cefepime and Cross-Infection

A variety of microorganisms can cause infective endocarditis (IE) in patients with native valves. Staphylococci and streptococci are most common in community-acquired IE; staphylococci are most common in nosocomial IE. Microbiology of prosthetic valve endocarditis (PVE) depends on timing. Early-onset PVE (ie, 60 days or fewer postsurgery) typically is nosocomial, with Staphylococcus aureus infection being most common. Intermediate-onset PVE (ie, 60 to 365 days postsurgery) typically involves a mix of nosocomial and non-nosocomial organisms. PVE that develops more than 1 year after surgery has microbiology similar to that of native valve endocarditis. Fever is the most common symptom; others include dyspnea, pleuritic pain, anorexia, and myalgias. The Modified Duke Criteria is the standard for diagnosis, with blood cultures being the most important test. If patients are in stable condition, three sets of blood cultures should be obtained more than 6 hours apart and from separate sites before starting antibiotics. Echocardiography aids in diagnosis and can identify conditions best managed with surgery. For empiric therapy for native valve IE, most patients should receive vancomycin. For PVE, vancomycin and gentamicin should be prescribed, plus cefepime or an antipseudomonal carbapenem. Treatment typically continues for 6 weeks after blood culture results are negative.

Topics: Anti-Bacterial Agents; Blood Culture; Carbapenems; Cefepime; Cephalosporins; Cross Infection; Echocardiography; Endocarditis; Endocarditis, Bacterial; Gentamicins; Heart Valve Prosthesis; Humans; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Vancomycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans

Sepsis and nosocomial infections continue to be a significant problem in intensive care, contributing heavily to mortality and prolonged hospital stay. Early and appropriate antibiotic therapy is critical for optimising outcomes. However, the emergence of highly resistant bacteria, coupled with reduced development of novel antibiotics, means that there is a real threat of development of untreatable nosocomial infections. Cefepime and ceftazidime are broad-spectrum cephalosporins that are widely used to treat Gram-negative nosocomial infections in critically ill patients. Available data suggest that cefepime may have advantages over ceftazidime owing to a broader spectrum of activity and reduced potential for development of bacterial resistance. However, whether either of these agents is superior can only be determined by a head-to-head study evaluating clinical and bacteriological outcomes. Such a study to determine whether apparent differences translate into clinically relevant differences in outcome is indicated.

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Community-Acquired Infections; Critical Illness; Cross Infection; Drug Resistance; Economics, Pharmaceutical; Humans; Pneumonia, Bacterial

Nosocomial infections caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria complicate therapy and limit treatment options. However, the clinical significance of infections caused by ESBL-producing bacteria remains unclear. A critical examination of the literature provides divergent views of the effect of ESBL carriage on morbidity and mortality and suggests that ESBL production may have its most marked effect on ceftazidime. Effective strategies for the empirical and directed treatment of infections caused by ESBL-producing pathogens include the use of carbapenems and, possibly, the fourth-generation cephalosporin cefepime. Studies indicate that the use of cefepime to treat serious nosocomial infections (e.g., bacteremia, pneumonia, and urinary tract infections) is associated with high rates of microbiological and clinical success. The probability of attaining time above the minimum inhibitory concentration targets of at least 70% of the dosing interval, an important pharmacodynamic indicator of clinical success, is higher with cefepime than with other antimicrobials against Escherichia coli and Klebsiella pneumoniae strains exhibiting ESBL phenotypes. However, for non-ESBL-producing strains, there is no difference in the time above the minimum inhibitory concentration between ceftazidime and cefepime. When used appropriately in institutional settings, cefepime reduces the overall use of cephalosporins, thereby decreasing selection pressure for presumptive ESBL-producing pathogens.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Treatment Outcome

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Humans; Pneumonia, Bacterial

Antibiotic resistance among medically important pathogens is curtailing the therapeutic value of many of the standard broad-spectrum antibiotics used for empiric treatment of serious infections. This article presents a brief overview of the etiology of serious infections and the threat of emerging resistance, and reviews the adverse impact of inadequate empiric treatment on patient outcomes and hospital ecology. The treatment of two clinically important infections with cefepime--pneumonia in hospitalized patients and febrile neutropenia--also is discussed.

