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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



Sequential therapy with cefuroxime followed by cefuroxime axetil in acute exacerbations of chronic bronchitis.  


A prospective, multicentre, randomized, open-label, parallel group study compared the efficacy, safety and tolerability of cefuroxime 750 mg iv administered either twice daily (bd) or three times daily (tds) for 48-72 h, followed by oral cefuroxime axetil 500 mg bd for 5-7 days in a sequential therapy regimen for the treatment of acute exacerbations of chronic bronchitis. A total of 628 adult patients entered the study; 323 in the cefuroxime tds group and 305 in the cefuroxime bd group. For clinically evaluable patients, the post-treatment clinical response rate was 86% and 88% in the cefuroxime tds and bd groups, respectively. Cure was maintained at follow-up (14-28 days after treatment completion) in 85% of the cefuroxime tds group and 84% of patients in the cefuroxime bd group. A total of 189 pathogens was isolated, the most common being Haemophilus influenzae (17%), other Haemophilus spp. (15%), Streptococcus pneumoniae (15%) and Enterobacteriaceae (23%). At the post-treatment assessment, 66% and 70% of pathogens were cleared in the cefuroxime tds and bd groups, respectively. Both treatment regimens were well tolerated. The incidence of drug-related adverse events was 7% in the cefuroxime tds group and 6% in the cefuroxime bd group; the most common side-effects were gastrointestinal. Qualitative and quantitative markers were used to determine the optimal time to switch from iv to oral therapy and, of these, peak expiratory flow rate was shown to be the most useful in the present study. In conclusion, the findings of this study support the use of a bd dosing schedule of cefuroxime in a sequential therapy regimen with oral cefuroxime axetil, demonstrating it to be clinically equivalent to the standard tds dosage currently used, as well as being simpler and more convenient to administer at a lower cost. PMID:9462439

Vogel, F; Droszcz, W; Vondra, V; Reisenberg, K; Marr, C; Staley, H



Reduction in postoperative endophthalmitis with intracameral cefuroxime.  


Postoperative endophthalmitis is an uncommon complication of cataract surgery with grave consequences. This report describes the trend of endophthalmitis in a district general hospital in England over eight years, and attempts made to modify this trend. An outbreak of endophthalmitis in 2007 led to a detailed investigation and subsequent changes in practice. Intracameral cefuroxime (ICC) was introduced in place of subconjunctival cefuroxime. Use of ICC in patients with 'penicillin allergy' was explored, found to be safe and resulted in a change of policy. This led to a four-fold reduction in the rate of endophthalmitis. PMID:23834989

Myneni, J; Desai, S P; Jayamanne, D G R



[Potential nephrotoxicity of 2nd generation cephalosporins: cefuroxime versus cefotiam].  


Forty-one hospitalized patients were randomized to be treated with cefuroxime (4.05 g/die) or cefotiam (5.30 g/die). Several patients received additionally furosemide (0.5 mg/kg body weight) intravenously. Serum creatinine and creatinine clearance did not show significant differences during versus after treatment in any of the groups. Cefotiam or cefotiam/furosemide treated patients displayed higher proteinuria and higher urinary excretion of lysosomal enzymes (leucine aminopeptidase) than patients treated with cefuroxime or cefuroxime/furosemide. Our data indicate higher tubulotoxicity of cefotiam compared to cefuroxime. PMID:8314287

Riegel, W; Hörl, W H



Comparison of dose doubling with probenecid for sustaining serum cefuroxime levels.  


Serum cefuroxime concentrations were measured over a 12 h period in ten healthy adults following three iv dosing regimens: 750 mg cefuroxime, 1.5 g cefuroxime, and 750 mg cefuroxime with 1 g of probenecid given orally 3 h before the cefuroxime infusion. Probenecid prolonged the serum cefuroxime half-life by 63% (P < 0.05) with a significant increase in the mean time for which serum cefuroxime concentrations exceeded the MIC90 for common respiratory pathogens (2 mg/L) compared with either 750 mg cefuroxime (2.2 h, P < 0.05) or 1.5 g of cefuroxime (0.9 h, P < 0.05) without probenecid. The cost of the 750 mg cefuroxime dose plus probenecid is approximately half that of a 1.5 g cefuroxime dose. PMID:9462447

Garton, A M; Rennie, R P; Gilpin, J; Marrelli, M; Shafran, S D



Pharmacokinetics of cefuroxime axetil suspension in infants and children.  

PubMed Central

The pharmacokinetics of cefuroxime axetil suspension in 28 infants and children, ranging in age from 3 months to 12 years (mean, 23 months), were studied. Mean maximum serum cefuroxime concentrations of 3.3, 5.1, and 7.0 micrograms/ml were achieved 3.6, 2.7, and 3.1 h after the administration of doses of 10, 15, and 20 mg, respectively, of cefuroxime axetil suspension per kg of body weight together with milk or milk formula. These concentrations exceed the MICs for common respiratory tract pathogens, including beta-lactamase-producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Following a 10- or 15-mg/kg dose, serum cefuroxime concentrations are similar to those achieved in adults following the administration of a 250-mg cefuroxime axetil tablet. There were linear relationships between dose and both maximum serum cefuroxime concentration and area under the serum drug concentration-verus-time curve. The mean half-life of cefuroxime in serum was independent of dose and ranged from 1.4 to 1.9 h. No cefuroxime axetil (intact ester) was detected in the blood. The intact ester in the urine of four children was measured; however, the amount recovered represented less than 0.1% of the administered dose.

Powell, D A; James, N C; Ossi, M J; Nahata, M C; Donn, K H



[Cefuroxim, a new beta-lactamase stable cephalosporin].  


In vitro activity of cefuroxime, a new cephalosporin stable to bacterial beta-lactamases, was compared with that of cefalothin and other cephalosporins by serial dilution test in more than 600 bacterial strains. Cefuroxime was more active than cefalothin on most strains of Gram negative bacilli (except Salmonella species) and also on most strains of cefalothin-resistant bacteria. In comparison to cefalothin, cefoxitin and cefamandol, cefuroxime exerted the strongest activity on meningococci, streptococci of group A and B and also on Citrobacter freundii. It was as active as cefamandol and more active than cefalothin and cefoxitin on Haemophilus influenzae (also in ampicillin-resistant strains). Pharmacokinetic studies were performed in 10 healthy adult volunteers after i.v. injection of 0.75 g, 1 g, and 1.5 g cefuroxime and of 1 g cefalothin. Cefuroxime was superior to cefalothin by slower renal excretion, longer half-life, lesser or no metabolization and better tissue penetration. Cefuroxime is well tolerated and should be administered in adequate doses corresponding to the severity of the disease and the susceptibility of the causative agent. PMID:309178

Simon, C



Cefuroxime versus cefazolin as prophylaxis in vascular surgery.  


Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication. In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures. To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin. Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation. Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation. Both agents were continued every 6 hours after operation for 24 hours. Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2). Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients. In vitro evaluation of six of the study isolates plus an additional eight S. aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05). Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin. Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections. In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1728688

Edwards, W H; Kaiser, A B; Kernodle, D S; Appleby, T C; Edwards, W H; Martin, R S; Mulherin, J L; Wood, C A



Intraocular levels of cefuroxime in uninflamed rabbit eyes.  


Intraocular levels of cefuroxime following subconjunctival, intravitreal and combined intravitreal and intravenous administration were determined in uninflamed rabbit eyes. Intraocular levels of the antibiotic were assayed by a biological method. Penetration of cefuroxime into the vitreous following subconjunctival administration was poor. Subconjunctival administration produced higher levels of cefuroxime in the aqueous when compared to parenteral administration alone. Higher levels of cefuroxime were achieved both in the aqueous and in the vitreous after an intravitreal injection. Intravitreal injection of 100 and 1000 micrograms cefuroxime produced intravitreal levels close to the minimum inhibitory concentration (MIC) for most ocular pathogens up to 24 h after drug administration. Intravenous supplementation did neither enhance the intraocular levels nor did it delay the clearance of the intravitreally injected antibiotic. Mild histopathological changes were seen with equal frequency both in the control and the test eyes and are attributed to the sampling techniques. Electroretinography (ERG) showed no definite changes suggestive of retinal toxicity up to 55 days after intravitreal administration. PMID:2220364

Koul, S; Philipson, A; Philipson, B T; Kock, E; Nylén, P



Formulation and characterization of Cefuroxime Axetil nanoemulsion for improved bioavailability  

PubMed Central

Cefuroxime Axetil nanoemulsion was formulated to address the problem of poor oral bioavailability. Formulation was manufactured utilizing Capmul MCM, Soya lecithin, Deoxycholic acid, Pluronic F127 and distilled water. Mean globular size of 121.3 nm was obtained. Drug content of nanoemulsion was found to be 97.12±0.27%w/v. 80.7261% of the drug was diffused from nanoemulsion, as compared with 51.0048% diffused from the plain Cefuroxime axetil suspension. In vivo studies indicated AUC0-24: 325.3 for nanoemulsion in comparison to AUC0-24: 165.3 for plain suspension. Therefore a good orally bioavailable formulation was developed successfully.

Patel, Yomesh; Poddar, Aditi; Sawant, Krutika



Cefuroxime therapy for pneumonia in infants and children.  


Because Streptococcus pneumoniae, Haemophilus influenzae b and Staphylococcus aureus are the major causes of bacterial pneumonia in infancy, we customarily have given a beta-lactam antibiotic and chloramphenicol as initial antibiotic therapy. Cefuroxime (75 mg/kg/day divided every 8 hours iv or im) was evaluated as single drug therapy in an open study of 100 infants and children with suspected bacterial pneumonia. The mean serum concentration of cefuroxime 30 minutes after a 15-minute infusion of 25 mg/kg iv was 29.1 micrograms/ml, and the volume of distribution was 695 ml/kg. Pleural fluid concentrations in 3 specimens were 2.2, 8.5 and 11 micrograms/ml. Median age of patients was 15 months. Bacterial etiology was established in 20 patients: H. influenzae b (8 patients); pneumococcus (8 patients); S. aureus (2 patients); Group A streptococcus (1 patient); Neisseria meningitidis B (1 patient). All organisms were susceptible to 1.25-micrograms/ml doses or less of cefuroxime. The mean number of days was 3.1 until patients became afebrile and 5.1 until respiratory symptoms were gone. Eosinophilia occurred in 10 patients. Cefuroxime is safe and effective single drug therapy for pneumonia in infants and children. PMID:6755404

Nelson, J D; Kusmiesz, H; Shelton, S



Biomechanical properties of bone cement with addition of cefuroxime antibiotic.  


Antibiotic-loaded bone cement has been used as prophylaxis against infection in total joint replacement surgery. Its effect on the mechanical strength of cement is a major concern as high dose of antibiotic was associated with a significant reduction in mechanical strength of bone cement. However, the cut-off antibiotic that weakens the mechanical strength of cement remains to be determined. This study was undertaken to observe the changes in the mechanical properties of bone cement with gradual increments of Cefuroxime antibiotic. Cefuroxime at different doses: 0, 1.5, 3.0 and 4.5gm were added to a packet of 40gm bone cement (Simplex P) and study samples were prepared by using third generation cementing technique. Mechanical impact, flexural and tensile strength were tested on each sample. Significant impact and tensile strength reduction were observed after addition of 4.5 gm of Cefuroxime. However, flexural strength was significantly reduced at a lower dose of 3.0 gm. The maximum dose of Cefuroxime to be safely added to 40mg Surgical Simplex P is 1.5gm when third generation cementing technique is used. Further study is needed to determine whether it is an effective dose as regards to microbiological parameters. PMID:17042225

Mohd Fuad, D; Masbah, O; Shahril, Y; Jamari, S; Norhamdan, M Y; Sahrim, S H



Kinetics of cefuroxime in the groin wound after vascular prosthetic implantation.  


The kinetics of cefuroxime in serum and wound fluid were investigated in the period after vascular prosthetic implantation. Cefuroxime was administered as intravenous bolus injections in doses of 0.75 gm (five patients) or 1.5 gm (five patients). The concentration of cefuroxime in wound fluid increased after the injection and reached a maximal level corresponding to serum concentration levels with 1.5 hours. The subsequent elimination of cefuroxime from the wound fluid closely paralleled the elimination from the serum. The wound fluid concentrations were found to be greater than the minimum inhibitory concentration for Staphylococcus aureus and Escherichia coli in 8 and 5 hours, respectively, after injection of 0.75 gm of cefuroxime, and in 11 and 7 hours, respectively, after injection of 1.5 gm of cefuroxime. PMID:3398171

Sørensen, T S; Aabech, J; Utzon, N P; Bruun, B; Lorentzen, J E



Formulation and characterization of Cefuroxime Axetil nanoemulsion for improved bioavailability.  


Cefuroxime Axetil nanoemulsion was formulated to address the problem of poor oral bioavailability. Formulation was manufactured utilizing Capmul MCM, Soya lecithin, Deoxycholic acid, Pluronic F127 and distilled water. Mean globular size of 121.3 nm was obtained. Drug content of nanoemulsion was found to be 97.12±0.27%(w)/(v). 80.7261% of the drug was diffused from nanoemulsion, as compared with 51.0048% diffused from the plain Cefuroxime axetil suspension. In vivo studies indicated AUC(0-24): 325.3 for nanoemulsion in comparison to AUC(0-24): 165.3 for plain suspension. Therefore a good orally bioavailable formulation was developed successfully. PMID:23066200

Patel, Yomesh; Poddar, Aditi; Sawant, Krutika



Serum and bone concentrations of cefuroxime in patients undergoing knee arthroplasty.  


Concentrations of cefuroxime were measured in the serum and femoral and tibial bone of 12 patients undergoing knee arthroplasty, following cefuroxime 1.5 g iv. The mean serum cefuroxime concentration was 112.4 mg/l at the time of application of the mid thigh tourniquet. The mean femoral bone concentration was 18.6 mg/kg and tibial bone was 15.5 mg/kg. These concentrations of cefuroxime appear adequate for prophylaxis against post-operative infection in knee arthroplasty. PMID:3804882

Leigh, D A



Esters of cephalosporins. Part IV. Hydrolysis of 1-acetoxyethyl ester of cefuroxime in vitro and in vivo.  


Hydrolysis of 1-acetoxyethyl ester of cefuroxime [I] in blood was studied in vitro and in vivo. In vitro [I] hydrolyzes to biological active cefuroxime [II] and at the same time it undergoes isomerization to isomer delta 2 of 1-acetoxyethyl ester of cefuroxime [IV] and next hydrolyzes to biological inactive isomer delta 2 of cefuroxime [V]. As a result of hydrolysis [I] in vivo only [II] is formed. PMID:8960266

Tejchman, B; Jaromi?ska, M; Horodecka, M; Oszczapowicz, I



Role of liquid membrane phenomenon in the anti-bacterial activity of Cefuroxime Sodium  

PubMed Central

The role of liquid membrane phenomenon has been studied in the anti bacterial activity of cephalosporins i.e. Cefuroxime sodium. In our earlier publication [1] it was reported that hydraulic permeability data obtained to demonstrate the existence of liquid membrane in series with supporting membrane generated by Cefuroxime sodium. Transport of selected permeants (glucose, PABA, glycine, and ions like Mg++, NH4+, PO4-, Ca++, Na+, K+ and Cl-) through liquid membrane generated by Cefuroxime sodium in series with supporting membrane has been studied. The results indicated that the liquid membrane generated by Cefuroxime sodium inhibit the transport of various essential bio-molecules and permeants in to the cell. This modification in permeability of different permeants in the presence of the liquid membranes is likely to play significant role in the biological actions of Cefuroxime sodium. The anti-bacterial activity of Cefuroxime sodium further confirmed that the generation of liquid membrane by Cefuroxime sodium is also contributing for the antibacterial activity of them.

Nagesh, C.; Shankaraiah, M. M.; Venkatesh, J. S.; Setty, S. Ramachandra



[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



Pharmacokinetics of cefuroxime in traumatic wound secretion and antibacterial activity under vacuum therapy.  


The objective of this study was to investigate the pharmacokinetics of cefuroxime in wound secretion and the antibacterial activity of the traumatic wound secretion in patients receiving cefuroxime and in those not receiving antibiotics. Included in the present controlled, prospective, non-randomized study were 12 patients with an open fracture who needed vacuum therapy (group A) and 12 patients with a closed fracture, who, due to soft tissue damage, also underwent treatment with vacuum therapy (group B). Wound secretion was obtained on the first, third and fifth postoperative days and exposed to the test bacteria, Staphylococcus aureus and Staphylococcus epidermidis. Patients in group A underwent systemic antibiotic treatment with cefuroxime administered intravenously at a dose of 1.5 g every 8 hours. Patients in group B did not receive antibiotics. Cefuroxime concentrations were determined using high-performance liquid chromatography (HPLC). Antibacterial activity was determined using the inhibition test. Maximum cefuroxime concentrations in wound secretion were measured at 4-5 hours following intravenous administration and, with a mean concentration of 10 mg/l, remained consistently above the minimum inhibitory concentration (MIC) for the test bacteria at all points during the measurement period. As expected, the antibacterial activity of the wound secretion in patients in group A (cefuroxime) was higher than that in group B (no antibiotics). In group A, antibacterial activity against S. aureus was 94.6% and 100% against S. epidermidis. In group B, antibacterial activity against S. aureus was 61% and 81% against S. epidermidis. Cefuroxime reaches the highest level in wound secretion after 4 hours. The high antibacterial activity of the wound secretion in traumatic closed fractures is elevated by cefuroxime. in addition, our findings show that vacuum therapy of wounds is suitable as a non-invasive method for studying the pharmacokinetics of antibiotics. PMID:20435567

Bischoff, M; Beck, A; Frei, P; Bischoff, G



Antibiotic prophylaxis in open-heart surgery patients: comparison of cefamandole and cefuroxime.  


The efficacy of cefamandole and cefuroxime in preventing postoperative wound infections was compared in 3037 patients undergoing open-heart surgery. Antibiotic prophylaxis in 1467 patients having coronary artery bypass and valve replacement surgery was cefamandole 2 g iv preoperatively followed by 2 g q6h for five days postoperatively; 1570 patients received cefuroxime 1.5 g iv preoperatively then 1.5 g iv q 12h for three days postoperatively. Postoperative wound infections (sternal and leg wounds) were studied in each treatment group. In the cefamandole study group, 27 patients (1.8 percent) developed postoperative wound infections (9 sternal and 18 leg wounds). In the cefuroxime treatment group, 19 patients (1.2 percent) developed postoperative wound infections (9 sternal and 10 leg wounds). Overall, no statistical difference was found between the two antibiotics in preventing postoperative wound infections. However, in patients having valve replacement surgery, cefuroxime was found statistically more effective than cefamandole prophylaxis in preventing sternal wound infections (no infections in 284 patients compared with five infections in 205 patients, respectively, p = 0.01). The most common organism isolated from infected wounds with cefamandole was Staphylococcus aureus followed by S. epidermidis compared with cefuroxime which had S. epidermidis followed by S. aureus. Cefuroxime was found to be as effective as cefamandole and considerably less expensive in preventing postoperative wound infections in patients undergoing open-heart surgery. PMID:3498617

Peterson, C D; Lake, K D; Arom, K V; Love, K R



Cardiovascular surgery prophylaxis. A randomized, controlled comparison of cefazolin and cefuroxime.  


A prospective double-blind trial was performed at a tertiary care center to evaluate perioperative cephalosporin prophylaxis in cardiac operations. Patients were randomized to receive either cefazolin (n = 104) or cefuroxime (n = 109), the preoperative dose being given within 1 hour before the initial incision. Drugs were continued for 48 hours (cefazolin, 1 gm intravenously every 8 hours; cefuroxime, 1.5 gm intravenously every 12 hours). Postoperative infections were assessed by trained nurse clinicians, and data were analyzed by the intention-to-treat principle. Sternal wound infections or mediastinitis occurred in one of 104 patients treated with cefazolin and 10 of 109 treated with cefuroxime (p = 0.01). Deep sternal wounds (including mediastinitis and sternal osteomyelitis) occurred in none of the cefazolin-treated patients and five cefuroxime-treated patients (p = 0.06). Although overall nosocomial infection rates were similar (16.3 versus 19.3 per 100), wound infection occurred somewhat more frequently with streptococci (groups B and D) in patients receiving cefazolin (four versus zero, p = 0.110); conversely staphylococcal infections were more frequent in the cefuroxime group (seven versus one, p = 0.066). Mean and median postoperative stay was 1 day shorter in the cefazolin group. In contrast to findings of a previous report, our data indicate that cefazolin prevented more sternal wound infections than cefuroxime, a finding that supports prophylaxis with a first-generation cephalosporin. PMID:2193200

Doebbeling, B N; Pfaller, M A; Kuhns, K R; Massanari, R M; Behrendt, D M; Wenzel, R P



The renal clearance of cefuroxime and ceftazidime and the effect of probenecid on their tubular excretion.  

PubMed Central

1. The renal tubular excretion of cefuroxime and ceftazidime in relation to the coadministration of probenecid was investigated in eight and two healthy subjects, respectively. 2. Cefuroxime or ceftazidime were administered by i.v. infusion and 1 g probenecid was administered orally after steady state plasma concentrations of the cephalosporin were reached. 3. In a second session the same antibiotic was administered at increasing infusion rates such that three different levels of plasma drug concentration were achieved. 4. The renal clearance of antibiotic was calculated based upon unbound plasma concentration, and tubular clearance was estimated by subtracting inulin clearance from the renal clearance of the antibiotic. 5. Non-linear regression analysis was used to estimate parameters describing the saturability of tubular excretion and the effect of probenecid inhibition, i.e. EC50 and Rtub,max, could be established for cefuroxime: EC50 was 248 (s.d. 130) mg l-1 and Rtub,max was 1.852 (s.d. 0.577) mg h-1. Tubular excretion of ceftazidime was practically zero. The EC50 of probenecid for inhibition of the tubular excretion of cefuroxime was 0.80 (s.d. 0.31) mg l-1. 6. The results indicate that in the therapeutic plasma concentration range of cefuroxime its renal clearance is not saturated. Probenecid at therapeutic doses will block tubular excretion of cefuroxime almost completely.

Verhagen, C A; Mattie, H; Van Strijen, E



Assessment of cefazolin and cefuroxime tissue penetration by using a continuous intravenous infusion.  

PubMed Central

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) or cefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations of cefazolin (at incision, 9.3 micrograms/ml; at closure, 9.2 micrograms/ml) and cefuroxime in serum (at incision, 26.9 micrograms/ml; at closure, 31.8 micrograms/ml), there was no difference in the total concentrations in muscle at either surgical incision (cefazolin, 6.1 micrograms/g; cefuroxime, 5.6 micrograms/g) or wound closure (cefazolin, 7.7 micrograms/g; cefuroxime, 7.4 micrograms/g). There was a significant correlation between the pooled free serum and total muscle concentrations for cefazolin (P = 0.001); however, there was no correlation between these variables with the pooled cefuroxime data (P = 0.403). These findings indicate that the free drug concentration in serum alone is not consistently predictive of the total concentration of cephalosporin in muscle.

Connors, J E; DiPiro, J T; Hayter, R G; Hooker, K D; Stanfield, J A; Young, T R



Relationship between plasma and bone concentrations of cefuroxime and flucloxacillin. Three different parenteral administrations compared in 30 arthroplasties.  


(i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin. (ii) Six groups of five patients participated in the study. The first three groups (A-C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D-F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously. (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients. (iv) Large inter-individual variation in bone concentration was observed. (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent. PMID:7849235

Alvarez Ferrero, M M; Vree, T B; Van Ewijk-Beneken Kolmer, E W; Slooff, T J



Cefuroxime axetil versus clarithromycin in the treatment of acute maxillary sinusitis.  


Acute maxillary sinusitis is a common condition requiring broad-spectrum therapy to prevent development of chronic disease. A randomised, double-blind, multicentre study was performed to compare the efficacy and safety of cefuroxime axetil 250 mg twice daily (n = 185) and clarithromycin 250 mg twice daily (n = 185), both administered for 10 days, in the treatment of patients with acute sinusitis. Efficacy was determined by assessment of clinical response at post-treatment and follow-up, and by radiological assessment at pre-treatment and follow-up. Assessment of days absent from work due to illness was also made. In the cefuroxime axetil group, 169/185 (91%) patients were cured/improved at post-treatment, as were 172/185 (93%) patients receiving clarithromycin and, of these, 137/169 (81%) and 143/172 (83%) maintained their response at follow-up. Follow-up radiography showed a reduction in incidence of air fluid level and/or opacification from 96% to 15% (cefuroxime axetil) and from 96% to 11% (clarithromycin), and a decrease in frequency of mucosal thickening from 58% to 28% (cefuroxime axetil) and from 56% to 29% (clarithromycin). Only 10% of patients in either group experienced adverse events and days absent from work were comparable. This study demonstrated clinical equivalence between twice-daily cefuroxime axetil and clarithromycin, both treatments being effective and well tolerated. PMID:9923060

Stefansson, P; Jacovides, A; Jablonicky, P; Sedani, S; Staley, H



First-derivative spectrophotometric and LC determination of cefuroxime and cefadroxil in urine.  


Two methods are presented for the determination of cefuroxime and cefadroxil in human urine using first (1D) derivative spectrophotometry and high-performance liquid chromatography. Cefuroxime and cefadroxil were determined by measurement of their first-derivative amplitude in 0.1 N sodium hydroxide at 292.5 and 267.3 nm, respectively in the concentration range of 2-10 microg ml(-1) for each drug. The HPLC method depends upon using a LiChrospher 100 RP-18 (5 microm) column at ambient temperature for cefuroxime and 35 degrees C for cefadroxil with mobile phases consisting of water-acetonitrile-acetic acid (85:15:0.1 v/v) at a flow rate of 1.5 ml min(-1) for cefuroxime; and 0.02 M potassium dihydrogen phosphate-acetonitrile (95:5 v/v) containing 0.003% (w/v) hexanesulphonic acid sodium salt and adjusted to apparent pH 3 with phosphoric acid at a flow rate of 2 ml min(-1) for cefadroxil. Quantitation was achieved with UV detection at 275 and 260 nm for cefuroxime and cefadroxil, respectively, based on peak area with linear calibration curves at the concentration ranges of 2-10 microg ml(-1) for cefuroxime and 5-20 microg ml(-1) for cefadroxil. The proposed methods were applied to the determination of dissolution rate for tablets and capsules containing each drug. The urinary excretion patterns as the cumulative amounts excreted have been calculated for each drug using the proposed methods. PMID:10933526

El-Gindy, A; El Walily, A F; Bedair, M F



Antibiotic prophylaxis in pulmonary surgery. A prospective randomized double-blind trial of flash cefuroxime versus forty-eight-hour cefuroxime.  


The aim of this study was to determine whether a 48-hour antibiotic prophylaxis regimen with a second-generation cephalosporin was more efficient than a flash antibiotic prophylaxis regimen in pulmonary operations. All the included patients underwent lung resection. Patients with preoperative infection were excluded. All the patients were given cefuroxime (1.5 gm intravenously) at the time of the anesthetic induction and again 2 hours later. The randomization was done postoperatively: group 1 was given placebo intravenously (n = 102) and group 2 was given cefuroxime intravenously (n = 101), each every 6 hours for 48 hours. The overall rate of infections was 46% in the 48-hour cefuroxime group versus 65% in the flash group (p = 0.005). The difference remained significant even after an adjustment with prognosis variables (p = 0.01). Six empyemas (6%) in the flash group were noted versus one (1%) in the 48-hour group (p = 0.03). From day 3 to day 8 after the operation, chest x-rays films were more often assessed as being normal in the flash group than in the 48-hour group (p = 0.005). On day 3 after operation, white blood cell counts were 13,020 +/- 1,220 elements/mm3 in the flash group versus 11,620 +/- 1,220 elements/mm3 in the 48-hour group (p = 0.03). A 48-hour antibiotic prophylaxis regimen decreases the rate of deep infections and particularly the rate of empyemas. PMID:8127120

Bernard, A; Pillet, M; Goudet, P; Viard, H



Pharmacokinetics of cefuroxime axetil and cefaclor: relationship of concentrations in serum to MICs for common respiratory pathogens.  

PubMed Central

The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly Branhamella) catarrhalis were significantly greater (P less than 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxime compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime.

James, N C; Donn, K H; Collins, J J; Davis, I M; Lloyd, T L; Hart, R W; Powell, J R



Pharmacokinetics and absolute bioavailability of oral cefuroxime axetil in the rat.  


The objectives of this study were to determine the oral bioavailability of cefuroxime (C) and to evaluate the pharmacokinetic model that best describes the plasma concentration behaviour following single intravenous (IV), intraperitoneal (IP) and oral single doses. The same dose of C was administered by IV, IP and oral routes to three separate groups of rats (2.02 mg of cefuroxime axetil (CA) by the oral route or 1.78 mg of cefuroxime sodium (CNa) by IV and IP route). A two-compartment open model without lag time can predict the C disposition kinetics. The influence of the administration route on the pharmacokinetic parameters and AUC values was investigated by means of a one-way analysis of variance test. The results indicated that the first-pass effect in the intestine and liver reduce oral bioavailability when the drug is administered orally. Cefuroxime bioavailability after oral and IP administration estimated from the plasma levels was nearly 24 and 75%, respectively. PMID:10915930

Ruiz-Carretero, P; Nacher, A; Merino-Sanjuan, M; Casabo, V G



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



Effect of malnutrition on the pharmacokinetics of cefuroxime axetil in young rats  

Microsoft Academic Search

PURPOSE. To determine the pharmacokinetics of cefuroxime axetil in malnourished rats using a diet with a restriction in energy and nutrients (group M), a diet with a low quality protein (group K) and a good quality diet (group C) as a control. METHODS. The rats were fed with the corresponding diet for 21 days, after which a single oral dose

Iliana González-Hernández; Helgi Jung-Cook; Angela Sotelo



Cefuroxime-impregnated calcium phosphates as an implantable delivery system in experimental osteomyelitis  

Microsoft Academic Search

The study aimed to investigate the effectiveness of porous calcium phosphates viz., hydroxyapatite (HAp) and a bi-phasic calcium phosphate (BCP) with predominately ?-tricalcium phosphate (?-TCP) prepared by aqueous solution combustion method impregnated with cefuroxime axetil for the treatment of experimental osteomyelitis and compared with parenteral treatment. In vitro release of the drug was tested for its sustained elution characteristics for

Samit K. Nandi; Biswanath Kundu; Samir K. Ghosh; Tapan K. Mandal; Someswar Datta; Dipak K. De; Debabrata Basu



beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin.  


The stability to beta-lactamase hydrolysis of HR 756, a new cephalosporin antibiotic, was compared to the beta-lactamase stability of cefoxitin and cefuroxime. HR 756, cefoxitin, and cefuroxime were not hydrolyzed by Richmond type I, III, IV, and V beta-lactamases. Antibacterial activity of HR 756 correlated well with resistance to beta-lactamase hydrolysis except against Pseudomonas aeruginosa. HR 756, cefoxitin, and cefuroxime inhibited type I beta-lactamases, but not type III, IV, or V enzymes. HR 756 was the most active inhibitor. PMID:101128

Fu, K P; Neu, H C



In vitro protein binding of cefonicid and cefuroxime in adult and neonatal sera.  

PubMed Central

The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for each drug were determined within the concentration range of 25 to 3,000 micrograms/ml. Cefonicid exhibited concentration-dependent protein binding in both types of sera, with more extensive binding in adult serum at all concentrations. Two classes of binding sites were found: a high-affinity, saturable site and a low-affinity, nonspecific site. Cefuroxime also showed two-class, concentration-dependent protein binding in adult serum, but binding in neonatal serum was to a single class and was independent of drug concentration. Parameters for class 1 binding sites for cefonicid indicated one binding site per albumin molecule in both adult and neonatal sera, with association constants of 7.0 x 10(4) and 1.3 x 10(4) M-1, respectively. These parameters were also derived for cefuroxime in adult serum and were 0.15 and 7.1 x 10(4) M-1, respectively. In neonatal serum, the combined value (number of binding sites per molecule x equilibrium association constant) was similar to combined values calculated for class 2 binding sites for cefuroxime in adult serum and for cefonicid in neonatal serum (287 versus 195 and 261 M-1, respectively). Cephalosporins have been shown to compete with bilirubin for albumin binding sites. Lower levels of protein binding of cefuroxime in the therapeutic range may mean a lower potential for drug displacement of bilirubin in neonates, on the basis of these results. It may be prudent to select less highly protein-bound agents when treating neonatal infections.

Benson, J M; Boudinot, F D; Pennell, A T; Cunningham, F E; DiPiro, J T



Stability of cefuroxime in 1% and 5% buffered eye drops determined with HPLC method.  


The aim of the studies was to develop formulary technologies of 1% and 5% eye drops containing cefuroxime with stability of at least 10-12 days. The stability was defined as the time required to reach the cutoff value of 10% degradation of cefuroxime in the drops, as determined using an HPLC assay. The drops should have such properties as optical clarity, pH in the range of 3.5 to 8.5 and osmotic pressure not lower than 280 mOsm/L. Additionally, drops of enhanced viscosity within the range 7-9 mPaxs were developed. Drops (1% and 5%) were prepared under aseptic conditions by dissolving Biofuroksym (Cefuroxime natricum) IBA Bioton--the form of the drug for dry injections--in citrate buffer of pH 6.05-6.28. Polyvinyl alcohol was used to increase the viscosity of the drops. Phenylmercuric borate at the final concentration of 0.001% was used together with beta-phenylethyl alcohol at the final concentration of 0.4% to preserve the drops. The drops were stored for 30 days in tightly closed glass bottles at the temperature of 4 degrees C and 20 degrees C, protected from light. As the course of the infection may differ in intensity, location and the area of the infection in the eye, the composition of the drops was developed at two concentrations (1% and 5%), and five formulary versions for each concentration were prepared. The concentration of cefuroxime in the drops was determined every three days using HPLC. Such properties as pH, osmotic pressure and viscosity were also examined. Additionally, organoleptic analysis (clarity, color, odor) was performed. Physical and chemical properties of all formulations of 1% and 5% drops containing cefuroxime prepared in citrate buffer of pH 6.05-6.28 met the standards set in the objective of the work. The stability of cefuroxime in buffered drops stored at the temperature of 4 degrees C, determined with HPLC as the time of 10% degradation of cefuroxime, was 15 days for 1% and 5% drops. In the drops, which were buffered and of increased viscosity, the times of 10% cefuroxime degradation were 18 days for 1% drops and 30 days for 5% drops. The preservatives added to the buffered drops did not lower their stability. Osmotic pressure, pH and viscosity of the drops during the period of 30-day-storage at the temperature of 4 degrees C met the requirements acceptable for the eye drops. The stability of 1% and 5% buffered drops containing cefuroxime stored at the temperature of 4 degrees C allows preparing the drops in pharmacies on the basis of doctor's prescription. Depending on the character and the course of the infection the drops can be prepared at the concentration of 1% and 5% following the composition of the selected formulation which would meet the individual needs of the patient's therapy. PMID:21796938

Kodym, Anna; Wi?niewski, Andrzej; Knio?a, Dawid; Olejniczak, Monika



Development and in vivo evaluation of gastroretentive delivery systems for cefuroxime axetil.  


The purpose of this investigation was to design and develop gastroretentive dosage form for cefuroxime axetil using floating tablet approach with various grades of hydroxypropyl methyl cellulose. Cefuroxime axetil is known to have low bioavailability, short half-life and is absorbed largely from upper GIT. Sodium bicarbonate was used in the dosage form as a source of carbon-di-oxide to maintain buoyancy. In vitro dissolution study results indicated non-Fickian diffusion controlled drug release mechanism and was best fitted into Korsmeyer-Peppas equation. In vivo radiographic studies conducted in five healthy human volunteers for optimized formulation indicated over 6 h retention of tablet in the stomach region. Reproducible physical parameters indicated that the current formulation could be easily scaled-up. PMID:23960819

Rao, Govikari Koteshwar; Mandapalli, Praveen Kumar; Manthri, Rajendraprasad; Reddy, Veerareddy Prabhakar



Development and in vivo evaluation of gastroretentive delivery systems for cefuroxime axetil  

PubMed Central

The purpose of this investigation was to design and develop gastroretentive dosage form for cefuroxime axetil using floating tablet approach with various grades of hydroxypropyl methyl cellulose. Cefuroxime axetil is known to have low bioavailability, short half-life and is absorbed largely from upper GIT. Sodium bicarbonate was used in the dosage form as a source of carbon-di-oxide to maintain buoyancy. In vitro dissolution study results indicated non-Fickian diffusion controlled drug release mechanism and was best fitted into Korsmeyer–Peppas equation. In vivo radiographic studies conducted in five healthy human volunteers for optimized formulation indicated over 6 h retention of tablet in the stomach region. Reproducible physical parameters indicated that the current formulation could be easily scaled-up.

Rao, Govikari Koteshwar; Mandapalli, Praveen Kumar; Manthri, Rajendraprasad; Reddy, Veerareddy Prabhakar



Development, characterization and solubility study of solid dispersions of Cefuroxime Axetil by the solvent evaporation method  

PubMed Central

Cefuroxime Axetil (Poorly water soluble drug), when prepared as solid dispersion showed improved solubility and dissolution. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of Cefuroxime Axetil by the preparation of its solid dispersion with urea, using the solvent evaporation method. Physical mixtures and solid dispersions of Cefuroxime Axetil were prepared by using urea as a water-soluble carrier in various proportions (1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7 by weight), by employing the solvent evaporation method. The drug release profile was studied and it was found that the dissolution rate and the dissolution parameters of the drug from the physical mixture as well as solid dispersion were higher than those of the intact drug. The Fourier Transform Infrared (FTIR) spectra revealed no chemical incompatibility between the drug and urea. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC) and Powder X-Ray Diffraction (PXRD).

Arora, S. C.; Sharma, P. K.; Irchhaiya, Raghuveer; Khatkar, Anurag; Singh, Neeraj; Gagoria, Jagbir



Determination of bone and fat concentrations following systemic cefamandole and regional cefuroxime administration in patients undergoing knee arthroplasty.  


