaxis significantly reduces the incidence of SWI in high?risk patients, with a significant economic benefit in costs of antibiotics as well as hospital costs.

Dhadwal, Kay; Al-Ruzzeh, Sharif; Athanasiou, Thanos; Choudhury, Marina; Tekkis, Paris; Vuddamalay, Pynee; Lyster, Haifa; Amrani, Mohamed; George, Shane



Prevalence, antimicrobial resistance and relation to indicator and pathogenic microorganisms of Salmonella enterica isolated from surface waters within an agricultural landscape.  


During a 12 month period (June 2007-May 2008), the prevalence and susceptibility of Salmonella serovars and their relation to specific pathogenic and indicator bacteria in river and coastal waters was investigated. A total of 240 water samples were collected from selected sites in Acheron and Kalamas Rivers and the Ionian Sea coast in north western Greece. The samples were analyzed for Salmonella spp., Listeria spp., Campylobacter spp., Escherichia coli O157, Staphylococci, Pseudomonas spp., Total Coliforms, Fecal Coliforms, Fecal Streptococci, Total Heterotrophic Flora at 20°C and at 37°C, fungi and protozoa (Cryptosporidium, Giardia). Susceptibility tests to nine antimicrobials (ampicillin, amikacin, amoxicillin/clavulavic acid, cefuroxime, ciprofloxacin, cefoxitin, tetracycline, ticarcillin/clavulanic acid, ampicillin/sulbactam) were performed using the disk diffusion method for Salmonella isolates. We isolated 28 serovars of Salmonella spp. identified as Salmonella enteritidis (23), Salmonella thompson (3) and Salmonella virchow (2). Multi-drug resistant Salmonella serovars were isolated from both river and marine waters, with 34.8% of S. enteritidis and 100% of S. virchow being resistant to more than 3 antibiotics. Also we isolated 42 strains of Listeria spp. identified as L. monocytogenes (20), L. innocua (9), L. seeligeri (2) and L. ivanovii (11). All the Listeria isolates were susceptible to the tested antibiotics. No Campylobacter spp., E. coli O157, Cryptosporidium and Giardia were detected. The overall ranges (and average counts) of the indicator bacteria were: Total Coliforms 0-4×10(4)cfu/100ml (3.7×10(3)cfu/100ml), Fecal Coliforms 0-9×10(3)cfu/100ml (9.2×10(2)cfu/100ml), Fecal Streptococci 0-3.5×10(4)cfu/100ml (1.4×10(3)cfu/100ml), Total Heterotrophic Flora at 20°C 0-6×10(3)cfu/ml (10(3)cfu/ml) and at 37°C 0-5×10(3)cfu/ml (4.9×10(2)cfu/ml). Weak or non significant positive Spearman correlations (p<0.05, rs range: 0.13-0.77) were obtained between Salmonella, Listeria, fungi and indicator bacteria. The results underline the complexity of the interrelations between pathogens and indicator bacteria, and the necessity to assess the presence of resistant bacteria in the aquatic environments. PMID:22901425

Economou, Vangelis; Gousia, Panagiota; Kansouzidou, Athina; Sakkas, Hercules; Karanis, Panagiotis; Papadopoulou, Chrissanthy



Antimicrobial resistance patterns and prevalence of class 1 and 2 integrons in Shigella flexneri and Shigella sonnei isolated in Uzbekistan  

PubMed Central

Background Shigella is a frequent cause of bacterial dysentery in the developing world. Treatment with effective antibiotics is recommended for shigellosis, but options become limited due to globally emerging resistance. One of the mechanisms for the development of resistance utilizes integrons. This study described the antibiotic susceptibility and the presence of class 1 and 2 integrons in S. flexneri and S. sonnei isolated in Uzbekistan. Results We studied 31 isolates of S. flexneri and 21 isolates of S. sonnei isolated in Uzbekistan between 1992 and 2007 for the susceptibility or resistance to ampicillin (Am), chloramphenicol (Cl), tetracycline (Te), co-trimoxazole (Sxt), kanamycin (Km), streptomycin (Str), gentamicin (Gm), cefazolin (Czn), cefoperazone (Cpr), cefuroxime (Cur), ceftazidime (Ctz), nalidixic acid (NA) and ciprofloxacin (Cip). Am/Str/Cl/Te and Am/Str/Cl/Te/Sxt resistance patterns were found most frequently in S. flexneri. Single isolates were resistant to aminoglycoside, quinolones and cephalosporins. The resistance patterns were different in the two species. Integrons were detected in 93.5% of S. flexneri (29/31) and 81.0% of S. sonnei (17/21) isolates. In addition, 61.3% of S. flexneri (19/31) isolates and 19.0% of S. sonnei (4/21) isolates carried both classes of integrons. In 29.0% of S. flexneri (9/31) isolates, only class 1 integrons were identified. In S. flexneri isolates, the presence of class 1 integrons was associated with resistance to ampicillin and chloramphenicol. Only Class 2 integrons were present in 61.9% of S. sonnei (13/21) isolates. Conclusions Our study documents antibiotic resistance among Shigella spp. in Uzbekistan. Ninety percent of Shigella strains were resistant to previously used antibiotics. Differences among S. flexneri and S. sonnei isolates in patterns of antimicrobial resistance to routinely used shigellosis antibiotics were observed. The majority of S. flexneri were resistant to ampicillin, chloramphenicol, tetracycline and streptomycin. Class 1 and 2 integrons were widely present in these Shigella strains. Resistance to ampicillin/chloramphenicol was associated with the presence of class 1 integrons. Though several mechanisms are possible, the resistance of Shigella isolates to ampicillin/chloramphenicol may be associated with the expression of genes within class 1 integrons.