Topics: Cefepime; Cephalosporins; Cross Infection; Humans; Neutropenia; Pneumonia, Bacterial

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Humans

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Candida; Cefepime; Cephalosporins; Cross Infection; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Middle Aged; Pneumonia; Treatment Outcome

Cefepime (Maxipime), Maxcef, Cepimax, Cepimex, Axepim, a parenteral fourth-generation cephalosporin, is active against many organisms causative in pneumonia. Cefepime has in vitro activity against Gram-positive organisms including Staphylococcus aureus and penicillin-sensitive, -intermediate and -resistant Streptococcus pneumoniae similar to that of cefotaxime and ceftriaxone. Cefepime also has good activity against Gram-negative organisms, including Pseudomonas aeruginosa, similar to that of ceftazidime. Importantly, cefepime is stable against many of the common plasmid- and chromosome-mediated beta-lactamases and is a poor inducer of AmpC beta-lactamases. As a result, it retains activity against Enterobacteriaceae that are resistant to third-generation cephalosporins, such as derepressed mutants of Enterobacter spp. Cefepime may be hydrolyzed by the extended-spectrum beta-lactamases produced by some members of the Enterobacteriaceae, but to a lesser extent than the third-generation cephalosporins. Monotherapy with cefepime 1 or 2g, usually administered intravenously twice daily, was as effective for clinical and bacteriological response as ceftazidime, ceftriaxone or cefotaxime monotherapy (1 or 2g two or three times daily) in a number of randomized, clinical trials in hospitalized adult, or less commonly, pediatric, patients with generally moderate to severe community-acquired or nosocomial pneumonia. More limited data indicated that monotherapy with cefepime 2g three times daily was also as effective in treating patients with nosocomial pneumonia as imipenem/cilostatin 0.5g four times daily, and when combined with amikacin, cefepime was as effective as ceftazidime plus amikacin. Patients with pneumonia who failed to respond to previous antibacterial therapy with penicillins or other cephalosporins responded to treatment with cefepime. Cefepime is generally well tolerated, with a tolerability profile similar to those of other parenteral cephalosporins. In clinical trials, the majority of adverse events experienced by cefepime recipients were mild to moderate and reversible. The most common adverse events with a causal relationship to cefepime reported in clinical trials included rash and diarrhea. Other, less common, adverse events included pruritus, urticaria, nausea, vomiting oral candidiasis, colitis, headache, fever, erythema and vaginitis.. Cefepime is an established and generally well tolerated parenteral drug with a broad spectrum of antibacterial activity which, when administered twice daily, provides coverage of most of the pathogens that may be causative in pneumonia. In randomized clinical trials in hospitalized patients with generally moderate to severe community-acquired or nosocomial pneumonia, cefepime monotherapy exhibited good clinical and bacteriological efficacy. Cefepime may become a preferred antibacterial agent for infections caused by Enterobacter spp. With prudent use in order to prevent the emergence of resistant organisms, cefepime will continue to be a suitable option for the empiric treatment of pneumonia.

Topics: Cefepime; Cephalosporins; Community-Acquired Infections; Cross Infection; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial

Topics: Aminoglycosides; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Decision Making; Humans

Topics: beta-Lactam Resistance; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Humans

Topics: Bacterial Infections; Cefepime; Cephalosporins; Clinical Trials as Topic; Cross Infection; Female; Humans; Male