Five patients undergoing routine total knee replacement received standard antibiotic prophylaxis of 1000 mg of iv cefamandole and also regional administration of 750 mg of cefuroxime. Regional dosing was carried out at the start of the operation, following the application of a mid-thigh tourniquet, by administration into a foot vein. Samples of bone and fat were collected during the operation and assayed for cefuroxime and cefamandole by HPLC analysis. The mean cefuroxime bone (133.1 mg/l) and fat (88.4 mg/l) levels following regional administration were significantly higher (P less than 0.001) than the mean cefamandole bone (9.1 mg/l) and fat (9.8 mg/l) levels following systemic dosing. The possibility of administration of prophylaxis by the regional route is suggested. PMID:2081721

Hoddinott, C; Lovering, A M; Fernando, H C; Dixon, J H; Reeves, D S



Single dose mezlocillin versus three dose cefuroxime plus metronidazole for the prophylaxis of wound infection after large bowel surgery.  


A prospective, randomized, controlled trial was conducted in 116 consecutive patients undergoing colorectal surgery to compare single dose prophylaxis with mezlocillin to cefuroxime plus metronidazole in three doses. Patients were randomized to receive either a single dose of iv mezlocillin (5.0 g) or three doses of iv cefuroxime plus metronidazole at 8-hourly intervals. The first dose was given on the operating table. The overall wound infection rate in the mezlocillin treated patients (n = 54) was 30% and in the patients treated with cefuroxime plus metronidazole (n = 56) 25%. This difference is not statistically significant. When trivial wound infections were disregarded the wound infection rates were 11% and 16% respectively, which again was not statistically significant. PMID:2886534

Stubbs, R S; Griggs, N J; Kelleher, J P; Dickinson, I K; Moat, N; Rimmer, D M



Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil.  

PubMed Central

The present study was designed to investigate the effect of food and of a raised intragastric pH on the bioavailability of two prodrug beta-lactam, antibiotics, namely bacampicillin and cefuroxime axetil. Six healthy volunteers participated in an intraindividual comparison of absorption of (a) prodrug, (b) breakfast, followed by prodrug, (c) breakfast, ranitidine and sodium bicarbonate followed by prodrug, and (d) ranitidine and sodium bicarbonate, followed by prodrug. All volunteers were dosed with both bacampicillin and cefuroxime axetil under the above regimens. The drug-free periods between trials were 7 days. Blood samples were obtained before and 20, 40, 60, 90, 120, 150, 180, 210 min and 4, 5, 6, 8 and 10 h after administration. The urine was collected for a period of 10 h after dosing with the antibiotic. An estimation of the relative bioavailability of the drugs under the various regimens was made by comparing the average areas under the serum concentration time curves and also the amounts recovered in the urine. Both food and reduced gastric acidity decreased the bioavailability of bacampicillin (as ampicillin) and these variables had an additive lowering effect on the AUC and percentage urinary recovery. Possibly this ester becomes partially hydrolyzed prior to absorption on raising the intragastric pH. Adsorption onto food components or complexing with proteins may also play a role in the reduced bioavailability of bacampicillin in the presence of food. In contrast, the absorption of the cefuroxime ester was enhanced postprandially. This may be rationalized in terms of delayed gastric emptying and gastrointestinal transit which allows more complete dissolution or prolonged residence at the most favourable site of absorption in the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Sommers, D K; van Wyk, M; Moncrieff, J; Schoeman, H S



[Studies on the effect of cephradine, cefuroxime, lincomycin and amikacin on complement levels in experimental animals].  


Rabbits were injected intramuscularily with antibiotics in mean therapeutic doses (calculated by body weight) for the period of 7 days. Group I received cephradine, group II--cefuroxime, group III--lincomycin and group IV--amikacin. Determination of complement level by CH50 method was performed before application of antibiotics and at 7, 14, 28 and 42 day of the study. Application of the cephalosporin antibiotics did not result in any changes in the complement level. After application of lincomycin, complement level increased at the 17 day and after amikacin treatment it was higher after 7 days of investigation. PMID:8309295

Jasi?ska, B; Szeniawska, A; Hencner, Z; Fota-Markowska, H



Cefuroxime vs a dicloxacillin/chloramphenicol combination for the treatment of parapneumonic pleural effusion and empyema in children.  


The aim of this study was to evaluate the efficacy of cefuroxime, compared with the combination of dicloxacillin/chloramphenicol, for the treatment of children with parapneumonic pleural effusion or empyema. Forty patients, aged 3 months to 5 years, with pleural effusion or empyema were randomized to receive cefuroxime (100 mg/kg/day) IV (n=20) or chloramphenicol (100 mg/kg/day) plus dicloxacillin (200 mg/kg/day) IV (n=20). Both groups were similar in age, days of illness, clinical and radiological findings, and etiology. Most patients (70%) had an empyema at presentation. There was no difference in clinical outcomes, including days to defervescence, duration of respiratory distress, duration of chest tube drainage, and days to discharge from hospital. The complication rates were similar in both groups. Pleural thickening occurred in four patients, bronchopleural fistula in two, and loculated empyema in one patient of each treatment group. Adverse effects attributed to cefuroxime were mild and infrequent. These results suggest that cefuroxime is an effective and well-tolerated alternative for the treatment of children with pleural effusion and empyema. PMID:11969360

Palacios, G C; Gonzalez, S N; Perez, F L; Cuevas, S F; Solorzano, S F



A new approach to pharmacokinetic parameters: estimation of cefuroxime during haemodialysis.  


A linear three-compartment model is proposed as a means of estimating disposition and extracorporeal elimination pharmacokinetic parameters during haemodialysis. It was created by connecting a compartment, corresponding to the amount of drug present in the dialysis cell, to the central compartment of the standard two-compartment model from which elimination would normally take place. The transfer rate constants between the central compartment and the 'dialysis cell' and vice versa were given in terms of the plasma flow, central compartment volume, and volume of plasma contained in the dialysis cell, and thus cannot be considered to be independent parameters. The product of the rate constant for elimination from the dialysis cell, k30, and the plasma volume within the cell was used to quantify the extracorporeal elimination and termed intrinsic dialyser clearance, CLint,D. The model was used to interpret the plasma level curves obtained after administering 750 mg cefuroxime by IV bolus to a group of patients undergoing haemodialysis. The distribution parameters estimated by non-linear regression were similar to those given in the literature; however, in five of the twelve cases, no estimate of cefuroxime elimination from the central compartment (k10) could be derived. On the other hand, the estimates of the elimination rate constant (k30) from the deep peripheral compartment were greater than the values given in the literature, ranging from 50.6 h-1 to 151.0 h-1 and CLint,D ranging from 3.1 h-1 to 8.90 l h-1. The error in measuring the flow of plasma which reaches the dialyser, its influence upon the estimation of the model parameters and the relationship between the parameters themselves and those customarily used in the study of drug haemodialysis are all discussed. PMID:2328296

Sánchez, E; Evora, C M; Torres, A; Llabrés, M



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



Effect of Antibiotic Prophylaxis with Cefuroxime on Bacteriologic Quality of Intra- and Postoperatively Processed Wound Blood in Hip Joint Arthroplasty  

Microsoft Academic Search

SummaryObjective: Investigation of the bacteriological quality of processed wound blood in orthopedic hip surgery depending on antibiotic prophylaxis or not. Design: Prospective randomized study after approval of the Ethics Committee. Setting: Operation theatre\\/intensive care unit of an Orthopedic University Clinic. Patients: 40 patients underwent first hip arthroplasty under regional anesthesia. 20 received as antibiotic prophylaxis cefuroxime 1.5 g single shot,

K. H. Wollinsky; M. Büchele; M. Oethinger; P. Kluger; H.-H. Mehrkens; R. Marre; W. Puhl



Simple and Robust Analysis of Cefuroxime in Human Plasma by LC-MS/MS: Application to a Bioequivalence Study  

PubMed Central

A simple, robust LC-MS/MS assay for quantifying cefuroxime in human plasma was developed. Cefuroxime and tazobactam, as internal standard (IS), were extracted from human plasma by methanol to precipitate protein. Separation was achieved on a Zorbax SB-Aq (4.6 × 250?mm, 5??m) column under isocratic conditions. The calibration curve was linear in the concentration range of 0.0525–21.0??g/mL (r = 0.9998). The accuracy was higher than 90.92%, while the intra- and interday precision were less than 6.26%. The extraction procedure provides recovery ranged from 89.44% to 92.32%, for both analyte and IS. Finally, the method was successfully applied to a bioequivalence study of a single 500?mg dose of cefuroxime axetil in 22 healthy Chinese male subjects under fasting condition. Bioequivalence was determined by calculating 90% Cls for the ratios of Cmax, AUC0?t, and AUC0?? values for the test and reference products, using logarithmic transformed data. The 90% Cls for the ratios of Cmax (91.4%~104.2%), AUC0?t (97.4%~110.9%), and AUC0?? (97.6%~111.1%) values were within the predetermined range. It was concluded that the two formulations (test for capsule, reference for tablet) analyzed were bioequivalent in terms of rate and extent of absorption and the method met the principle of quick and easy clinical analysis.

Hu, Xingjiang; Huang, Mingzhu; Liu, Jian; Chen, Junchun; Shentu, Jianzhong



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



Estimation of cefuroxime dosage using pharmacodynamic targets, MIC distributions, and minimization of a risk function.  


An approach for estimation of dosing strategies based on data-derived models and assessment of the risk associated with deviation from the treatment target is presented. The work is illustrated by establishing a dosing strategy to be used for a priori individualization on the basis of renal function for the antibiotic cefuroxime. Treatment involved exposing patients to concentrations above the minimum inhibitory concentration (MIC) for 50% of the dosing interval. The risk (penalty) function incorporated both deviations from the target and the use of excess amount of drug. Dosing strategies were estimated for a target population by minimizing the risk function. The population was characterized by a population pharmacokinetic model, and distributions of CLcr and body weight were reflective of the target group. The estimated dosing strategies were assessed by evaluating population distributions of (1) percentage of dosing interval with concentrations above MIC, (2) time of drug exposure below MIC, and (3) drug administered in excess to reach the target. These distributions were generated using wild-type MIC distributions for Escherichia coli and Streptococcus pneumoniae. The authors illustrate how benefits and risks of drug treatment can be weighed quantitatively in decision-based risk functions and subsequently used in the estimation of drug dosing. PMID:18974282

Viberg, Anders; Cars, Otto; Karlsson, Mats O; Jönsson, Siv



Randomized, multicentre, comparative clinical evaluation of cefuroxime-sulbactam versus amoxicillin-clavulanic acid therapy in the treatment of lower respiratory tract infections.  


This randomized, multicentre, comparative study evaluated the efficacy and safety of treatment with cefuroxime-sulbactam compared with amoxicillin-clavulanic acid (co-amoxiclav) in patients with lower respiratory tract infections (LRTIs). The study enrolled 75 adult in-patients with moderate to severe LRTIs. Patients were treated intravenously for 7 - 10 days. The treatment groups were comparable at baseline with respect to demographic and disease characteristics. Efficacy was evaluated in 72 patients. The clinical success rate was statistically superior in patients treated with cefuroxime-sulbactam (100%) compared with patients treated with amoxicillin-clavulanic acid (88%). The bacteriological success rate was 95% and 100% for cefuroxime-sulbactam and amoxicillin-clavulanic acid, respectively, with no significant difference between treatments. Both treatments were safe and well tolerated. One patient in the cefuroxime-sulbactam group reported convulsions, which the investigator considered were probably not related to the study medication. Cefuroxime-sulbactam can be an effective alternative empirical treatment for LRTIs. PMID:19094439

Pareek, A; Pednekar, S; Prasad, H B; Salagre, S; Chandurkar, N



Comparison of short-course (5 day) cefuroxime axetil with a standard 10 day oral penicillin V regimen in the treatment of tonsillopharyngitis.  


Oral penicillin V given three times daily in doses of 50,000-100,000 IU daily has been the standard treatment for tonsillopharyngitis for the last few decades. These regimens, initially recommended by the American Heart Association, were extrapolated from i.v. dosing with long-acting forms of penicillin which had been shown to prevent post-streptococcal sequelae. More recently, several antibiotics, including cefuroxime axetil, have been shown to be at least as effective as penicillin G in eradicating group A beta-haemolytic streptococci (GABHS) but their influence on post-streptococcal sequelae has never been assessed in a large-scale trial. The German Society for Pediatric Infectious Diseases (DGPI) undertook a large study of culture-proven tonsillopharyngitis involving several agents and included a 1 year follow-up to establish the effect on sequelae. In one arm of this study, cefuroxime 250 mg bid was compared with 50,000 IU penicillin V given in three divided doses. Cefuroxime axetil was more effective than oral penicillin V in eradicating GABHS at the assessment 2-4 days post-treatment (441/490 (90%) patients versus 1196/1422 (84%) patients; P = 0.001). Clinically, the two agents were equivalent in efficacy, and carriage rates were similar (11.1% and 13.8%, respectively) in patients receiving cefuroxime axetil and penicillin V, 7-8 weeks post-treatment. One case of glomerular nephritis occurred in a patient given penicillin V. There were no post-streptococcal sequelae confirmed for patients treated with cefuroxime axetil. The findings confirm the previously reported efficacy of short-course (4-5 day) treatments with cefuroxime axetil and indicate that short-course treatment is comparable to the standard oral penicillin V regimen in preventing post-streptococcal sequelae. PMID:10759359

Adam, D; Scholz, H; Helmerking, M



Differentiating amorphous mixtures of cefuroxime axetil and copovidone by X-ray diffraction and differential scanning calorimetry.  


The amorphous, molecular solid dispersion of cefuroxime axetil and copovidone with the mass ratio 71/29 is compared to its pure components in the amorphous state and to an amorphous mechanical mixture with the same mass ratio. Calorimetric studies demonstrate that all these materials are vitreous. By using X-ray diffraction profiles, a clear difference can be observed between the local order of the solid dispersion and that of the mechanical mixture. More generally, it is shown how the presence or absence of additivity in the diffraction data can be used to distinguish between different amorphous mixtures. PMID:24630310

Nicolaï, B; Perrin, M-A; Céolin, R; Rietveld, I B



LC/UV determination of cefradine, cefuroxime, and cefotaxime in dairy milk, human serum and wastewater samples.  


Cephalosporins type antibiotics are widely used to treat infectious diseases. Their determination is not only important in blood/serum of patients under treatment but also in diverse matrices like wastewaters, milk etc. as contaminant. Keeping in view the need, a new high performance liquid chromatographic method for the determination of three cephalosporins (cefradine, cefuroxime and cefotaxime) has been developed. Separation was performed on an ODS column with binary solvent elution of aqueous formic acid (0.05%) and methanol in the ratio of 45: 55 (v/v) at a flow rate of 1 mL min(-1) and UV detection at 260 nm. Under optimised conditions, all three cephalosporins were baseline separated within 5 min. Linear responses for cefradine 5-20 ?g mL(-1), cefuroxime 0.5-15 ?g mL(-1) and cefotaxime 1.0-20 ?g mL(-1) were established. LOD of 0.05-0.25 ?g mL(-1) after preconcentration was achieved. The method was applied to serum samples of patients under treatment with these antibiotics and to screen the selected cephalosporins from hospital wastewater and milk samples. Moreover, method was applied to study stability of aqueous solutions and acid/base induced degradation of all three drugs. PMID:24255868

Qureshi, Tahira; Memon, Najma; Memon, Saima Q; Abro, Kamran; Shah, Syed Waliullah



[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



[Therapeutic efficacy assessment of cefuroxime axetil in short 4 day course of empirical antibiotic therapy in patients with bacterial infections of upper respiratory tract and otitis media].  


There were examined 261 patients aged 18-62 ambulatory treated and divided into five groups: I--65 patients with acute maxillary sinusitis, II--43 patients with exacerbation of chronic maxillary sinusitis, III--40 patients with angina, IV--61 patients with acute otitis media and V--52 patients with exacerbation of chronic otitis media. Cefuroxime axetil have applied 2 times a day in 500 mg oral dose by 4 days. The therapeutic efficacy of cefuroxime axetil was assessed on the basis: fever chart and self assessment chart of showed symptoms which were assessed from 0 to 4.4 days course antibiotic therapy showed that the total receding of illness symptoms stated in 90.8% patients with acute maxillary sinusitis, in 69.8% patients with exacerbation of chronic maxillary sinusitis, in 62.5% patients with angina, in 91.8% patients with acute otitis media and receding of acute symptoms of exacerbation with chronic otitis media--a ear pain in 88.5% patients and a ear leakage in 44.2% patients. The obtained results stated that the 4 days course of cefuroxime axetil can be sufficient and efficacy in treatment of acute bacterial infections of maxillary sinuses and ear media. PMID:11868321

Olszewski, J; Ku?mierczyk, K



Spectrophotometric determination of certain cephalosporins using molybdophosphoric acid. Part II. Determination of cefadroxil, cefapirin, ceforanide and cefuroxime.  


The use of molybdophosphoric acid as an oxidising agent for the spectrophotometric determination of four cephalosporin derivatives, viz., cefadroxil monohydrate (I), cefapirin sodium (II), ceforanide L-lysine (III) and cefuroxime sodium (IV), either in the pure form or in pharmaceutical formulations is described. Beer's law is obeyed up to 100 micrograms ml-1 for I, up to 60 micrograms ml-1 for II and IV and up to 80 micrograms ml-1 for III. The molar absorptivities were 4.58 X 10(3), 11.3 X 10(3), 9.8 X 10(3) and 10.9 X 10(3) l mol-1 cm-1 and the Sandell sensitivities were 83.3, 39.3, 53.0 and 41.0 ng cm-2 for I, II, III and IV, respectively. The slopes and intercepts of the equations of the regression line were calculated for each of these drugs with the following correlation coefficients: I, 0.9993; II, 0.9999; III, 1.000; and IV, 0.9999. These antibiotics were determined successfully both in the pure form and in pharmaceutical preparations. The results demonstrated that the proposed procedure is at least as accurate, precise and reproducible as the official methods, while being simpler and less time consuming. A statistical analysis indicated that there was no significant difference between the results obtained by the proposed procedure and those of the official methods. PMID:2712321

Issopoulos, P B



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



Designing a self-associated cationic polymer for enhanced compatibility, palatability, and gastric release of cefuroxime axetil.  


Cefuroxime axetil (CA) has exhibited interactions with the polymers hydroxypropyl methylcellulose phthalate, cellulose acetate trimellitate, and Eudragit E resulting in the generation of unacceptable amounts of impurities and degradation. Formulations, which mask the bitter taste of CA and release it immediately in the stomach, have therefore not been possible. In an attempt to overcome the interaction with CA, we report a self-associated cationic polymer (NREP) containing methyl methacrylate (MMA), 2-hydroxy ethylmethacrylate (HEMA), and 4-vinyl pyridine (4-VP). The hydrogen bonding between the pyridine nitrogen and the hydroxyl groups of HEMA results in strong intrachain associations, prevents interactions between NREP and CA, and inhibits degradation of CA. This has been validated by differential scanning calorimetry, Fourier transform infrared spectroscopy, NMR, and high-performance liquid chromatography analysis. These self-associations restrict polymer chain motions, enhance biocompatibility, and lead to a higher Tg, which ensures that NREP does not become tacky in processes involving heat. The judicious choice of the hydrophobic and hydrophilic monomers renders the polymer hydrophobic enough as to mask the bitter taste of CA at near neutral pH. Incorporation of the basic monomer 4-VP ensures rapid dissolution of the polymer and release of CA at the acidic pH prevalent in the stomach. The work indicates an approach to design pH-sensitive polymers for dosage forms that meet the pharmacokinetic requirements of the drug. PMID:17253762

Menjoge, Anupa R; Kulkarni, Mohan G



Clostridium difficile 027-associated pseudomembranous colitis after short-term treatment with cefuroxime and cephalexin in an elderly orthopedic patient: a case report  

PubMed Central

Background Clostridium difficile ribotype 027 has become increasingly prevalent in European countries. The clinical picture varies from self-limiting diarrhea to pseudomembranous colitis with toxic megacolon and ultimately death. Use of antibiotics is the principal risk factor; others include comorbidity, advanced age and hospitalization. However even with extensive knowledge of risk factors, it remains difficult to define “minimum risk,” as illustrated by the following case. Case presentation An 80-year-old Danish man in good health was hospitalized for a penetrating knee injury. He received 5 days of intravenous cefuroxime after surgical revision and was discharged with oral cephalexin. Post-discharge he suffered from abdominal discomfort and was readmitted with ileus 4 days after discharge, i.e. 10 days after initiation of antibiotic treatment. His condition deteriorated, and pseudomembranous colitis was diagnosed. Due to lack of response to vancomycin and metronidazole, a total colectomy was performed. Stool cultures were positive for CD 027. Conclusion Short-term use of cephalosporins may have induced CD 027 infection, and the patient’s age was the only identifiable risk factor for the fulminant course. Thus, even short-term prophylactic treatment with cephalosporins cannot be considered entirely safe.



Multicenter comparison of in vitro activities of FK-037, cefepime, ceftriaxone, ceftazidime, and cefuroxime.  

PubMed Central

In a multicenter study, the MICs of FK-037 for 90% of the strains tested (MIC90s) were < or = 1 microgram/ml for members of the family Enterobacteriaceae other than Citrobacter freundii, Enterobacter spp., and Serratia marcescens. Activity against Pseudomonas aeruginosa was variable, with a MIC50 and a MIC90 of 4 and 32 micrograms/ml, respectively. Relative to cefepime, however, FK-037 was less active against ceftazidime-resistant isolates of Enterobacter cloacae. The MIC90 of FK-037 for methicillin-resistant staphylococci was > 16 micrograms/ml.

Washington, J A; Jones, R N; Gerlach, E H; Murray, P R; Allen, S D; Knapp, C C



Thrombotic Thrombocytopenic Purpura After Prophylactic Cefuroxime Axetil Administered in Relation to a Liposuction Procedure  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz’s syndrome is characterized by platelet and von Willebrand factor\\u000a (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad\\u000a characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations,\\u000a and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes

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


Antibiotic Prophylaxis in Primary Hip and Knee Arthroplasty  

Microsoft Academic Search

This is a prospective randomized study comparing cefuroxime to 2 antistaphylococal agents (fusidic acid and vancomycin), for prophylaxis in total hip arthroplasty (THA) and total knee arthroplasty (TKA) in an institute, where methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) prevalence exceeds 25% of orthopedic infections. There were 3 patient groups. Group A included the patients who received cefuroxime,

Minos E. Tyllianakis; Athanasios Ch. Karageorgos; Markos N. Marangos; Alkis G. Saridis; Elias E. Lambiris



In Vitro Comparison of Combination- and Mono-therapy for the Empiric and Optimal Coverage of Bacterial Keratitis Based on Incidence of Infection  

PubMed Central

Purpose Cefazolin/tobramycin, Cefuroxime/gentamicin, and moxifloxacin were compared using bacterial keratitis isolates to determine whether empiric therapy constituted optimal anti-bacterial treatment. Methods Based on percent incidence of corneal infection, 27 Staphylococcus aureus, 16 Pseudomonas aeruginosa, 10 Serratia marcescens, 4 Moraxella lacunata, 3 Haemophilus influenzae, 9 coagulase-negative Staphylococci, 7 Streptococcus viridans, 6 Streptococcus pneumoniae, 7 assorted Gram-positive isolates, and 11 assorted Gram-negative isolates were tested for MICs to cefazolin, tobramycin, cefuroxime, gentamicin, and moxifloxacin using E-tests to determine susceptibility and potency. Results The in vitro coverage (susceptible to at least one antibiotic) of cefuroxime/gentamicin (97%) was statistically equal to cefazolin/tobramycin (93%) and moxifloxacin (92%) (p=0.29). Double coverage (susceptible to both antibiotics) was equivalent (p=0.77) for cefuroxime/ gentamicin (42%) and cefazolin/tobramycin (40%). The susceptibilities of individual coverage were moxifloxacin (92%), gentamicin (89%), tobramycin (74%), cefazolin (58%), and cefuroxime (52%). Methicillin-resistant Staphylococcus aureus was best covered by gentamicin 100% (9 of 9). Tobramycin was more potent (p=0.00001) than gentamicin for Pseudomonas aeruginosa, while cefazolin was more potent (p=0.0004) than cefuroxime for Staphylococcus aureus. Conclusions Although there appears to be no in vitro empiric coverage advantage between cefazolin/tobramycin, cefuroxime/gentamicin, and moxifloxacin monotherapy, potency differences may occur, and optimal treatment can best be determined with laboratory studies.

Kowalski, Regis P.; Kowalski, Tyler A.; Shanks, Robert M.Q.; Romanowski, Eric G.; Karenchak, Lisa M.; Mah, Francis S.



beta-Lactamase stability and in vitro activity of oral cephalosporins against strains possessing well-characterized mechanisms of resistance.  


The in vitro activity of four oral cephalosporins was assessed in dilution tests with 50 isolates of the family Enterobacteriaceae possessing well-characterized mechanisms of resistance to beta-lactam antibiotics. The interaction of the drugs with a broad array of beta-lactamases was also determined in spectrophotometric assays and tests for enzyme induction. Overall, the percentages of strains susceptible to each of the study drugs were 82% for cefixime, 62% for cefuroxime, 58% for cephalexin, and 44% for cefaclor. The poor activity of the older cephalosporins was due to a high degree of susceptibility to hydrolysis by both plasmid-mediated and chromosomally mediated beta-lactamases. For cefaclor, higher MICs were associated with higher levels of plasmid-mediated beta-lactamases in the strains. Resistance to cefuroxime was seen primarily among strains expressing high levels of class I or IV beta-lactamase. Resistance to cefixime was seen only among strains expressing high levels of class I enzymes. Neither cefixime nor cefuroxime was a strong inducer of class I beta-lactamases, although enzyme induction did appear to play a role in cefuroxime resistance in a strain of Serratia marcescens. The consistently greater activity of cefixime over cefuroxime was found not to be due to greater drug permeation into the cell. Rather, it appeared to result from the high affinity of the drug for target enzymes. PMID:2802558

Sanders, C C



Treatment of cytotoxic drug-related infections.  


Twenty-six patients with a malignancy who were receiving intermittent cytotoxic chemotherapy acquired putative bacterial infections while neutropenic. Fourteen patients with neutrophil counts less than 100 X 10(6)/L received cefuroxime plus amikacin. Twelve patients with neutrophil counts between 100 and 500 X 10(6)/L were given cefuroxime alone. The dosages were amikacin, 500 mg BID, and cefuroxime, 1.5 gm TID, although the dose of cefuroxime was halved in three patients because of low body weight and in one patient because of impaired renal function. Bacteriological proof of infection was obtained in 14 patients. In all but two, the bacteria were eradicated by therapy; those two had strains resistant to cefuroxime. Clinical cure was obtained in 15 patients (58%); marked improvement, in seven (27%). One of the patients not cured was probably not infected. In another, the organism was eradicated but the patient did not recover from preexisting shock and renal failure. There were minimal side effects. One patient had diarrhea, one complained of pain on injection, and two had slight increases in transaminase levels. Of particular note is the lack of renal toxicity, particularly in the five patients previously treated with cisplatin. PMID:6871921

McVie, J G; Stuart, J F; Mullinger, B M



Beneficial antimicrobial effect of the addition of an aminoglycoside to a ?-lactam antibiotic in an E. coli porcine intensive care severe sepsis model.  


This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p<0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome. PMID:24587365

Skorup, Paul; Maudsdotter, Lisa; Lipcsey, Miklós; Castegren, Markus; Larsson, Anders; Jonsson, Ann-Beth; Sjölin, Jan



Pharmacokinetics of some cephalosporins in normal and nephrectomized rabbits.  


We made a pharmacokinetic study of the cephalosporins cephazolin, cephaloridine, cefoperazone, and cefuroxime in the rabbit. We computed the pharmacokinetic parameters of a two-compartment open model from the plasma concentration time curves obtained at different increasing doses. Cephazolin, cephaloridine and cefoperazone demonstrated a dose dependent kinetics since the constants of apparent rate of elimination and apparent volume of distribution varied with the doses. In order to evaluate the extra-renal of elimination, we performed pharmacokinetic analysis on the same animals after nephrectomy. While cephazolin, cephaloridine and cefuroxime were eliminated primarily through the kidneys, cefoperazone was largely eliminated by extrarenal pathways. PMID:7121129

Eandi, M; Viano, I; Santiano, M



Oral ciprofloxacin as prophylaxis in gastroduodenal surgery.  


One hundred and fifty patients undergoing gastroduodenal surgery were randomly allocated to receive intravenous (iv) cefuroxime, iv ciprofloxacin or oral ciprofloxacin as prophylaxis. There were no differences in the incidence of postoperative infection complications or duration of stay among the three groups. Oral ciprofloxacin offers obvious advantages in terms of ease of administration and cost. PMID:8522777

McArdle, C S; Morran, C G; Anderson, J R; Pettit, L; Gemmell, C G; Sleigh, J D; Tillotson, G S



Cefalosporiner inte längre självskrivna vid oklara infektioner  

Microsoft Academic Search

Många bakterier har förmågan att producera betalaktamas, dvs enzymer som bryter ned penicilliner och cefalosporiner. ESBL står för extended-spectrum betalactamases och är en grupp be- talaktamasenzymer med utvidgat spektrum, omfattande i stort sett samtliga penicilliner och cefalosporiner. Ett av sjukhusens mest använda antibiotika, cefuroxim, är således verkningslöst mot infektioner med ESBL-bildande bakterier. Vanligtvis är bakterien via andra samvarierande mekanismer resistent



Synthesis and antimicrobial spectrum of FCE 22101 and its orally available ester FCE 22891.  


The most efficient routes for the synthesis of FCE 22101, a penem antibiotic characterized by a carbamoyloxymethyl sidechain at C-2 identical to that of cefuroxime and cefotaxime, and of FCE 22891, its orally absorbed pro-drug, are described. On the basis of in-vitro antimicrobial profile and other characteristics the compounds have been considered worthy of further development. PMID:2659569

Franceschi, G; Perrone, E; Alpegiani, M; Bedeschi, A; Battistini, C; Zarini, F; Della Bruna, C



Susceptibilities of 228 Penicillin and Erythromycin-Susceptible and Resistant Pneumococci to RU 64004, a New Ketolide, Compared with Susceptibilities to 16 Other Agents  

Microsoft Academic Search

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, spar- floxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. RU 64004 was very active against all strains tested, with MICs at




In Vitro Activities of Oral b-Lactams at Concentrations Achieved in Humans against Penicillin-Susceptible and Resistant Pneumococci and Potential to Select Resistance  

Microsoft Academic Search

The b-lactam susceptibilities of 65 strains of Streptococcus pneumoniae for which penicillin MICs covered a broad range were assessed. The order of potency was amoxicillin (AMX) 5 amoxicillin-clavulanate (AMC) > penicillin G > cefpodoxime (CPO) > cefuroxime (CXM) > cefprozil > cefaclor > loracarbef > cefixime. No decrease in susceptibility was seen following repeated subculture of two penicillin-susceptible strains of




In vitro antimicrobial susceptibility of Listeria monocytogenes isolated in the UK and other Listeria species  

Microsoft Academic Search

The MICs and MBCs of 21 antimicrobial agents were determined for 103 strains ofListeria monocytogenes isolated in the UK and 27 strains of otherListeria species. Ampicillin, penicillin, azlocillin, imipenem, gentamicin, netilmicin, amikacin, erythromycin, rifampicin, trimethoprim, clindamycin and vancomycin had good activity, while cephalothin, chloramphenicol, ciprofloxacin and ofloxacin were less active, and cefuroxime, enoxacin, norfloxacin and fosfomycin were the least active.

A. P. MacGowan; H. A. Holt; M. J. Bywater; D. S. Reeves



Incidence of erythromycin resistance in Streptococcus pyogenes: a 10-year study  

Microsoft Academic Search

We studied the evolution of susceptibility of Streptococcus pyogenes isolated in our hospital from 1987 to 1996. Susceptibility to penicillin, ampicillin, cefotaxime, cefuroxime, imipenem, erythromycin, clindamycin, tetracycline, vancomycin, ciprofloxacin, rifampin, and chloramphenicol was determined by the National Committee for Clinical Laboratory Standards broth microdilution method. Differentiation of phenotypes of erythromycin-resistant strains was performed using the double-disc method. All isolates remained

Carmen Betriu; M. Carmen Casado; María Gómez; Ana Sanchez; M. Luisa Palau; Juan J Picazo



In Vitro and In Vivo Activities of LB 10827, a New Oral Cephalosporin, against Respiratory Pathogens  

Microsoft Academic Search

The in vitro antibacterial activities of LB 10827, a new oral cephalosporin, against common respiratory tract pathogens were compared with those of six b-lactams (cefdinir, cefuroxime, cefprozil, penicillin G, amoxicillin- clavulanate, and ampicillin), two quinolones (trovafloxacin and ciprofloxacin), and one macrolide (clarithro- mycin). The MIC of LB 10827 at which 90% of the penicillin-resistant strains of Streptococcus pneumoniae tested were




Beta-lactam antibiotics modulate T-cell functions and gene expression via covalent binding to cellular albumin  

PubMed Central

Recent work has suggested that beta-lactam antibiotics might directly affect eukaryotic cellular functions. Here, we studied the effects of commonly used beta-lactam antibiotics on rodent and human T cells in vitro and in vivo on T-cell–mediated experimental autoimmune diseases. We now report that experimental autoimmune encephalomyelitis and adjuvant arthritis were significantly more severe in rats treated with cefuroxime and other beta-lactams. T cells appeared to mediate the effect: an anti-myelin basic protein T-cell line treated with cefuroxime or penicillin was more encephalitogenic in adoptive transfer experiments. The beta-lactam ampicillin, in contrast to cefuroxime and penicillin, did not enhance encephalomyelitis, but did inhibit the autoimmune diabetes developing spontaneously in nonobese diabetic mice. Gene expression analysis of human peripheral blood T cells showed that numerous genes associated with T helper 2 (Th2) and T regulatory (Treg) differentiation were down-regulated in T cells stimulated in the presence of cefuroxime; these genes were up-regulated in the presence of ampicillin. The T-cell protein that covalently bound beta-lactam antibiotics was found to be albumin. Human and rodent T cells expressed albumin mRNA and protein, and penicillin-modified albumin was taken up by rat T cells, leading to enhanced encephalitogenicity. Thus, beta-lactam antibiotics in wide clinical use have marked effects on T-cell behavior; beta-lactam antibiotics can function as immunomodulators, apparently through covalent binding to albumin.

Mor, Felix; Cohen, Irun R.



Comparative In Vitro Activities of Amoxicillin-Clavulanate against Aerobic and Anaerobic Bacteria Isolated from Antral Puncture Specimens from Patients with Sinusitis  

Microsoft Academic Search

By an agar dilution method, the antimicrobial susceptibilities of antral sinus puncture isolates were studied. Pneumococci were generally susceptible to amoxicillin, azithromycin, and clarithromycin, but 17% of pneu- mococcal isolates were resistant to cefuroxime. Haemophilus influenzae isolates were resistant to amoxicillin and clarithromycin. b-Lactamase production occurred in 69% of Prevotella species. One-third of Peptostrepto- coccus magnus isolates were resistant to



Antimicrobial Susceptibility and Clinical Sources of Dolosigranulum pigrum Cultures  

PubMed Central

Antimicrobial susceptibilities of 27 clinical isolates of Dolosigranulum pigrum were determined. All were susceptible to amoxicillin, cefotaxime, cefuroxime, clindamycin, levofloxacin, meropenem, penicillin, quinupristin-dalfopristin, rifampin, tetracycline, and vancomycin. Fifteen of the isolates were intermediate to chloramphenicol. One isolate was resistant to trimethoprim-sulfamethoxazole. Two isolates were susceptible, 10 were intermediate, and 15 were resistant to erythromycin.

Laclaire, L.; Facklam, R.



Antimicrobial susceptibility and clinical sources of Dolosigranulum pigrum cultures.  


Antimicrobial susceptibilities of 27 clinical isolates of Dolosigranulum pigrum were determined. All were susceptible to amoxicillin, cefotaxime, cefuroxime, clindamycin, levofloxacin, meropenem, penicillin, quinupristin-dalfopristin, rifampin, tetracycline, and vancomycin. Fifteen of the isolates were intermediate to chloramphenicol. One isolate was resistant to trimethoprim-sulfamethoxazole. Two isolates were susceptible, 10 were intermediate, and 15 were resistant to erythromycin. PMID:10858372

Laclaire, L; Facklam, R



An assessment of the hidden and total antibiotic costs of four parenteral cephalosporins.  


The aim of this study was to compare the hidden costs, and their impact on total antibiotic costs, of ceftriaxone therapy with those of cefotaxime, ceftazidime and cefuroxime in nosocomial infection. The total antibiotic costs of 7-day standard courses of the 4 cephalosporins were compared. The costs were divided into 3 parts: (i) the cost of the drug itself; (ii) the preparation and administration (labour) costs; and (iii) the consumables and waste costs. The latter 2 costs together comprised the hidden cost of an antibiotic course. Hidden costs were higher for cefotaxime, ceftazidime and cefuroxime, which are normally administered 3 times a day, than for ceftriaxone, which is administered once daily. The percentage contribution of hidden costs to total antibiotic costs increased with decreasing antibiotic cost, and were lower with higher dosages of all antibiotics. With cefotaxime, ceftazidime and cefuroxime, and with ceftriaxone at the lower dosage given by bolus intravenous (IV) injection, the labour component of hidden costs exceeded the consumables/waste component. However, when costs were calculated for ceftriaxone administered at the higher dosage by IV infusion, the costs of consumables and waste were greater than the labour costs. Ceftriaxone had the lowest hidden costs of all the antibiotics studied. The total antibiotic cost of low dosage ceftriaxone (1 g per dose) was comparable with that of cefuroxime, and was substantially less than the costs of cefotaxime and ceftazidime. At the high ceftriaxone dosage (2g per dose), the total antibiotic cost of cefuroxime was less than that of ceftriaxone; however, the total antibiotic cost of ceftriaxone remained substantially less than that of cefotaxime or ceftazidime. PMID:10160082

Smyth, E T; Barr, J G; O'Neill, C A; Hogg, G M



Antibacterial susceptibility of intestinal lactobacilli of healthy children.  