Antipneumococcal activity of DK-507k, a new quinolone, compared with the activities of 10 other agents.  


Agar dilution MIC determination was used to compare the activity of DK-507k with those of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, sitafloxacin, amoxicillin, cefuroxime, erythromycin, azithromycin, and clarithromycin against 113 penicillin-susceptible, 81 penicillin-intermediate, and 67 penicillin-resistant pneumococci (all quinolone susceptible). DK-507k and sitafloxacin had the lowest MICs of all quinolones against quinolone-susceptible strains (MIC at which 50% of isolates were inhibited [MIC50] and MIC90 of both, 0.06 and 0.125 microg/ml, respectively), followed by moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. MICs of beta-lactams and macrolides rose with those of penicillin G. Against 26 quinolone-resistant pneumococci with known resistance mechanisms, DK-507k and sitafloxacin were also the most active quinolones (MICs, 0.125 to 1.0 microg/ml), followed by moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Mutations in quinolone resistance-determining regions of quinolone-resistant strains were in the usual regions of the parC and gyrA genes. Time-kill testing showed that both DK-507k and sitafloxacin were bactericidal against all 12 quinolone-susceptible and -resistant strains tested at twice the MIC at 24 h. Serial broth passages in subinhibitory concentrations of 10 strains for a minimum of 14 days showed that development of resistant mutants (fourfold or greater increase in the original MIC) occurred most rapidly for ciprofloxacin, followed by moxifloxacin, DK-507k, gatifloxacin, sitafloxacin, and levofloxacin. All parent strains demonstrated a fourfold or greater increase in initial MIC in <50 days. MICs of DK-507k against resistant mutants were lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, and levofloxacin. Four strains were subcultured in subinhibitory concentrations of each drug for 50 days: MICs of DK-507k against resistant mutants were lowest, followed by those of sitafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. Exposure to DK-507k and sitafloxacin resulted in mutations, mostly in gyrA. PMID:14638489

Browne, Frederick A; Bozdogan, Bülent; Clark, Catherine; Kelly, Linda M; Ednie, Lois; Kosowska, Klaudia; Dewasse, Bonifacio; Jacobs, Michael R; Appelbaum, Peter C



Relationship between antibiotic resistance and sickle cell anemia: preliminary evidence from a pediatric carriage study in Ghana  

PubMed Central

Background Antibiotics are frequently used among people with sickle cell anemia (homozygous SS or HbSS disease), especially for prophylaxis. However, the relationship between antibiotic resistance and people with HbSS disease has not been adequately studied, especially in the developing world. The objectives of the study were (1) to compare antibiotic resistance patterns of nasal Staphylococcus aureus between children with HbSS disease and children without HbSS disease (healthy children) and (2) to evaluate nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among children with HbSS disease. Methods This was a prospective cross-sectional study, and the subjects were children under 12 years old. Nasal swabs were collected from 50 children with HbSS disease and 50 children without HbSS disease. Nasopharyngeal swabs were collected from another group of 92 children with HbSS disease. The nasal and nasopharyngeal swabs were cultured for S. aureus and S. pneumoniae, respectively. Susceptibility testing was carried out on the S. aureus and S. pneumoniae isolates for various antibiotics, including penicillin, ampicillin, cefuroxime, erythromycin, cloxacillin, and cotrimoxazole. Results The carriage rates of S. aureus among pediatric subjects with HbSS disease and those without HbSS disease were 48% and 50%, respectively (P > 0.05). S. pneumoniae carriage among the pediatric subjects with HbSS disease was 10%. Antibiotic resistance patterns of S. aureus carried by children with HbSS disease and children without HbSS disease were similar, and the S. aureus resistance rates were >40% for the various antibiotics, with the exception of erythromycin and cloxacillin. Low levels of S. pneumoniae resistance (0%–11%) were observed for the various antibiotics tested except cotrimoxazole, which showed an extremely high-percentage resistance (100%). Conclusion Sickling status is not a risk factor for carriage of S. aureus. In this cohort of Ghanaian children with HbSS disease, S. aureus is higher in carriage and more antibiotic-resistant, compared to S. pneumoniae.

Donkor, Eric S; Foster-Nyarko, Ebenezer; Enweronu-Laryea, Christabel C