Treatment of aspiration pneumonia is an important problem due to aging of populations worldwide. However, the effectiveness of cefepime in aspiration pneumonia has not yet been evaluated.. To compare the clinical efficacy and safety of cefepime and meropenem in patients with moderate-to-severe aspiration pneumonia.. In this open-label, randomized study, either cefepime 1 g or meropenem 0.5 g was administered intravenously every 8 h to patients with moderate-to-severe community-acquired or nursing-home acquired pneumonia at risk for aspiration for an average of 10.5 days. The primary outcome was the clinical response rate at the end of treatment (EOT) in the validated per-protocol (VPP)-population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in the VPP-population, and survival at day 30 in the modified intention-to-treat (MITT)-population.. There was no difference between the groups in the primary or secondary outcomes or safety. Significant improvement was observed in each group on day 4.. Cefepime is as effective and safe as meropenem in the treatment of moderate-to-severe aspiration pneumonia.. UMIN000001349.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Community-Acquired Infections; Cross Infection; Female; Humans; Male; Meropenem; Pneumonia, Aspiration; Prospective Studies; Severity of Illness Index; Treatment Outcome

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC).. This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem.. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC.. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC.. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Cross Infection; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Republic of Korea; Tazobactam; Urinary Tract Infections

Spontaneous bacterial peritonitis (SBP), in the presence of bacterial resistance or failure of third generation cephalosporins (3rd GC) has poor outcome. Empirical antibiotic(s) options are limited in these scenarios.. Consecutive cirrhotics with SBP because of hospital acquired SBP (>48 h of admission), microbial resistance or non-response (no resolution of SBP at 48 h) were randomized to Cefepime (n = 88) or Imipenem (n = 87) plus standard medical therapy. We assessed for 'response at 48 h' (reduction in ascitic fluid absolute neutrophil count (ANC) by >25% at 48 h), resolution of SBP (<250 cu/mm ANC at day 5) and their clinical outcome.. Of 957 paracentesis in 1200 hospitalized cirrhotics, 253 (26.4%) had SBP and 175 (69.6%) were randomized. Baseline parameters were comparable in two groups. Response at 48 h (58.6% vs. 51.7%; P = 0.4) and resolution of SBP in those with response at 48 h were comparable with no difference in mortality at week 2, month 1 and 3. Patients with 'No response at 48 h' had higher mortality compared with responders (73.8% vs. 25%; P < 0.001). Resolution of SBP was associated with 'response at 48 h' and septic shock, latter being main pre-terminal event. AKI at enrolment [Hazard ratio (HR), 2.6], pneumonia [HR, 2.9], septic shock [HR, 2.2] and response at 48 h [HR, 4.6] predicted poor outcome.. In hospitalized cirrhotics with SBP and risk factors for treatment failure, cefepime showed comparable efficacy and survival to imipenem. Non-response to therapy at 48 h is a reliable predictor of treatment failure and mortality. Antibiotic combinations and novel options are needed for these patients.

Topics: Adult; Anti-Bacterial Agents; Ascitic Fluid; Bacterial Infections; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Humans; Imipenem; India; Liver Cirrhosis; Male; Middle Aged; Paracentesis; Peritonitis; Risk Factors; Severity of Illness Index; Survival Analysis; Time Factors

ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results.. To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection.. We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011).. A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329).. Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Missouri; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

Nosocomial pneumonia is the most frequent and leading cause of morbidity and mortality. Pseudomonas aeruginosa, the most frequent causative agent, is intrinsically resistant to most antibiotics. The study was aimed at comparing the efficacy and safety of fixed dose combination (FDC) of Cefepime and Amakacin with that of Cefepime alone in treatment of patients suffering from nosocomial pneumonia. Patients suffering from nosocomial pneumonia participated in an open-labeled, two-arm, randomized, comparative, multicentric trial. One group (n=100) of patients were treated with intravenous injection of Cefepime and Amakacin FDC 2.5g b.i.d and other group (n=100) were treated with intravenous injection of Cefepime alone 2.0g b.i.d, for 7-10 days. Outcome of therapy was evaluated on the basis of clinical and bacteriological evaluation. Clinical and bacteriological successful outcomes were significantly higher in the patients treated with Cefepime and Amakacin FDC than Cefepime alone treated patients. Analysis of patients infected with Pseudomonas aeruginosa amongst the two treatment arms indicated that clinical and bacteriological success is significantly higher in Cefepime and Amakacin FDC treated patients than Cefepime alone treated group. No major adverse events with observed in both the treatment arms. In conclusion, fixed dose combination of Cefepime and Amakacin was more effective in the treatment of nosocomial pneumonia than Cefepime alone.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Drug Combinations; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas Infections; Treatment Outcome