We investigated the antibacterial susceptibility of intestinal lactobacilli of Estonian and Swedish children aged 1-2 y. Sixty isolates (10 species) of lactobacilli (29 Estonian and 31 Swedish strains) were tested against ampicillin, cefuroxime, cefoxitin, gentamicin, ciprofloxacin, tetracycline, vancomycin, metronidazole and erythromycin. We observed that intestinal lactobacilli do not display uniform susceptibility to antibiotics. None of the tested lactobacilli was resistant to ampicillin, gentamicin and erythromycin. Single strains were resistant to cefuroxime and tetracycline, about half of the strains to cefoxitin and ciprofloxacin and 73% of the strains to vancomycin. All studied strains were resistant to metronidazole. Most of the strains investigated were resistant to two or three antibiotics out of nine. Some differences in susceptibility were noted between strains belonging to different fermentation types. No differences in susceptibility were found between Estonian and Swedish isolates. Metronidazole, cefoxitin, vancomycin and ciprofloxacin seem to be safer for gastrointestinal lactoflora than other tested antibiotics in both countries. PMID:11440219

Mändar, R; L?vukene, K; Hüftt, P; Karki, T; Mikelsaar, M



[Antibiotic prophylaxis in orthopedic surgery].  


In orthopaedics where a great number of implants are in use, the chance for infection is high. To keep up the aseptic condition and giving antibiotic in the perioperative time is necessary. According to the effect on postoperative bleeding authors did compare two second generation cephalosporin, the cefamandol and the cefuroxim, which are mainly used in antibiotic prophylaxis. The gamma carboxylation of glutaminic acid is inhibited by cefamandol in the liver, which is necessary in the prothrombin synthesis. The cefuroxim is without any effect on prothrombin synthesis. The postoperative bleeding was significantly higher following cefamandol administration. According to the authors in orthopaedics, where the blood loss could be high, that type of antibiotic prophylaxis is recommended, which has no effect on bleeding. PMID:7833988

Faluhelyi, A; Vánkos, L



In vitro activity of ertapenem (MK-0826) against multi-drug resistant Streptococcus pneumoniae compared with 13 other antimicrobials  

Microsoft Academic Search

We tested ertapenem (MK-0826), a new carbapenem, and 13 other antimicrobials by microbroth dilution against 102 isolates of Streptococcus pneumoniae, selected to include organisms resistant to a variety of drug classes. Ertapenem MICs ranged from ?0.008 to 4 mg\\/l, MIC50=0.5 mg\\/l, and MIC90=2 mg\\/l. Based on MIC90, ertapenem potency was 4-fold greater than cefuroxime, 2-fold greater than amoxycillin\\/clavulanate, =penicillin, 2-fold

Nicholaus J Hilliard; Crystal N Johnson; Sarah H Armstrong; Stephanie Quarles; Ken B Waites



The value of oral antibiotic prophylaxis in biliary tract surgery.  


In this study the relationship between the presence or absence of organisms in bile or on closing wound swabs and the subsequent development of wound sepsis was confirmed. There was no significant difference in the incidence of septic complications among three treatment groups in which cefuroxime (iv) and ciprofloxacin (iv or oral) were administered. Consideration of costs attributable to the choice of antibiotic prophylaxis suggests that oral ciprofloxacin in biliary tract surgery may offer significant advantages. PMID:1684196

McArdle, C S; Morran, C G; Pettit, L; Gemmell, C G; Sleigh, J D; Tillotson, G S



In Vitro Selection of Resistance to Four b-Lactams and Azithromycin in Streptococcus pneumoniae  

Microsoft Academic Search

Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 mg\\/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing




Molecular and Biochemical Characterization of VEB-1, a Novel Class A Extended-Spectrum bLactamase Encoded by an Escherichia coli Integron Gene  

Microsoft Academic Search

A clinical isolate, Escherichia coli MG-1, isolated from a 4-month-old Vietnamese orphan child, produced a b-lactamase conferring resistance to extended-spectrum cephalosporins and aztreonam. In a disk diffusion test, a typical synergistic effect between ceftazidime or aztreonam and clavulanic acid was observed along with an unusual synergy between cefoxitin and cefuroxime. The gene for VEB-1 (Vietnamese extended-spectrum b- lactamase) was cloned



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



Occurrence and Phenotypic Characteristics of Extended-Spectrum -Lactamases among Members of the Family Enterobacteriaceae at the TelAviv Medical Center (Israel) and Evaluation of Diagnostic Tests  

Microsoft Academic Search

We assessed the prevalence and phenotypic characteristics of extended-spectrum -lactamase (ESBL) producers among cefuroxime-resistant (CXM-R) (MIC > 32 g\\/ml) members of the family Enterobacteriaceae in our institution. The 438 CXM-R clinical isolates obtained from nonurine sources among inpatients were screened. ESBL production was confirmed by disk diffusion assay using cefpodoxime (CPD), cefotaxime (CTX), and ceftazidime (CTZ) with and without clavulanate

Shiri Navon-Venezia; Orly Hammer-Munz; David Schwartz; Dan Turner; Boris Kuzmenko; Yehuda Carmeli



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

PubMed Central

Summary 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 c-di-AMP 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.

Luo, Yun; Helmann, John D.



Resistance pattern of clinical isolates involved in surgical site infections.  


Wound infections due to the incursion of microbes need to be averted or to heal the wounds by antibiotics. Antibiotics are not only aid in cure of infections but also help to prevent the flourishing and production of one or more species of microorganism, resultant in purulent discharge. This current study was carried out to evaluate the resistance pattern of clinical isolates from surgical site infections by the Kirby Bauer disc diffusion method. A total of 257 clinical isolates were collected from different hospitals in Karachi and evaluated by using fifteen antibiotics belonging to different groups. Staphylococcus aureus (n=87), Escherichia coli (n=76), Pseudomonas aeruginosa (n=56), Proteus (n=21) and Klebsiella (n=17) species are the most common clinical isolates of surgical site infections. Among the semi-synthetic penicillins, ampicillin was found to be resistant to nearly all clinical isolates but amoxicillin was moderately sensitive to S. aureus. Combinations of semi-synthetic penicillins are more sensitive than the penicillin alone. Co-amoxiclave exhibits superior sensitivity to all the surgical infection isolates except Pseudomonas aeruginosa which showed 68.75% resistance. Pseudomonas aeruginosa was highly resistant to cephalosporin except ceftraixone which showed 21.88% resistance. S. aureus was slightly responsive to cefazolin, cephradine, cefaclor, ceftizoxime, cefuroxime and ceftriaxone. E. coli, Gram-negative clinical isolate was showed 25% and 31.25% resistance to ceftriaxone and cefuroxime. In the Klebsiella species, 71.42% and 64.29% resistance to cefazolin and cefuroxime respectively, was observed. Aminoglycosides such as gentamycin and tobramycin were found to be more susceptible to all the clinical isolates. Quinolones like ofloxacin and enoxacin were showed good sensitivity to nearly all the clinical isolates.On the basis of the present study, it is recommended to adopt a rational use of antibiotics in prophylaxis and the utilization of a coordinated scheme of surgical wound inspections. PMID:24374459

Arsalan, Adeel; Naqvi, Syed Baqar-Shyum; Sabah, Arif; Bano, Rahila; Ali, Syed Imran



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.



InVitro Selective Antibiotic Concentrations ofP-Lactams for Penicillin-Resis tant Streptococcus pneumoniae Populations  

Microsoft Academic Search

S.pneumo- niae wasevaluated inaninvitro modelwithmixedpopulations withpenicillin susceptibilities of0.015, 0.5, 1, and2,ug\\/ml. Theantibiotic concentration selecting forlow-level resistance strongly reduced thesusceptible population. Increasing antibiotic concentrations tended todecrease thetotal proportion ofpenicillin-resis tant bacteria because ofreduced numbers ofthelow-level-resistant population. Theantibiotic concentration selecting forhigh-level resistance produced fewer resistant populations, butmostoftheorganisms selected represented high-level resistance. Ingeneral, amoxicillin wasa goodselector forthelow-level-resistant population andapoorselector forhigh-level resistance; cefuroxime andcefotaxime




West Nile meningo-encephalitis infection in a kidney transplant recipient.  


West Nile virus is an arbovirus known to cause meningo-encephalitis in immuno-competent as well as in immunocompromised patients. Herein, we describe a kidney transplant recipient in whom meningo-encephalitis infection was caused by the West Nile virus. The clinical presentation was fever, headache, photophobia, confusion, neck stiffness, and positive Kerning test. The patient was treated with IV acyclovir, cefuroxime, ampicillin, and fluids. During hospital stay, the patient did not experience any episode of allograft rejection. Fever resolved and at follow up he was doing well. West Nile virus infection should be considered in immunocompromised patients including transplant recipients with meningo-encephalitis, especially during epidemic outbreaks. PMID:14697942

Armali, Z; Ramadan, R; Chlebowski, A; Azzam, Z S



Sequential therapy with intravenous and oral cephalosporins.  


The pharmacokinetic, economic and practical aspects of sequential therapy with iv and oral cephalosporins are reviewed. New broad spectrum oral cephalosporins, such as cefixime, cefpodoxime proxetil and cefetamet pivoxil achieve serum concentrations above the MICs for most Enterobacteriaceae for at least as long as for parenteral cefuroxime. Substantial cost reductions are possible with an early switch from iv to oral cephalosporins. The clinical studies that have been performed so far have important shortcomings. Well designed clinical studies are necessary to prove the feasibility of sequential therapy with cephalosporins for serious infections in hospitalized patients. PMID:8157558

Janknegt, R; van der Meer, J W



Activities and Postantibiotic Effects of Gemifloxacin Compared to Those of 11 Other Agents against Haemophilus influenzae and Moraxella catarrhalis  

Microsoft Academic Search

The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, <0.125 mg\\/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were b-lactamase positive); cefixime (MICs, <0.125 mg\\/ml) and amoxicillin- clavulanate (MICs <4.0 mg\\/ml) were active, followed by cefuroxime (MICs, <16.0 mg\\/ml); azithromycin MICs were <4.0




Etiology and Epidemiology of Catheter Related Bloodstream Infections in Patients Receiving Home Parenteral Nutrition in a Gastromedical Center at a Tertiary Hospital in Denmark  

PubMed Central

We conducted a retrospective epidemiologic study of catheter related bloodstream infections (CRBSI) in patients receiving long-term home parenteral nutrition (HPN) from January 2002 to December 2005. Our results showed that coagulase negative staphylococci (CoNS) were the most prevalent pathogens (44.7% of all CRBSI episodes), followed by Enterobacteriaceae (33.2%). Prevalence for candidemia and Enterococcus bacteremia was relatively high (14.4% and 10.8%, respectively). Cefuroxime resistance was observed in 65.4% CoNS and 31.5% Enterobacteriaceae. Based on the results from the study, a new empiric antimicrobial treatment regiment was suggested.

Nielsen, Xiaohui Chen; Chen, Ming; Helles?e, Anne-Marie Blok; Jeppesen, Palle Bekker; Gyldenlykke, Jonna; Tvede, Michael; Andersen, Leif Percival



In vitro susceptibility of Alcaligenes denitrificans subsp. xylosoxidans to 24 antimicrobial agents.  

PubMed Central

The in vitro susceptibilities of 37 clinical isolates of Alcaligenes denitrificans subsp. xylosoxidans to 24 antimicrobial agents were determined. Imipenem was the only drug with consistent activity (MIC for 90% of isolates, 2 micrograms/ml). Piperacillin, ticarcillin-clavulanic acid, ceftazidime, and co-trimoxazole were active against most strains. All the isolates were resistant to ampicillin, cefazolin, cefuroxime, cefamandole, cefotetan, ceftriaxone, cefotaxime, aztreonam, amdinocillin, and temocillin. Most isolates were resistant to the aminoglycosides tested, including amikacin. Lack of activity was also observed for all new 4-quinolone antimicrobial agents.

Glupczynski, Y; Hansen, W; Freney, J; Yourassowsky, E



Evaluation of eight different cephalosporins for detection of cephalosporin resistance in Salmonella enterica and Escherichia coli.  


This study evaluates the efficacy of eight different cephalosporins for detection of cephalosporin resistance mediated by extended spectrum beta-lactamases (ESBL) and plasmidic AmpC beta-lactamases in Salmonella and Escherichia coli. A total of 138 E. coli and 86 Salmonella isolates with known beta-lactamase genes were tested for susceptibility toward cefoperazone, cefotaxime, cefpodoxime, cefquinome, ceftazidime, ceftiofur, ceftriaxone, and cefuroxime using minimum inhibitory concentration determinations and disc diffusion. The collection consisted of 84 ampicillin-susceptible, 57 ampicillin-resistant but cephalosporin-susceptible, 56 ESBL isolates and 19 isolates with plasmidic AmpC, as well as 10 ampC hyper-producing E. coli. The minimum inhibitory concentration distributions and zone inhibitions varied with the tested compound. Ampicillin-resistant isolates showed reduced susceptibility to the cephalosporins compared to ampicillin-susceptible isolates. Cefoperazone, cefquinome, and cefuroxime were not useful in detecting isolates with ESBL or plasmidic AmpC. The best substances for detection were cefotaxime, cefpodoxime, and ceftriaxone, whereas ceftazidime and ceftiofur were not as efficient. Ceftriaxone may be the recommended substance for monitoring because of some ability in separating ampC hyper-producing E. coli from ESBL and plasmidic AmpC isolates. PMID:20624078

Aarestrup, Frank M; Hasman, Henrik; Veldman, Kees; Mevius, Dik



[Susceptibility to selected antibiotics of Yersinia enterocolitica 03 strains, carrying and not carrying plasmid pYV].  


A total of 199 clinical strains of Yersinia enterocolitica serotype O3, biotype 4 were tested for their susceptibility to antibiotics (158 strains carried the virulence plasmid pYV and 41 strains did not). 114 isolates were tested by standard disk diffusion method for 21 antibiotics. Almost all tested strains were resistant to ampicillin and cefazolin and susceptible to amoxycillin/clavulanate, cefaclor, cefamandole, cefuroxime, cefotaxime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, tetracycline, doxycycline, chloramphenicol, ciprofloxacin, sulphamethoxazole, co-trimoxazole, trimethoprim and furazolidone. In addition minimal inhibitory concentrations (MICs) of 15 antibiotics were determined by agar dilution method for all 199 strains (158 plasmid positive and 41 strains plasmid negative). Third-generation cephalosporins such as cefotaxime and ceftriaxone and a fluoroquinolone (ciprofloxacin) were the most active antimicrobial agents, tested followed by aztreonam, imipenem, trimethoprim, tetracycline, gentamicin, chloramphenicol, amoxycillin/clavulanate, cefaclor, cefuroxime, amikacin, furazolidone and sulphamethoxazole. The present study demonstrated a high susceptibility of clinical strains of Y. enterocolitica to most of the tested antibiotics. In general, there was no significant difference between susceptibility of virulence plasmid pYV positive and virulence plasmid negative strains to antibacterial agents. PMID:10803262

Rastawicki, W; Gierczy?ski, R; Jagielski, M; Ka?uzewski, S; Jeljaszewicz, J



Susceptibility of Polish clinical strains of Yersinia enterocolitica serotype O3 to antibiotics.  


A total of 199 clinical strains of Yersinia enterocolitica serotype O3, biotype 4 were tested for their susceptibility to antibiotics (158 strains carried the virulence plasmid pYV and 41 strains did not). A total of 114 isolates were tested by a standard disk diffusion method for 21 antibiotics. Almost all strains tested were resistant to ampicillin and cefazolin and susceptible to amoxycillin/clavulanate, cefaclor, cefamandole, cefuroxime, cefotaxime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, tetracycline, doxycycline, chloramphenicol, ciprofloxacin, sulphamethoxazole, trimethoprim, co-trimoxazole and furazolidone. In addition, minimal inhibitory concentrations of 15 antibiotics were determined by the agar dilution method for all 199 strains (158 carrying plasmid pYV and 41 strains that did not). Third-generation cephalosporins such as cefotaxime and ceftriaxone and a fluoroquinolone (ciprofloxacin) were the most active antimicrobial agents tested followed by aztreonam, imipenem, trimethoprim, tetracycline, gentamicin, chloramphenicol, amoxycillin/clavulanate, cefaclor, cefuroxime, amikacin, furazolidone and sulphamethoxazole. The present study demonstrated a high susceptibility of clinical strains of Y. enterocolitica to most of the tested antibiotics. In general there was no significant difference between susceptibility to antibacterial agents of strains with or without plasmid pYV. PMID:10755244

Rastawicki, W; Gierczy?ski, R; Jagielski, M; Ka?uzewski, S; Jeljaszewicz, J



Antimicrobial Resistance of Salmonella enterica Isolates from Tonsil and Jejunum with Lymph Node Tissues of Slaughtered Swine in Metro Manila, Philippines  

PubMed Central

Due to frequent antibiotic exposure, swine is now recognized as potential risk in disseminating drug-resistant Salmonella enterica strains. This study thus subjected 20 randomly selected S. enterica isolates from tonsil and jejunum with lymph node (JLN) tissues of swine slaughtered in Metro Manila, Philippines, to VITEK 2 antimicrobial susceptibility testing (AST). The test revealed all 20 isolates had resistance to at least one antimicrobial agent, in which highest occurrence of resistance was to amikacin (100%), cefazolin (100%), cefuroxime (100%), cefuroxime axetil (100%), cefoxitin (100%), and gentamicin (100%), followed by ampicillin (50%), and then by sulfamethoxazole trimethoprim (30%). Three multidrug-resistant (MDR) isolates were detected. The sole S. enterica serotype Enteritidis isolate showed resistance to 12 different antibiotics including ceftazidime, ceftriaxone, amikacin, gentamicin, and tigecycline. This study is the first to report worldwide on the novel resistance to tigecycline of MDR S. enterica serotype Enteritidis isolated from swine tonsil tissues. This finding poses huge therapeutic challenge since MDR S. enterica infections are associated with increased rate of hospitalization or death. Thus, continual regulation of antimicrobial use in food animals and prediction of resistant serotypes are crucial to limit the spread of MDR S. enterica isolates among hogs and humans.

Ng, Kamela Charmaine S.; Rivera, Windell L.



In vitro antibiotic resistance in bacterial keratitis in London  

PubMed Central

AIM—To document changes in the profile of bacterial isolates from cases of keratitis and changes in their susceptibility to first line antibiotic therapies.?METHODS—A retrospective review was performed of all bacterial isolates from cases of keratitis seen between 1984 and 1999. In vitro laboratory susceptibilities to antibiotics were determined by the Kirby-Bauer disc diffusion method. The number of isolates, changes in the proportion of bacterial types, and the number that were fully resistant to monotherapy (ofloxacin), dual therapy (gentamicin and cefuroxime), and prophylactic treatment (chloramphenicol) were calculated.?RESULTS—There were 1312 bacterial isolates over 16 years. Gram positive bacteria accounted for 54.7% of isolates and Staphylococcus species (33.4%) were the most frequently isolated organisms. During the study period there has been an increase in the proportion of Pseudomonas species isolates but no overall increase in the proportion of Gram negative isolates. There has not been an increase in the proportion of isolates resistant to ofloxacin since 1995 or an increase in resistance to the combination of gentamicin and cefuroxime. However, since 1984 there has been a significant increase in proportion of Gram negative organisms resistant to chloramphenicol (p=0.0019).?CONCLUSIONS—An increase in the in vitro resistance of organisms to first line therapies for bacterial keratitis has not been observed. An increased resistance to chloramphenicol indicates that this drug is unlikely to provide prophylactic cover when Gram negative infection is a risk. Continued monitoring for the emergence of antibiotic resistance is recommended.??

Tuft, S.; Matheson, M.



Symposium on antimicrobial therapy. IV. The cephalosporins.  


Hopefully this review has brought some cephalosporin contentment to replace cephalosporin confusion. From the classification of these antibiotics in Table 1, we have made some significant reductions. One should know how to use cefazolin for staphylococcal/streptococcal infections and for surgical prophylaxis. One should know that cephalexin is massively overused, and really now not all that useful an agent. Cefuroxime is a useful agent for beta-lactamase producing H. influenzae infections. Cefotetan has a role in surgical prophylaxis in ob/gyn and represents the best antianaerobic activity of the cephalosporins; although no cephalosporin is a primary drug for anaerobic infections. Cefuroxime axetil or cefprozil can be useful for comparatively minor infections due to beta-lactamase producing H. influenzae. A third generation cephalosporin represents a reasonable alternative, in certain situations, to aminoglycoside therapy for infections due to multiply drug-resistant Gram-negative bacilli. Ceftazidime is an alternative antipseudomonal beta-lactam antibiotic. Despite the lack of indications for use of cephalosporins as drugs of choice, rational use of these agents can provide safe, effective, and efficient therapy for a variety of infectious diseases. They will likely remain an important part of the physicians' antimicrobial armamentarium for the foreseeable future. PMID:8426246

Greenfield, R A



Serotypes, biotypes and antibiotic susceptibility of 126 clinical isolates of Haemophilus influenzae.  


Serotypes, biotypes, and antibiotic susceptibility of 126 Haemophilus influenzae isolates were determined. Five of the 126 isolates were from blood and were encapsulated type b strains; those taken from other sites were not typable. There were 13% biotype I, 36% biotype II, 38% biotype III, 5% biotype IV, 4% biotype V, and 4% biotype VI isolates. Antibiotic susceptibility tests using the standard disk diffusion method showed the following resistance: ampicillin 51%, cefamandole 10%, cefuroxime 3%, chloramphenicol 28%, tetracycline 37% and sulfamethoxazole-trimethoprim 49%. None of the five type b isolates were resistant to cefotaxime, a third generation cephalosporin. The second generation cephalosporins, cefamandole and cefuroxime, showed a superior activity against H. influenzae isolates, compared to other antibiotics. Multiple drug resistance was found in 64 (51%) isolates. Four of the five type b isolates were resistant to multiple drugs. The multiple-resistance pattern most frequently observed was to ampicillin, chloramphenicol, tetracycline and sulfamethoxazole-trimethoprim. Most clinical isolates did not contain plasmids; therefore, the antibiotic resistance of these H. influenzae strains was probably chromosome-mediated. PMID:7549556

Chiu, C H; Ou, J T; Su, H C



Susceptibility of female pelvic pathogens to oral antibiotic agents in patients who develop postpartum endometritis.  


Fifteen hundred patients were enrolled in a prospective, randomized study on the effect of antibiotic prophylaxis during cesarean section. Two hundred thirty-one patients developed postpartum endometritis, and the isolates obtained from the endometrium were tested for sensitivity to ampicillin, cefuroxime, ofloxacin, ciprofloxacin, and clindamycin. Minimum inhibitory concentrations of 50% and 90% of ampicillin, cefuroxime, and clindamycin were similar to previously reported values; however, slight differences were noted in the activity of the two quinolones to common pelvic isolates. The minimum inhibitory concentrations of 90% of ofloxacin and ciprofloxacin to 119 isolates of Enterococcus faecalis were 4.0 and 2.0, to 17 isolates of Staphylococcus aureus 1.0 and 0.5, to 39 isolates of Escherichia coli 0.5 and 1.0, to 46 isolates of Bacteroides bivius 4.0 and 8.0, to 57 isolates of Gardnerella vaginalis 1.0 and 2.0, to 71 isolates of Staphylococcus epidermidis 0.5 and 0.5, to 16 isolates of Proteus mirabilis 0.25 and 0.12, and to 50 isolates of Lactobacillus species 32.0 and 8.0 micrograms/ml, respectively. In summary, the quinolones have activity comparable with a variety of other oral agents versus female pelvic pathogens, with the quinolones ofloxacin and ciprofloxacin having better activity against most of the gram-negative isolates. Anaerobic activities were comparable with the beta-lactams, but inferior to clindamycin and metronidazole as expected. PMID:2031518

Martens, M G; Faro, S; Maccato, M; Riddle, G; Hammill, H A



[Antibiotic resistance and plasmid profiles of Vibrio isolates from cultured Sparus sarba].  


A total of 51 potential pathogenic vibrios were isolated from moribund silver seabream Sparus sarba, which were collected from local fish farms of Hong Kong. All the isolates were classified and identified as 7 species by the API 20 E system and the scheme of Alsina & Blanch. These species were Vibrio alginolyticus (24 strains), Vibrio vulnificus (12 strains), Vibrio parahaemolyticus(7 strains), Vibrio logei(4 strains), Vibrio pelagius II(2 strains), Vibrio fluvialis (1 strains) and Vibrio meditterranei (1 strains). Among these isolates, the three predominant species (V. alginolyticus, V. vulnificus and V. parahaemolyticus) were confirmed to be virulent to sea bream by experimental challenge. All isolates were also screened for plasmid DNA by agarose gel electrophoresis and tested for susceptibility to 16 antimicrobial agents by the agar dilution method. Of the 51 isolates examined, all strains were sensitive to ceftriaxone, streptomycin, nalidixic acid and rifampicin, and almost all were sensitive to ceftazidime, netilimicin, chloramphenicol and sulfamethoxazole except one or two strains. Most isolates were resistant to ampicillin (60. 8%), cefuroxime (66.7%), amikacin(55%), kanamycin(58.8%) and trimethoprinm (76.5%). Fifteen of the 51 isolates harboured 1-4 plasmids, with sizes ranging from 9 to 123 kb. Both the plasmids and the associated antimicrobial resistance (ampicillin, cefuroxime and trimethoprim) of 9 isolates could be transferred to recipient by single-step conjugation, however, the frequencies were very low, ranging from 10(-11) to 10(-9). The present results indicate that resistance to these antibiotics is chromosomal. PMID:12555529

Li, J; Yie, J; Fu, W; Foo, R W; Hu, Y; Woo, N Y; Xu, H



[Chemotherapy of listeriosis (author's transl)].  


Despite the occasional lack of antibacterial activity ampicillin is considered to be the drug of choice for antibacterial chemotherapy in listeriosis. In vitro comparison with new penicillins (mezlocillin, piperacillin) and cephalosporins (cefamandol, cefoxitin, cefuroxime, cefotaxime) showed ampicillin to have the most potent activity against Listeria monocytogenes. Minimal inhibition concentrations (MIC) were between 0.06 and 1 microgram/ml and minimal bactericidal concentrations (MBC) from 0.25 to 32 micrograms/ml. The MIC90 (minimal concentration inhibiting 90% of tested strains) was 0.48 for ampicillin, 8.0 for mezlocillin and 5.2 micrograms/ml for piperacillin. Among cephalosporins cefalotin was most effective with an MIC90 of 5.8 micrograms/ml. The MIC90 was 7.8 for cefamandol and 89.6 micrograms/ml for cefoxitin. Cefuroxime and ecfotoxime had MIC values of more than 128 micrograms/ml and showed no clinically relevant anti-listeria activity. Gentamicin and doxycyclin showed MIC90 values of 12 and 8 micrograms/ml, respectively. MBC and MIC values were closest together in gentamicin. Ampicillin, potentially combined with gentamicin, should remain treatment of choice in generalised Listeria monocytogenes infection. PMID:6277589

Marklein, G



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



Prophylactic antibiotic treatment prevents infection after cardiopulmonary bypass: a study in dogs.  


The effect of two prophylactic antibiotic regimens during cardiopulmonary bypass (CPB) was investigated in dogs. Airborne contamination was determined by spraying two different bacterial strains (Staphylococcus aureus and Serratia marcescens) into the air of the operating room. Dogs were operated on and underwent CPB with a bubble oxygenator. Pericardial suction, either conventional (blood-air) or selective (only blood), was used. Particularly in the first situation, an impaired humoral host defense is induced. In dogs given the regimen consisting of penicillin G (benzylpenicillin), gentamicin sulfate, and flucloxacillin, the number of contaminated sites for both bacteria was reduced (p less than .01) compared with those given cefuroxime. The effectiveness of the combined antibiotic regimen could be ascribed to increased serum bactericidal activity and polymorphonuclear leukocyte (PMN) killing capacity. Cefuroxime enhanced the PMN respiratory burst. As a result, two weeks postoperatively the rate of infection was small in both groups. We conclude that prior to CPB, antibiotics should be administered prophylactically to overcome a period of impaired humoral host defense during CPB. PMID:3555371

van Oeveren, W; Dankert, J; Wildevuur, W; Wildevuur, C R



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


In order to gather more data on the use of teicoplanin for reducing MRSA infections in high-risk populations, the present study was conducted. At a hospital in Barcelona, Spain, there was a high prevalence of MRSA infections among patients who underwent surgery for femoral neck fracture during the first 5 months of 2002 (period A) when cefuroxime was the antibiotic prophylaxis. During the following 12 months (period B) 600 mg of teicoplanin was added to cefuroxime. The rates of overall and MRSA infection during period A were 5.07 and 2.73%, respectively. Pulsed-field gel electrophoresis demonstrated there was no clonal relationship among MRSA strains. No nasal carriers of MRSA were detected among health workers. During period B the rates of overall and MRSA infection were 2.36 and 0.19%, respectively. Both rates were statistically significantly lower than those in period A (p<0.05). These results suggest teicoplanin may be useful in patients undergoing orthopedic surgery when the prevalence of MRSA is high. PMID:16424973

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



Inhibition of WTA synthesis blocks the cooperative action of PBPs and sensitizes MRSA to ?-lactams.  


Rising drug resistance is limiting treatment options for infections by methicillin-resistant Staphylococcus aureus (MRSA). Herein we provide new evidence that wall teichoic acid (WTA) biogenesis is a remarkable antibacterial target with the capacity to destabilize the cooperative action of penicillin-binding proteins (PBPs) that underlie ?-lactam resistance in MRSA. Deletion of gene tarO, encoding the first step of WTA synthesis, resulted in the restoration of sensitivity of MRSA to a unique profile of ?-lactam antibiotics with a known selectivity for penicillin binding protein 2 (PBP2). Of these, cefuroxime was used as a probe to screen for previously approved drugs with a cryptic capacity to potentiate its activity against MRSA. Ticlopidine, the antiplatelet drug Ticlid, strongly potentiated cefuroxime, and this synergy was abolished in strains lacking tarO. The combination was also effective in a Galleria mellonella model of infection. Using both genetic and biochemical strategies, we determined the molecular target of ticlopidine as the N-acetylglucosamine-1-phosphate transferase encoded in gene tarO and provide evidence that WTA biogenesis represents an Achilles heel supporting the cooperative function of PBP2 and PBP4 in creating highly cross-linked muropeptides in the peptidoglycan of S. aureus. This approach represents a new paradigm to tackle MRSA infection. PMID:23062620

Farha, Maya A; Leung, Alexander; Sewell, Edward W; D'Elia, Michael A; Allison, Sarah E; Ejim, Linda; Pereira, Pedro M; Pinho, Mariana G; Wright, Gerard D; Brown, Eric D



Antipneumococcal activity of BAY 12-8039, a new quinolone, compared with activities of three other quinolones and four oral beta-lactams.  

PubMed Central

Activities of BAY 12-8039 against 205 pneumococci were tested by agar dilution. MICs (in micrograms per milliliter) at which 50 and 90% of the isolates are inhibited (MIC50s and MIC90s, respectively) were 0.125 and 0.25 (BAY 12-8039), 2.0 and 4.0 (ciprofloxacin and ofloxacin), and 0.25 and 0.5 (sparfloxacin). Beta-lactam MIC50s and MIC90s for penicillin-susceptible, -intermediate, and -resistant strains, in that order, were 0.016 and 0.03, 0.25 and 2.0, and 2.0 and 4.0 (amoxicillin); 0.03 and 0.06, 0.25 and 4.0, and 4.0 and 8.0 (ampicillin); 0.03 and 0.06, 0.5 and 4.0, and 4.0 and 8.0 (cefuroxime); and 0.03 and 0.125, 0.25 and 2.0, and 4.0 and 8.0 (cefpodoxime). At two times their MICs after 24 h, BAY 12-8039, ciprofloxacin, ampicillin, and cefuroxime were uniformly bactericidal (99.9% killing) against 12 strains; other compounds were bactericidal at four times their MICs.

Visalli, M A; Jacobs, M R; Appelbaum, P C



Antimicrobial Resistance of Salmonella enterica Isolates from Tonsil and Jejunum with Lymph Node Tissues of Slaughtered Swine in Metro Manila, Philippines.  


Due to frequent antibiotic exposure, swine is now recognized as potential risk in disseminating drug-resistant Salmonella enterica strains. This study thus subjected 20 randomly selected S. enterica isolates from tonsil and jejunum with lymph node (JLN) tissues of swine slaughtered in Metro Manila, Philippines, to VITEK 2 antimicrobial susceptibility testing (AST). The test revealed all 20 isolates had resistance to at least one antimicrobial agent, in which highest occurrence of resistance was to amikacin (100%), cefazolin (100%), cefuroxime (100%), cefuroxime axetil (100%), cefoxitin (100%), and gentamicin (100%), followed by ampicillin (50%), and then by sulfamethoxazole trimethoprim (30%). Three multidrug-resistant (MDR) isolates were detected. The sole S. enterica serotype Enteritidis isolate showed resistance to 12 different antibiotics including ceftazidime, ceftriaxone, amikacin, gentamicin, and tigecycline. This study is the first to report worldwide on the novel resistance to tigecycline of MDR S. enterica serotype Enteritidis isolated from swine tonsil tissues. This finding poses huge therapeutic challenge since MDR S. enterica infections are associated with increased rate of hospitalization or death. Thus, continual regulation of antimicrobial use in food animals and prediction of resistant serotypes are crucial to limit the spread of MDR S. enterica isolates among hogs and humans. PMID:24724034

Ng, Kamela Charmaine S; Rivera, Windell L



Plasmid-encoded multidrug resistance: A case study of Salmonella and Shigella from enteric diarrhea sources among humans.  


Salmonellosis and shigellosis are significant and persistent causes of diarrheal diseases among humans in developing countries. With that in mind, the current study investigates the occurrence of plasmid-encoded multidrug resistances in Salmonella and Shigella from diarrheal cases among humans. The isolates were characterized by serotyping, antimicrobial-susceptibility testing, transfer experiments and curing. The extended spectrum ?-lactamase (ESBL) was detected by the double disc diffusion synergy test (DDST). A significant number of the plasmid-encoded multidrug resistant (PEMDR) Salmonella and Shigella isolates were found to harbour transferable plasmid genes resistant to antibiotics like ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, ceftriaxone, cefuroxime and to a lesser extent to ciprofloxacin and ofloxacin. The conjugative R-plasmids-encoded extended-spectrum ?-lactamase also showed resistances to cephalosporins (ceftriaxone and cefuroxime) and ampicillin. Curing experiments showed chromosomal resistances to varied antibiotics. The findings confirmed the presence of PEMDR in Salmonella and Shigella strains as a suitable adaptation to a changing antibiotic environment. The results therefore suggest the limited use of the commonly prescribed/or third generation cephalosporins as an empirical treatment of multidrug resistant Salmonella and Shigella because this may affect therapeutic outcomes. PMID:21031258

Suh Yah, Clarence



RU 29 246, the active compound of the cephalosporin prodrug-ester HR 916. III. Pharmacokinetic properties and antibacterial activity in vivo.  


The pharmacokinetics of the broad spectrum cephem RU 29 246 and its prodrug-ester HR 916 B were investigated in mice, rats and dogs and compared to those of cefpodoxime proxetil, cefuroxime axetil and cefixime. HR 916 B is well absorbed following oral administration and efficiently converted to the antibacterially active form. In mice, mean peak blood levels of 31.1 micrograms/ml of the parent compound were recorded within 20 minutes after oral administration of a single dose equivalent to 40 mg/kg RU 29 246. The bioavailability calculated on the basis of the areas under the concentration-time curves (AUC) and the urinary recoveries was about 90%. In rats, peak blood levels of 14.5 micrograms/ml were obtained 1 hour after an oral 20 mg/kg dose. The bioavailability was calculated as 70%. In dogs, 40% of an oral 10 mg/kg dose was recovered in the urine within 24 hours. Cmax was 15.9 micrograms/ml at 4.6 hours. Mean elimination half-lives of RU 29 246 were 0.35, 0.5 and 2.1 hours in mice, rats and dogs, respectively. After an oral HR 916 B dose equivalent to 50 mg/kg of RU 29 246, tissue concentrations at 0.5 hour ranged between 0.8 micrograms/g in brain and 95.7 micrograms/g in murine kidneys. These values of HR 916 B are similar to, or distinctly higher than, those of the reference compounds. Of the oral cephalosporins tested, HR 916 B had the most balanced antibacterial spectrum. With ED50s of between 0.9 and 11.5 mg/kg against staphylococci, its activity was similar to that of the additional reference compound cefaclor and higher than that of cefuroxime. Cefixime and cefpodoxime proxetil displayed low antistaphylococcal activity or were inactive. In septicemias with Enterobacteriaceae, cefixime and cefpodoxime proxetil were more potent than HR 916 B and cefaclor. Cefuroxime axetil was inactive against most of these infections. HR 916 B was also highly effective against murine lung infections caused by Klebsiella pneumoniae DT-S or Streptococcus pneumoniae 1147. PMID:1500360

Klesel, N; Adam, F; Isert, D; Limbert, M; Markus, A; Schrinner, E; Seibert, G



Characterization of extended-spectrum beta-lactamase-producing Salmonella enterica serotype Brunei and Heidelberg at the Hussein Dey hospital in Algiers (Algeria).  


The purpose of this work was to study the genetic determinants responsible for extended-spectrum cephalosporin (ESC) resistance of Salmonella collected during the period of 1995-2008 at the Hussein Dey hospital in Algiers (Algeria). Fourteen ESC-resistant Salmonella isolates were tested towards 22 antimicrobial agents. Polymerase chain reaction (PCR) and sequencing were used to determine the underlying genetic determinants responsible for the extended-spectrum beta-lactamase (ESBL) phenotypes. Enterobacterial Repetitive Intergenic Consensus PCR was employed to type the isolates. All tested isolates were resistant to ticarcillin, ticarcillin-clavulanate, piperacillin, cefuroxime, aztreonam, ceftazidime, cefotaxime (except two isolates), cefepime, and cefpirome. PCR and DNA sequencing identified these ESBLs as TEM-48 (n=6), TEM-4 (n=3), CTX-M-15 (n=4), and one new TEM, designated TEM-188. Thus, continued surveillance for the presence of ESBL-producing (non-typhoidal) salmonellae in Algeria is essential. PMID:22871227

Kermas, Rachida; Touati, Abdelaziz; Brasme, Lucien; Le Magrex-Debar, Elisabeth; Mehrane, Sadjia; Weill, François-Xavier; De Champs, Christophe



Activities of RPR 106972 (a new oral streptogramin), cefditoren (a new oral cephalosporin), two new oxazolidinones (U-100592 and U-100766), and other oral and parenteral agents against 203 penicillin-susceptible and -resistant pneumococci.  