The purpose of our study was to define and validate a population-pharmacokinetic model including the influence of patients' characteristics on the pharmacokinetics of cefepime.. A total of 55 patients were randomized in Group 1 (34 patients, 320 cefepime concentrations) for the model building and Group 2 (21 patients, 196 cefepime concentrations) for the validation group. They received cefepime as 2 g A 2 or as 4 g continuously. The population pharmacokinetic analysis was carried out using NONMEM and a baseline model was constructed for studying the influence of demographic and biological variables. The model was then validated by a comparison of the predicted and observed concentrations in Group 2. A final model was elaborated from the whole population.. Total clearance (CL) was significantly correlated with the serum creatinine (CREA) and the central volume of distribution (V1) was correlated with the body weight (WT). The final model was: CL = 7.14 + (-0.0133 A CREA). V1 = (-16.8) + (0.475 A WT). Q (intercompartmental clearance) = 10.5. V2 = 18.1. The mean pharmacokinetic parameters and their individual variability were: CL (8.24 l/h, 45%), V1 (20.89 l, 60%), V2 (17.95 l, 49%), total volume (38.85 l, 42%) and Q (10.56 l/h, 9%). The bias (1.07 mg/l, IC 95% = -40.46 -+42.60), precision (21.19%) and AFE (1.15) demonstrated the performance of the model.. We have developed and validated a pharmacokinetic model to estimate cefepime concentrations. We showed that serum creatinine and body weight are factors that may influence the standard dose of cefepime. Our model enabled us to predict cefepime concentrations in other patients.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Creatinine; Cross Infection; France; Humans; Infusions, Intravenous; Intensive Care Units; Metabolic Clearance Rate; Middle Aged; Models, Biological; Nonlinear Dynamics; Prospective Studies

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Dominican Republic; Female; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Klebsiella pneumoniae; Male; Meningitis, Bacterial

To compare once-daily intramuscular cefepime with ceftriaxone controls.. Double-blind study.. Six skilled nursing facilities.. Residents aged 60 and older with nursing home-acquired pneumonia.. Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours.. Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed.. Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age+/-standard deviation of 85+/-6, with a mean 5.8+/-1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35+/-7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were 117+/-40 dollars for cefepime- and 215+/-68 dollars for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost 597 dollars and ceftriaxone 1,709 dollars per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust.. Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Ceftriaxone; Cephalosporins; Cross Infection; Double-Blind Method; Drug Administration Schedule; Drug Costs; Female; Humans; Injections, Intramuscular; Male; Nursing Homes; Pneumonia, Bacterial

This study evaluated retrospectively the efficacy of treatment with cefepime vs. a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill patients infected with ESBL-producing Enterobacter aerogenes who were admitted to an intensive care unit. Forty-four episodes of infection were investigated in 43 patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment groups did not differ statistically in terms of age, APACHE II scores, and infection sites, but the average duration of antibiotic exposure was significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04). Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of patients receiving a carbapenem (p 0.59). Bacteriological eradication was achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome parameters did not differ significantly between the two groups. Nevertheless, a statistically significant increase in failure to eradicate ESBL-producing E. aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel electrophoresis revealed three distinct clones, but one predominant clone harbouring the bla(TEM-24) gene was associated with most (42/44) of the episodes of infection. It was concluded that cefepime may be an alternative agent for therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes, although further studies are required to confirm these observations.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Critical Illness; Cross Infection; Drug Therapy, Combination; Enterobacter aerogenes; Enterobacteriaceae Infections; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome

The study presented here compared the efficacy and safety of ertapenem and cefepime as initial treatment for adults with pneumonia acquired in skilled-care facilities or in hospital environments outside the intensive care unit (ICU). Non-ventilated patients developing pneumonia in hospital environments outside the ICU, in nursing homes, or in other skilled-care facilities were enrolled in this double-blind non-inferiority study, stratified by APACHE II score (15) and randomized (1:1) to receive cefepime (2 g every 12 h with optional metronidazole 500 mg every 12 h) or ertapenem (1 g daily). After 3 days of parenteral therapy, participants demonstrating clinical improvement could be switched to oral ciprofloxacin or another appropriate oral agent. Probable pathogens were identified in 162 (53.5%) of the 303 randomized participants. The most common pathogens were Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus, isolated from 59 (19.5%), 39 (12.9%), and 35 (11.6%) participants, respectively. At the test-of-cure assessment 7-14 days after completion of all study therapy, pneumonia had resolved or substantially improved in 89 (87.3%) of 102 clinically evaluable ertapenem recipients and 80 (86%) of 93 clinically evaluable cefepime recipients (95% confidence interval for the difference, -9.4 to 11.8%), fulfilling pre-specified criteria for statistical non-inferiority. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study population, ertapenem was as well-tolerated and efficacious as cefepime for the initial treatment of pneumonia acquired in skilled-care facilities or in hospital environments outside the ICU.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Cross Infection; Double-Blind Method; Drug Administration Schedule; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Skilled Nursing Facilities

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (-16 to 8%) failed to exclude the predefined lower limit for noninferiority of -15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum beta-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, -9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, -23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

Topics: Adult; Aged; APACHE; Cefepime; Cephalosporins; Cilastatin; Critical Care; Cross Infection; Double-Blind Method; Drug Therapy, Combination; Endpoint Determination; Female; Humans; Imipenem; Male; Middle Aged; Pneumonia, Pneumococcal; Prospective Studies; Protease Inhibitors; Respiration, Artificial; Thienamycins

To compare the associations of cefepime (2 g x 2/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefe-ami) and ceftazidime (2 g x 3/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefta-ami) in patients under mechanical ventilation suffering from a nosocomial pneumonia.. Multi-centre, open, comparative, randomised study.. The study included 275 ICU patients enrolled either in the cefe-ami group (n = 141) or in the cefta-ami group (n = 134).. All cases were reviewed in a blinded fashion by the steering committee.. Microbiology laboratory tests were positive in 74% of patients of the cefe-ami group and in 63% of the cefta-ami group respectively; 319 presumed causative strains of bacteria were isolated. The mean duration of treatment was 12 days for cefepime, 11 days for ceftazidime and 8 days for amikacin. In intention to treat, the clinical recovery rate was 48.2% in the cefe-ami group and 44.8% in the cefta-ami group respectively. In the population with a documented pneumonia, the clinical recovery was significantly better in the cefe-ami group (53.3%), than in the cefta-ami group (39.3%) (P = 0.05). In per protocol analysis, these rates reached 67.7% in the cefe-ami group and 68.2% in the cefta-ami group respectively. In the bacteriologically documented cases the eradication rates were 86.5% and 89.3% respectively.. The efficacy rates of cefe-ami and cefta-ami combinations were similar in ICU patients under mechanical ventilation with a nosocomial pneumonia. However the cefe-ami association was significantly more efficient in the population with a bacteriologically documented pneumonia.

Topics: Amikacin; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Double-Blind Method; Drug Therapy, Combination; Female; France; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Middle Aged; Pneumonia, Bacterial; Respiration, Artificial; Survival Rate

A multicentre trial was performed on the activity of cefepime in comparison with ceftazidime, ceftriaxone, piperacillin/tazobactam, imipenem and ciprofloxacin against severe hospital infection pathogens in intensive care units. The isolates of Escherichia coli and Proteus spp. from the majority of the centres were highly susceptible to the antibiotics (90 to 100 per cent of the isolates). In some centres up to 40 per cent of the isolates produced ESBL. The isolates of Klebsiella spp. were characterized by lower susceptibility, in some centres the frequency of the strains producing ESBL exceeded 90 per cent, by the MIC geometric mean cefepime was superior to the third generation cephalosporins, the frequency of resistance to ciprofloxacin ranged from 0 to 31 per cent, no resistance to imipenem was recorded. The frequency of resistance to the third generation cephalosporins and piperacillin/tazobactam in Enterobacter spp., Serratia spp., Citrobacter spp., Morganella spp., and Providencia spp. ranged from 10 to 52 per cent, the resistance to cefepime equaled 0-11 per cent, 0 to 17 per cent of the isolates were resistant to ciprofloxacin, some isolates were resistant to imipenem. As for the nonfermenting microorganisms their resistance to all the antibiotics tested was comparatively high and markedly differed in various centres. As a whole, 7 per cent of all the isolates of the nonfermenting organisms was resistant to cefepime, 10 per cent was resistant to imipenem, 17 per cent was resistant to ceftazidime, 21 per cent was resistant to piperacillin/tazobactam and 36 per cent was resistant to ciprofloxacin.

Topics: Acute Disease; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Russia

Cephalosporins are one of the mainstays of antibiotic therapy, and third-generation cephalosporins are first-line agents for the treatment of many types of serious infections, including those of nosocomial origin. Gaps in activity of currently available third-generation cephalosporins such as cefotaxime, cefoperazone, ceftriaxone, and ceftazidime, and increasing reports of gram-negative bacilli resistance to some of these agents, especially Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp., make it necessary to investigate new compounds. Cefepime, a fourth-generation cephalosporin with a wide range of activity against gram-positive and gram-negative bacteria, including multi-resistant strains of Enterobacteriaceae, was evaluated in comparison with ceftazidime for the treatment of serious infections in hospitalized patients. Ceftazidime is a commonly prescribed third-generation cephalosporin used for empiric treatment of serious infections such as pneumonia, urinary tract infection, and skin and skin-structure infection. This investigation was an open, randomized comparative study involving 882 patients in North America. Cefepime 2 g every 12 hours demonstrated similar efficacy to that of ceftazidime 2 g every 8 hours for the treatment of pneumonia and urinary tract infection (including cases associated with concurrent bacteremia), and skin and skin-structure infections. The bacteriologic responses were generally >85%. The most common pathogens isolated were Escherichia coll, Streptococcus pneumoniae, P. aeruginosa, K. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus, group B. Overall, approximately 94% of pathogens isolated in pretreatment cultures were susceptible to cefepime and ceftazidime. Cefepime and ceftazidime were well tolerated; only 3% of patients in each group discontinued therapy because of an adverse event. The most common adverse events were headache, diarrhea, nausea, vomiting, pruritus, and rash. The results of this study indicate that cefepime is a promising, effective, and safe single-agent therapy for serious infections in hospitalized patients.

Topics: Acute Disease; Analysis of Variance; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Female; Humans; Infusions, Intravenous; Male; Middle Aged; United States