PubMed Central

Agar dilution was used to determine the MICs of RPR 106972 (a new oral streptogramin), cefditoren (a new oral cephalosporin), two new oxazolidinones (U-100592 and U-100766), and other oral and parenteral agents for 203 penicillin-susceptible and -resistant pneumococci. All pneumococci were inhibited by RPR 106972 at < or = 0.5 microgram/ml. Cefditoren was very active against all pneumococcal groups, with MICs of < or = 2.0 micrograms/ml. Amoxicillin with or without clavulanate was the next most active oral beta-lactam, followed by cefdinir, cefuroxime, cefpodoxime, and cefprozil. U-100592 and U-100766 were very active against all classes of pneumococci, with all MICs < or = 1.0 microgram/ml.

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



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



Catatonia and parkinsonism as a sequelae of typhoid fever: a rare experience.  


Although neurological manifestations of typhoid fever was thought to be obsolete from modern world, emergence of multidrug resistant typhoid bacilli and reporting of outbreak of typhoid fever with a range of early neuropsychiatric manifestations from various parts of world has led clinicians and investigators to re-evaluate the clinical spectrum of this endemic sinister disease. An 18-year-old male student was admitted in psychiatry ward with mutism, staring look, posturing and rigidity. There was history of typhoid fever 1 week before for which he was prescribed cefuroxime. Although investigations fail to provide any clue, his catatonic symptoms disappeared 2 weeks later giving way to resting tremor, bradykinesia, cog-wheel rigidity but without gait abnormality. He was successfully treated with lorazepam, amantidine, olanzapine and pramiprexole. The patient was asymptomatic within a month. He had no recurrence of symptoms till last follow-up, 6 months from the illness. PMID:23814211

Talukdar, Payel; Dutta, Arghya; Rana, Sukriti; Talukdar, Arunansu



Role of cephalosporins in gonorrhoea and other sexually transmitted diseases.  


Cephalosporins have a role in the treatment of gonorrhoea, and especially infections caused by strains that are penicillin-resistant, either because they produce plasmid-mediated beta-lactamase or they have chromosomally mediated diminished permeability or modified penicillin-binding proteins. Although none of the oral or Group I agents are useful, most of the Group II, III and IV agents are, and especially cefuroxime, cefotaxime, ceftriaxone and cefoxitin. In addition to uncomplicated urethral, cervical or rectal infections, appropriate regimens are also effective for the treatment of pharyngeal infections, disseminated infections and gonococcal ophthalmia. The cephalosporins have no clear role in the treatment of syphilis, granuloma inguinale, Mycoplasma or chlamydial infections or bacterial vaginosis, but ceftriaxone may be effective in chancroid, and cefoxitin in combination with an antichlamydial agent (such as a tetracycline) might be used for the treatment of pelvic inflammatory disease. PMID:3319500

Phillips, I



The in vitro activity of tigemonam: a comparison with other antimicrobial agents.  


The activity of tigemonam was compared with that of aztreonam, cefuroxime, cephalexin, amoxicillin/clavulanate potassium, gentamicin, and ofloxacin, using an agar dilution method. Tigemonam was active against strains containing known beta-lactamases of Tem and Oxa types, but strains containing broad-spectrum (group IV) enzymes were less susceptible. The MIC90 of tigemonam against the common Enterobacteriaceae was less than or equal to 0.25 mg/L. The MIC90S against Haemophilus influenzae and Neisseria gonorrhoeae were 0.5 and 0.06 mg/L, respectively. Pseudomonas, staphylococci, and Bacteroides sp. were less susceptible (MIC90 greater than 128 mg/L). Protein binding in human serum was found to be 62.5%; the presence of serum had only a modest effect on the activity of tigemonam. PMID:2509645

Andrews, J M; Wise, R



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



Emergence of Extensively Drug-Resistant Haemophilus parainfluenzae in Switzerland  

PubMed Central

Two homosexual men were colonized in the urethra with Haemophilus parainfluenzae nonsusceptible to ampicillin (MIC, 8 ?g/ml), amoxicillin-clavulanate (MIC, 4 ?g/ml), cefotaxime (MIC, 1.5 ?g/ml), cefepime (MIC, 3 ?g/ml), meropenem (MIC, 0.5 ?g/ml), cefuroxime, azithromycin, ciprofloxacin, tetracycline, and chloramphenicol (all MICs, ?32 ?g/ml). Repetitive extragenic palindromic PCR (rep-PCR) showed that the strains were indistinguishable. The isolates had amino acid substitutions in PBP3, L4, GyrA, and ParC and possessed Mef(A), Tet(M), and CatS resistance mechanisms. This is the first report of extensively drug-resistant (XDR) H. parainfluenzae.

Tinguely, Regula; Seiffert, Salome N.; Furrer, Hansjakob; Perreten, Vincent; Droz, Sara



Treating acute otitis media post-PCV-7: judicious antibiotic therapy.  


Acute otitis media (AOM) is treated with antibiotics in the United States, but the changing distribution of bacterial pathogens that cause the disorder can present physicians with several challenges. Most physicians treat AOM empirically, and their treatment choice should target Streptococcus pneumonia, nontypeable Haemophilus influenzae, and Moraxella catarrhalis, as those bacteria are most often isolated in AOM. First-line treatment for new onset AOM remains amoxicillin (80-90 mg/kg/d, divided twice daily). For persistent or recurrent AOM, guidelines recommend high-dose amoxicillin-clavulanate, cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Improved diagnosis and optimizing the choice of therapy by considering in vitro and in vivo efficacy of the different antibiotics will improve patient outcomes. Improved patient outcomes will result in fewer AOM episodes, decreased antibiotic resistance, and reduced direct and indirect health care costs. PMID:19667702

Casey, Janet R



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



Penetration of eight beta-lactam antibiotics into the peritoneal fluid. A pharmacokinetic investigation.  


Serial serum and peritoneal fluid samples were taken after intravenous injection of cefuroxime sodium, cefoxitin sodium, cefotaxime sodium, cefoperazone sodium, ceftazidime, moxalactam disodium, mezlocillin sodium, and piperacillin sodium. Time-concentration curves were obtained for both pharmacokinetic compartments. The geometric mean of peritoneal fluid concentrations from eight to ten patients was used to define the time-concentrations curve for each substance. Serum pharmacokinetic values were calculated using an open two-compartment model. The concentrations (Cps) were calculated from peritoneal fluid concentrations by quadratic interpolation. The time for which one fourth of the Cp (Cp1/4) is maintained within the peritoneal cavity varied according to the substance and can be used to estimate dosage intervals. The Cp1/4 was compared with the minimal inhibitory concentrations for 1,344 pathogens encountered in 415 intra-abdominal infections from 31 studies. PMID:6849637

Wittman, D H; Schassan, H H



An outbreak of Fusarium solani endophthalmitis after cataract surgery in an eye training and research hospital in Istanbul.  


To report an outbreak of Fusarium solani endophthalmitis after uneventful cataract surgeries performed on the same day in the same operating room. Nine patients underwent phacoemulsification at 4th Clinic of Beyoglu Eye Training and Research Hospital in Istanbul. Cefuroxime axetyl was injected intracamerally from the same vial to all patients at the end of surgery. All patients developed acute postoperative endophthalmitis. Presentation, cultural studies, treatment, clinical responses and risk factors were evaluated. Cultural and DNA sequence findings revealed F. solani. Antifungal therapy was begun and pars plana vitrectomy, intraocular lens and capsule extraction were performed. Corneal involvement was correlated with old age and systemic disease. Fusarium solani should be considered in acute postoperative endophthalmitis. This infection can be controlled with early and aggressive combined antifungal and surgical treatment. The patients with corneal involvement had poor prognosis. It is important to use solutions prepared separately for each patient. PMID:21627695

Güngel, Hülya; Eren, Mümin Hakan; P?narc?, Eylem Yaman; Altan, Ci?dem; Baylançiçek, Deniz Oygar; Kara, Necip; Gürsel, Tan?l; Yegeno?lu, Yildiz; Susever, Serdar



Problem of antimicrobial resistance of fecal aerobic gram-negative bacilli in the elderly.  

PubMed Central

In this study, we assessed the magnitude of risk (odds ratio [OR]) of patients being colonized with fecal aerobic gram-negative bacilli in two geriatric hospitals compared with the community, and we associated the use of antimicrobial agents with bacterial resistance. One fecal sample was collected from each of 341 patients, aged 60 years or older, during the hospital stay or when visiting the outpatient service. Samples were collected in 1988 and 1993 to 1994. The aerobic gram-negative bacilli from all samples were examined for resistance to seven antimicrobials by a replica plating method. The long-term-hospitalized patients had a significantly higher risk of being colonized with bacilli resistant to ampicillin (OR, 14.3; 95% confidence interval [95% CI], 6.0 to 34.1), cefuroxime (OR, 7.5; 95% CI, 2.7 to 20.8), trimethoprim (ORs, 22.3; 95% CI, 8.6 to 57.8), and tetracycline (OR, 5.2; 95% CI, 2.4 to 10.9) than the outpatients. The respective ORs among the short-term-hospitalized patients compared with the outpatients were 4.0 (95% CI, 1.9 to 8.4), 7.5 (95% CI, 2.7 to 20.8), 5.5 (95% CI, 2 to 14), and 2.0 (95% CI, 1 to 4). In 1993 to 1994 compared with 1988, in both hospitals there was a significantly increased risk of colonization by bacilli resistant to ampicillin (OR, 3.1; 95% CI, 1.9 to 5.1), cefuroxime (OR, 3.8; 95% CI, 2.1 to 6.7), and tetracycline (OR, 1.6; 95% CI, 1.0 to 2.5). However, the total use of antimicrobial agents increased only among the patients of the short-term-care hospital.

Leistevuo, T; Toivonen, P; Osterblad, M; Kuistila, M; Kahra, A; Lehtonen, A; Huovinen, P



Extremely High Prevalence of Nasopharyngeal Carriage of Penicillin-Resistant Streptococcus pneumoniae among Children in Kaohsiung, Taiwan  

PubMed Central

Resistance (intermediate and high) to penicillin among Streptococcus pneumoniae strains is an emerging problem worldwide. From 1995 to 1997, isolates of S. pneumoniae not susceptible to penicillin were seen with increasing frequency from blood, cerebrospinal fluid, pleural fluid, and middle ear fluid from pediatric patients at the Veterans General Hospital-Kaohsiung. To determine the prevalence of carriage of these penicillin-nonsusceptible S. pneumoniae isolates, we obtained nasopharyngeal swab specimens from 2,905 children (ages, 2 months to 7 years) attending day-care centers or kindergartens or seen in our outpatient clinic. S. pneumoniae was isolated from 611 children, and 584 strains were available for analysis. The oxacillin disc test was used as a screening test to evaluate penicillin susceptibility. The MICs of 11 antibiotics (penicillin, cefaclor, cefuroxime, ceftriaxone, cefotaxime, imipenem, chloramphenicol, clarithromycin, rifampin, vancomycin, and teicoplanin) were determined by the E-test. Only 169 (29%) of the strains were susceptible to penicillin; 175 (30%) strains were intermediately resistant and 240 (41%) were highly resistant. The isolates also demonstrated high rates of resistance to other ?-lactams (46% were resistant to cefaclor, 45% were resistant to cefuroxime, 45% were resistant to ceftriaxone, 31% were resistant to cefotaxime, and 46% were resistant to imipenem). The rate of resistance to macrolide antimicrobial agents was strikingly high; 95% of the isolates were not susceptible to clarithromycin. However, 97% were susceptible to rifampin and 100% were susceptible to the two glycopeptides (vancomycin and teicoplanin). While reports of penicillin-resistant S. pneumoniae increased worldwide through the 1980s, the high prevalence (71%) of resistance reported here is astonishing. Surveillance of nasopharyngeal swab specimen cultures may provide useful information on the prevalence of nonsusceptible strains causing invasive disease. Such information could be used to guide therapy of pneumococcal infections.

Chiou, Chen-Chia Christine; Liu, Yung-Ching; Huang, Tsi-Shu; Hwang, Wen-Kuei; Wang, Jen-Hsien; Lin, Hsi-Hsun; Yen, Muh-Yong; Hsieh, Kai-Sheng



Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships.  


In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5-substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized. The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 microg/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice. PMID:16618017

Altinta?, Handan; Ate?, Oznur; Uyde-Do?an, B Sönmez; Alp, F Ilkay; Kaleli, Deniz; Ozdemir, Osman; Birteksöz, Seher; Otük, Gülten; Atana, Dilek; Uzun, Meltem



Application of ultrasound-assisted matrix solid-phase dispersion extraction to the HPLC confirmatory determination of cephalosporin residues in milk.  


Ultrasound-assisted matrix solid-phase dispersion (MSPD) was applied to isolate eight cephalosporins (cefadroxil, cefaclor, cephalexin, cefotaxime, cefazolin, cefuroxime, cefoperazone and ceftiofur) from milk. Multi-residue analysis was subsequently performed by HPLC-diode array detection. Extraction yield by matrix solid-phase dispersion using Nexus sorbent was higher than various investigated SPE protocols. Three analytical columns, two conventional silica based and one monolithic, were compared based on resolution, peak shape and retention time. The optimum method using Chromolith RP-18e (100×4.6 mm) achieved separation in less than 16 min. Method validation was performed according to the European Union Decision 2002/657/EC, determining linearity, selectivity, stability, decision limit, detection capability, accuracy and precision. RSD values observed were lower than 15.3%. Recovery rates of examined antimicrobials from milk ranged from 93.8 to 101.9% for cefadroxil, from 94.7 to 103.6% for cefaclor, from 93.4 to 106.6% for cephalexine, from 104.1 to 115.3% for cefotaxime, from 97.1 to 105.6% for cefazolin, from 97.4 to 108.6% for cefuroxime, from 98.8 to 103.4% for cefoperazone and from 95.5 to 103.6% for ceftiofur. Correlation coefficients ranged from 0.9926 to 0.9999. CC(b) values were in the range from 103.5 to 112.3 ?g/kg for analytes with a maximum residue limit of 100 ?g/kg and from 54.4 to 56.3 ?g/kg for those with a maximum residue limit of 50 ?g/kg. PMID:20715145

Karageorgou, Eftichia G; Samanidou, Victoria F



In vitro activity of the tricyclic beta-lactam GV104326.  


GV104326 is a novel tricyclic beta-lactam (a trinem or, formerly, tribactam). The in vitro activity of GV104326 was compared with those of cefuroxime, cefixime, amoxicillin, amoxicillin-clavulanic acid, cefpirome, and ciprofloxacin. GV104326 had in vitro activity generally similar to that of cefixime against members of the family Enterobacteriaceae (MIC at which 90% of the isolates are inhibited [MIC90], < or = 2 micrograms/ml), with cefuroxime and amoxicillin-clavulanic acid being 8- to 32-fold less active and with cefpirome being 4- to 8-fold more active against members of this family. The trinem had no activity against Pseudomonas aeruginosa or Stenotrophomonas maltophilia (MIC90, > 128 micrograms/ml) but was the most active agent against Acinetobacter calcoaceticus. GV104326 was particularly active against gram-positive cocci. Ninety percent of methicillin-susceptible Staphylococcus aureus strains were susceptible to 0.03 microgram of GV104326 per ml, making it the most active agent studied. Enterococci and Lancefield group A and B streptococci were generally equally or somewhat more susceptible to GV104326 than they were to amoxicillin. Streptococcus pneumoniae strains were highly susceptible to GV104326, and those strains which showed decreased susceptibility to penicillin were generally twofold more susceptible to the trinem than to amoxicillin. Haemophilus influenzae and Moraxella catarrhalis were highly susceptible to GV104326 (MIC90s, 0.12 and 0.03 microgram/ml, respectively). The anaerobes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus spp. were more susceptible to the trinems (formerly tribactams) than to the other agents studied. PMID:8723475

Wise, R; Andrews, J M; Brenwald, N



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.



In vitro activity of the tricyclic beta-lactam GV104326.  

PubMed Central

GV104326 is a novel tricyclic beta-lactam (a trinem or, formerly, tribactam). The in vitro activity of GV104326 was compared with those of cefuroxime, cefixime, amoxicillin, amoxicillin-clavulanic acid, cefpirome, and ciprofloxacin. GV104326 had in vitro activity generally similar to that of cefixime against members of the family Enterobacteriaceae (MIC at which 90% of the isolates are inhibited [MIC90], < or = 2 micrograms/ml), with cefuroxime and amoxicillin-clavulanic acid being 8- to 32-fold less active and with cefpirome being 4- to 8-fold more active against members of this family. The trinem had no activity against Pseudomonas aeruginosa or Stenotrophomonas maltophilia (MIC90, > 128 micrograms/ml) but was the most active agent against Acinetobacter calcoaceticus. GV104326 was particularly active against gram-positive cocci. Ninety percent of methicillin-susceptible Staphylococcus aureus strains were susceptible to 0.03 microgram of GV104326 per ml, making it the most active agent studied. Enterococci and Lancefield group A and B streptococci were generally equally or somewhat more susceptible to GV104326 than they were to amoxicillin. Streptococcus pneumoniae strains were highly susceptible to GV104326, and those strains which showed decreased susceptibility to penicillin were generally twofold more susceptible to the trinem than to amoxicillin. Haemophilus influenzae and Moraxella catarrhalis were highly susceptible to GV104326 (MIC90s, 0.12 and 0.03 microgram/ml, respectively). The anaerobes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus spp. were more susceptible to the trinems (formerly tribactams) than to the other agents studied.

Wise, R; Andrews, J M; Brenwald, N



RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. I. Antibacterial activity in vitro.  


The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin-sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram-positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective. PMID:1592683

Bauernfeind, A; Jungwirth, R; Eberlein, E; Klesel, N; Adam, F; Isert, D; Limbert, M; Markus, A; Schrinner, E; Seibert, G



The identification, typing, and antimicrobial susceptibility of Pseudomonas aeruginosa isolated from mink with hemorrhagic pneumonia.  


The biological characteristics and molecular epidemiology of Pseudomonas aeruginosa associated with mink hemorrhagic pneumonia from Shandong province of eastern China were determined in this study. From 2010 to 2011, 30 mink P. aeruginosa isolates were identified from lung, fecal and feed samples of clinical cases and subjected to serotyping, antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) using SpeI. The P. aeruginosa isolates belonged to four serotypes-21 of type G, four of type I, three of type M, one of type B, and one non-typable strain. The strains were divided into four large groups as determined by PFGE. Isolates from the group 2 were highly homologous and were obtained from the same region as an epidemic. All of the isolates were sensitive to piperacillin, piperacillin/tazobactam, ceftazidime, cefepime, imipenem, amikacin, gentamicin and tobramycin and resistant to ampicillin, cefuroxime and cefuroxime axetil. A high frequency of resistance was found to ampicillin/sulbactam, cefazolin, cefotetan, ceftriaxone, nitrofurantoin, and trimethoprim/sulfamethoxazole (96.7%). Resistance to ticarcillin/clavulanic acid, ciprofloxacin and levofloxacin was less common (13.3%). There was no relationship between antibiotic resistance and serotype distribution of the isolates. The epidemic serotype of P. aeruginosa from the mink hemorrhagic pneumonia in Shandong province was type G, which was a clone of commonly found in this province. These findings reveal the genetic similarities and antimicrobial susceptibility profiles of P. aeruginosa from clinical cases of mink hemorrhagic pneumonia and will facilitate the prevention and control of the disease in Shandong province of China. PMID:24629901

Qi, Jing; Li, Lulu; Du, Yijun; Wang, Shourong; Wang, Jinwen; Luo, Yanbo; Che, Jie; Lu, Jinxing; Liu, Hui; Hu, Guangchun; Li, Jixia; Gong, Yanwen; Wang, Guisheng; Hu, Ming; Shiganyan; Liu, Yuqing



Heat inactivation of beta-lactam antibiotics in milk.  


The presence of residues of antimicrobial substances in milk is one of the main concerns of the milk industry, as it poses a risk of toxicity to public health, and can seriously influence the technological properties of milk and dairy products. Moreover, the information available on the thermostability characteristics of these residues, particularly regarding the heat treatments used in control laboratories and the dairy industry, is very scarce. The aim of the study was, therefore, to analyze the effect of different heat treatments (40 degrees C for 10 min, 60 degrees C for 30 min, 83 degrees C for 10 min, 120 degrees C for 20 min, and 140 degrees C for 10 s) on milk samples fortified with three concentrations of nine beta-lactam antibiotics (penicillin G: 3, 6, and 12 microg/liter; ampicillin: 4, 8, and 16 microg/liter; amoxicillin: 4, 8, and 16 microg/liter; cloxacillin: 60, 120, and 240 microg/liter; cefoperazone: 55, 110, and 220 microg/liter; cefquinome: 100, 200, and 400 microg/liter; cefuroxime: 65, 130, and 260 microg/liter; cephalexin: 80, 160, and 220 microg/ liter; and cephalonium: 15, 30, and 60 microg/liter). The method used was a bioassay based on the inhibition of Geobacillus stearothermophilus var. calidolactis. The results showed that heating milk samples at 40 degrees C for 10 min hardly produced any heat inactivation at all, while the treatment at 83 degrees C for 10 min caused a 20% loss in penicillin G, 27% in cephalexin, and 35% in cefuroxime. Of the three dairy industry heat treatments studied in this work, low pasteurization (60 degrees C for 30 min) and treatment at 140 degrees C for 10 s only caused a small loss of antimicrobial activity, whereas classic sterilization (120 degrees C for 20 min) showed a high level of heat inactivation of over 65% for penicillins and 90% for cephalosporins. PMID:18592745

Zorraquino, M A; Roca, M; Fernandez, N; Molina, M P; Althaus, R



A Systematic Review and Meta-Analysis of Antibiotic-Impregnated Bone Cement Use in Primary Total Hip or Knee Arthroplasty  

PubMed Central

Background Antibiotic-impregnated bone cement (AIBC) has been widely used for the treatment of infected revision arthroplasty, but its routine use in primary total joint arthroplasty (TJA) remains considerably controversial. With this meta-analysis of published randomized controlled trials, we intended to assess the antimicrobial efficacy and safety of AIBC for its prophylactic use in primary TJA. Methods A literature search was performed in MEDLINE, Embase, CBMdisc and the Cochrane Library until June, 2013. The studies were divided into two sub-groups according to the type of the control group. Outcomes of interest included postoperative infection rates, radiographic outcomes and clinical joint score. Study quality was evaluated using the Jadad scale (five points). Results In total, eight studies were included, with a sample size of 6,381 arthroplasties. The overall pooled data demonstrated that, compared with the control (plain cement or systemic antibiotic), AIBC did not reveal an advantage in decreasing the rate of superficial infection (relative risk [RR] = 1.47; 95% CI, 1.13–1.91; P=0.004), while there were significant differences in deep infection rate between the AIBC and control group (RR = 0.41; 95% CI, 0.17–0.97; P=0.04). For the analysis of gentamicin and cefuroxime subgroups, the gentamicin was superior to the cefuroxime in reducing deep infection rate (P=0.0005 versus P= 0.10). However, no significant differences were found in their radiographic outcomes and clinical joint score. Conclusion This meta-analysis had proven that the prophylactic use of AIBC could lower the deep infection rate in primary TJA, while AIBC did not show an improvement in reducing the superficial infection rate compared with the control. More sufficiently powered studies would be required to further evaluate the efficacy and safety of AIBC for primary TJA.

Cheng, Tao; Peng, Xiaochun; Zhang, Wen; Qin, Hui; Zhang, Xianlong



Neonatal sepsis at Muhimbili National Hospital, Dar es Salaam, Tanzania; aetiology, antimicrobial sensitivity pattern and clinical outcome  

PubMed Central

Background Neonatal sepsis contributes significantly to morbidity and mortality among young infants. The aetiological agents as well as their susceptibility to antimicrobial agents are dynamic. This study determined aetiology, antimicrobial susceptibility and clinical outcome of neonatal sepsis at Muhimbili National Hospital. Methods Three hundred and thirty neonates admitted at the Muhimbili National Hospital neonatal ward between October, 2009 and January, 2010 were recruited. Standardized questionnaires were used to obtain demographic and clinical information. Blood and pus samples were cultured on MacConkey, blood and chocolate agars and bacteria were identified based on characteristic morphology, gram stain appearance and standard commercially prepared biochemical tests. Antimicrobial sensitivity testing was performed for ampicillin, cloxacillin, gentamicin, amikacin, cefuroxime and ceftriaxone on Mueller Hinton agar using the Kirby Bauer diffusion method. Results Culture proven sepsis was noted in 24% (74/330) of the study participants. Isolated bacterial pathogens were predominantly Staphylococcus aureus, Klebsiella spp and Escherichia coli. Klebsiella spp 32.7% (17/52) was the predominant blood culture isolate in neonates aged below seven days while Staphylococcus aureus 54.5% (12/22) was commonest among those aged above seven days. Staphylococcus aureus was the predominant pus swabs isolate for both neonates aged 0–6 days 42.2% (98/232) and 7–28 days 52.3% (34/65). Resistance of blood culture isolates was high to ampicillin 81.1% (60/74) and cloxacillin 78.4% (58/74), moderate to ceftriaxone 14.9% (11/74) and cefuroxime 18.9% (14/74), and low to amikacin 1.3% (1/74). Isolates from swabs had high resistance to ampicillin 89.9% (267/297) and cloxacillin 85.2 (253/297), moderate resistance to ceftriaxone 38.0% (113/297) and cefuroxime 36.0% (107/297), and low resistance to amikacin 4.7% (14/297). Sepsis was higher in neonates with fever and hypothermia (p=0.02), skin pustules (p<0.001), umbilical pus discharge and abdominal wall hyperemia (p=0.04). Presence of skin pustules was an independent predictor of sepsis OR 0.26, 95% CI (0.10-0.66) p=0.004. The overall death rate was 13.9% (46/330), being higher in neonates with sepsis 24.3% (18/74) than those without 10.9% (28/256), p=0.003. Conclusions Staphylococcus aureus was predominant isolate followed by Klebsiella and Escherichia coli. There was high resistance to ampicillin and cloxacillin. Mortality rate due to neonatal sepsis was high in our setting. Routine antimicrobial surveillance should guide the choice of antibiotics for empirical treatment of neonatal sepsis.



Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study.  

PubMed Central

A total of 1,527 clinically significant outpatient isolates of Streptococcus pneumoniae were prospectively collected in 30 different U.S. medical centers between November 1994 and April 1995. Overall, 23.6% of strains were not susceptible to penicillin, with 14.1% intermediate and 9.5% high-level resistant. The frequencies of recovery of intermediate and high-level resistant strains varied considerably between different medical centers and in different geographic areas. In general, intermediate and high-level penicillin resistance was most common with isolates of S. pneumoniae recovered from pediatric patients. The in vitro activities of 22 other antimicrobial agents were assessed against this collection of isolates. Ampicillin was consistently 1 twofold dilution less active than penicillin. Amoxicillin and amoxicillin-clavulanate were essentially equivalent to penicillin in activity. The rank order of activity for cephalosporins was cefotaxime = ceftriaxone > or = cefpodoxime > or = cefuroxime > cefprozil > or = cefixime > cefaclor = loracarbef > cefadroxil = cephalexin. The National Committee for Clinical Laboratory Standards [Performance Standards for Antimicrobial Susceptibility Testing, Sixth Information Supplement (M100-S6), 1995] has established MIC breakpoints for resistance (i.e., > or = 2 micrograms/ml) with three cephalosporins versus S. pneumoniae, namely, cefotaxime, ceftriaxone, and cefuroxime. The overall percentages of strains resistant to these three antimicrobial agents were 3, 5, and 12, respectively. The overall frequency of resistance was 10% with all three macrolides examined in this study, clarithromycin, erythromycin, and azithromycin. The overall percentages of chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole resistance were 4.3, 7.5, and 18, respectively. The resistance percentages among the cephalosporins, macrolides, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole were consistently higher among penicillin-intermediate strains than among susceptible isolates and even higher still among organisms expressing high-level penicillin resistance. Multiply resistant strains represented 9.1% of the organisms examined in this study. Finally, rifampin resistance was uncommon (i.e., 0.5%), and vancomycin resistance was not detected. The quinopristin-dalfopristin combination was consistently active at concentrations of 0.25 to 4 micrograms/ml, but rates of resistance could not be determined in the absence of established interpretive criteria for MIC results.

Doern, G V; Brueggemann, A; Holley, H P; Rauch, A M



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



Susceptibility patterns of bacterial isolates from hospitalised patients with respiratory tract infections (MOXIAKTIV Study).  


The objective of this study was to determine: (i) the prevalence of resistance in current clinical isolates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae; (ii) the prevalence of production of extended-spectrum beta-lactamases (ESBLs) and methicillin resistance in S. aureus; and (iii) regional differences in the prevalence of ESBL production and clonality of K. pneumoniae isolates. Pathogens causing respiratory tract infections in hospitalised patients were prospectively collected from all over Germany. Drugs tested by Etest included moxifloxacin, levofloxacin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and penicillin G. ESBL production by K. pneumoniae was determined using cefotaxime/ceftazidime +/- clavulanic acid. Deutsches Institut für Normung (German Institute for Standardisation)/European Committee on Antimicrobial Susceptibility Testing (DIN/EUCAST) breakpoints were used where applicable. Overall, 1859 pathogens were analysed. For all species tested the fluoroquinolones achieved the highest overall susceptibility rate (92.8%) compared with clarithromycin (60.5%), amoxicillin/clavulanic acid (85.7%) and cefuroxime (89.6%). From 438 K. pneumoniae isolates, 13.0% produced an ESBL. The ESBL prevalence was 38.8% in Eastern Germany with a trend towards clonality in some centres, but ranged from 4.7% to 7.1% in Southern, Northern and Western Germany. Among the methicillin-susceptible S. aureus isolates, 10.1% were moxifloxacin- and levofloxacin-resistant. Of the S. pneumoniae isolates, 99.3% were moxifloxacin- and levofloxacin-susceptible, 93.9% were penicillin G-susceptible and 85.7% were clarithromycin-susceptible. With a MIC90 value (minimal inhibitory concentration for 90% of the isolates) of 0.19 mg/L, moxifloxacin was more potent than levofloxacin (MIC90 = 1 mg/L) against S. pneumoniae. Haemophilus influenzae and M. catarrhalis were almost 100% susceptible to the quinolones; 100% of the M. catarrhalis but only 4.5% of the H. influenzae strains were clarithromycin-susceptible. Moxifloxacin was the most active agent amongst the drugs tested, in particular against Gram-positive pathogens. PMID:18835763

Jacobs, Enno; Dalhoff, Axel; Korfmann, Gisela



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



Biliary tract infections: a guide to drug treatment.  


Initial therapy of acute cholecystitis and cholangitis is directed towards general support of the patient, including fluid and electrolyte replacement, correction of metabolic imbalances and antibacterial therapy. Factors affecting the efficacy of antibacterial therapy include the activity of the agent against the common biliary tract pathogens and pharmacokinetic properties such as tissue distribution and the ratio of concentration in both bile and serum to the minimum inhibitory concentration for the expected micro-organism. Antimicrobial therapy is usually empirical. Initial therapy should cover the Enterobacteriaceae, in particular Escherichia coli. Activity against enterococci is not required since their pathogenicity in biliary tract infections remains unclear. Coverage of anaerobes, in particular Bacteroides spp., is warranted in patients with previous bile duct-bowel anastomosis, in the elderly and in patients in serious clinical condition. In patients with acute cholecystitis or cholangitis of moderate clinical severity, monotherapy with a ureidopenicillin--mezlocillin or piperacillin--is at least as effective as the combination of ampicillin plus aminoglycoside. In severely ill patients with septicaemia, an antibacterial combination is preferable. Therapy with aminoglycosides, mostly for Pseudomonas aeruginosa-related infections, should not exceed a few days because the risk of nephrotoxicity seems to be increased during cholestasis. Relief of biliary obstruction is mandatory, even if there is clinical improvement with conservative therapy, because cholangitis is most likely to recur with continued obstruction. Emergency invasive therapy is reserved for patients who fail to show a clinical response to antibacterial therapy within the first 36 to 48 hours or for those who deteriorate after an initial clinical improvement. Immediate surgery is indicated for gangrenous cholecystitis and perforation with peritonitis. Long-term administration of antibacterials is required for recurrent cholangitis, as seen in bile duct-bowel anastomosis. Oral cotrimoxazole (trimethoprim/sulfamethoxazole) is the preferred agent. Wound infection rates after biliary tract surgery can be significantly reduced by preoperative administration of prophylactic antibacterials. Newer generation beta-lactams have not proven to be of greater benefit than older agents such as cefuroxime or cefazolin. Antibacterial prophylaxis before endoscopic retrograde cholangiopancreatography (ERCP) should be reserved for patients with obstructive jaundice, since the risk of infectious complications seems to be strongly associated with this clinical condition. Failure to achieve full biliary drainage is the most important factor in predicting septicaemia, and prophylaxis should be prolonged until the bile duct is unobstructed. Piperacillin, cefazolin, cefuroxime, cefotaxime and ciprofloxacin are effective for this indication. PMID:9951953

Westphal, J F; Brogard, J M



Multidrug resistant AmpC ?-lactamase producing Escherichia coli isolated from a paediatric hospital  

PubMed Central

Objective : The objective of the study was to observe the antimicrobial resistance of AmpC ?-lactamase producing E. coli. Methods: Six hundred and seventy E. coli were isolated from 20,257 various pathological samples collected from The Children’s Hospital and Institute of Child Health, Lahore, Pakistan. The isolates showed resistance to ceftazidime which were further examined for AmpC ?-lactamase activity by Disc Potentiation method. Results: There were 670 isolates of E. coli out of which 85 (12.6%) were AmpC ?-lactamase producers. Risk factors like intravenous line (76.5%), endotracheal tube (22.4%), surgery (12.9%) and urinary catheters (7.1%) were found to be associated with infection caused by AmpC ?-lactamase producing E. coli. Antimicrobial resistance pattern revealed that AmpC producing E. coli were highly resistant to co-amoxiclav, ceftazidime, cefotaxime, cefuroxime, cefixime, ceftriaxone and cefoxitin (100% each). Least resistance was observed against sulbactam-cefoperazone (14.1%), cefepime (7.1%), piperacillin-tazobactam (5.9%) and none of the isolates were resistant to imipenem and meropenem. Conclusion: The minimum use of invasive devices and strict antibiotic policies can reduce the spread of AmpC ?-lactamase producing E. coli.

Jameel, Noor-ul-Ain; Ejaz, Hasan; Zafar, Aizza; Amin, Hafsa



Zygomatic abscess with temporal myositis - a rare extracranial complication of acute otitis media.  


Acute mastoiditis is the most common complication of acute otitis media (AOM) and its early recognition and management still poses a challenge due to potentially serious consequences. The incidences of extracranial and intracranial suppurative complications of AOM in children have decreased significantly, yet they remain a serious clinical problem, especially when caused by bacteria resistant to antibiotics. The authors presented a case of rare AOM complication - zygomatic abscess with temporal myositis. A 6-year-old boy was admitted to the ENT Department with 4 weeks of ear pain, treated for AOM with cefuroxime axetyl and amoxicilline, with acute mastoiditis and subsequent abscess formation in zygomatic and preauricular region. The inflammatory process spread through anterior air cells to the zygomatic cells leading to a fistula formation in the zygomatic bone and breakthrough into the temporal muscle. The surgical procedures applied were: myringotomy with drainage, cortical mastoidectomy and revision of zygomatic area and treatment with antibiotics (ceftriaxon). Enterococcus faecalis and Streptococcus viridans were found in the culture of middle ear and mastoid effusion. After half a year of follow-up the child had a normal hearing. Severe complications of AOM are rare today. An early diagnosis in order to promote adequate management and prevent inherently suppurative complications is essential. PMID:15763297

Kuczkowski, Jerzy; Narozny, Waldemar; Stankiewicz, Czeslaw; Mikaszewski, Boguslaw; Izycka-Swieszewska, Ewa



Cost-effectiveness and value of an IV switch.  


A few antibiotics (i.e. metronidazole, clindamycin and ciprofloxacin) are available in both parenteral and oral formulations, and have good bioavailability, ensuring equivalent systemic drug concentrations. During a 4-year period subsequent to the initiation of a parenteral to oral (IV-PO) stepdown programme for metronidazole and clindamycin, Vancouver General Hospital saved approximately $C85 000. However, many parenteral antibacterials lack an oral formulation, requiring oral stepdown to a different antibacterial with a similar spectrum of activity. Alternatively, the oral formulation of a parenteral antibacterial may have poor bioavailability (i.e. cefuroxime axetil, ampicillin, cloxacillin, erythromycin, and tetracycline) and it is not possible to maintain equivalent systemic drug concentrations. While rigid criteria are not applicable to all clinical scenarios, the general criteria for oral stepdown include the following: the patient 1) continues to need an antibiotic; 2) is clinically stable; 3) is capable of tolerating the oral dosage form; and 4) has no factors present (e.g. gastrointestinal abnormalities or drug interactions) that would adversely affect oral bioavailability. A review of subsequent IV-PO stepdown programmes at Vancouver General Hospital revealed that 1) not all patients receiving parenteral therapy are candidates for oral stepdown; 2) oral stepdown is delayed in a large proportion of treatment courses; 3) oral stepdown is not occurring in many patients for whom it is deemed appropriate; and 4) in a very few treatment courses stepdown may occur prematurely and may contribute to clinical deterioration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10147285

Jewesson, P



Staging of chronic hyperplastic rhinosinusitis: treatment strategies.  


In 1990 we reported an initial prospective study of 100 patients using a four-stage system for classification of chronic rhinosinusitis. Between January 1988 and July 1992, we used this system in staging an additional 1814 patients, on whom 2980 intranasal sphenoethmoidectomies were performed. In this staging system a protocol trial of medication was given for 2 weeks, followed by axial and coronal computed tomography. Medication consisted of a second-generation cephalosporin antibiotic, usually cefuroxime; a 4-day burst of intraoral steroids, usually prednisone; and an antihistamine decongestant if not contraindicated. The stages of chronic hyperplastic rhinosinusitis included the stages described in the 1990 report (i.e., stage I, single-focus disease; stage II, discontiguous disease throughout the ethmoid labyrinth; stage III, diffuse disease responsive to medication; and stage IV, diffuse disease unresponsive to or poorly responsive to medication). The results of this study have shown that the computed tomography staging system based on computed tomography extent of disease after medical therapy is a simple, easily remembered, and very effective modality for the classification of chronic sinusitis. This system provides a rationale for discussing and planning surgery with patients and physicians and is a convenient reference for the reporting of end results. More importantly, a linear relationship between disease stage and outcomes is demonstrated. This statistically highly significant feature of the staging system provides a firm basis for the production of outcomes after various treatment strategies, particularly ethmoidectomy and the treatment of sinusitis. PMID:7530831

Friedman, W H; Katsantonis, G P; Bumpous, J M



Emergence of a multidrug-resistant Haemophilus influenzae strain causing chronic pneumonia in a patient with common variable immunodeficiency.  


We report the emergence of a multidrug-resistant Haemophilus influenzae strain in a patient with common variable immunodeficiency suffering from recurrent bronchopneumonia caused by H. influenzae. After the patient had received several antibiotic therapies, a strain was isolated showing resistance to ampicillin, ampicillin/sulbactam, cefazolin, cefuroxime, ciprofloxacin, and clarithromycin. Polymerase chain reaction analyses and sequencing revealed the presence of the beta-lactamase gene bla(TEM-1), two mutations (A502T and R517H) in the ftsI gene encoding the transpeptidase region of the penicillin-binding protein 3, and one mutation in the ribosomal protein gene L4 (G65D) conferring resistance to beta-lactams and macrolides, respectively. Additionally, the plasmid-encoded aac(6')-Ib-cr gene mediating slightly reduced susceptibility to quinolones and two mutations in the DNA gyrase gene gyrA and one mutation in the topoisomerase IV gene parC were identified leading to a high-level fluoroquinolone-resistant phenotype. In conclusion, the treatment of H. influenzae infections accompanied by high bacterial loads such as bronchopneumonia can be complicated by the selection of multidrug-resistant strains. Moreover, the emergence of aac(6')-Ib-cr in H. influenzae causing low fluoroquinolone resistance levels might have contributed to the selection of DNA gyrase and topoisomerase IV mutants. PMID:23095085

Pfeifer, Yvonne; Meisinger, Ines; Brechtel, Klaus; Gröbner, Sabine



Antimicrobial prophylaxis in coronary bypass surgery: a critical appraisal.  


The literature has been examined to assess the optimal prophylactic antimicrobial regimen for patients undergoing coronary bypass surgery. Antimicrobial surgical prophylaxis should be based on the two main potential pathogens, Staphylococcus epidermidis and S. aureus. It is unclear whether the prophylactic use of antimicrobials can or should be guided by in vitro antimicrobial susceptibility testing; data from well-performed clinical trials should be evaluated. The data fail to demonstrate consistently a significant difference within the cephalosporin class of antimicrobials with regard to prevention of infectious complications. Although it does not reach statistical difference, the trend with respect to efficacy appears to be cefuroxime, then cefamandole, and then cefazolin. The lack of significant difference among antimicrobials suggests an institution-individualized approach to the selection of the optimal antimicrobial for prophylaxis. For our facilities we recommend the following regimen: cefazolin sodium 1-2 g iv q8h for two days. There are not enough data at this time to recommend less than two days of antimicrobial prophylaxis for this type of surgery. In addition, aminoglycosides provide no added benefit when added to cephalosporins. PMID:2068834

Ariano, R E; Zhanel, G G



Susceptibility of Moraxella catarrhalis to 21 antimicrobial drugs: validity of current NCCLS criteria for the interpretation of agar disk diffusion antibiograms.  


Ninety-four clinical isolates of Moraxella catarrhalis were examined for susceptibility to 21 antimicrobial drugs; 67 isolates (= 71.3%) produced beta-lactamase(s). In terms of antibiotic resistance, the number of isolates resistant to penicillin G, ampicillin, and cotrimoxazole were 56, 32, and 1, respectively. The number of isolates with intermediate susceptibility to penicillin G, ampicillin, ciprofloxacin, ofloxacin, cotrimoxazole, and fosfomycin were 11, 34, 1, 2, 2, and 47, respectively. All 94 isolates proved susceptible to ampicillin + 10 micrograms/ml of sulbactam, amoxicillin + 4 micrograms/ml of clavulanic acid, cefuroxime, cefotaxime, cefepime, cefepime, cefixime, imipenem, meropenem, chloramphenicol, doxycycline, tetracycline, fusidic acid, erythromycin, clarithromycin, and rifampin, as based on currently valid NCCLS criteria, where applicable. There were no very major or major discrepancies between agar dilution and agar disk diffusion test results. There were only a few minor discrepancies between test results, specifically: penicillin G (category IV = 4, category VI = 1); ampicillin (category IV = 4, category V = 1, category VI = 7), amoxicillin + clavulanic acid (category III = 11), cotrimoxazole (category IV = 1, category V = 1, category VI = 1), ciprofloxacin (category V = 1), and ofloxacin (category VI = 2). The sole exception was fosfomycin, with a total of 25 minor discrepancies encountered (category III = 14, category V = 9, category VI = 2). Wilkins-Chalgren agar compared favorably with Mueller-Hinton agar following examination with 11 selected antimicrobial drugs against 31 representative isolates of M. catarrhalis. PMID:9142455

Traub, W H; Leonhard, B



Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital.  


Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections. PMID:2810183

Kingston, R D; Kiff, R S; Duthie, J S; Walsh, S; Spicer, A; Jeacock, J



BMY-28100, a new oral cephalosporin: antimicrobial activity against nearly 7,000 recent clinical isolates, comparative potency with other oral agents, and activity against beta-lactamase producing isolates.  


The antimicrobial activity of BMY-28100 was tested against approximately 7,000 bacterial pathogens in a multicenter, multiphased collaborative investigation. The BMY-28100 spectrum and antimicrobial potency was most similar to that of cefaclor and superior to that of cephalexin among currently available cephalosporins. Species that had greater than or equal to 90% of clinical strains inhibited by BMY-28100 (less than or equal to 8.0 micrograms/ml) were: Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, N. meningitidis, methicillin-susceptible Staphylococcus supp., Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. bovis, serogroup C and G streptococci, Listeria monocytogenes and gm-positive anaerobes. BMY-28100 inhibited 9% more of the 6286 fresh clinical isolates at less than or equal to 8.0 micrograms/ml than cefaclor at the same concentration. BMY-28100 was generally bactericidal, but MICs for some species were markedly increased when an inoculum concentration of 10(7) CFU/ml was used. Strains producing plasmid-mediated beta-lactamases (TEM, OXA, SHV, HMS) were susceptible to BMY-28100, cefaclor, and cefuroxime. BMY-28100 was less active against strains producing chromosomal-mediated beta-lactamases (Types I and IV). BMY-28100 was not hydrolyzed significantly by the tested plasmid-mediated beta-lactamases, but was destroyed by Type I cephalosporinases and Klebsiella K1 enzymes. PMID:3259489

Jones, R N; Barry, A L



[Pharmacokinetics and pharmacodynamics of antimicrobial therapy used in child osteoarticular infections].  


The progress in the knowledge of antibiotic action mechanisms have led to determine phamacodynamic/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. According to the antibiotic compound, the implicated bacterial specie, the localization of the infection, the severity of the disease, these parameters could vary. The PK/PD parameters described in this paper focus only on blood compartment and S. aureus, (main bacteria implicated in bone and joint tissue infections). All beta-lactamase resistant beta-lactam compounds given by IV route, if they are prescribed at the good dosage and frequency, fulfill these PK/PD parameters. In contrast, by oral route, M penicillins and cefuroxime-axetil should not be considered as acceptable regimens. Only amoxicillin-clavulanate and some first generation cephalosporin compounds fulfill the PK/PD parameters predictive of clinical efficacy if S. aureus strains are methicillin susceptible and dosages of cephalosporins are increased. Clindamycin is a very interesting alternative, if the strains are susceptible to macrolides. PMID:17956820

Cohen, R; Grimprel, E



Glutamate Dehydrogenase Affects Resistance to Cell Wall Antibiotics in Bacillus subtilis  

PubMed Central

The glutamate dehydrogenase RocG of Bacillus subtilis is a bifunctional protein with both enzymatic and regulatory functions. Here we show that the rocG null mutant is sensitive to ?-lactams, including cefuroxime (CEF), and to fosfomycin but that resistant mutants arise due to gain-of-function mutations in gudB, which encodes an otherwise inactive glutamate dehydrogenase. In the presence of CEF, ?rocG ?gudB mutant cells exhibit growth arrest when they reach mid-exponential phase. Using microarray-based transcriptional profiling, we found that the ?W regulon was downregulated in the ?rocG ?gudB null mutant. A survey of ?W-controlled genes for effects on CEF resistance identified both the NfeD protein YuaF and the flotillin homologue YuaG (FloT). Notably, overexpression of yuaFG in the rocG null mutant prevents the growth arrest induced by CEF. The YuaG flotillin has been shown previously to localize to defined lipid microdomains, and we show here that the yuaFGI operon contributes to a ?W-dependent decrease in membrane fluidity. We conclude that glutamate dehydrogenase activity affects the expression of the ?W regulon, by pathways that are yet unclear, and thereby influences resistance to CEF and other antibiotics.

Lee, Yong Heon; Kingston, Anthony W.



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



In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns.  

PubMed Central

Hyperbilirubinemia is frequently observed in neonates, and serious neurological complications such as kernicterus can be precipitated when the concentration of unconjugated bilirubin is abnormally increased. The administration of drugs which bind to albumin and compete with bilirubin can increase the possibility of such a complication. To test the bilirubin-displacing activity of pharmacological agents that are used with newborns, 52 antimicrobial agents were investigated in vitro. A glycine conjugate of salicylate, 2-hydroxybenzoylglycine, which is known to be present at elevated levels in newborns and has a potent bilirubin-displacing property, was used as a positive control agent. Pooled cord serum was used as a source of hyperbilirubinemic serum. A centrifugal ultrafiltration method with semipermeable cones was employed to determine the effects of potential bilirubin-displacing agents on the levels of total bilirubin. 2-Hydroxybenzoylglycine was demonstrated to be the most potent bilirubin-displacing agent. Antibiotics could be classified into four groups: high-level displacers (sulfisoxazole, sulfamethoxazole, dicloxacillin, cefoperazone, and ceftriaxone), intermediate-level displacers (moxalactam, nafcillin, and 14 others), low-level displacers (aztreonam, carbenicillin, and 11 others), and nondisplacers (mezlocillin, cefuroxime, kanamycin, and 15 others). It is concluded that the ultrafiltration method is a rapid and readily reproducible for the determination of bilirubin displacement and that antibiotics with a tendency to displace bilirubin should be avoided in jaundiced newborns whenever appropriate alternatives are available.

Wadsworth, S J; Suh, B



Kinetic Spectrophotometric Determination of Certain Cephalosporins in Pharmaceutical Formulations  

PubMed Central

A simple, reliable, and sensitive kinetic spectrophotometric method was developed for determination of eight cephalosporin antibiotics, namely, Cefotaxime sodium, Cephapirin sodium, Cephradine dihydrate, Cephalexin monohydrate, Ceftazidime pentahydrate, Cefazoline sodium, Ceftriaxone sodium, and Cefuroxime sodium. The method depends on oxidation of each of studied drugs with alkaline potassium permanganate. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 610?nm. The initial rate and fixed time (at 3 minutes) methods are utilized for construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 5–15??g?mL?1 and 5–25??g?mL?1 using the initial rate and fixed time methods, respectively. The results are validated statistically and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. Statistical comparisons of the results with the reference methods show the excellent agreement and indicate no significant difference in accuracy and precision.

Omar, Mahmoud A.; Abdelmageed, Osama H.; Attia, Tamer Z.



The Escherichia coli phylogenetic group B2 with integrons prevails in childhood recurrent urinary tract infections.  


The aim of our study was to characterize the phylogenetic groups of Escherichia coli, antibiotic resistance, and containment of class 1 integrons in the first attack of pyelonephritis and in subsequent recurrences in young children. Altogether, 89 urine E. coli isolates from 41 children with urinary tract infection (UTI) were studied for prevalence and persistence of phylogenetic groups by pulsed-field gel electrophoresis (PFGE), antibacterial resistance by minimal inhibitory concentrations (MIC) and class 1 integrons by PCR. Phylogenetic group B2 was most common (57%), followed by D (20%), A (18%) and B1 (5%). Overall resistance to betalactams was 61%, trimethoprim-sulfamethoxazole 28%, and was not associated with phylogenetic groups. According to PFGE, the same clonal strain persisted in 77% of patients. The persistence was detected most often in phylogenetic group B2 (70%). Phylogenetic group B2 more often contained class 1 integrons than group A. Integron positive strains had higher MIC values of cefuroxime, cefotaxime, and gentamicin. In conclusion, phylogenetic group B2 was the most common cause of the first episode of pyelonephritis, as well as in case of the persistence of the same strain and contained frequently class 1 integrons in childhood recurrent UTI. An overall frequent betalactam resistance was equally distributed among phylogenetic groups. PMID:24033434

Kõljalg, Siiri; Truusalu, Kai; Stsepetova, Jelena; Pai, Kristiine; Vainumäe, Inga; Sepp, Epp; Mikelsaar, Marika



[Antimicrobial sensitivity of 402 strains of Neisseria gonorrhoeae isolated in 7 Spanish cities].  


To study N. gonorrhoeae resistance in Spain. We evaluate 402 strains consecutively isolated in 7 Spanish cities (Barcelona, Bilbao, Madrid, Murcia, Seville, Valencia and Valladolid). The MIC to 9 antimicrobial agents was determined by agar-dilution (DST) method. We found a high incidence (15.7%) of penicillinase producer strains (NGPP). Most (53.3%) of all non-NGPP strains showed reduced sensitivity to penicillin and 1.5% of the strains had chromosomally mediated resistance. All NGPP strains and 90% of non-NGPP strains showed reduced sensitivity to tetracycline (MIC greater than 0.23 mg/l). We did not found any strain with high-level tetracycline resistance. MIC90 for the other drugs tested were: erythromycin, 0.125 mg/l; spectinomycin, 16 mg/l; cefoxitin, 2 mg/l; cefuroxime 0.06 mg/l; ceftriaxone 0.0037 mg/l; ofloxacin 0.06 mg/l and ciprofloxacin, 0.0018 mg/l. NGPP are very prevalent in Spain. Most of these strains had chromosomally mediated resistance to penicillin and tetracycline. We did not found resistance to other antimicrobial agents. PMID:1822152

Perea, E J; García-López, J L; Martín, R; Calmet, M; Cisterna, R; Estébanez, V; Vázquez, J A; Martín Luengo, F; Altuna, A; Merino, C



Molecular identification and antimicrobial susceptibility of Nocardia spp. isolated from bovine mastitis in Brazil.  


Nocardia spp. infections can cause severe damage to the mammary gland due to suppurative pyogranulomatous lesions and lack of clinical cure in response to conventional antimicrobial therapy. Although Nocardia infections are considered relatively uncommon in cows, there has been an apparent worldwide increase in the incidence of bovine mastitis caused by Nocardia spp, perhaps due to environmental transmission of this ubiquitous pathogen. The objectives of present study were to determine: (i) species distribution of 80 Nocardia isolates involved in bovine mastitis (based on molecular methods); and (ii) antimicrobial susceptibility pattern of all isolates from three geographical areas in Brazil. In this study, Nocardia nova (80%) was the most frequently isolated species, followed by Nocardia farcinica (9%). Additionally, Nocardia puris, Nocardia cyriacigeorgica, Nocardia veterana, Nocardia africana, and Nocardia arthritidis were detected using 16S rRNA sequencing. This is apparently the first report of N. puris, N. veterana, N. cyriacigeorgica, N. arthritidis and N. africana in association with bovine mastitis. Based on the disk diffusion test, isolates were most frequently resistant to cloxacillin (75%), ampicillin (55%) and cefoperazone (47%), whereas few Nocardia spp. were resistant to amikacin, cefuroxime or gentamicin. PMID:24060098

Condas, Larissa A Z; Ribeiro, Márcio G; Yazawa, Katsukiyo; de Vargas, Agueda P Castagna; Salerno, Tatiana; Giuffrida, Rogério; Langoni, Hélio; Melville, Priscila A; Biesdorf, Sônia; Matsuzawa, Tetsuhiro; Gonoi, Tohru; Kastelic, John P; Barkema, Herman W



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.



An unusual post-traumatic case of extrahepatic bile duct compression.  


Jaundice and cholestatic disease by external bile duct compression may be caused by several conditions, including pancreatic masses, portal cavernoma, Ormond's disease, metastases from gallbladder cancer, neurinomas, and hydronephrotic kidney. We report a case of bile duct compression in a 56-year-old man with a known small (28 mm) right renal cyst and crossed, fused renal ectopia. The patient had a history of recent abdominal trauma due to a motorcycle accident and recurrent septic-type fever and jaundice. He also reported a weight loss of 5 kg in the last two months. Abdominal ultrasonography showed intra- and extra-hepatic bile duct dilatation, and computed tomography scan showed hydronephrosis, dilatation of intra- and extra-hepatic biliary tract, and a right renal complex cyst of more than 9 cm. One can hypothesize a relationship between the abdominal trauma and the increase in size of the renal cyst, which, moreover, had changed its original shape. The patient underwent cefuroxime and metronidazole therapy, with complete recovery from the cholangitis within one week. The treatment of choice would have been surgical excision or, alternatively, an image-guided percutaneous aspiration of the cyst, in order to avoid further episodes of cholangitis. Unfortunately, the patient refused either surgical or more conservative treatment and was lost to follow-up. PMID:17285201

Zardi, Enrico Maria; Malafarina, Vincenzo; Ambrosino, Giovanni; Uwechie, Valentina; Rollo, Massimo; Picardi, Antonio; Afeltra, Antonella; Lumachi, Franco



Consumption of antibiotics in Sweden, 1975 to 1992: pharmacoeconomic and clinical aspects.  


Using official statistics for the consumption of antibiotics in Sweden during the period 1975 to 1991, the pharmacoeconomic consequences were analysed. An increase of more than 25% in Swedish consumption of antibiotics during the study period was found. There is no obvious clinical explanation; indeed, improved hospital hygiene as well as decreased frequencies of some common bacterial infections should have resulted in a decrease in total consumption. Overconsumption was most marked for oral antibiotics. In 1991 the most often used antibiotic, phenoxymethylpenicillin, was given in about 20 million defined daily doses (DDD), corresponding to 2.4 DDDs per member of the population per year. From a pharmacoeconomic viewpoint, this overconsumption is acceptable because the drug has a low price and causes a minimum of severe adverse reactions. More serious is the marked misuse of tetracyclines (12 million DDDs in 1991) and macrolides (5.3 million DDDs in 1991), with which adverse reactions are more common, and where the high consumption has led to increasing frequencies of resistance among common bacterial pathogens. This emergent resistance often leads to a need to use newer more expensive antibiotics, in addition to the costs resulting from therapeutic failures of the initial treatment. Of the parenteral antibiotics, the cephalosporins, particularly cefuroxime, dominate in Sweden. The introduction of 'diagnosis-related groups' (DRGs) for reimbursement of hospitals for in-patient care is likely to result in the development of antibiotic use in 'intensive home care' as has occurred in the US.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10147013

Norrby, S R



[Antibiotic prophylaxis in surgery].  


Infection remains a serious complication after surgical produces. The main risk factors for developing infection are: 1. endogenous-host related, 2. exogenous-produce related, 4. environmental-related ones. Systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications. It is indicated in procedures with incidence of infective complications more as 5%, in clean contaminated wounds and also in produces, in which infection has fatal consequences (vascular surgery, heart surgery, traumatology). The decision to use antibiotic prophylaxis depends upon the operation to be performed, the findings at operations, the general health of the patient and pharmacological and antibacterial properties of the agent. Timing of the first dose (administration not more as 1 hour preoperatively) and duration not more as 24 hours are very important. We use the second generations of cephalosporins (cefuroxim and after antibiotic rotation cefamandol) in antibiotic prophylaxis obligatory in vascular surgery, pacemaker implantation, traumatology and in colorectal surgery (there in combination with metronidasol) with mean infection rate in clean surgical procedures from 0.5 to 1.5%. Complications after antibiotic prophylaxis are very rare. However antibiotic prophylaxis can not compensate the correction of medical problems preoperatively and the meticulous surgical technique. PMID:10847748

Simo, J; Matis, P; Durdík, S; Martinec, A; Kubis, J



[Comparative susceptibility of Ochrobactrum anthropi, Agrobacterium tumefaciens, Alcaligenes faecalis, Alcaligenes denitrificans subsp. denitrificans, Alcaligenes denitrificans subsp. xylosidans and Bordetella bronchiseptica against 35 antibiotics including 17 beta-lactams].  


Ochrobactrum anthropi, formerly known as "Achromobacter sp." or CDC group Vd has been isolated from water, hospital environment (antiseptic solutions, dialysis fluids ... ). O. anthropi is a Gram negative, motile, strictly aerobic, oxydase positive and non-fermentative bacteria with a strong urease activity. The susceptibility of 13 strains of O. anthropi was determined by agar diffusion method and compared to those of type strains of Agrobacterium tumefaciens, Alcaligenes faecalis, Alcaligenes denitrificans subsp. denitrificans, Alcaligenes denitrificans subsp. xylosoxydans and Bordetella bronchiseptica. The MICs of 20 antimicrobial agents confirmed the distinct phenotype susceptibility of O. anthropi. All the strains of O. anthropi are sensitive to imipenem, amikacin, gentamicin, netilmicin, nalidixic acid, pefloxacin, ciprofloxacin, tetracyclin, colistin, sulphonamides and rifampicin and resistant to ampicillin, amoxycillin + clavulanic acid, ticarcillin, mezlocillin, cefuroxime, cefamandol, cefoxitin, cefotaxime, cefoperazon, ceftazidime, cefsulodin, aztreonam, streptomycin, kanamycin, pipemidic acid, chloramphenicol, erythromicin, pristinamycin, trimethoprim and fosfomycin. O. anthropi is implicated in nosocomial infections. O. anthropi was the species with the greatest resistance to beta-lactamins. PMID:7567111

Bizet, C; Bizet, J



[A new method for evaluation of beta-lactamase production of resistant enterobacteriaceae strains (author's transl)].  


Resistant strains of Enterobacteriaceae were investigated with a chemical and microbiological test on beta-lactamase activity. The chemical method was needed as screening-test basing on the enzymatic hydrolysis of the chromogenic cephalosporin compound 87/312. The microbiological test is a modified cup plate method using Staph. aureus SG 511 as sensitive test strain for penicillins and cephalosporins. In one of the two cups of the blood agar plate 20 microliter of the beta-lactam antibiotic, in the other cup 20 microliter of the supernatant of the 24 h broth of the bacterial strain was pipettet. If the lactamase in the supernatant neutralises the antibiotic, a halfemoonlike blank is forming on the left site of the inhibition zone. An unchangeable inhibition zone demonstrates stability of the antibiotic to the enzyme. Each of 10 ampicillin- and/or cephalothin-resistant strains of E. coli, Klebsiella, Enterobacter and Serratia were investigated against 6 penicillins (penicillin G, ampicillin, ticarcillin, mezlocillin, azlocillin, bay k 4999) and 6 cephalosporins (cefoxitin, cefuroxime, cefamandol, cephalothin, cefazolin, cefradine). The microbiological method allows the statement, against which beta-lactam antibiotic the enzyme is effective. A correlation between the beta-lactamase activity and the MIC values in Enterobacteriaceae was not found. PMID:371259

Schassan, H H



Antimicrobial Susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes Isolates and Their Ecological Relationships: Results of a 1-Year (1998-1999) Multicenter Surveillance Study in Spain  

PubMed Central

A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039 S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. For S. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was ?4 ?g/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, ?4 ?g/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae.

Perez-Trallero, E.; Fernandez-Mazarrasa, C.; Garcia-Rey, C.; Bouza, E.; Aguilar, L.; Garcia-de-Lomas, J.; Baquero, F.



Identification of penicillinase producing Neisseria gonorrhoeae in Chile during clinical and microbiological study of gonococcal susceptibility to antimicrobial agents.  

PubMed Central

The first penicillinase producing isolates of Neisseria gonorrhoeae (PPNG) identified in Chile were discovered during a clinical and microbiological study to compare the efficacy of penicillin (4.8 MIU aqueous procaine penicillin G plus 1 g oral probenecid) and tetracycline (1.5 g followed by 500 mg four times daily for four days) treatment regimens for acute uncomplicated gonorrhoea. Penicillin treatment was effective in 93.1% (282) of 303 patients, whereas tetracycline was effective in 98.3% (233) of 237 patients. Six of the penicillin treatment failures were attributable to PPNG strains. In all, 21 PPNG strains were identified during the study. They were genetically identical, having a wild type auxotype, a WII/III serotype (serovar Bajk), and carrying cryptic and transfer plasmids and an Asian type penicillinase producing plasmid. In addition, 674 non-PPNG isolates were tested for their susceptibility to eight antimicrobials. Over 95% were sensitivie to 1 mg/l of penicillin, ampicillin, cefotaxime, cefuroxime, and erythromycin, over 90% were sensitive to 1 mg/l of tetracycline and 2 mg/l of thiamphenicol, and all were sensitive to spectinomycin. Of 226 non-PPNG isolates characterised for plasmid content and auxotype, 90% (205) were either wild type or proline requiring, 67% (153) carried only the cryptic plasmid, and a further 31% (71) carried both cryptic and transfer plasmids. Unusually, three of four isolates lacking the cryptic plasmid carried only the transfer plasmid. Images

Garcia Moreno, J; Dillon, J R; Arroyave, R; Maldonado, A; Fich, F; Salvo, A; Villalobos, D; Vincent, P; Pauze, M



A Case of Giant Hepatic Hydatid Cyst Infected with Morganella morganii and the Literature Review  

PubMed Central

Hydatid cyst disease is a common worldwide zoonosis. Most of the cysts are located in the liver. Abscess formation due to infection of the cyst is an important complication. M. morganii, a Gram-negative Bacillus, is a quite rare cause of liver abscess. A 77-year-old woman was admitted to hospital with complaints of fever, chills, nausea, vomiting, loss of appetite, and abdominal pain located in the right-upper quadrant. Her history was positive for hepatic hydatid cyst disease ten years ago. Physical examination revealed a painful mass filling the right-upper quadrant and extending down to umbilicus. Indirect hemagglutinin test for hydatid cyst was positive at a titer of 1/320. Giant liver abscess due to infected hydatid cyst was found in computed tomography scan. Surgeons performed cystectomy and cholecystectomy. Cefazoline, cefuroxime, and metronidazole were administered empirically, but all the three agents were replaced with intravenous ceftriaxone after M. morganii was isolated from the cultures of the abscess material. Clinical signs of the patient resolved at the second week of treatment, and she was discharged.

Hakyemez, Ismail Necati; Sit, Mustafa; Aktas, Gulali; Tas, Tekin; Mengeloglu, F?rat Zafer; Kucukbayrak, Abdulkadir



Multidrug-Resistant Streptococcus pneumoniae Serotype 6D Clones in South Korea  

PubMed Central

To investigate the characteristics of main Streptococcus pneumoniae clones of serotype 6D (ST282 and ST3171) in South Korea, antimicrobial susceptibility testing was performed, and 11 genes around the cps locus were sequenced on ST2826D, ST31716D, and ST816A isolates. The antimicrobial susceptibility patterns were very similar between clones belonging to the same clonal complex, ST816A and ST2826D; nonsusceptibilities to penicillin and cefuroxime, high MICs of ceftriaxone, and high resistance rates to trimethoprim-sulfamethoxazole. However, ST31716D isolates showed resistance to only macrolides and clindamycin. The sequences of 11 genes around the cps locus indicated the same genetic backgrounds between the ST816A and ST2826D isolates. On the other hand, ST31716D isolates showed nucleotide and amino acid differences from ST816A and ST2826D isolates in most genes, indicating a different genetic background. The mosaic structure of dexB gene in ST2826D isolates indicated that recombination might occur in the dexB gene. Our results suggest that the multidrug-resistant ST2826D pneumococcal clone has emerged by serial genetic recombination, including capsular switch.

Baek, Jin Yang



Multi-drug resistant gram-negative enteric bacteria isolated from flies at Chengdu Airport, China.  


We collected flies from Chengdu Shuangliu International Airport to examine for the presence of bacteria and to determine the sensitivity patterns of those bacteria. A total of 1,228 flies were collected from 6 sites around Chengdu Shuangliu International Airport from April to September 2011. The predominant species was Chrysomya megacephala (n=276, 22.5%). Antimicrobial-resistant gram-negative enteric bacteria (n=48) were isolated from flies using MacConkey agar supplemented with cephalothin (20 microg/ml). These were identified as Escherichia coli (n=37), Klebsiella pneumoniae (n=6), Pseudomonas aeruginosa (n=3) and Aeromonas hydrophila (n=2). All isolated bacteria were tested for resistance to 21 commonly used antimicrobials: amoxicillin (100%), ticarcillin (100%), cephalothin (100%), cefuroxime (100%), ceftazidime 1 (93.8%), piperacillin (93.8%), cefotaxime (89.6%), ticarcillin-clavulanate (81.3%), trimethoprim-sulfamethoxazole (62.5%), ciprofloxacin (54.2%), gentamicin (45.8%), cefepime (39.6%), tobramycin (39.6%), ceftazidime (22.9%), cefoxitin (16.7%), amikacin (16.7%), netilmicin (14.6%), amoxicillin-clavulanate (6.3%) and piperacillin-tazobactam (2.1%). No resistance to meropenem or imipenem was observed. Antibiotic resistance genes among the isolated bacteria were analyzed for by polymerase chain reaction. Thirty of the 48 bacteria with resistance (62.5%) possessed the blaTEM gene. PMID:24450236

Liu, Yang; Yang, Yu; Zhao, Feng; Fan, Xuejun; Zhong, Wei; Qiao, Dairong; Cao, Yi



Antibiotic susceptibility of Riemerella anatipestifer field isolates.  


Kirby-Bauer tests were used to analyze the antibiotic resistance of 224 isolates of Riemerella anatipestifer isolated between 1998 and 2005. Among the 36 antibiotics tested, 50% of the analyzed isolates were resistant to ampicillin, ceftazidime, aztreonam, cefazolin, cefepime, cefuroxime, oxacillin, penicillin G, rifampin, and trimethoprim/sulfamethoxazole. Higher levels of resistance were detected for aztreonam, cefepime, oxacillin, penicillin G, ceftazidime, and trimethoprim/sulfamethoxazole (87.8%, 64.3%, 88.6%, 86.9%, 75.9%, and 79.2% resistance, respectively). The lowest resistance rates were observed for amikacin (9.5%), cefoperazone (7.2%), imipenem (3.2%), and neomycin (9.5%). Four isolates were found to be resistant to 29 different antimicrobials. Riemerella anatipestifer drug resistance profiles changed over time, and the only consistent patterns observed were the resistance of R. anatipestifer to cefoperazone, piperacillin, spectinomycin, and aztreonam. In addition to determining the antibiotic-resistance profiles of R. anatipestifer isolates, we also examine the therapeutic efficacy of these antibiotics against lethal R. anatipestifer infection in ducks in vivo. According to these data, we have extrapolated an antibiotic treatment approach for veterinarians attending flocks of ducks. These data suggest that disk-diffusion analyses can be extrapolated to predict in vivo efficacy, thereby facilitating the identification of effective antibacterial treatments and potentially diminishing the irresponsible use of antibiotics. PMID:20095163

Zhong, Chong Yue; Cheng, An Chun; Wang, Ming Shu; Zhu, De Kang; Luo, Qi Hui; Zhong, Chuan De; Li, Ling; Duan, Ze



Antibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections.  


Isolates from urine samples obtained during 1999 were identified and their susceptibility to antimicrobial agents studied along with any production of extended-spectrum beta-lactamases (ESBL) by Escherichia coli and Klebsiella pneumoniae. A total of 13774 samples were analysed using an automatic system for the detection of bacterial ATP (Coral, USA). Of these samples, 49% were reported to be positive and uncontaminated; bacteria most frequently isolated were E. coli (47%), Proteus mirabilis (7%), Enterococcus faecalis (6%) and K. pneumoniae (5%). The susceptibility studies showed 37% E. coli strains resistant to amoxycillin+clavulanate 33% to cotrimoxazole and 22% to ciprofloxacin. Seven strains of E. coli produced ESBL. Thirteen per cent of strains were resistant to cefuroxime but only (1%) to fosfomycin. Resistance to nitrofurantoin in K. pneumoniae was 38%. P. mirabilis showed 52% resistance to cotrimoxazole and 13% Staphylococcus aureus, were methicillin-resistant. E. faecalis did not show any special resistance to normal medication. Fosfomycin continued to show high activity against Gram-negative bacilli. However, enterococci, some species of staphylococci and yeasts were difficult to treat empirically. ESBL were detected in the isolates of E. coli and there were some methicillin-resistant strains of S. aureus. PMID:11673032

Daza, R; Gutiérrez, J; Piédrola, G



Thoracic empyema in children: Clinical presentation, microbiology analysis and therapeutic options.  


Thoracic empyema is an accumulation of purulent fluid in the pleural space presenting as a complication of bacterial pneumonia. The aims of the study were to present the incidence, demographic results, clinical presentation, laboratory and microbiology results, imaging and the therapeutic options. From January 1992 until December 2009 we collected data of children hospitalized with empyema in our medical center in north of Israel. Empyema was found in 53 pediatric patients. The median age of the patients was 3 years and 31 (58%) were male. Forty one (77%) of the cases were diagnosed in the last nine years. Fever, cough and respiratory distress were the most frequent clinical signs. In 29 (55%) patients pleural effusion was found at admission. Chest ultrasound was performed in 44 (83%) of the patients. Causative organisms were confirmed by culture in 35 patients. Positive culture was found in 17 (32%) patients in the pleural fluid. Streptococcus pneumoniae was the leading pathogen. The drugs the patients received at admission were penicillin in 21 cases, cefuroxime in19 cases and ceftriaxone in 11 cases. During hospitalization a change of antibiotic therapy was required, using mainly ceftriaxone and clindamycin. The pleural purulent fluid was drained by video assisted thoracoscopy surgery in 34 (64%) patients. All the children recovered. The incidence of empyema as a complication of community acquired pneumonia had increased in the last decade in our region. Streptococcus pneumoniae is the most common pathogen. Third generation cephalosprins and clindamycin can be suggested as a good empiric treatment. PMID:24486171

Sakran, Waheeb; Ababseh, Zahr El Din; Miron, Dan; Koren, Ariel



Natural antibiotic susceptibility of Ewingella americana strains.  


The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics was examined. MIC values were determined using a microdilution procedure in cation-adjusted Mueller-Hinton broth. Evaluation of natural antibiotic susceptibility was performed applying the German standard (where applicable). Beta-lactamases were examined with a conventional nitrocefin colony testing procedure, activity and induction assays, and SDS-PAGE. Ewingella strains were naturally resistant or of intermediate susceptibility to cefaclor, loracarbef, cefazoline, cefuroxime, cefoxitin, benzylpenicillin, oxacillin, fosfomycin, erythromycin, roxithromycin, clarithromycin, lincosamides, dalfopristin-quinupristin, ketolides, linezolid, glycopeptides, fusidic acid and rifampicin. Uniform natural sensitivity was found with acylureidopenicillins except for azlocillin, ticarcillin, several cephalosporins, carbapenems, aztreonam, tetracyclines, aminoglycosides, quinolones, azithromycin, folate-pathway inhibitors and chloramphenicol. Strains of E. americana were naturally sensitive or of intermediate susceptibility to aminopenicillins (with and without beta-lactamase inhibitors), azlocillin and nitrofurantoin. All ewingellae yielded beta-lactamases; testing of representative strains revealed that these enzymes belong to Ambler class C. Inducibility of beta-lactamase was shown for E. americana ATCC 33852T, CCUG 35675 and CCUG 42782. The present study describes a database concerning the natural susceptibility of E. americana strains to a range of antibiotics, which can be applied to validate forthcoming antibiotic susceptibility tests of these bacteria. It enlarges the number of Enterobacteriaceae expressing naturally-occurring AmpC beta-lactamases. PMID:14598935

Stock, I; Sherwood, K J; Wiedemann, B



Antimicrobial Susceptibilities of Aeromonas spp. Isolated from Environmental Sources?  

PubMed Central

Aeromonas spp. are ubiquitous aquatic bacteria that cause serious infections in both poikilothermic and endothermic animals, including humans. Clinical isolates have shown an increasing incidence of antibiotic and antimicrobial drug resistance since the widespread use of antibiotics began. A total of 282 Aeromonas pure cultures were isolated from both urban and rural playa lakes in the vicinity of Lubbock, Texas, and several rivers in West Texas and New Mexico. Of these, at least 104 were subsequently confirmed to be independent isolates. The 104 isolates were identified by Biolog and belonged to 11 different species. The MICs of six metals, one metalloid, five antibiotics, and two antimicrobial drugs were determined. All aeromonads were sensitive to chromate, cobalt, copper, nickel, zinc, cefuroxime, kanamycin, nalidixic acid, ofloxacin, tetracycline, and sulfamethoxazole. Low incidences of trimethoprim resistance, mercury resistance, and arsenite resistance were found. Dual resistances were found in 5 of the 104 Aeromonas isolates. Greater numbers of resistant isolates were obtained from samples taken in March versus July 2002 and from sediment versus water. Plasmids were isolated from selected strains of the arsenite- and mercury-resistant organisms and were transformed into Escherichia coli XL1-Blue MRF?. Acquisition of the resistance phenotypes by the new host showed that these resistance genes were carried on the plasmids. Mercury resistance was found to be encoded on a conjugative plasmid. Despite the low incidence of resistant isolates, the six playa lakes and three rivers that were sampled in this study can be considered a reservoir for antimicrobial resistance genes.

Huddleston, Jennifer R.; Zak, John C.; Jeter, Randall M.



Betalactam therapy and intestinal flora.  