Clinical and in vitro data indicate that cefepime, a fourth-generation cephalosporin, may be a valuable addition in the treatment of serious infections. In this study, hospitalized patients with complicated and uncomplicated urinary tract infection (UTI), for which parenteral therapy was appropriate, were enrolled in a 2:1 ratio open, randomized trial comparing the efficacy and safety of cefepime and ceftazidime. A total of 180 patients, including 6 with concurrent bacteremia, were evaluated for their response to cefepime (n = 118) or ceftazidime (n = 62), both of which were administered by intravenous infusion or intramuscular injection in doses of 500 mg every 12 hours. In cases of complicated UTI, cefepime produced a satisfactory clinical response in 83 of 93 (89%) patients and eradicated 83 of 98 (85%) pathogens. A satisfactory clinical response to ceftazidime was experienced by 43 of 50 (86%) patients; and in 39 of 50 (78%) cases pathogens were eradicated. In uncomplicated cases, the clinical response and bacterial eradication rates for cefepime were 23 of 25 (92%) and 22 of 26 (85%), respectively, and for ceftazidime 12 of 12 (100%) and 11 of 12 (92%). Of the 6 patients with concomitant bacteremia, 5 received cefepime and 1, ceftazidime. The infecting organisms, Escherichia coli and Proteus mirabilis, were eradicated in all cases, although one cefepime-treated patient had an unsatisfactory clinical response. The most common adverse events in both groups were headache, diarrhea, and vomiting; most events were unrelated to therapy. Adverse events forced only a 2% withdrawal of patients in either group. There was local tolerance to both agents, and abnormalities in laboratory values were judged to be clinically insignificant. The results of this study indicate that cefepime can be used safely and successfully to treat both complicated and uncomplicated nosocomial infection of the urinary tract, including cases associated with concurrent bacteremia. Moreover, its safety profile appears comparable to those of other cephalosporins, and local tolerance is similar to that of ceftazidime. No patient in either group required discontinuation of therapy because of local intolerance at the infusion or injection site.

Topics: Bacteremia; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Female; Humans; Male; Middle Aged; Time Factors; United States; Urinary Tract Infections

Patients in intensive care units (ICUs) are at increased risk of developing nosocomial infections. This is of special concern in the immunocompromised patient, particularly with regard to multiresistant pathogens. We evaluated the effectiveness of cefepime 2 g bd in combination with amikacin 7.5 mg/kg bd for the treatment of severe bacterial infection in 118 ICU patients, including 113 patients with nosocomial lower respiratory tract infections (LRTI) (mean age, 51 years). Ninety-six per cent (108/113) of the LRTI patients required respiratory assistance and 12% (14/113) had associated septicaemia/bacteraemia. Eighty-four per cent (95/113) had clinical signs of sepsis and 35% (39/113) had features of septic shock. The mean Simplified Acute Physiologic Score (SAPS) was 12 at inclusion. Seventy-nine patients with LRTI were clinically and bacteriologically evaluable. The causative pathogens were representative of those usually isolated in ICUs: Staphylococcus aureus (19%); Pseudomonas aeruginosa (14%); and Klebsiella, Enterobacter and Serratia spp. (17%). The clinical cure rate was 86% (68/79) while the pathogen eradication rate was 91% (107/117). Of the patients with associated septicaemia/bacteraemia, 89% (8/9) of the pathogens were eliminated. Cefepime-amikacin combination therapy was well tolerated; two patients discontinued treatment due to rashes. Combination therapy with cefepime 2 g bd and amikacin 7.5 mg/kg bd appears safe and effective for the treatment of nosocomial pneumonia in patients hospitalized in ICUs. Further comparative controlled studies are justified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Bacteremia; Bacterial Infections; Cefepime; Cephalosporins; Critical Care; Cross Infection; Drug Therapy, Combination; Female; Follow-Up Studies; France; Humans; Male; Middle Aged; Respiratory Tract Infections; Shock, Septic

The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer.. This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors.. We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9).. C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.

Topics: Anti-Bacterial Agents; Asparaginase; Busulfan; Cancer Care Facilities; Carboplatin; Case-Control Studies; Cefepime; Child; Clostridioides difficile; Clostridium Infections; Cross Infection; Humans; Melphalan; Meropenem; Neoplasms; Retrospective Studies; Risk Factors; Vancomycin

Topics: Anti-Bacterial Agents; Cefepime; Cross Infection; Diagnosis, Differential; Diaphragm; Humans; Hydropneumothorax; Male; Middle Aged; Pleural Effusion; Point-of-Care Testing; Radiography, Thoracic; Teicoplanin; Thoracentesis; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