Betalactams, mainly when orally administered, may lead to intestinal flora modifications related to their spectrum of activity, rate of absorption and degradation. therefore it is important to investigate the possible influence of recently developed oral cephem derivatives on normal human microflora. We have investigated the impact on normal human intestinal flora in a 10-day course with cefetamet-pivoxil (CET, 500 mg BID) in comparison to cefixime (CFX, 400 mg qD) or cefuroxime axetil (CA, 250 mg BID) in 24 patients suffering from acute exacerbation of chronic bronchitis. Stool specimens were taken before (day 0), at the end (day 10) and 14 days after treatment (day 24) and quali-quantitative microflora composition was determined with a detection limit of 10 CFU/g dry weight. Treatment with CET caused slight and non-significant modifications of normal intestinal flora. On the contrary CFX and CA significantly affect Enterobacteriaceae and clostridia with a concomitant increase in enterococci for CFX. With both CFX and CA there was a new appearance of Salmonella spp. as well as Clostridium difficile in 4 and 2 cases, respectively. Therefore CET seems to affect normal bowel flora minimally in comparison to other oral cephalosporins. This aspect might contribute to the low incidence of GI related side effects in patients treated with CEt for longer than 1 week. PMID:8618110

Novelli, A; Mazzei, T; Fallani, S; Dei, R; Cassetta, M I; Conti, S



Isolation and antibiotic susceptibility of E. coli from urinary tract infections in a tertiary care hospital.  


Objective: The study was conducted to isolate and determine the antibiotic resistance in E. coli from urinary tract infections in a tertiary care hospital, Lahore. Methods: Urine samples (n=500) were collected from patients with signs and symptoms of Urinary tract infections. Bacteria were isolated and identified by conventional biochemical profile. Antibiotic resistance pattern of E. coli against different antibiotic was determined by Kirby-Baur method. Results: Bacterial etiological agent was isolated from 402 samples with highest prevalence of E. coli (321, 80%) followed by Staphylococcus aureus (9.4%), Proteus species (5.4%) and Pseudomonas species (5.2%). The E. coli were highly resistant to penicillin (100%), amoxicillin (100%) and cefotaxime (89.7%), followed by intermediate level of resistance to ceftazidime (73.8%), cephradine (73.8%), tetracycline (69.4%), doxycycline (66.6%), augmentin (62.6%), gentamycin (59.8%), cefuroxime (58.2%), ciprofloxacin (54.2%), cefaclor (50%), aztreonam (44.8%), ceftriaxone (43.3%), imipenem (43.3%), and low level of resistance to streptomycin (30%), kanamycin (19.9%), tazocin (14%), amikacin (12.7%) and lowest to norfloxacin (11.2%). Out of 321 E. coli isolates, 261 (81%) were declared as multiple drug resistant and 5 (1.5%) were extensive drug resistant. Conclusion: It is concluded that most of the urinary tract infections in human are caused by multiple drug resistant E. coli. PMID:24772149

Sabir, Sumera; Ahmad Anjum, Aftab; Ijaz, Tayyaba; Asad Ali, Muhammad; Ur Rehman Khan, Muti; Nawaz, Muhammad



Evidence-based treatment limitations prevent any therapeutic recommendation for acute poststreptococcal glomerulonephritis in children.  


The majority of children with the epidemic form of acute post-streptococcal glomerulonephritis (APSGN) have an excellent prognosis, which contrasts with the poor long-term outcome of sporadic cases. Therapy is largely supportive. Rarely, the disease shows long-term complications, worsening to chronic kidney disease requiring long-term interventional measures. To compare the effectiveness of different therapeutic strategies for the prevention and treatment of APSGN in childhood, the authors reviewed randomized controlled trials on the prevention and treatment of APSGN in children. Nine studies fit the inclusion criteria. Primary outcomes were the development of APSGN, the effectiveness of medication for controlling hypertension, and the development of chronic renal failure in patients with crescentic glomerulonephritis. No advantages of antimicrobials (cefuroxim, ceftibuten, and others) given for 5 days were found over penicillin V given for 10 days (4 trials). Nifedipine showed advantages in controlled acute hypertension (1 trial). ACE inhibitors (captopril and enalapril) had better control of blood pressure and echocardiographic changes than other antihypertensive drugs/diuretics (2 trials). The use of combined immunosuppressants for crescentic poststreptococcal glomerulonephritis showed no advantages over supportive therapy alone (1 study). The studies were of small number and with limitations that seriously weaken the results. PMID:20357732

Zaffanello, Marco; Cataldi, Luigi; Franchini, Massimo; Fanos, Vassilios



Development and validation of a fast and uniform approach to quantify ?-lactam antibiotics in human plasma by solid phase extraction-liquid chromatography-electrospray-tandem mass spectrometry.  


Monitoring of plasma antibiotic concentrations is necessary for individualization of antimicrobial chemotherapy dosing in special patient populations. One of these special populations of interest are the post-bariatric surgery patients. Until today, little is known on the effect of this procedure on drug disposition and efficacy. Therefore, close monitoring of antimicrobial plasma concentrations in these patients is warranted. A fast and uniform ultra-high-performance liquid chromatography (UPLC) method with tandem mass spectrometric detection (MS/MS) has been developed and qualified for the simultaneous quantification of ?-lactam antibiotics in human plasma. Compounds included in this multi-component analysis are: amoxicillin, ampicillin, phenoxymethylpenicillin, piperacillin, cefuroxime, cefadroxil, flucloxacillin, meropenem, cefepime, ceftazidime, tazobactam, linezolid and cefazolin. After spiking of five different stable isotope labelled internal standards, plasma samples were prepared for UPLC-MS/MS analysis by mixed-mode solid phase extraction. The developed method was proven to be free of (relative) matrix effects and proved to be reliable for the quantification of 12 out of 13 ?-lactam antibiotics. As a proof of concept the method has been applied to plasma samples obtained from a healthy volunteer treated with amoxicillin. The analytical method is suitable for use in a therapeutic drug monitoring setting, providing the clinician with reliable measurements on ?-lactam antibiotic plasma concentrations in a timely manner. PMID:23200389

Colin, Pieter; De Bock, Lies; T'jollyn, Huybrecht; Boussery, Koen; Van Bocxlaer, Jan



Epidemiology and antibiotic resistance of gram-negative urinary pathogens in pediatric patients.  


In order to determine the etiological agents and the rate of resistance to various antibiotics, 209 consecutive gram-negative bacteria isolated from children admitted to Hacettepe University Children's Hospital with urinary tract infections were investigated over a three-month period. Of these, 46 (22%) were nosocomial isolates. The most frequently isolated organism was E.coli (n: 141) followed by Klebsiella spp. (39), Proteus spp. (19), Pseudomonas spp. (8) and Enterobacter spp. (2). In vitro susceptibilities were evaluated by microbroth dilution method, following NCCLS guidelines. Overall, 75 percent of the isolates were resistant to ampicillin, 52 percent were resistant to TMP/SMX and 25 percent to cefuroxime. Amikacin was the most active aminoglycoside; 93 percent of the isolates were susceptible to this agent, while resistance to gentamicin was 21 percent. Resistance to ceftazidime and ceftriaxone was 12 percent and 19 percent, respectively. Overall, resistance to imipenem was one percent and to ciprofloxacin three percent. These in vitro results should be taken into account before initiating empirical therapy; broad spectrum antibiotics should not be used if the isolate is susceptible to the older drugs in order to prevent the increase in resistance. PMID:10770674

Gür, D; Kanra, G; Ceyhan, M; Seçmeer, G; Kanra, B; Kaymako?lu, I



TelA Contributes to the Innate Resistance of Listeria monocytogenes to Nisin and Other Cell Wall-Acting Antibiotics?  

PubMed Central

Nisin is a class I bacteriocin (lantibiotic), which is employed by the food and veterinary industries and exhibits potent activity against numerous pathogens. However, this activity could be further improved through the targeting and inhibition of factors that contribute to innate nisin resistance. Here we describe a novel locus, lmo1967, which is required for optimal nisin resistance in Listeria monocytogenes. The importance of this locus, which is a homologue of the tellurite resistance gene telA, was revealed after the screening of a mariner random mutant bank of L. monocytogenes for nisin-susceptible mutants. The involvement of telA in nisin resistance was confirmed through an analysis of a nonpolar deletion mutant. In addition to being 4-fold-more susceptible to nisin, the ?telA strain was also 8-fold-more susceptible to gallidermin and 2-fold-more susceptible to cefuroxime, cefotaxime, bacitracin, and tellurite. This is the first occasion upon which telA has been investigated in a Gram-positive organism and also represents the first example of a link being established between a telA gene and resistance to cell envelope-acting antimicrobials.

Collins, Barry; Joyce, Susan; Hill, Colin; Cotter, Paul D.; Ross, R. Paul



TelA contributes to the innate resistance of Listeria monocytogenes to nisin and other cell wall-acting antibiotics.  


Nisin is a class I bacteriocin (lantibiotic), which is employed by the food and veterinary industries and exhibits potent activity against numerous pathogens. However, this activity could be further improved through the targeting and inhibition of factors that contribute to innate nisin resistance. Here we describe a novel locus, lmo1967, which is required for optimal nisin resistance in Listeria monocytogenes. The importance of this locus, which is a homologue of the tellurite resistance gene telA, was revealed after the screening of a mariner random mutant bank of L. monocytogenes for nisin-susceptible mutants. The involvement of telA in nisin resistance was confirmed through an analysis of a nonpolar deletion mutant. In addition to being 4-fold-more susceptible to nisin, the ?telA strain was also 8-fold-more susceptible to gallidermin and 2-fold-more susceptible to cefuroxime, cefotaxime, bacitracin, and tellurite. This is the first occasion upon which telA has been investigated in a Gram-positive organism and also represents the first example of a link being established between a telA gene and resistance to cell envelope-acting antimicrobials. PMID:20713661

Collins, Barry; Joyce, Susan; Hill, Colin; Cotter, Paul D; Ross, R Paul



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



Automated ribotyping and antibiotic resistance determining of Bacillus spp from conjunctiva of diabetic patients.  


Objective(s): We aimed to characterize the phenotype and genotype of Bacillus spp isolated from diabetic patients' eyes, by studying the drug sensitivity patterns with a disc-diffusion method. Materials and Methods: Fifty eyes of 25 patients with type II diabetes mellitus, with at least 10 years of diabetes history, were included in the study. We analyzed the eyes for the presence of Bacillus spp.; presumptive isolates were identified by morphological, and biochemical tests, and confirmed by the VITEK system. Automated EcoRI ribotyping was performed with a RiboPrinter(®) Microbial Characterization System. We determined the antibiotic resistance of the isolates by the Kirby-Bauer disc diffusion test. Results: Seven out of 25 patients were on insulin treatment; 7 on oral anti-diabetic medication; and 11 on combination therapy of insulin and oral medications. Among the 28 Bacillus spp isolates, 14 were B. cereus, 11 were B. pumilus, 2 were B. mojavensis and 1 was B. subtilis. Almost all the strains were either resistant or multiresistant, particularly towards cefuroxime, methicillin, and ceftazidime. Conclusion: Diabetic patients seem to be more prone to B. cereus infections than healthy individuals. It would be greatly beneficial to understand and recognize the prevalence of microorganisms and their resistance patterns for better outcome in ocular surgeries. PMID:24711899

Argun K?vanç, Sertaç; K?vanç, Merih; Güllülü, Gülay



[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



A simple assay to screen antimicrobial compounds potentiating the activity of current antibiotics.  


Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract of Juglans regia tree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract of J. regia bark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria, Salmonella typhi or enteropathogenic E. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as controls. The results showed a significant increase (>30%) in the zone of inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with bacteria incubated with the antibiotics/extract alone. In conclusion, our assay is able to detect either synergistic or additive action of J. regia extract against multiple drug-resistant bacteria when tested with a range of antibiotics. PMID:23865073

Iqbal, Junaid; Siddiqui, Ruqaiyyah; Kazmi, Shahana Urooj; Khan, Naveed Ahmed



[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



Antibiotic resistance and molecular typing among cockle (Anadara granosa) strains of Vibrio parahaemolyticus by polymerase chain reaction (PCR)-based analysis.  


Genomic DNA of Vibrio parahaemolyticus were characterized by antibiotic resistance, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis. These isolates originated from 3 distantly locations of Selangor, Negeri Sembilan and Melaka (East coastal areas), Malaysia. A total of 44 (n = 44) of tentatively V. parahaemolyticus were also examined for the presence of toxR, tdh and trh gene. Of 44 isolates, 37 were positive towards toxR gene; while, none were positive to tdh and trh gene. Antibiotic resistance analysis showed the V. parahaemolyticus isolates were highly resistant to bacitracin (92%, 34/37) and penicillin (89%, 33/37) followed by resistance towards ampicillin (68%, 25/37), cefuroxime (38%, 14/37), amikacin (6%, 2/37) and ceftazidime (14%, 5/37). None of the V. parahaemolyticus isolates were resistant towards chloramphenicol, ciprofloxacin, ceftriaxone, enrofloxacin, norfloxacin, streptomycin and vancomycin. Antibiogram patterns exhibited, 9 patterns and phenotypically less heterogenous when compared to PCR-based techniques using ERIC- and RAPD-PCR. The results of the ERIC- and RAPD-PCR were analyzed using GelCompare software. ERIC-PCR with primers ERIC1R and ERIC2 discriminated the V. parahaemolyticus isolates into 6 clusters and 21 single isolates at a similarity level of 80%. While, RAPD-PCR with primer Gen8 discriminated the V. parahaemolyticus isolates into 11 clusters and 10 single isolates and Gen9 into 8 clusters and 16 single isolates at the same similarity level examined. Results in the presence study demonstrated combination of phenotypically and genotypically methods show a wide heterogeneity among cockle isolates of V. parahaemolyticus. PMID:24068534

Sahilah, A M; Laila, R A S; Sallehuddin, H Mohd; Osman, H; Aminah, A; Ahmad Azuhairi, A



Antibiotic susceptibility of potentially probiotic Bifidobacterium isolates from the human gastrointestinal tract.  


Sixteen Bifidobacterium isolates from the human gastrointestinal tract were assayed for susceptibility to 44 antibiotics by soft agar overlay disc diffusion on TPY agar. Five isolates (3/7 B. bifidum and 2/3 B. breve) exhibited atypical antibiotic susceptibility profiles. Poor growth in the agar overlay accounted for susceptibility of B. bifidum but not B. breve isolates. All other isolates were resistant to cefoxitin (30 micrograms), aztreonam (30 micrograms), vancomycin (30 micrograms), amikacin (30 micrograms), gentamicin (10 micrograms), kanamycin (30 micrograms), streptomycin (10 micrograms), fusidic acid (10 micrograms), trimethoprim (5 micrograms), norfloxacin (10 micrograms), nalidixic acid (30 micrograms), metronidazole (5 micrograms), polymyxin B (300 micrograms) and colistin sulphate (10 micrograms), and they were susceptible to the six penicillins studied, cephalothin (30 micrograms), cefuroxime (30 micrograms), cefaclor (30 micrograms), ceftizoxime (30 micrograms), cefotaxime (30 micrograms), bacitracin (10 micrograms), chloramphenicol (30 micrograms), erythromycin (15 micrograms), clindamycin (2 micrograms), rifampicin (5 micrograms) and nitrofurantoin (300 micrograms). In addition, they varied in their susceptibility to cephradine (30 micrograms), cephazolin (30 micrograms), cefoperazone (75 micrograms), ceftriaxone (30 micrograms), ofloxacin (5 micrograms) and furazolidone (15 micrograms). They were resistant, or only marginally moderately susceptible, to ceftazidime (30 micrograms), netilmicin (10 micrograms), sulphamethoxazole (100 micrograms), cotrimoxazole (25 micrograms) and ciprofloxacin (5 micrograms), and susceptible or marginally moderately susceptible to tetracycline (30 micrograms). All B. bifidum isolates were susceptible to cefixime (5 micrograms). Four microorganism-drug combinations were evaluated for beta-lactamase activity but its absence suggested that cell wall impermeability was responsible for cephalosporin resistance among bifidobacteria. The antibiotic susceptibility of B. animalis 25527T was similar to that of the human isolates. PMID:9674160

Charteris, W P; Kelly, P M; Morelli, L; Collins, J K



Natural antimicrobial susceptibilities of strains of 'unusual' Serratia species: S. ficaria, S. fonticola, S. odorifera, S. plymuthica and S. rubidaea.  


The natural susceptibility to 71 antibiotics of 104 Serratia strains of Serratia ficaria (n = 15), Serratia fonticola (n = 18), Serratia odorifera (n = 16), Serratia plymuthica (n = 32) and Serratia rubidaea (n = 23) was examined. MICs were determined using a microdilution procedure in IsoSensitest broth for all the strains and in cation-adjusted Mueller-Hinton broth for some strains. With few exceptions, all species tested were uniformly naturally resistant to penicillin G, oxacillin, cefazolin, cefuroxime, all tested macrolides, lincosamides, streptogramins, glycopeptides, fusidic acid and rifampicin, and naturally sensitive to several aminoglycosides, piperacillin, piperacillin/tazobactam, carbapenems, some cephalosporins, fluoroquinolones and folate-pathway inhibitors. Major species-related differences in natural susceptibility affecting clinical assessment criteria were seen with tetracyclines, some aminoglycosides, aminopenicillins, ticarcillin, cefaclor, loracarbef, cefoxitin, pipemidic acid, chloramphenicol, nitrofurantoin and fosfomycin. Differences in susceptibility dependent on the medium were seen with macrolides, tetracycline, fosfomycin and some beta-lactams. The natural antibiotic susceptibility patterns suggest novel species-specific mechanisms of antibiotic resistance. Uncharacterized species-specific aminoglycoside-modifying enzymes and multidrug efflux systems affecting tetracyclines, quinolones and chloramphenicol are probably responsible for some of the phenotypes observed. The natural amoxicillin sensitivity of several strains of some species combined with natural resistance to some narrow-spectrum cephalosporins indicate the expression of naturally occurring beta-lactamases with unique substrate profiles. beta-Lactamases of representative strains of each species were characterized phenotypically and genotypically. It was shown that all species expressed naturally occurring AmpC beta-lactamases and, with respect to S. fonticola, also a species-specific class A beta-lactamase. Inducibility of these enzymes was shown in all species with the exception of S. rubidaea and four of five strains of S. plymuthica. PMID:12654765

Stock, Ingo; Burak, Sonja; Sherwood, Kimberley Jane; Gruger, Thomas; Wiedemann, Bernd



In Vitro Activities of Oral ?-Lactams at Concentrations Achieved in Humans against Penicillin-Susceptible and -Resistant Pneumococci and Potential to Select Resistance  

PubMed Central

The ?-lactam susceptibilities of 65 strains of Streptococcus pneumoniae for which penicillin MICs covered a broad range were assessed. The order of potency was amoxicillin (AMX) = amoxicillin-clavulanate (AMC) > penicillin G > cefpodoxime (CPO) > cefuroxime (CXM) > cefprozil > cefaclor > loracarbef > cefixime. No decrease in susceptibility was seen following repeated subculture of two penicillin-susceptible strains of S. pneumoniae in AMX, AMC, cefaclor, or loracarbef, whereas repeated exposure to CPO and CXM resulted in 4- to 32-fold decreases in susceptibility for both strains. When one of these strains was exposed to concentrations of CPO, CXM, AMX, and AMC achieved in the serum of humans following the administration of an oral dose, all agents were rapidly bactericidal, with no decrease in susceptibility up to 72 h. This was consistent with antibiotic concentrations exceeding the MICs for 100% of the dosing interval. For a penicillin-resistant strain, MICs were exceeded for 29% of the 12-h dosing interval for 500 mg of AMX, 42% of the interval for AMC with 875 mg of AMX and 125 mg of clavulanate (875/125 mg of AMC) 21% of the interval for 500 mg of CXM, and 0% of the interval for 200 mg of CPO. Consequently, only 875/125 mg of AMC produced a sustained bactericidal effect. A four- to eightfold reduction in susceptibility to CPO and CXM and cross-resistance with cefotaxime, but not penicillin or AMC, were selected following exposure to simulated serum CPO and CXM concentrations. In addition, AMX and AMC were the only agents which consistently produced a >99% reduction in bacterial numbers in time-kill studies using concentrations of antibiotic achieved in middle ear fluid for all three strains of penicillin-resistant S. pneumoniae tested.

Thorburn, Christine E.; Knott, Sarah J.; Edwards, David I.



Comparison of the pharmacokinetics of cefamandole and other cephalosporin compounds.  


The pharmacokinetic properties of cefamandole were determined and compared with the properties of other cephalosporin agents. Cefamandole was found to be approximately 70% bound to protein. The mean peak concentration in serum after intramuscular (im) injection of 1 g of cefamandole was 20 microgram/ml at 0.5 hr, whereas the level at 6 hr was 1 microgram/ml. After intravenous (iv) infusion of 1 g of cefamandole, levels in serum ranged from 68 to 147 microgram/ml depending on the period of infusion. At 4 hr after infusion, levels were less than 1 microgram/ml. Probenecid elevated serum levels and prolonged excretion. The half-life (t1/2) of cefamandole after im injection ranged from 1 to 1.5 hr and from 0.45 to 1.2 hr after iv injection. Rates of serum and renal clearance of cefamandole ranged from 210 to 300 microliter/min per 1.73 m2. The apparent volume of distribution ranged from 12.4 to 17.9 liters/1.73 m2. Urinary excretion was rapid, with 60% of a dose excreted in the first 2 hr after injection. In 6 hr 90% of a dose was excreted. The pharmacokinetic properties of cefamandole were similar to those of cephalothin and cefoxitin, but the serum t1/2 was shorter than that reported for cefazolin and cefuroxime. Correlation of in vitro studies with pharmacokinetic properties revealed that cefamandole would inhibit most susceptible gram-positive and gram-negative bacteria if given by suggested im or iv regimens. PMID:650006

Neu, H C



Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure.  


To compare the efficacy of a selective parenteral and enteral antimicrobial regimen in patients with fulminant liver failure, we classified 104 patients on reaching grade II encephalopathy as infected or non-infected. Patients who were infected were randomly assigned to receive IV cefuroxime (group 1) or selective parenteral and enteral antimicrobial regimen (group 2). Noninfected patients were randomly selected to receive either selective parenteral and enteral antimicrobial regimen (group 3) or no initial antimicrobials until clinically indicated (group 4). The four groups were comparable regarding age, sex, cause of disease, coma grade, international normalization ratio, presence of kidney failure and indicators of poor prognosis on admission to the study. Clinical parameters such as white cell count, temperature or changes in the chest radiograph, which were used to stratify patients into those infected or not, were not good predictors of infection because early infection rates were similar in the two groups. Three patients died within 24 hr and were excluded from the analysis. We found 42 microbiologically confirmed infections: group 1, 6 of 21; group 2, 8 of 21; group 3, 9 of 28; and group 4, 19 of 31. A reduction in infection was seen between groups 3 and 4 (p < 0.05). Patients receiving the selective parenteral and enteral antimicrobial regimen (groups 2 and 3) had fewer infections than the control group (group 4) (p < 0.005). Groups receiving early antimicrobial therapy (groups 1, 2 and 3) had a lower incidence of infection compared with group 4 (p < 0.0005). Overall, 55.5% survived, with no significant difference between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8428715

Rolando, N; Gimson, A; Wade, J; Philpott-Howard, J; Casewell, M; Williams, R



[Treatment of community-acquired pneumonia in adults].  


Appropriate antibiotic treatment reduces the duration of symptoms associated to pneumonia, the risk of complications and mortality. In most cases, it is not possible to identify the etiologic agent so antibiotic treatment is empirically prescribed. In Chile, one third of Streptococcus pneumoniae strain isolates has diminished susceptibility to penicillin; in-vitro erythromycin resistance is about 10-15% and cefotaxime resistance 2-10%. It is recommended to classify patients with community acquired pneumonia in four risk categories: Group 1: patients under 65 years without co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin 1 g TID, 7 days. Group 2: patients over 65 years and / or co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID, or cefuroxime 500 mg BID, 7 days. Group 3: patients admitted to general wards with criteria of moderate severity. Treatment: ceftriaxone 1-2 g once a day or cefotaxime 1 g TID, IV, 7-10 days. Group 4: patients with severe CAP that must be interned into ICU. Treatment: ceftriaxone 2 g once a day or cefotaxime 1 g TID, IV, associated to erythromycin 500 QID, levofloxacin 500-1.000 mg once a day, or moxifloxacin 400 mg/once a day, IV, 10-14 days. In the presence of allergy to or treatment failure with betalactam drugs and/or positive serology for Mycoplasma, Chlamydia or Legionella sp it is recommended to add: erythromycin 500 mg QID, IV or oral, oral clarithromycin 500 mg BID, or oral azythromycin 500 mg once a day. PMID:16163420

Díaz F, Alejandro; Labarca L, Jaime; Pérez C, Carlos; Ruiz C, Mauricio; Wolff R, Marcelo



Molecular epidemiology and mutations at gyrA and parC genes of ciprofloxacin-resistant Escherichia coli isolates from a Taiwan medical center.  


Sixty-five ciprofloxacin-resistant clinical Escherichia coli isolates were collected from a Taiwan Medical Center from December 1998 to February 1999. All 65 clinical isolates were resistant (MICs > or = 4 microg/mL) to the following fluoroquinolones: ofloxacin, levofloxacin, sparfloxacin, and trovafloxacin. These isolates were cross-resistant to chloramphenicol (65 isolates, 100%), tetracycline (65 isolates, 100%), cefuroxime (64 isolates, 98.5%), ampicillin (57 isolates, 87.7%), gentamicin (53 isolates, 81.5%), and cephalothin (24 isolates, 36.9%). Pulsed-field gel electrophoresis (PFGE) revealed a high diversity among the genomes of these isolates and indicated that clonal spread was not responsible for the prevalence of ciprofloxacin resistance in the hospital. Sequencing of the polymerase chain reaction (PCR) amplified products of the quinolone resistance determining regions (QRDRs) of gyrA and parC showed that all isolates carrying double mutations in gyrA at codon 83 and 87 and at least one parC mutation at codon 80 and/or 84. The mutation at codon 83 of GyrA from serine to leucine (S83L) was present in all the clinical isolates. The most prevalent pattern was the S83L mutation and the mutation at codon 87 from an aspartate to an asparagine (D87N) of GyrA plus a mutation from a serine to an isoleucine (S80I) at codon 80 of ParC (63.2%). This indicated that the presence of high-level resistance to quinolones in clinical E. coli isolates were associated with mutations at hot spots, codon 83 and 87 in GyrA and followed by subsequent mutation in either codon 80 and/or 84 in ParC. PMID:11310803

Chen, J Y; Siu, L K; Chen, Y H; Lu, P L; Ho, M; Peng, C F



Prevalence of ?-lactamase-negative ampicillin-resistant haemophilus influenzae isolated from patients of a teaching hospital in Thailand.  


The aim of this study was to investigate the prevalence of ?-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae isolated from patients of a teaching hospital in Thailand. Eighty-eight isolates of H. influenzae were collected between September 2005 and March 2008. All isolates were identified and characterized for biotypes and capsular types. The ?-lactamase production of these isolates was examined, and their susceptibility to the following 12 antimicrobial agents was determined: ampicillin (AMP), amoxicillin-clavulanate (AMC), cefotaxime (CTX), cefuroxime (CXM), meropenem (MEM), clarithromycin (CLR), telithromycin (TEL), tetracycline (TET), ciprofloxacin (CIP), levofloxacin (LEV), trimethoprim-sulfamethoxazole (SXT), and chloramphenicol (CHL). Of the 88 H. influenzae isolates, 69 (78.4%), 13 (14.8%), 4 (4.5%), and 2 (2.3%) were from the respiratory tract, pus, the genital tract, and blood, respectively. Half of the isolates were biotype II (44 isolates, 50%). The other half comprised biotypes I (23 isolates, 26.1%), III (15 isolates, 17.1%), and IV (6 isolates, 6.8%). All isolates were capsular non-typeable, except for 2 isolates that were type f. Antimicrobial susceptibility showed that all isolates were susceptible to AMC, CTX, MEM, TEL, CIP, and LEV (100%), whereas 96.6%, 94.3%, 80.7%, 68.2%, 50.0%, and 44.3% were susceptible to CXM, CLR, CHL, TET, AMP, and SXT, respectively. The ?-lactamase-production rate of H. influenzae isolates was 40.9%, and the prevalence of BLNAR was 18.2%. PMID:22446118

Lulitanond, Aroonlug; Chanawong, Aroonwadee; Pienthaweechai, Keskaew; Sribenjalux, Pipat; Tavichakorntrakool, Ratree; Wilailuckana, Chotechana; Puang-Ngern, Pirom; Saetung, Pairshompoo



Health care resource utilization and antimicrobial use in elderly patients with community-acquired lower respiratory tract infection who develop Clostridium difficile-associated diarrhoea.  


We conducted a prospective observational study on the medical management and health service resource utilization associated with the hospital care of patients with community-acquired lower respiratory tract infection. Between January 1994 and June 1995, 28 such patients developed Clostridium difficile-associated diarrhoea; these 28 patients were matched with 56 age-matched patients, who were used as a control group in a comparative study. Progress during the first week after admission was similar as measured by fever days and pathology or radiology use. The use of iv cephalosporins (g/day) during the first week was greater in the group who developed C. difficile-associated diarrhoea than in controls. The length of hospital stay was 36.4 +/- 21.6 days in patients with C. difficile-associated diarrhoea compared with 19.8 +/- 13.3 days in controls. Cases also required more pathological and radiological tests and greater use of antimicrobials and other drugs; however, if pathology and radiology use was calculated per day of patient stay there was no difference between the two groups. When antimicrobial use was compared, controlling for the time taken until found to be C. difficile toxin positive, patients with C. difficile infection received more iv cefuroxime as well as more total cephalosporins, beta-lactams and macrolides measured in g/day. Interestingly, in this study we could not show an increased mortality associated with C. difficile diarrhoea despite obvious evidence of morbidity. The development of C. difficile-associated diarrhoea substantially increases health care resource utilization for individual patients who are admitted to hospital with lower respiratory tract infection. PMID:9145829

MacGowan, A P; Feeney, R; Brown, I; McCulloch, S Y; Reeves, D S; Lovering, A M



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



A Mutation of the RNA Polymerase ?? Subunit (rpoC) Confers Cephalosporin Resistance in Bacillus subtilis  

PubMed Central

In bacteria, mutations affecting the major catalytic subunits of RNA polymerase (encoded by rpoB and rpoC) emerge in response to a variety of selective pressures. Here we isolated a Bacillus subtilis strain with high-level resistance to cefuroxime (CEF). Whole-genome resequencing revealed only one missense mutation affecting an invariant residue in close proximity to the C-terminal DNA-binding domain of RpoC (G1122D). Genetic reconstruction experiments demonstrate that this substitution is sufficient to confer CEF resistance. The G1122D mutation leads to elevated expression of stress-responsive regulons, including those of extracytoplasmic function (ECF) ? factors (?M, ?W, and ?X) and the general stress ? factor (?B). The increased CEF resistance of the rpoCG1122D strain is lost in the sigM rpoCG1122D double mutant, consistent with a major role for ?M in CEF resistance. However, a sigM mutant is very sensitive to CEF, and this sensitivity is still reduced by the G1122D mutation, suggesting that other regulatory effects are also important. Indeed, the ability of the G1122D mutation to increase CEF resistance is further reduced in a triple mutant strain lacking three ECF ? factors (?M, ?W, and ?X), which are known from prior studies to control overlapping sets of genes. Collectively, our findings highlight the ability of mutations in RNA polymerase to confer antibiotic resistance by affecting the activity of alternative ? factors that control cell envelope stress-responsive regulons.

Lee, Yong Heon; Nam, Ki Hyun



Anti-inflammatory effects of antibacterials on human bronchial epithelial cells  

PubMed Central

Background Human Bronchial epithelial cells (hu-BEC) have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. Methods Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-? (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. Results The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l) by 37 ± 20% and 45 ± 31%, respectively (both p < 0.01). IL-8 release in TNF-? stimulated hu-BEC decreased by 16 ± 8% (p < 0.05) with AZM (1.5 mg/l). With MXF a concentration dependent decrease of IL-8 release was noted up to 39 ± 7% (p < 0.05). GM-CSF release from TNF-? stimulated hu-BEC was maximally decreased by 35 ± 24% (p < 0.01) with MXF (4 mg/l). Conclusion Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-? induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.



Does the adoption of EUCAST susceptibility breakpoints affect the selection of antimicrobials to treat acute community-acquired respiratory tract infections?  

PubMed Central

Background In several European Countries, by the end of 2012, CLSI guidelines will be replaced by EUCAST. We compared antimicrobial susceptibility results of a large number of respiratory pathogens using both EUCAST and previously adopted CLSI criteria to evaluate the impact on susceptibility patterns and the possible consequences that could occur in clinical practice due to this replacement. For S. pyogenes and S. aureus, the interpretation of susceptibility data using the EUCAST criteria did not produce relevant changes in comparison to CLSI. Against S. pneumoniae, more restrictive EUCAST breakpoints could lead to increased benzylpenicillin and/or amoxicillin-clavulanate resistance rates, which in turn could translate in increased dosages of these antibiotics or usage of alternative agents for respiratory tract infections. Against S. pneumoniae, M. catarrhalis and H. influenzae, cefuroxime-axetil and cefaclor produced the most divergent results depending on the breakpoints adopted and these striking differences could lead to the revision of those guidelines suggesting these two cephalosporins as alternatives in the management of upper respiratory tract infections. Discussion Many differences exist between CLSI and EUCAST breakpoints. However, only in a few cases do these differences translate in major interpretive category discrepancies. In countries adopting more restrictive EUCAST breakpoints, clinicians should be aware of these discrepancies and that they could be faced with antibiotic-resistant respiratory pathogens more frequently than before. Summary The interpretive discrepancies between EUCAST and CLSI suggest that the discussion on the management of community-acquired respiratory tract infections is still open and further studies are desirable to better define the role of some antibiotics.



Risk Factors for Acute Endophthalmitis following Cataract Surgery: A Systematic Review and Meta-Analysis  

PubMed Central

Background Acute endophthalmitis is one of the most serious complications of cataract surgery and often results in severe visual impairment. Several risk factors for acute postoperative endophthalmitis (POE) following cataract surgery have been reported but the level of evidence and strength of association is varied. The purpose of this study was to critically appraise published reports on and to summarize clinical risk factors associated with acute POE which could be easily assessed by ophthalmologists for the introduction and implementation of preventive measure. Methods A systematic review and meta-analysis of observational studies was performed. Six databases were searched with no limits on the year or language of publication. Study-specific odds ratios (Ors) or relative risk (RR) of each risk factor were pooled using a random effect model. Results A total of 6 686 169 participants with 8 963 endophthalmitis in 42 studies were analyzed. Of the nine risk factors identified in our systematic review and meta-analysis, extra- or intracapsular cataract extraction, a clear corneal incision, without intracameral cefazolin (1 mg in 0.1 ml solution), without intracameral cefuroxime (1 mg in 0.1 ml solution), post capsular rupture, silicone intraocular lenses and intraoperative complications were found strongly associated with acute endophthalmitis. Other significant factors with a lower strength of association (risk estimates generally 1.5 or less) were male gender and old age (85 years and older). Conclusions Our study provides summary data on the risk factors for acute POE. Identifying patients at high risk of this sight-threatening eye disease is important from both the public health and clinical perspectives as this would facilitate detection of disease before the onset of irreversible visual loss enabling earlier intervention.

Li, Liping; Lo, SingKai




PubMed Central

Objective: This study was designed to determine the frequency and causative agent(s) of urinary tract infections (UTIs) in individuals with symptoms of urinary tract infections in Enugu State of Southeast Nigeria, and to determine the antibiotic susceptibility pattern of microbial agents isolated from urine culture. Methods: The study involved 211 individuals (149 females and 62 males) clinically suspected for UTI. Urine samples were collected by the mid-stream ‘clean catch’ method and tested using standard procedures. Antibiotic susceptibility of the isolated pathogens was tested using the Kirby-Bauer technique according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Microscopy of centrifuged urine samples showed 16 patients had pyuria while 54 had pus cells. Calcium oxalate crystals were found in 14 samples. Urinalysis performed with urine samples showed 17 had protein; seven were nitrite positive and three had moderate to high glucose concentration. Fifty-four urine samples (36.2%) from females and 12 (19.4%) from males showed significant growth upon culture. Gram stain and biochemical tests identified nine different organisms with Escherichia coli as the most common isolated species. Forty three randomly selected strains were further tested for their susceptibility against a panel of antibiotics. Thirty isolates (81.08%) were resistant to four or more antibiotics with the highest resistance shown by E. coli (76.67%). All the Gram- negative isolates were resistant to Ampicilox, Cefuroxime and Amoxicillin. Conclusion: Urinary tract infections were found more in females in the area under study. As found in other studies, E. coli was the most predominant isolate, although other organisms seem to be on the increase.

Dibua, Uju M.E.; Onyemerela, Ifeoma S.; Nweze, Emeka I.



Epidemiological Characteristics of Corneal Ulcers in South Sharqiya Region  

PubMed Central

Objectives To understand the epidemiology, predisposing factors, etiology and the outcome of management of corneal ulcers in South Sharqiya Region of Oman. Methods 188 patients who presented to us in eye Ophthalmology Department of Sur regional hospital with corneal ulcers were analyzed retrospectively. The historical aspects including the systemic and local predisposing factors, clinical picture of the ulcer which was noted on slit lamp at the time of presentation, results of culture for which material was taken by scraping of the ulcer, and its sensitivity pattern, type of management, and its outcome, were noted and the results were interpreted. Results 60.83% were males above the age of 60 years. Severe ulcers were seen in 36.17% of cases. 43.18% of cases showed positive culture of which 88.2% were bacteria and rest were fungal isolates. Of the bacteria 53.84% were pseudomonas, and 20% staphylococcus. 83.5% were put on fortified gentamycin and 68.61% were on cefuroxime in the initial dual therapy. 37.23% were on ciprofloxacin one time or another during the course of the ulcer. 69.14% of cases recovered fully and 9.57% improved. 54.25% needed hospitalization for less than 1 week and 34% for less than 2 weeks. 58.76% of cases recovered in less than 3 weeks. As local predisposing factors 45 cases (24%) were post surgery, and 29 cases (15.4%) were having CDK (climatic droplet keratopathy). Diabetes was seen in 8.5% of cases. Conclusion Corneal ulcer was seen predominantly in males above the age of 60 years, pseudomonas being the main etiological organism. Dual therapy was the commonest empirical therapy. No major systemic risk factor was identified. Post surgical and CDK were the predominant local risk factors.



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



Prevalence of Asymptomatic Bacteriuria and its Antibacterial Susceptibility Pattern Among Pregnant Women Attending the Antenatal Clinic at Kanpur, India  

PubMed Central

Background: Symptomatic and asymptomatic bacteriuria (ASB) is common in pregnant women. Pregnancy enhances the progression from ASB to symptomatic bacteriuria, which if left untreated, could lead to acute pyelonephritis and other adverse outcomes such as prematurity, postpartum, hypertensive disease, anaemia, UTIs and higher foetal mortality rates. Aim: To identify the prevalence of ASB, the most common causative microorganisms and the antibacterial susceptibilities of the isolated microorganisms at a tertiary care centre at Kanpur, India. Materials and Methods: A total number of 300 asymptomatic pregnant women were screened for ASB by urine culture by using a semi quantitative culture method. Results: In this study, significant bacteriuria was found in only 22 cases (7.3%). Growth of contaminants was seen in 40 cases (13.3%). Among cases which showed positive cultures, 48.9% were primigravidae and 51.1% were multigravidae. Highest incidence was reported in age group of 21-30 years. The predominant organisms which were isolated were Escherichia coli, followed by Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus and Proteus mirabilis. Escherichia coli, the most common isolate, was found to be only 61% and 70% sensitive to ampicillin and amoxicillin + clavulanate, respectively. Sensitivity to ceftriaxone and ciprofloxacin was 95%, and sensitivity to amikacin was 99%. Hundred percent sensitivity was found for the broad spectrum pencillins, imipenem, and meropenem. Klebsiella pneumoniae, the second most frequent organism which was grown on culture, was only 11% sensitive to ampicillin, while sensitivity to amoxicillin + clavulanate and cefuroxime was 86%. 100% sensitivity was found for cefepime, ceftriaxone, ciprofloxacin, imipenem and meropenem. Conclusion: Routine urine culture test should be carried out for all antenatal women, to detect asymptomatic bacteriuria, and every positive case should be treated with appropriate antibiotic therapy, to prevent any obstetric complication which is associated with pregnancy.

Nawani, Manju



Antimicrobial Resistance Pattern and Their Beta-Lactamase Encoding Genes among Pseudomonas aeruginosa Strains Isolated from Cancer Patients  

PubMed Central

This study was designed to investigate the prevalence of metallo-?-lactamases (MBL) and extended-spectrum ?-lactamases (ESBL) in P. aeruginosa isolates collected from two different hospitals in Cairo, Egypt. Antibiotic susceptibility testing and phenotypic screening for ESBLs and MBLs were performed on 122 P. aeruginosa isolates collected in the period from January 2011 to March 2012. MICs were determined. ESBLs and MBLs genes were sought by PCR. The resistant rate to imipenem was 39.34%. The resistance rates for P. aeruginosa to cefuroxime, cefoperazone, ceftazidime, aztreonam, and piperacillin/tazobactam were 87.7%, 80.3%, 60.6%, 45.1%, and 25.4%, respectively. Out of 122 P. aeruginosa, 27% and 7.4% were MBL and ESBL, respectively. The prevalence of blaVIM-2, blaOXA-10-, blaVEB-1, blaNDM-, and blaIMP-1-like genes were found in 58.3%, 41.7%, 10.4%, 4.2%, and 2.1%, respectively. GIM-, SPM-, SIM-, and OXA-2-like genes were not detected in this study. OXA-10-like gene was concomitant with VIM-2 and/or VEB. Twelve isolates harbored both OXA-10 and VIM-2; two isolates carried both OXA-10 and VEB. Only one strain contained OXA-10, VIM-2, and VEB. In conclusion, blaVIM-2- and blaOXA-10-like genes were the most prevalent genes in P. aeruginosa in Egypt. To our knowledge, this is the first report of blaVIM-2, blaIMP-1, blaNDM, and blaOXA-10 in P. aeruginosa in Egypt.

Zafer, Mai M.; Al-Agamy, Mohamed H.; El-Mahallawy, Hadir A.; Amin, Magdy A.; Ashour, Mohammed Seif El-Din



Characterization of a novel extended-spectrum beta-lactamase from Pseudomonas aeruginosa.  

PubMed Central

A clinical isolate of Pseudomonas aeruginosa RNL-1 showed resistance to extended-spectrum cephalosporins which was inhibited by clavulanic acid. Although this strain contained three plasmids ca. 80, 20, and 4 kb long, the resistance could not be transferred by mating-out assays with P. aeruginosa or Escherichia coli. Cloning of a 2.1-kb Sau3A fragment from P. aeruginosa RNL-1 into plasmid pACYC184 produced pPZ1, a recombinant plasmid that encodes a beta-lactamase. This beta-lactamase (PER-1) had a relative molecular mass of 29 kDa and a pI of 5.4 and was biosynthesized by P. aeruginosa RNL-1 along with a likely cephalosporinase with a pI of 8.7. PER-1 showed a broad substrate profile by hydrolyzing benzylpenicillin, amoxicillin, ticarcillin cephalothin, cefoperazone, cefuroxime, HR 221, ceftriaxone, ceftazidime, and (moderately) aztreonam but not oxacillin, imipenem, or cephamycins. Vmax values for extended-spectrum cephalosporins were uncommonly high, and the affinity of the enzyme for most compounds was relatively low (i.e., high Km). PER-1 activity was inhibited by clavulanic acid, sulbactam, imipenem, and cephamycins but not by EDTA. A 1.1-kb SnaBI fragment from pPZ1 failed to hybridize with plasmids that encode TEM-, SHV-, OXA-, or CARB/PSE-type beta-lactamase or with the ampC gene of P. aeruginosa. However, the same probe appeared to hybridize with chromosomal but not plasmid DNA from P. aeruginosa RNL-1. This study reports the properties of a novel extended-spectrum beta-lactamase in P. aeruginosa which may not be derived by point mutations from previously known enzymes of this species. Images

Nordmann, P; Ronco, E; Naas, T; Duport, C; Michel-Briand, Y; Labia, R



Cloning of a Chryseobacterium (Flavobacterium) meningosepticum Chromosomal Gene (blaACME) Encoding an Extended-Spectrum Class A ?-Lactamase Related to the Bacteroides Cephalosporinases and the VEB-1 and PER ?-Lactamases  

PubMed Central

In addition to the BlaB metallo-?-lactamase, Chryseobacterium (Flavobacterium) meningosepticum CCUG 4310 (NCTC 10585) constitutively produces a 31-kDa active-site serine ?-lactamase, named CME-1, with an alkaline isoelectric pH. The blaACME gene that encodes the latter enzyme was isolated from a genomic library constructed in the Escherichia coli plasmid vector pACYC184 by screening for cefuroxime-resistant clones. Sequence analysis revealed that the CME-1 enzyme is a new class A ?-lactamase structurally divergent from the other members of this class, being most closely related to the VEB-1 (also named CEF-1) and PER ?-lactamases and the Bacteroides chromosomal cephalosporinases. The blaACME determinant is located on the chromosome and exhibits features typical of those of C. meningosepticum resident genes. The CME-1 protein was purified from an E. coli strain that overexpresses the cloned gene via a T7-based expression system by means of an anion-exchange chromatography step followed by a gel permeation chromatography step. Kinetic parameters for several substrates were determined. CME-1 is a clavulanic acid-susceptible extended-spectrum ?-lactamase that hydrolyzes most cephalosporins, penicillins, and monobactams but that does not hydrolyze cephamycins and carbapenems. The enzyme exhibits strikingly different kinetic parameters for different classes of ?-lactams, with both Km and kcat values much higher for cephalosporins than for penicillins and monobactams. However, the variability of both kinetic parameters resulted in overall similar acylation rates (kcat/Km ratios) for all types of ?-lactam substrates.

Rossolini, Gian Maria; Franceschini, Nicola; Lauretti, Laura; Caravelli, Berardo; Riccio, Maria Letizia; Galleni, Moreno; Frere, Jean-Marie; Amicosante, Gianfranco



[Penicillin-resistance as indicator of resistance of Staphylococcus aureus towards cephalosporines and structure-related substances (author's transl)].  


81 strains of Staphylococcus aureus (41 methicillin-resistant and 40 -sensitive ones) were tested against older and newer cephalosporines in both broth-dilution and agardiffusion-tests using Mueller-Hinton (MH)-broth and MH-agar respectively in order to establish the degree of parallel-resistance. The substances used were cephalothin, cefazolin, cephalexin, cefamandol, cefuroxim, cefoxitin, cefotaxim and cefsulodin. Furthermore, for reasons of comparison the relatively new substance "Oxabetalaktam" was included in the investigation. As shown in Fig. 1 and Table 1 all methicillin-resistant strains required at the average at least 10 times the concentrations of cephalosporine (excepting cefsulodin) which was necessary to inhibit methicillin-sensitive strains. Again excepting cefsulodin, for each cephalosporine there was a clear bimodal distribution indicating a clear separation of both populations of strains: methicillin-sensitive and -resistant ones. Cephalothin cannot be used as test substance in agardiffusion-tests with staphylococci as there is no correlation between MIC and the inhibition zone size (Fig. 2). This is not necessary, anyway, since all methicillin-resistant strains must be regarded as resistant against virtually all cephalosporines available on the market (with the possible exception of cefamandol). By contrast, all methicillin-sensitive strains may be attacked successfully by concentrations of cephalosporines that are thought to be also effective in vivo. Since in agardiffusion-tests methicillin-resistant strains of staphylococcus aureus are recognizable as easily as are otherwise merely penicillinase-producing ones (5) by using a paper disk loaded with 6 microgram benzyl-penicillin and since infections due to other grampositive organisms than staphylococci are no indication for treatment with cephalosporines there is no need to test any other betalactam-antibiotic than benzyl-penicillin with gram-positive organisms. PMID:6784390

Hirschl, A; Stanek, G; Rotter, M



High prevalence of antibiotic resistance in pathogenic Escherichia coli from large- and small-scale poultry farms in Bangladesh.  


Antibiotic resistance in avian bacterial pathogens is a common problem in the Bangladesh poultry industry. The aim of the present study was to provide information on the present status of antibiotic resistance patterns in avian pathogenic Escherichia coli in Bangladesh. Of 279 dead or sick poultry of different ages, 101 pathogenic E coli strains isolated from broilers and layer hens with colibacillosis infections were screened to determine phenotypic expression of antimicrobial resistance against 13 antibiotics used in both veterinary and human medicine in Bangladesh. Of 101 pathogenic E. coli isolates, more than 55% were resistant to at least one or more of the tested compounds, and 36.6% of the isolates showed multiple-drug-resistant phenotypes. The most common resistances observed were against tetracycline (45.5%), trimethoprim-sulphamethoxazole (26.7%), nalidixic acid (25.7%), ampicillin (25.7%), and streptomycin (20.8%). Resistance to ciprofloxacin (12.9%), chlormaphenicol (8.9%), nitrofurantoin (2%), and gentamicin (2%) was also observed, and none of the isolates were resistant to tigecycline as well as extended spectrum beta-lactamase (ESBL) producers. One isolate was resistant to cefuroxime (1%), cefadroxil (1%), and mecillinam (1%) but was not an ESBL producer. Resistance rates, although significant in Bangladeshi isolates, were found to be lower than those reported for avian isolates from the Republic of Korea and clinical, avian, and environmental isolates from Bangladesh. The high level of antibiotic resistance in avian pathogens from Bangladesh is worrisome and indicates that widespread use of antibiotics as feed additives for growth promotion and disease prevention could have negative implications for human and animal health and the environment. PMID:22312993

Hasan, Badrul; Faruque, Rayhan; Drobni, Mirva; Waldenström, Jonas; Sadique, Abdus; Ahmed, Kabir Uddin; Islam, Zahirul; Parvez, M B Hossain; Olsen, Björn; Alam, Munirul



Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus  

PubMed Central

Background The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding ?-hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the ?-lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr.



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



Natural antibiotic susceptibility of strains of Serratia marcescens and the S. liquefaciens complex: S. liquefaciens sensu stricto, S. proteamaculans and S. grimesii.  


The natural susceptibility of 77 strains of Serratia marcescens and 41 strains of the S. liquefaciens complex (S. liquefaciens sensu stricto (n=21), S. grimesii (n=10), S. proteamaculans (n=10)) to 70 antibiotics was examined using a microdilution procedure in Isosensitest broth (all strains) and cation-adjusted Mueller Hinton broth (some strains). All species were naturally resistant to benzylpenicillin, oxacillin, cefaclor, cefazolin, cefuroxime, numerous macrolides, lincosamides, streptogramins, glycopeptides, rifampicin and fusidic acid. Uniform natural sensitivity was found to most aminoglycosides, several acylureidopenicillins, ticarcillin, newer cephalosporins, carbapenems, aztreonam, quinolones and antifolates. Species-related differences in susceptibility affecting clinical assessment criteria were found for several agents. S. marcescens was less susceptible to some aminoglycosides than species of the S. liquefaciens group. It was the only species that was uniformly naturally resistant to tetracycline, amoxycillin, amoxycillin/clavulanate and loracarbef. Species of the S. liquefaciens group were naturally resistant and intermediate or naturally intermediate to the latter agents. Differences in susceptibility among the species of the S. liquefaciens complex were generally small. S. proteamaculans was most susceptible to sulphamethoxazole. S. liquefaciens sensu stricto was less susceptible than S. grimesii and S. proteamaculans to tetracyclines, chloramphenicol and nitrofurantoin; it was the only species uniformly naturally resistant to fosfomycin. This study suggested that all species examined probably express chromosomally-encoded AmpC beta-lactamases, but the amount of enzyme may vary from species to species. The naturally-occurring low-level expression of the S. marcescens aminoglycoside 6'-acetyltransferase AAC(6')-Ic and its absence in other Serratia spp. was supported by the data. All species of the S. liquefaciens complex should be considered as probable agents of human diseases. PMID:12842326

Stock, I; Grueger, T; Wiedemann, B



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.



Clinical Study of Acute Childhood Diarrhoea Caused by Bacterial Enteropathogens  

PubMed Central

Objective:There are not a large number of studies in India which can enlighten us regarding acute childhood diarrhoea and far lesser in number when it comes to its bacterial enteropathogenesis. The present study is specially targeted to determine the prevalence of various bacterial enteropathogens causing acute childhood diarrhoea and to find out their respective pattern of clinical features. Method: All children under 12 years of age enrolled between 1st June, 2012 and 31st July 2012, in the Outpatient department, Inpatient department of pediatrics section and casualty of hospital, who presented with acute diarrhoea. Data collected by mean of study questionnaire. Stool sample were processed for bacteriological analysis. In 280 samples bacteria were isolated with the help of microscopy, culture and biochemical reactions. The isolates obtained were tested for antimicrobial sensitivity over Mueller Hinton agar by Kirby Bauer-disk diffusion method. Results:Out of 280 children frequency of diarrhoeagenic bacteria isolated from the samples showed that Escherichia coli was recorded as the predominant bacteria with 44.2% of prevalence followed by Shigella, Salmonella, Klebsiella and Campylobacter with 28.2%, 13.6%, 7.8% and 6.1% respectively. Patients falling in the age group of 1-3 years. were the major sufferers of diarrhoea due to all etiologies except Klebsiella which mainly had impact on the patients below six months. Majority of isolated bacterial agents were resistant to Co-trimoxazole and Shigella being highly resistant enteropathogen isolated. Salmonella spp. were least resistant isolates. None of the isolates were resistant to Cefotaxime, Cefuroxime and Azetronam. Conclusion: Results of study reveal that Escherichia coli is a predominant bacterial enteropathogen causing diarrhoea and Salmonella is a major contributor to the diarrhoea causing severe dehydration and to the clinical features like fever, vomiting and more than 10 times of frequency of stools. Shigella is among highly resistant isolates while Salmonella isolates had least resistance to majority of antibiotics.

Rathaur, Vyas Kumar; Jayara, Aparna; Yadav, Neeraj



Drug utilization patterns in the emergency department: A retrospective study  

PubMed Central

Objectives: The aim of this study was to assess the prescribing trends and costs of drugs in the emergency department (ED) at Sultan Qaboos University Hospital (SQUH), a tertiary care hospital, in Muscat, the Sultanate of Oman. Materials and Methods: This was a retrospective cross-sectional study of all patients (n = 300) who attended the ED at SQUH in May 2012. Analyses were performed using descriptive and univariate statistics. Results: The average age of patients was 34 ± 19 years. The average number of drugs prescribed per patients was 3.2 ± 1.9 and the majority of the patients (n = 78; 26%) received two drugs. The most common route of drug administration was the oral route (n = 481; 51%) followed by parenterally (n = 357; 38%). Non-steroidal anti-inflammatory drugs (NSAIDs) were the most commonly prescribed class of drugs (38%) followed by the gastro-intestinal tract drugs (19%) and central nervous system drugs (13%). The average cost per prescription was 242 ± 632 US$. Morphine had the highest cost (1885 US$) followed by cefuroxime (1404 US$) and filgrastim (939 US$) over the 1-month period. There was a significant positive correlation between hospital cost and age (P < 0.001), duration of stay at the ED (P = 0.008) and emergency types (P < 0.001). Conclusion: NSAIDs were the most frequent class of drugs administered to patients. Highest number of drugs was prescribed for cardiovascular diseases followed by respiratory and gastrointestinal diseases. Anti-infective drugs cost was the highest among all other classes. The results of the present study are attempts to highlight the importance of strategies that have to be implemented to optimize medication use at the ED.

Al Balushi, K. A.; Al-Shibli, S.; Al-Zakwani, I.



Assessment of the Phoenix™ automated system and EUCAST breakpoints for antimicrobial susceptibility testing against isolates expressing clinically relevant resistance mechanisms.  


EUCAST breakpoint criteria are being adopted by automatic antimicrobial susceptibility testing systems. The accuracy of the Phoenix Automated System in combination with 2012 EUCAST breakpoints against recent clinical isolates was evaluated. A total of 697 isolates (349 Enterobacteriaceae, 113 Pseudomonas spp., 25 Acinetobacter baumannii, 11 Stenotrophomonas maltophilia, 95 Staphylococcus aureus, 6 coagulase negative staphylococci, 77 enterococci and 21 Streptococcus pneumoniae) with defined resistance phenotypes and well-characterized resistance mechanisms recovered in Spain (n?=?343) and Italy (n?=?354) were tested. Comparator antimicrobial susceptibility testing data were obtained following CLSI guidelines. Experimental agreement (EA), defined as MIC agreement?±1 log(2) dilution, category agreement (CA) and relative discrepancies (minor (mD), major (MD) and very major discrepancies (VMD)) were determined. The overall EA and CA for all organism-antimicrobial agent combinations (n?=?6.294) were 97.3% and 95.2%, respectively. mD, MD and VMD were 4.7%, 1.3% and 2.7%, all of them in agreement with the ISO (ISO20776-2:2007) acceptance criteria for assessment of susceptibility testing devices. VMD were mainly observed in amoxicillin-clavulanate and cefuroxime in Enterobacteriaceae and gentamicin in Pseudomonas aeruginosa, whereas MD were mainly observed in amoxicillin-clavulante in Enterobacteriaceae. mD were mainly observed in Enterobacteriaceae but distributed in different antimicrobials. For S. aureus and enterococci relative discrepancies were low. The Phoenix system showed accuracy assessment in accordance with the ISO standards when using EUCAST breakpoints. Inclusion of EUCAST criteria in automatic antimicrobial susceptibility testing systems will facilitate the implementation of EUCAST breakpoints in clinical microbiology laboratories. PMID:22909279

Giani, T; Morosini, M I; D'Andrea, M M; García-Castillo, M; Rossolini, G M; Cantón, R



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.



Antimicrobial resistance of Campylobacter jejuni and Campylobacter coli from poultry in Italy.  


This study was aimed at assessing the antimicrobial resistance (AMR) of Campylobacter isolates from broilers and turkeys reared in industrial farms in Northern Italy, given the public health concern represented by resistant campylobacters in food-producing animals and the paucity of data about this topic in our country. Thirty-six Campylobacter jejuni and 24 Campylobacter coli isolated from broilers and 68 C. jejuni and 32 C. coli from turkeys were tested by disk diffusion for their susceptibility to apramycin, gentamicin, streptomycin, cephalothin, cefotaxime, ceftiofur, cefuroxime, ampicillin, amoxicillin+clavulanic acid, nalidixic acid, flumequine, enrofloxacin, ciprofloxacin, erythromycin, tilmicosin, tylosin, tiamulin, clindamycin, tetracycline, sulfamethoxazole+trimethoprim, chloramphenicol. Depending on the drug, breakpoints provided by Comité de l'antibiogramme de la Société Française de Microbiologie, Clinical and Laboratory Standards Institute, and the manufacturer were followed. All broiler strains and 92% turkey strains were multidrug resistant. Very high resistance rates were detected for quinolones, tetracycline, and sulfamethoxazole+trimethoprim, ranging from 65% to 100% in broilers and from 74% to 96% in turkeys. Prevalence of resistance was observed also against ampicillin (97% in broilers, 88% in turkeys) and at least three cephalosporins (93-100% in broilers, 100% in turkeys). Conversely, no isolates showed resistance to chloramphenicol and tiamulin. Susceptibility prevailed for amoxicillin+clavulanic acid and aminoglycosides in both poultry species, and for macrolides and clindamycin among turkey strains and among C. jejuni from broilers, whereas most C. coli strains from broilers (87.5%) were resistant. Other differences between C. jejuni and C. coli were observed markedly in broiler isolates, with the overall predominance of resistance in C. coli compared to C. jejuni. This study provides updates and novel data on the AMR of broiler and turkey campylobacters in Italy, revealing the occurrence of high resistance to several antimicrobials, especially key drugs for the treatment of human campylobacteriosis, representing a potential risk for public health. PMID:24320689

Giacomelli, Martina; Salata, Cristiano; Martini, Marco; Montesissa, Clara; Piccirillo, Alessandra



Multidrug Resistance and Plasmid Patterns of Escherichia coli O157 and Other E. coli Isolated from Diarrhoeal Stools and Surface Waters from Some Selected Sources in Zaria, Nigeria  

PubMed Central

We have assessed the prevalence of Escherichia coli O157 in diarrhoeal patients and surface waters from some selected sources in Zaria (Nigeria), evaluating the antibiotic susceptibility and plasmid profiles of 184 E. coli isolates, obtained from 228 water samples and 112 diarrhoeal stool specimens (collected from children aged <15 years), using standard methods. The detection rate of E. coli O157 in surface waters was 2.2% and its prevalence in children with diarrhoea was 5.4%. The most active antibiotics were gentamicin, chloramphenicol and fluoroquinolones. Seventy-nine (42.9%) of 184 E. coli isolates were resistant to four or more antibiotics. Multidrug resistance (MDR) was higher amongst aquatic isolates than the clinical isolates. Out of 35 MDR isolates (20 of which were O157 strains), 22 (62.9%) harboured plasmids all of which were no less than 2.1 kb in size. Amongst the 20 E. coli O157 strains, only seven (35.0%) contained multiple plasmids. An aquatic O157 isolate containing two plasmids was resistant to seven drugs, including ampicillin, cefuroxime, ciprofloxacin, cotrimoxazole, nalidixic acid, nitrofurantoin and tetracycline. Loss of plasmid correlated with loss of resistance to antibiotics in cured (mutant) strains selected in tetracycline (50 ?g/mL)-nutrient agar plates. Our findings revealed that plasmids were prevalent in both the aquatic and clinical isolates, and suggest that the observed MDR is plasmid-mediated. The occurrence of plasmid-mediated multidrug resistant E. coli O157 in surface waters used as sources for drinking, recreation and fresh produce irrigation heightens public health concern.

Chigor, Vincent N.; Umoh, Veronica J.; Smith, Stella I.; Igbinosa, Etinosa O.; Okoh, Anthony I.



Beta- Lactam Antibiotics Stimulate Biofilm Formation in Non-Typeable Haemophilus influenzae by Up-Regulating Carbohydrate Metabolism  

PubMed Central

Non-typeable Haemophilus influenzae (NTHi) is a common acute otitis media pathogen, with an incidence that is increased by previous antibiotic treatment. NTHi is also an emerging causative agent of other chronic infections in humans, some linked to morbidity, and all of which impose substantial treatment costs. In this study we explore the possibility that antibiotic exposure may stimulate biofilm formation by NTHi bacteria. We discovered that sub-inhibitory concentrations of beta-lactam antibiotic (i.e., amounts that partially inhibit bacterial growth) stimulated the biofilm-forming ability of NTHi strains, an effect that was strain and antibiotic dependent. When exposed to sub-inhibitory concentrations of beta-lactam antibiotics NTHi strains produced tightly packed biofilms with decreased numbers of culturable bacteria but increased biomass. The ratio of protein per unit weight of biofilm decreased as a result of antibiotic exposure. Antibiotic-stimulated biofilms had altered ultrastructure, and genes involved in glycogen production and transporter function were up regulated in response to antibiotic exposure. Down-regulated genes were linked to multiple metabolic processes but not those involved in stress response. Antibiotic-stimulated biofilm bacteria were more resistant to a lethal dose (10 µg/mL) of cefuroxime. Our results suggest that beta-lactam antibiotic exposure may act as a signaling molecule that promotes transformation into the biofilm phenotype. Loss of viable bacteria, increase in biofilm biomass and decreased protein production coupled with a concomitant up-regulation of genes involved with glycogen production might result in a biofilm of sessile, metabolically inactive bacteria sustained by stored glycogen. These biofilms may protect surviving bacteria from subsequent antibiotic challenges, and act as a reservoir of viable bacteria once antibiotic exposure has ended.

Wu, Siva; Li, Xiaojin; Gunawardana, Manjula; Maguire, Kathleen; Guerrero-Given, Debbie; Schaudinn, Christoph; Wang, Charles; Baum, Marc M.; Webster, Paul



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.



Clinical study of acute childhood diarrhoea caused by bacterial enteropathogens.  


Objective:There are not a large number of studies in India which can enlighten us regarding acute childhood diarrhoea and far lesser in number when it comes to its bacterial enteropathogenesis. The present study is specially targeted to determine the prevalence of various bacterial enteropathogens causing acute childhood diarrhoea and to find out their respective pattern of clinical features. Method: All children under 12 years of age enrolled between 1st June, 2012 and 31st July 2012, in the Outpatient department, Inpatient department of pediatrics section and casualty of hospital, who presented with acute diarrhoea. Data collected by mean of study questionnaire. Stool sample were processed for bacteriological analysis. In 280 samples bacteria were isolated with the help of microscopy, culture and biochemical reactions. The isolates obtained were tested for antimicrobial sensitivity over Mueller Hinton agar by Kirby Bauer-disk diffusion method. Results:Out of 280 children frequency of diarrhoeagenic bacteria isolated from the samples showed that Escherichia coli was recorded as the predominant bacteria with 44.2% of prevalence followed by Shigella, Salmonella, Klebsiella and Campylobacter with 28.2%, 13.6%, 7.8% and 6.1% respectively. Patients falling in the age group of 1-3 years. were the major sufferers of diarrhoea due to all etiologies except Klebsiella which mainly had impact on the patients below six months. Majority of isolated bacterial agents were resistant to Co-trimoxazole and Shigella being highly resistant enteropathogen isolated. Salmonella spp. were least resistant isolates. None of the isolates were resistant to Cefotaxime, Cefuroxime and Azetronam. Conclusion: Results of study reveal that Escherichia coli is a predominant bacterial enteropathogen causing diarrhoea and Salmonella is a major contributor to the diarrhoea causing severe dehydration and to the clinical features like fever, vomiting and more than 10 times of frequency of stools. Shigella is among highly resistant isolates while Salmonella isolates had least resistance to majority of antibiotics. PMID:24995223

Rathaur, Vyas Kumar; Pathania, Monika; Jayara, Aparna; Yadav, Neeraj



In Vitro Selection of ramR and soxR Mutants Overexpressing Efflux Systems by Fluoroquinolones as Well as Cefoxitin in Klebsiella pneumoniae?  

PubMed Central

The relationship between efflux system overexpression and cross-resistance to cefoxitin, quinolones, and chloramphenicol has recently been reported in Klebsiella pneumoniae. In 3 previously published clinical isolates and 17 in vitro mutants selected with cefoxitin or fluoroquinolones, mutations in the potential regulator genes of the AcrAB efflux pump (acrR, ramR, ramA, marR, marA, soxR, soxS, and rob) were searched, and their impacts on efflux-related antibiotic cross-resistance were assessed. All mutants but 1, and 2 clinical isolates, overexpressed acrB. No mutation was detected in the regulator genes studied among the clinical isolates and 8 of the mutants. For the 9 remaining mutants, a mutation was found in the ramR gene in 8 of them and in the soxR gene in the last one, resulting in overexpression of ramA and soxS, respectively. Transformation of the ramR mutants and the soxR mutant with the wild-type ramR and soxR genes, respectively, abolished overexpression of acrB and ramA in the ramR mutants and of soxS in the soxR mutant, as well as antibiotic cross-resistance. Resistance due to efflux system overexpression was demonstrated for 4 new antibiotics: cefuroxime, cefotaxime, ceftazidime, and ertapenem. This study shows that the ramR and soxR genes control the expression of efflux systems in K. pneumoniae and suggests the existence of efflux pumps other than AcrAB and of other loci involved in the regulation of AcrAB expression.

Bialek-Davenet, Suzanne; Marcon, Estelle; Leflon-Guibout, Veronique; Lavigne, Jean-Philippe; Bert, Frederic; Moreau, Richard; Nicolas-Chanoine, Marie-Helene



In vitro selection of ramR and soxR mutants overexpressing efflux systems by fluoroquinolones as well as cefoxitin in Klebsiella pneumoniae.  


The relationship between efflux system overexpression and cross-resistance to cefoxitin, quinolones, and chloramphenicol has recently been reported in Klebsiella pneumoniae. In 3 previously published clinical isolates and 17 in vitro mutants selected with cefoxitin or fluoroquinolones, mutations in the potential regulator genes of the AcrAB efflux pump (acrR, ramR, ramA, marR, marA, soxR, soxS, and rob) were searched, and their impacts on efflux-related antibiotic cross-resistance were assessed. All mutants but 1, and 2 clinical isolates, overexpressed acrB. No mutation was detected in the regulator genes studied among the clinical isolates and 8 of the mutants. For the 9 remaining mutants, a mutation was found in the ramR gene in 8 of them and in the soxR gene in the last one, resulting in overexpression of ramA and soxS, respectively. Transformation of the ramR mutants and the soxR mutant with the wild-type ramR and soxR genes, respectively, abolished overexpression of acrB and ramA in the ramR mutants and of soxS in the soxR mutant, as well as antibiotic cross-resistance. Resistance due to efflux system overexpression was demonstrated for 4 new antibiotics: cefuroxime, cefotaxime, ceftazidime, and ertapenem. This study shows that the ramR and soxR genes control the expression of efflux systems in K. pneumoniae and suggests the existence of efflux pumps other than AcrAB and of other loci involved in the regulation of AcrAB expression. PMID:21464248

Bialek-Davenet, Suzanne; Marcon, Estelle; Leflon-Guibout, Véronique; Lavigne, Jean-Philippe; Bert, Frédéric; Moreau, Richard; Nicolas-Chanoine, Marie-Hélène



Design, synthesis and in vitro kinetic study of tranexamic acid prodrugs for the treatment of bleeding conditions.  


Based on density functional theory (DFT) calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives four tranexamic acid prodrugs were designed. The DFT results on the acid catalyzed hydrolysis revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. When the amine leaving group was a primary amine or tranexamic acid moiety, the tetrahedral intermediate collapse was the rate-limiting step, whereas in the cases by which the amine leaving group was aciclovir or cefuroxime the rate-limiting step was the tetrahedral intermediate formation. The linear correlation between the calculated DFT and experimental rates for N-methylmaleamic acids 1-7 provided a credible basis for designing tranexamic acid prodrugs that have the potential to release the parent drug in a sustained release fashion. For example, based on the calculated B3LYP/6-31G(d,p) rates the predicted t1/2 (a time needed for 50 % of the prodrug to be converted into drug) values for tranexamic acid prodrugs ProD 1-ProD 4 at pH 2 were 556 h [50.5 h as calculated by B3LYP/311+G(d,p)] and 6.2 h as calculated by GGA: MPW1K), 253 h, 70 s and 1.7 h, respectively. Kinetic study on the interconversion of the newly synthesized tranexamic acid prodrug ProD 1 revealed that the t1/2 for its conversion to the parent drug was largely affected by the pH of the medium. The experimental t1/2 values in 1 N HCl, buffer pH 2 and buffer pH 5 were 54 min, 23.9 and 270 h, respectively. PMID:23881217

Karaman, Rafik; Ghareeb, Hiba; Dajani, Khuloud Kamal; Scrano, Laura; Hallak, Hussein; Abu-Lafi, Saleh; Mecca, Gennaro; Bufo, Sabino A



Antimicrobial resistance pattern and their beta-lactamase encoding genes among Pseudomonas aeruginosa strains isolated from cancer patients.  


This study was designed to investigate the prevalence of metallo-?-lactamases (MBL) and extended-spectrum ? -lactamases (ESBL) in P. aeruginosa isolates collected from two different hospitals in Cairo, Egypt. Antibiotic susceptibility testing and phenotypic screening for ESBLs and MBLs were performed on 122 P. aeruginosa isolates collected in the period from January 2011 to March 2012. MICs were determined. ESBLs and MBLs genes were sought by PCR. The resistant rate to imipenem was 39.34%. The resistance rates for P. aeruginosa to cefuroxime, cefoperazone, ceftazidime, aztreonam, and piperacillin/tazobactam were 87.7%, 80.3%, 60.6%, 45.1%, and 25.4%, respectively. Out of 122 P. aeruginosa, 27% and 7.4% were MBL and ESBL, respectively. The prevalence of bla(VIM-2), bla(OXA-10(-)), bla(VEB-1), bla(NDM(-)), and bla(IMP-1)-like genes were found in 58.3%, 41.7%, 10.4%, 4.2%, and 2.1%, respectively. GIM-, SPM-, SIM-, and OXA-2-like genes were not detected in this study. OXA-10-like gene was concomitant with VIM-2 and/or VEB. Twelve isolates harbored both OXA-10 and VIM-2; two isolates carried both OXA-10 and VEB. Only one strain contained OXA-10, VIM-2, and VEB. In conclusion, bla(VIM-2)- and bla(OXA-10)-like genes were the most prevalent genes in P. aeruginosa in Egypt. To our knowledge, this is the first report of bla(VIM-2), bla(IMP-1), bla(NDM), and bla(OXA-10) in P. aeruginosa in Egypt. PMID:24707471

Zafer, Mai M; Al-Agamy, Mohamed H; El-Mahallawy, Hadir A; Amin, Magdy A; Ashour, Mohammed Seif El-Din



Antimicrobial activity among multidrug-resistant Streptococcus pneumoniae isolated in the United States, 2001-2005.  


Infections caused by multidrug-resistant (MDR) Streptococcus pneumoniae remain a major concern when selecting an appropriate antimicrobial agent. In this analysis, 27 781 isolates of S pneumoniae collected from 2001 to 2005 in the United States were tested for MDR phenotypes. About 25% of all isolates were MDR, defined as resistant to 2 or more of the following agents: cefuroxime, a macrolide, penicillin, tetracycline (if available), and trimethoprim-sulfamethoxazole (TMP-SMX). There was a slight decreasing trend over time in multidrug resistance prevalence with erythromycin. Among MDR strains, the most common coresistance pair was erythromycin and TMP-SMX (74% of isolates, irrespective of resistance to other agents), although penicillin-erythromycin and penicillin-TMP-SMX coresistance patterns were also found in more than 56% of MDR strains. Resistance to 4 antimicrobial agents tested was observed in 33% of all antimicrobial-resistant isolates. Levofloxacin, which was used as a representative of the fluoroquinolone class, was active against at least 98% of all MDR isolates, and the minimum inhibitory concentration (90%) (MIC(90)) for this population was 1 microg/mL (identical to the total S pneumoniae, population). Multidrug-resistant isolates from 2003 to 2005 were found to be equally susceptible (98%) to other respiratory fluoroquinolones (gatifloxacin and moxifloxacin; data not shown), although only 88% of MDR isolates (from 2001-2005) were susceptible to ciprofloxacin. Careful monitoring of multidrug resistance patterns will help guide appropriate therapeutic selection and may provide early detection of changes in resistance to more potent agents. PMID:18931469

Thornsberry, Clyde; Brown, Nina P; Draghi, Deborah C; Evangelista, Alan T; Yee, Y Cheung; Sahm, Daniel F



Tracking resistance among bacterial respiratory tract pathogens: summary of findings of the TRUST Surveillance Initiative, 2001-2005.  


Antimicrobial resistance observed among common respiratory tract pathogens--Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis--may complicate empiric therapeutic selection to treat community-acquired respiratory tract infections. The Tracking Resistance in the United States Today (TRUST) study determined the in vitro activities of frequently prescribed antimicrobial agents against isolates collected from all 50 states from 2001 to 2005. For S pneumoniae (N = 27,781), susceptibility of selected agents in ascending order were penicillin (oral) (65.4%), trimethoprim-sulfamethoxazole (TMP-SMX) (69.5%), erythromycin (72.0%), cefuroxime (oral) (75.9%), tetracycline (85.3%), amoxicillinclavulanate (92.6%), ceftriaxone (nonmeningitis) (96.6%), and levofloxacin (99.0%). Susceptibility to levofloxacin, which was used as a representative of the respiratory fluoroquinolones, was near 99% from 2001 to 2005, and the minimum inhibitory concentration (90%) (MIC(90)) remained unchanged at 1 microg/mL. Levofloxacin and the other respiratory fluoroquinolones remained highly effective against penicillin-resistant S pneumoniae(PRSP) (98%-99% susceptible). However, susceptibility of PRSP to amoxicillin-clavulanate decreased from 62%S in 2003 to 48%S in 2005. Haemophilus influenzae susceptibility to ampicillin averaged near 70%, and near 75% to TMP-SMX. Susceptibility rates to levofloxacin and the other respiratory fluoroquinolones for H influenzae and M catarrhalis remained at or near 100%. Although resistance rates among S pneumoniae have stabilized for penicillin (oral) at elevated levels and increased for macrolides, susceptibility to the respiratory fluoroquinolones has consistently remained high, as they have for H influenzae and M catarrhalis. PMID:18931466

Sahm, Daniel F; Brown, Nina P; Draghi, Deborah C; Evangelista, Alan T; Yee, Y Cheung; Thornsberry, Clyde



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



The Prevalence and Antibiotic Susceptibility Pattern of Salmonella typhi among Patients Attending a Military Hospital in Minna, Nigeria.  


The threat to human health posed by antibiotic-resistant bacterial pathogens is of growing concern to medical practice. This study investigated the antibiotic sensitivity pattern of Salmonella typhi isolated from blood specimen. One hundred blood samples were collected from suspected typhoid fever patients in 31 Artillery Brigade Medical Centre, Minna, and were analyzed for S. typhi while antibiotic sensitivity testing was done Kirby-Bauer method. Sixty (60.0%) samples out of the total 100 were positive for bacterial growth. The organisms isolated 2 include Salmonella typhi; 45 (75.0%), Shigella; 6 (10.0%), E. coli; 3 (5.0%), Klebsiella; 3 (5.0%), Enterobacter; 2 (3.3%), and Citrobacter; 1 (1.7%). Result of the sensitivity test showed that the isolates were resistant to all the antibiotics; ceftriaxone, cefuroxime, amoxicillin, ampicillin, ciprofloxacin, and augmentin, which are the drug of choice routinely used in the study area for the treatment of typhoid fever. They were however sensitive to chloramphenicol and ofloxacin, which, unfortunately, are not used in this study area for the treatment of typhoid fever. There appear to be multiple drug resistant (MDR) strain of S. typhi in the study area. These may be as a result of overdependence or uncontrolled use of the few available antibiotics and/or inaccurate or inconclusive diagnosis resulting in the development and spread of resistant strains of S. typhi. The study, therefore, highlights the need for a strong collaboration between the physicians and the laboratory in the choice of antibiotics for the treatment of bacterial diseases in order to discourage the development of resistant strain of bacterial pathogen. PMID:23056954

Adabara, N U; Ezugwu, B U; Momojimoh, A; Madzu, A; Hashiimu, Z; Damisa, D



Changing trends in frequency and antimicrobial resistance of urinary pathogens in outpatient clinics and a hospital in Southern Israel, 1991-1995.  


In order to monitor changes in the frequency and antimicrobial resistance of urinary pathogens over several years, urinary cultures received from outpatient clinics and from a hospital during a period of one month each in 1991 and 1995 were analyzed at a clinical microbiology laboratory. In 1991 and 1995, 1366 and 1534 significant monomicrobic cultures respectively were reviewed. The frequency of Escherichia coli dropped significantly in the outpatient clinics from 70.5% to 61.2% (p < 0.0001). The frequency of Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and other gram-negative bacteria also decreased, but the frequency of Klebsiella spp. and Enterobacter spp. increased from 2.6% to 5.8% (p < 0.0001). In the hospital, the frequency of Enterobacter spp. (p < 0.04), Escherichia coli and Morganella morganii declined from 1991 to 1995, whereas the frequency of Pseudomonas aeruginosa (p = 0.001), Acinetobacter spp. (p < 0.05), Klebsiella spp., Proteus mirabilis and other gram-negative rods increased considerably. The frequency of gram-positive aerobic bacteria rose markedly in outpatient specimens from 6.1% to 13.5% (p < 0.0001), while a decline from 14.4% to 9.3% was noted in hospital specimens (p < 0.02). A significant rise in the resistance of Escherichia coli to gentamicin and ciprofloxacin (p < 0.0001) was detected in outpatient isolates. In the hospital, gram-negative urinary pathogens demonstrated increased resistance to ampicillin (p = 0.042), cefuroxime (p = 0.005), gentamicin (p = 0.002) and ciprofloxacin (p < 0.0001) during the study period. The changing etiology of urinary tract infections and the increasing resistance of organisms indicate that periodic monitoring and possibly also modification of empirical therapy are required. PMID:9447906

Weber, G; Riesenberg, K; Schlaeffer, F; Peled, N; Borer, A; Yagupsky, P



Assessment of methylthioadenosine/S-adenosylhomocysteine nucleosidases of Borrelia burgdorferi as targets for novel antimicrobials using a novel high-throughput method  

PubMed Central

Background Lyme disease is the most prevalent tick-borne disease in the USA with the highest number of cases (27 444 patients) reported by CDC in the year 2007, representing an unprecedented 37% increase from the previous year. The haematogenous spread of Borrelia burgdorferi to various tissues results in multisystemic disease affecting the heart, joints, skin, musculoskeletal and nervous system of the patients. Objectives Although Lyme disease can be effectively treated with doxycycline, amoxicillin and cefuroxime axetil, discovery of novel drugs will benefit the patients intolerant to these drugs and potentially those suffering from chronic Lyme disease that is refractory to these agents and to macrolides. In this study, we have explored 5?-methylthioadenosine/S-adenosylhomocysteine nucleosidase as a drug target for B. burgdorferi, which uniquely possesses three genes expressing homologous enzymes with two of these proteins apparently exported. Methods The recombinant B. burgdorferi Bgp and Pfs proteins were first used for the kinetic analysis of enzymatic activity with both substrates and with four inhibitors. We then determined the antispirochaetal activity of these compounds using a novel technique. The method involved detection of the live–dead B. burgdorferi by fluorometric analysis after staining with a fluorescent nucleic acids stain mixture containing Hoechst 33342 and Sytox Green. Results Our results indicate that this method can be used for high-throughput screening of novel antimicrobials against bacteria. The inhibitors formycin A and 5?-p-nitrophenythioadenosine particularly affected B. burgdorferi adversely on prolonged treatment. Conclusions On the basis of our analysis, we expect that structure-based modification of the inhibitors can be employed to develop highly effective novel antibiotics against Lyme spirochaetes.

Cornell, Kenneth A.; Primus, Shekerah; Martinez, Jorge A.; Parveen, Nikhat



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



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.



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.  


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. PMID:18402186

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



Relationship between structure and convulsant properties of some beta-lactam antibiotics following intracerebroventricular microinjection in rats.  

PubMed Central

The epileptogenic activities of several beta-lactam antibiotics were compared following their intracerebroventricular administration in rats. Different convulsant potencies were observed among the various beta-lactam antibiotics tested, but the epileptogenic patterns were similar. The patterns consisted of an initial phase characterized by wet-dog shakes followed by head tremor, nodding, and clonic convulsions. After the largest doses of beta-lactam antibiotics injected, clonus of all four limbs and/or the trunk, rearing, jumping, falling down, escape response, transient tonic-clonic seizures, and sometimes generalized seizures were observed, followed by a postictal period with a fatal outcome. At a dose of 0.033 mumol per rat, cefazolin was the most powerful epileptogenic compound among the drugs tested. It was approximately three times more potent than benzylpenicillin in generating a response and much more potent than other cephalosporins, such as ceftriaxone, cefoperazone, and cefamandole. No epileptogenic signs were observed with equimolar doses of cefotaxime, cefonicid, cefixime, and ceftizoxime in this model. The more convulsant compounds (i.e., cefazolin and ceftezole) are both characterized by the presence of a tetrazole nucleus at position 7 and show a marked chemical similarity to pentylenetetrazole. Imipenem and meropenem, the two carbapenems tested, also showed epileptogenic properties, but imipenem was more potent than meropenem, with a convulsant potency similar to those of ceftezole and benzylpenicillin. In addition, the monobactam aztreonam possessed convulsant properties more potent than those of cefoperazone and cefamandole. This suggest that the beta-lactam ring is a possible determinant of production of epileptogenic activity, with likely contributory factors in the substitutions at the 7-aminocephalosporanic or 6-aminopenicillanic acid that may increase or reduce the epileptogenic properties of the beta-lactam antibiotics. While the structure-activity relationship was also investigated, there seem to be no convincing correlations among the rank order of lipophilicities and the convulsant potencies of the compounds studied. The lack of marked convulsant properties of cefixime, cefonicid, cefuroxime, and cephradine suggests that these antibiotics may interact with a binding site which is different from that by which the beta-lactam antibiotics exert their convulsant effects or may demonstrate a reduced affinity for the relevant site(s).

De Sarro, A; Ammendola, D; Zappala, M; Grasso, S; De Sarro, G B



Antibiotic susceptibility testing (agar disk diffusion and agar dilution) of clinical isolates of Enterococcus faecalis and E. faecium: comparison of Mueller-Hinton, Iso-Sensitest, and Wilkins-Chalgren agar media.  


Forty-two isolates of Enterococcus faecalis and 56 isolates of Enterococcus faecium, including 8 vancomycin-resistant strains, were examined for comparative susceptibility to 27 antimicrobial drugs with the agar dilution method, employing Mueller-Hinton (MHA), Iso-Sensitest (ISTA), and Wilkins-Chalgren (WCA) agar. The Bauer-Kirby agar disk diffusion method was used to comparatively test 24 of the agents in parallel. The enterococci yielded better growth on ISTA and WCA. However, WCA completely antagonized co-trimoxazole and, though less, fosfomycin. Importantly, WCA slightly reduced the activities of teicoplanin (minimal inhibitory concentrations, MICs, raised up to twofold) and vancomycin (MICs raised two- to fourfold) against enterococci and staphylococcal quality control strains. Therefore, WCA was judged unsuitable for susceptibility testing of enterococci. For E. faecalis no discrepancies between agar dilution MICs and inhibition zone diameters were encountered with augmentin, ampicillin, ampicillin-sulbactam, chloramphenicol, mupirocin, oxacillin, teicoplanin, and co-trimoxazole. Overall, MHA yielded fewer very major (category I) and major (category II) discrepancies than ISTA. However, numerous minor (category III), slight (category IV), minimal (category V), and/or negligible (category VI) discrepancies were encountered with ciprofloxacin, doxycycline, erythromycin, fosfomycin, fusidic acid, meropenem, ofloxacin and rifampin. With respect to E. faecium, only cefotaxime, mupirocin, oxacillin, and teicoplanin yielded nondiscrepant results. Several very major (I) and major (II) discrepancies were observed with augmentin, ampicillin, ampicillin-sulbactam, doxycycline, fusidic acid, imipenem, and penicillin G. Minor discrepancies (categories III-VI) were particularly numerous with augmentin, chloramphenicol, ciprofloxacin, doxycycline, and piperacillin. The largest numbers of negligible (VI) discrepancies were noted with fosfomycin, fusidic acid, and ofloxacin. It is recommended to test one cephalosporin (cefuroxime or the like) in parallel for educational purposes and to exclude fosfomycin, fusidic acid, and rifampin from test batteries because of the wide scatter of test results. The large number of minimal (V) discrepancies of ciprofloxacin against E. faecalis, the numerous minor (III) and slight (IV) discrepancies of chloramphenicol against E. faecium, and the not insignificant number of very major (I) and minor (III) discrepancies observed with meropenem against isolates of E. faecalis necessitated proposals for new disk intermediate susceptibility criteria. PMID:9681198

Traub, W H; Geipel, U; Leonhard, B



Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum beta-lactamase encoded by an Escherichia coli integron gene.  


A clinical isolate, Escherichia coli MG-1, isolated from a 4-month-old Vietnamese orphan child, produced a beta-lactamase conferring resistance to extended-spectrum cephalosporins and aztreonam. In a disk diffusion test, a typical synergistic effect between ceftazidime or aztreonam and clavulanic acid was observed along with an unusual synergy between cefoxitin and cefuroxime. The gene for VEB-1 (Vietnamese extended-spectrum beta-lactamase) was cloned and expressed in E. coli JM109. The recombinant plasmid pRLT1 produced a beta-lactamase with a pI of 5.35 and conferred high-level resistance to extended-spectrum (or oxyimino) cephalosporins and to aztreonam. Vmax values for extended-spectrum cephalosporins were uncommonly high, while the affinity of the enzyme for ceftazidime and aztreonam was relatively low. blaVEB-1 showed significant homology at the DNA level with only blaPER-1 and blaPER-2. Analysis of the deduced protein sequence showed that VEB-1 is a class A penicillinase having very low levels of homology with any other known beta-lactamases. The highest percentage of amino acid identity was 38% with PER-1 or PER-2, two uncommon class A extended-spectrum enzymes. Exploration of the genetic environment of blaVEB-1 revealed the presence of gene cassette features, i.e., (i) a 59-base element associated with blaVEB-1; (ii) a second 59-base element just upstream of blaVEB-1, likely belonging to the aacA1-orfG gene cassette; (iii) two core sites (GTTRRRY) on both sides of blaVEB-1; and (iv) a second antibiotic resistance gene 3' of blaVEB-1, aadB. blaVEB-1 may therefore be the first class A extended-spectrum beta-lactamase that is part of a gene cassette, which itself is likely to be located on a class 1 integron, as sulfamide resistance may indicate. Furthermore, blaVEB-1 is encoded on a large (> 100-kb) transferable plasmid found in a Klebsiella pneumoniae MG-2 isolated at the same time from the same patient, indicating a horizontal gene transfer. PMID:10049269

Poirel, L; Naas, T; Guibert, M; Chaibi, E B; Labia, R; Nordmann, P



In vitro activities of garenoxacin (BMS-284756) against Haemophilus influenzae isolates with different fluoroquinolone susceptibilities.  


The in vitro activity of garenoxacin (BMS-284756) against 62 clinical Haemophilus influenzae isolates with different fluoroquinolone susceptibilities was determined by the microdilution susceptibility testing method and compared with the activities of other oral quinolones and nonquinolone oral antimicrobial agents. Cefixime presented the highest intrinsic activity (MIC at which 50% of the isolates tested were inhibited [MIC(50)], 0.01 microg/ml), followed by garenoxacin, moxifloxacin, and ciprofloxacin (MIC(50), 0.06 microg/ml), levofloxacin (MIC(50), 0.12 microg/ml), cefuroxime (MIC(50), 1.0 microg/ml), and amoxicillin-clavulanate (MIC(50), 1.0/0.5 microg/ml), amoxicillin (MIC(50), 2 microg/ml), azithromycin (MIC(50), 4 microg/ml), and erythromycin (MIC(50), 8 microg/ml). In strains with ciprofloxacin MICs of < or =0.06 microg/ml, ciprofloxacin and garenoxacin displayed similar MIC(50)s and MIC(90)s, one dilution lower than those of moxifloxacin and levofloxacin. For strains for which ciprofloxacin MICs were > or = 0.12 microg/ml, MIC(50)s were similar for the four quinolones tested, although garenoxacin presented the widest activity range (0.03 to 32 microg/ml) and the highest MIC at which 90% of the isolates tested were inhibited (16.0 microg/ml). For strains without amino acid changes in the quinolone resistance determining region (QRDR) of GyrA and ParC, garenoxacin MICs were < or =0.03 microg/ml; with a single amino acid change in GyrA, garenoxacin MICs were 0.06 to 0.12 microg/ml; with one amino acid change each in GyrA and ParC, garenoxacin MICs were 0.5 to 2.0 micro g/ml; one amino acid change in ParC combined with two amino acid changes in GyrA increased the MICs to > or = 4 microg/ml for all assayed quinolones. We conclude that garenoxacin has excellent activity against H. influenzae, although progressive acquired resistance was observed by step-by-step mutation in the QRDR of gyrA and parC. PMID:14576114

Pérez-Vázquez, María; Román, Federico; Aracil, Belen; Cantón, Rafael; Campos, José



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.



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.



Diversity and Antibiograms of Bacterial Organisms Isolated from Samples of Household Drinking-water Consumed by HIV-positive Individuals in Rural Settings, South Africa  

PubMed Central

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 2.4×104 CFU/100 mL. Values of total coliform counts ranged from 17 CFU/100 mL to 7.9×105/100 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.

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



Access to antibiotics in New Delhi, India: implications for antibiotic policy  

PubMed Central

Objective The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology. Methods Data on procurement price and availability was collected from three public healthcare providers in the state: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n?=?40) and chain pharmacies (n?=?40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). Results Public sector: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin?+?clavulanic acid, azithromycin, and cefuroxime aexitl. Conclusions Inappropriate availability and pricing of newer generation antibiotics, which may currently be bought without prescription, is likely to lead to their over-use and increased resistance. All providers should follow the EML of whichever of the three concerned Delhi public sector agencies that it is under and these EMLs should follow the essential medicine concept. The Indian regulatory authorities need to consider urgently, drug schedules and pricing policies that will curtail inappropriate access to new generation antibiotics.



Causative organisms of post-traumatic endophthalmitis: a 20-year retrospective study  

PubMed Central

Background A wide range of organisms that enter the eye following ocular trauma can cause endophthalmitis. This study was to investigate the spectrum of pathogens and antibiotic susceptibility of bacterial isolates from a large cohort of post-traumatic endophthalmitis cases. Methods A retrospective study of 912 post-traumatic endophthalmitis patients treated at a tertiary eye-care center in China was performed. The associations between risk factors and the most common isolated organisms were investigated by Chi square Test. The percent susceptibilities for the first 10 years (1990–1999) and the second 10 years (2000–2009) were compared by Chi square test. p < 0.05 was considered statistically significant. Results Three-hundred-forty-seven (38.1%) cases of endophthalmitis were culture-positive, and 11 (3.2%) showed mixed infections (Gram-negative bacilli and fungi), yielding a total of 358 microbial pathogens. Culture proven organisms included 150 (41.9%) Gram-positive cocci, 104 (29.1%) Gram-negative bacilli, 44 (12.3%) Gram-positive bacilli, and 60 (16.8%) fungi. The coagulase-negative staphylococcal (CNS) species S. epidermidis (21.8%) and S. saprophyticus (12.0%) were the predominant pathogens, followed by Bacillus subtilis (8.7%), Pseudomonas aeruginosa (7.8%), and Escherichia coli (6.4%). Delayed repair over 24 h (p < 0.001) and metallic injury (p < 0.01) were significantly associated with positive culture of CNS. The most frequent fungal species were Aspergillus (26/60), followed by yeast-like fungi (18/60). P. aeruginosa was relatively sensitive to ciprofloxacin (83.3%), cefoperazone (75%), tobramycin (75%), cefuroxime (75%), and ceftazidime (75%) during the second decade. Multi-drug resistance was observed in the predominant Gram-negative bacteria. Conclusion We identified a broad spectrum of microbes causing post-traumatic endophthalmitis, with Gram-positive cocci the most frequently identified causative organism, followed by Bacillus species, fungi, and mixed infections. CNS infection was statistically associated with delayed repair and metallic injury. Variation in antibiotic susceptibility was observed among isolated bacteria and between different periods. Ciprofloxacin and ceftazidime in the first and second decades of the study, respectively, showed the highest activity against bacterial post-traumatic endophthalmitis. For infections caused by P. aeruginosa, a combination therapy of ciprofloxacin, tobramycin, and one of the cephalosporins might provide optimal coverage according to data from the second decade.



Bacterial bloodstream infections in HIV-infected adults attending a Lagos teaching hospital.  


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 degrees C for 18-24 hours. The CD4+ counts were generally low as 67% of 140 patients sampled had < 200 cells/microL 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 coagulase-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. PMID:20824974

Adeyemi, Adeleye I; Sulaiman, Akanmu A; Solomon, Bamiro B; Chinedu, Obosi A; Victor, Inem A



Salvage procedures in lower-extremity trauma in a child with hereditary motor and sensory neuropathy type I: a case report  

PubMed Central

Introduction Fractures of the lower extremity are a common type of childhood injury and many can be treated without surgery. Dislocated and open fractures are an indication for fracture stabilization via either intramedullary nailing or, in the case of complicated fractures, external fixation. But if complications are likely because of diseases and disabilities (for example, a neuropathy) that can complicate the post-operative procedure and rehabilitation, what options does one have? Case presentation We report a nine-year-old Caucasian girl who had hereditary motor and sensory neuropathy type I and who was admitted with a grade I open tibia fracture after a fall from a small height. Plain radiographs showed a dislocated tibia and fibula fracture. An open reduction with internal fixation with a compression plate osteosynthesis was performed, and soft tissue debridement combined with an external fixateur was undertaken. Three months later, she was re-admitted with localized swelling and signs of a local soft tissue infection in the middle of her tibia. Plain radiographs showed a non-union of the tibia fracture, and microbiological analysis confirmed a wound infection with cefuroxime-sensitive Staphylococcus aureus. Because of the non-union, the osteosynthesis was replaced with an Ilizarov external fixateur, and appropriate antibiotic therapy was initiated. Four months after the initial accident, the fracture was consolidated and we removed the external fixateur. Conclusions If there is a pre-existing neuropathy and if disease makes it difficult for a child to follow all post-operative instructions, salvage procedures should be kept in mind in case of complications. There are multiple therapeutic options, including osteosynthesis, intramedullary nailing systems, cast therapy, or an external fixateur like the Ilizarov or Taylor spatial frame system. The initial use of an external fixateur such as an Ilizarov or Taylor spatial frame in patients with pre-existing neuropathies should be kept in mind as a possible treatment option in complicated fractures, especially in a child with pre-existing neurological or endocrine pathologies.



Community acquired infections in older patients admitted to hospital from care homes versus the community: cohort study of microbiology and outcomes  

PubMed Central

Background Residents of care homes are at risk of colonisation and infection with antibiotic resistant bacteria, but there is little evidence that antibiotic resistance among such patients is associated with worse outcomes than among older people living in their own homes. Our aim was to compare the prevalence of antibiotic resistant bacteria and clinical outcomes in older patients admitted to hospital with acute infections from care homes versus their own homes. Methods We enrolled patients admitted to Ninewells Hospital in 2005 who were older than 64 years with onset of acute community acquired respiratory tract, urinary tract or skin and soft tissue infections, and with at least one sample sent for culture. The primary outcome was 30 day mortality, adjusted for age, sex, Charlson Index of co-morbidity, sepsis severity, presence of resistant isolates and resistance to initial therapy. Results 161 patients were identified, 60 from care homes and 101 from the community. Care home patients were older, had more co-morbidities, and higher rates of resistant bacteria, including MRSA and Gram negative organisms resistant to co-amoxiclav, cefuroxime and/or ciprofloxacin, overall (70% versus 36%, p?=?0.026). 30 day mortality was high in both groups (30% in care home patients and 24% in comparators). In multivariate logistic regression we found that place of residence did not predict 30 day mortality (adjusted odds ratio (OR) for own home versus care home 1.01, 95% CI 0.40-2.52, p?=?0.984). Only having severe sepsis predicted 30 day mortality (OR 10.09, 95% CI 3.37-30.19, p?



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



Susceptibility of bacterial etiological agents to commonly-used antimicrobial agents in children with sepsis at the Tamale Teaching Hospital  

PubMed Central

Background Bloodstream infections in neonates and infants are life-threatening emergencies. Identification of the common bacteria causing such infections and their susceptibility patterns will provide necessary information for timely intervention. This study is aimed at determining the susceptibilities of bacterial etiological agents to commonly-used antimicrobial agents for empirical treatment of suspected bacterial septicaemia in children. Methods This is a hospital based retrospective analysis of blood cultures from infants to children up to 14 years of age with preliminary diagnosis of sepsis and admitted to the Neonatal Intensive Care Unit (NICU) and Paediatric Wards of the Teaching Hospital Tamale from July 2011 to January 2012. Results Out of 331 blood specimens cultured, the prevalence of confirmed bacterial sepsis was 25.9% (86/331). Point prevalence for confirmed cases from NICU was 44.4% (28/63) and 21.6% (58/268) from the Paediatric ward. Gram positive cocci (GPC) were the predominant isolates with Coagulase positive (32.2%) and Coagulase-negative (28.7%) Staphylococci accounting for 60.9% of the total isolates. Gram negative rods (GNR) comprised 39.1% of all isolates with Klebsiella, E.coli and Salmonella being the most common organisms isolated. Klebsiella was the most frequent GNR from the NICU and Salmonella typhi was predominantly isolated from the paediatric ward. Acinetobacter showed 100.0% susceptibility to Ceftriaxone and Cefotaxime but was resistant (100.0%) to Ampicillin, Tetracycline and Cotrimoxazole. Escherichia coli and Klebsiella were 80.0% and 91.0% susceptible to Ceftriaxone and Cefotaxime respectively. Klebsiella species showed 8.3% susceptibility to Tetracycline but was resistant to Ampicillin and Cotrimoxazole. Escherichia coli showed 40.0% susceptibility to Ampicillin, Chloramphenicol and Cotrimoxazole; 20.0% susceptibility to Tetracycline and 80.0% susceptible to Gentamicin and Cefuroxime. Coagulase negative Staphylococci was susceptible to Gentamicin (72.0%) but Coagulase positive Staphylococci showed intermediate sensitivity to Gentamicin (42.9%). Conclusion Coagulase Negative, Coagulase Positive Staphylococci, Salmonella and Klebsiella were the aetiological agents of bloodstream infection among children at TTH. While gram-positive and gram-negative bacteria showed low susceptibility to Ampicillin, Tetracycline and Cotrimoxazole, the GNR were susceptible to Gentamicin and third-generation cephalosporins.



Detection limits of four antimicrobial residue screening tests for beta-lactams in goat's milk.  


This study was conducted to compare the detection limits (DL) of several antibiotic residue screening tests with the maximum residue limits (MRL) authorized by the EU according to the guidance for the standardized evaluation of microbial inhibitor tests of the International Dairy Federation. Composite antibiotic-free milk samples from 30 primiparous Murciano-Granadina goats in good health condition were used to prepare test samples spiked with different concentrations of each antimicrobial. In total, 5,760 analytical determinations of 10 beta-lactam antibiotics (penicillin-G, ampicillin, amoxicillin, cloxacillin, oxacillin, dicloxacillin, cefadroxyl, cefalexin, cefoperazone, and cefuroxime) were performed using 4 antibiotic residue screening tests: the brilliant black reduction test BRT AiM (AiM-Analytik in Milch Produktions-und Vertriebs GmbH, München, Germany), Delvotest MCS (DSM Food Specialties, Delft, the Netherlands), Eclipse 100 (ZEU-Inmunotec SL, Zaragoza, Spain), and the Copan Milk Test (CMT; Copan Italia SpA, Brescia, Italy). For each method, we estimated the detection limits of the antimicrobial agents using a logistic regression model. Using the CMT and Delvotest on samples spiked with the 8 antibiotics for which MRL were available, DL were at or below the MRL. The BRT test provided DL at or below the MRL for all of the agents except cefalexin, whereas the Eclipse 100 method failed to detect 4 antibiotics (ampicillin, amoxicillin, cloxacillin, and cefoperazone) at MRL or below. Logistic regression-determined levels of agreement were highest for the CMT method (98.6 to 100%) and lowest for Eclipse 100 (66.3 to 100%). In general, agreement levels indicated good correlation between observed results and those predicted by logistic regression. The lowest b values (closely related to test sensitivity) were recorded for the cephalosporins (0.074 to 0.430) and highest for penicillin G, ampicillin, and amoxicillin (11.270 to 11.504). Delvotest and CMT best fulfilled IDF criteria for the ideal test for detecting antibiotic residues in milk. PMID:19620639

Sierra, D; Sánchez, A; Contreras, A; Luengo, C; Corrales, J C; Morales, C T; de la Fe, C; Guirao, I; Gonzalo, C



Randomised controlled trial of intrapleural streptokinase in community acquired pleural infection  

PubMed Central

BACKGROUND: Standard treatment for pleural infection includes catheter drainage and antibiotics. Tube drainage often fails if the fluid is loculated by fibrinous adhesions when surgical drainage is needed. Streptokinase may aid the process of pleural drainage, but there have been no controlled trials to assess its efficacy. METHODS: Twenty four patients with infected community acquired parapneumonic effusions were studied. All had either frankly purulent/culture or Gram stain positive pleural fluid (13 cases; 54%) or fluid which fulfilled the biochemical criteria for pleural infection. Fluid was drained with a 14F catheter. The antibiotics used were cefuroxime and metronidazole or were guided by culture. Subjects were randomly assigned to receive intrapleural streptokinase, 250,000 i.u. daily, or control saline flushes for three days. The primary end points related to the efficacy of pleural drainage--namely, the volume of pleural fluid drained and the chest radiographic response to treatment. Other end points were the number of pleural procedures needed and blood indices of inflammation. RESULTS: The streptokinase group drained more pleural fluid both during the days of streptokinase/control treatment (mean (SD) 391 (200) ml versus 124 (44) ml; difference 267 ml, 95% confidence interval (CI) 144 to 390; p < .001) and overall (2564 (1663) ml, 95% CI 465 to 2545; p < 0.01). They showed greater improvement on the chest radiograph at discharge, measured as the fall in the maximum dimension of the pleural collection (6.0 (2.7) cm versus 3.4 (2.7) cm; difference 2.9 cm, 95% CI 0.3 to 4.4; p < 0.05) and the overall reduction in pleural fluid collection size (p < 0.05, two-tailed Fisher's exact test). Systemic fibrinolysis and bleeding complications did not occur. Surgery was required by three control patients but none in the streptokinase group. CONCLUSIONS: Intrapleural streptokinase probably aids the treatment of pleural infections by improving pleural drainage without causing systemic fibrinolysis or local haemorrhage. ???

Davies, R. J.; Traill, Z. C.; Gleeson, F. V.



Comparison of the incidence and predicted risk of early surgical site infections after breast reduction.  


In plastic surgery, clean, elective operations such as breast reductions are anticipated to have low risk factors for infections (1.1-2.1%). To further lower or prevent surgical site infections (SSI), the efficacy of a prophylactic administration of anti-microbacterials remains a current controversial issue in plastic surgery. We report here the findings of a retrospective study in which we examined two groups of patients with breast reductions, one of which received a single-shot antimicrobacterial prophylaxis with cefuroxime preoperatively and the other who were given no anti-microbacterials. The aims were to determine the early SSI incidence of both groups, to classify breast reductions with respect to their inherent SSI risk by two widespread, combined risk scores, i.e., the National Nosocomial Infection Surveillance (NNIS) score and the Study on the Efficacy of Nosocomial Infection Control (SENIC) score, and to compare the actual SSI incidence to the predicted risk of the scores. In the divisions of plastic surgery at two hospitals, 153 patients (group I) and 136 patients (group II) could be included in the study in the 4-year period April 1997 to December 2001. Excluded were all patients with unilateral breast reduction or breast reconstruction and patients who were followed up less than 30 days postoperatively. The two groups were comparable with respect to demographic and clinical features such as age and risk factors, and there were no detectable significant intergroup differences in the general perioperative data. According to the NNIS and the SENIC scores, all operations were "clean," and the American Society of Anesthesiologists (ASA) score was < 3 in all patients. Although the mean duration of the operation was significantly different in the two groups (190 min in group I, 160 min in group II; p < 0.001, Mann-Whitney test; 75th percentile at and 4 and 3 h, respectively), it was longer than 2 h in both groups. The incidence of early infections was 3.9% in the first group, compared with 3.6% in the second group (p = 1.0, odds ratio = 1.07, 95% CI = 0.32-3.6). All infections were local and superficial; no general symptoms were noticed. Three patients had to be readmitted and two of these were reoperated. The rate of infections for both groups was higher than generally anticipated for this kind of clean operations and higher than predicted by the NNIS score for medium risk (predicted risk of 2.9%). The reason for this discrepancy is that the NNIS score is an inpatient risk score which does not include a postdischarge SSI surveillance. Using the NNIS definition of SSI we would have had an infection rate of 0% in both groups in our study. According to the SENIC score, breast reductions can be classified also as medium risk of SSI with a predicted risk of 3.9%, which showed a nearly perfect correspondence with the actual SSI incidence in both study groups. The reason for this increased, medium risk is the factor "operation time > 2 h," which is obviously an inherent risk factor in breast reductions. Among the multitude of patient and nonpatient SSI risk factors, in healthy women operation time was the only factor which could be clearly identified. PMID:15058556

Kompatscher, Peter; von Planta, Andreas; Spicher, Ivo; Seifert, Burkhardt; Vetter, Sebastian; Minder, Jacqueline; Beer, Gertrude M



Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy  

PubMed Central

Background Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. Objectives To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (March 2010) and reference lists of retrieved studies. Selection criteria Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Data collection and analysis Review authors independently screened the studies for inclusion and extracted data. Main results We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid® (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks, nausea, or preterm birth. Comparing cycloserine with sulphadimidine, no significant differences in symptomatic, persistent, or recurrent infections were noted. Authors’ conclusions We cannot draw any definite conclusion on the most effective and safest antibiotic regimen for the initial treatment of asymptomatic bacteriuria in pregnancy. One study showed advantages with a longer course of nitrofurantoin, and another showed better tolerability with ampicillin compared with pivmecillinam; otherwise, there was no significant difference demonstrated between groups treated with different antibiotics. Given this lack of conclusive evidence, it may be useful for clinicians to consider factors such as cost, local availability and side effects in the selection of the best treatment option.

Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese



Neonatal septicaemia in Ilorin: bacterial pathogens and antibiotic sensitivity pattern.  


All cases of septicemia among neonates admitted to the neonatal intensive care unit of the University of Ilorin Teaching Hospital, Ilorin, Nigeria between Jan 1995 and Dec 1996 were studied. Our aims were (1) to assess the incidence and microbial epidemiology of neonatal sepsis, (2) to generate baseline data and necessary research question for a proposed study on predictors of neonatal sepsis in our centre. Microbiology records of patients with confirmed septicemia was reviewed. Each of these babies had a single venous blood sample from a peripheral vein taken under aseptic conditions and before commencement of antibiotics. The needed data were entered into a proforma. Of the 198 neonates screened for sepsis, there were 61 (30.8%) positive blood cultures. Twenty-nine (48%) of these were inborn. The total number of live births in the hospital during the study period was 4118, thus giving a hospital-based incidence of neonatal sepsis of 7.04/1000 for in-born patients. The male:female ratio was 1.2:1. Overall Staphylococcus aureus was the commonest pathogen, accounting for 18 (29.5%) of the total isolates. Other pathogens were as follows; coagulase negative Saphylococcus albus 15 (24.6%), Klebsiella spp 10 (16.4%) and unclassified Coliforms 9 (14.8%). The predominant organisms in the first 48 hours were Gram negative bacilli; accounting for (70%) of the 10 isolates. Between 3 and 7 days of life the Gram positive cocci accounted for 12 (60%) of the 20 isolates while the Gram negative bacilli represented 40%. After 7 days, the predominant organism was Staphylococcus aureus (38.8%) while coagulase-negative Staphylococci were isolated in 7 of 31 isolates (22.6%). The sensitivity pattern showed that 94% of the organisms were sensitive to azythromicin, 77.8% to streptomycin, 73.3% to gentamicin and 69.2% to ampicillin-sulbactam. For the cephalosporins the isolates showed a sensitivity rate of 69% to ceftriaxone, 66.7% to ceftazidime and 58.3% to cefuroxime. As a group the Gram positive organisms had 100% sensitivity to Azythromcin, 85% to ampicillin-sulbactam, 63% to ceftazidime and 62.5% to gentamicin. In the Gram negative group, the best overall sensitivity was to ceftriaxone (86.4%). Gentamicin had 85.7% while sensitivity to ceftazidime was 60%. The distribution of the organisms causing early and late onset sepsis were different. For early onset sepsis, the Gram negative bacilli as a group were the commonest organisms while Staphylococcus aureus was the commonest cause of late onset sepsis. There was a lower incidence of sepsis compared to reports from other parts of the country. This, in addition to differences in antibiotic sensitivity pattern call for more multi-centre studies on predictors of neonatal sepsis. The antibiotic sensitivity profiles suggest that the initial empirical choice of ampicillin-sulbactam and gentamicin appears to be the most rational for our environment. PMID:12518907

Mokuolu, A O; Jiya, N; Adesiyun, O O



[Tonsillitis and sore throat in childhood].  


Surgery of the tonsils is still one of the most frequent procedures during childhood. Due to a series of fatal outcome after hemorrhage in children in Austria in 2006, the standards and indications for tonsillectomy slowly change in Germany since that. However, there exist no national guidelines and the frequency of tonsil surgery varies in the country. In some districts eight times more children were tonsillectomized than in others. A tonsillectomy in children under 6 years should only be done if the child suffers from recurrent acute bacterially tonsillitis. In all other cases (i. e. hyperplasia of the tonsils) the low risk partial tonsillectomy should be the first line therapy. Postoperative pain and the risk of hemorrhage are much lower in partial tonsillectomy (=?tonsillotomy). No matter whether the tonsillotomy is done by laser, radiofrequency, shaver, coblation, bipolar scissor or Colorado needle, as long as the crypts are kept open and some tonsil tissue is left behind. Total extracapsular tonsillectomy is still indicated in severely affected children with recurrent infections of the tonsils, allergy to antibiotics, PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) and peritonsillar abscess. With regard to the frequency and seriousness of the recurrent tonsillitis the indication for tonsillectomy in children is justified if 7 or more well-documented, clinically important, adequately treated episodes of throat infection occur in the preceding year, or 5 or more such episodes occur in each of the 2 preceding years (according to the paradise criteria). Diagnosis of acute tonsillitis is clinical, but sometimes it is hard to distinguish viral from bacterial infections. Rapid antigen testing has a very low sensitivity in the diagnosis of bacterial tonsillitis and swabs are highly sensitive but take a long time. In all microbiological tests the treating physician has to keep in mind, that most of the bacterials, viruses and fungi belong to the healthy flora and do no harm. Ten percent of the healthy children bear even streptococcus pyogenes all the time in the tonsils with no clinical signs. In these children decolonization is not necessary. Therefore, microbiological screening tests in children without symptoms are senseless and do not justify an antibiotic treatment (which is sometimes postulated by the kindergartens). The acute tonsillitis should be treated with steroids (e.g. dexamethasone), NSAIDs (e.g. ibuprofene) and betalactam antibiotics (e.g. penicillin or cefuroxime). With respect to the symptom reduction and primary healing the short-term late-generation antibiotic therapy (azithromycin, clarithromycin or cephalosporine for 3 to 5 days) is comparable to the long-term penicilline therapy. There is no difference in the course of healing, recurrence or microbiological resistance between the short-term penicilline therapy to the standard 10 days therapy, as well. On the other hand, only the 10 days antibiotic therapy has prooven to be effective in the prevention of rheumatic fever and glomerulonephritic diseases. The incidence of rheumatic heart disease is currently 0.5 per 100.000 children in school age. The main morbidity after tonsillectomy is pain and the late hemorrhage. Posttonsillectomy bleeding can occur till the whole wound is completely healed, which is normally after 3 weeks. Life-threatening hemorrhages occur often after smaller bleedings, which can spontaneously cease. That is why every hemorrhage, even the smallest, has to be treated properly and in ward. Patients and parents have to be informed about the correct behavior in case of hemorrhage with a written consent before the surgery. The handout should contain important adresses, phone numbers and contact persons. Almost all cases of fatal outcome after tonsillectomy were due to false management of hemorrhage. Especially in small children hemorrhage can be life-threatening because of the lower blood volume and the danger of aspiration with asphyxia. A massive hemorrhage is an extreme challenge for every pa

Stelter, K