Pseudomonas aeruginosa has recently shown to be one of the most important strains of bacteria and alert pathogens in Europe among Intensive Care Unit patients that provide serious therapeutic problems because of its multidrug resistance.. The purpose of this microbiological study was data analysis of device associated- healthcare associated infections (DA-HAIs) in an ICU in terms of the incidents of P.aeruginosa strain infections and its susceptibility within an 8.5-year observation.. Among 919 isolated strains responsible for 799 DA-HAIs (17,62 ± 1,98/1000 patient-days) in 4010 ICU patients P.aeruginosa was the pathogen in 108/799 (13.52%) cases. Incidence rate (density) of: VAP/1000 MV- days, UTI /1000 UC- days and CLA-BSI/1000 CL- days were 11,15 ± 2.5, 6.82 ± 0.81, 2.35 ± 1.54.respectivelly. P.aeruginosa was the pathogen most frequently responsible for VAP 69/108 (63.88%). Mean frequency of VAP, UTI and CLA-BSI with P.aeruginosa etiology was 69/493 (14.28%), 32/299 (11.1%) and 7/127 (5.77%) respectively. The mean density of P.aeruginosa infection amounted to 2.43/1000 patient-days. The decrease was observed in the total number of DA-HAIs caused by the P.aeruginosa from 15.75% and 3.23/1000 patient-days in 2011 to 5.0% and 1.17/1000 in 2016 (p = 0.0104, p = 0.0348). Starting from 2016 to 2019 incidence and density of P.aeruginosa DA-HAIs increased to 12.33% and 2.63/1000 (p = 0.1388, p = 0.0818). P.aeruginosa was susceptible to ceftazidime, cefepime, amikacin, meropenem, ciprofloxacin, colistin, in 55.55, 58.33, 70.37, 53.73, 50, and 100% respectively. MDR characterised it in 40% in 2011 and 66.7% in 2019, (p = 0.177).. The study revealed a changeable prevalence of P. aeruginosa strain infections; however their frequency was never highest in our ICU patients as it presented in the last years in Europe. The study showed a significant decrease in 2016 and increase in 2019, a nearly 3-fold increase of P.aeruginosa infections among Gram-negative strain infections, and a 2-fold increase of the P.aeruginosa DA-HAIs frequency between 2016 and 2019 as well as an increased resistance. Microbiological analysis of DA-HAIs in each hospital should be a standard method used in hospital infection control and antibiotic policy. In the case of P.aeruginosa, in order to minimize transmission, preventive infection methods should be assessed mainly in case of VAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Catheter-Related Infections; Cefepime; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Hospitals, University; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Poland; Prospective Studies; Pseudomonas aeruginosa; Urinary Tract Infections

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; beta-Lactams; Betacoronavirus; Cefepime; Coinfection; Confusion; Coronavirus Infections; COVID-19; Critical Illness; Cross Infection; Deep Sedation; Delirium; Drug Monitoring; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Pandemics; Pneumonia, Ventilator-Associated; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Sepsis

Topics: Aged, 80 and over; Amino Acid Substitution; Anti-Bacterial Agents; beta-Lactamases; Brazil; Cefepime; Ceftazidime; Chromosomes, Bacterial; Chryseobacterium; Ciprofloxacin; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Flavobacteriaceae Infections; Gene Expression; Humans; Microbial Sensitivity Tests; Middle Aged; Models, Molecular; Phylogeny; Plasmids; Point Mutation; Protein Structure, Secondary; Tigecycline

Our objective was to systematically study the influence of length of hospital stay on bacterial resistance in relevant respiratory tract isolates.. Using prospective epidemiological data from the National Swiss Antibiotic Resistance Surveillance System, susceptibility testing results for respiratory isolates retrospectively retrieved from patients hospitalised between 2008 and 2014 were compiled. Generalized additive models were used to illustrate resistance rates relative to hospitalisation duration and to adjust for co-variables.. In all, 19 622 isolates of six relevant and predominant species were included. Resistance patterns for the predominant species showed a species-specific and antibiotic-resistance-specific profile in function of hospitalisation duration. The oxacillin resistance profile in Staphylococcus aureus isolates was constantly increasing (monophasic). The pattern of resistance to cefepime in Pseudomonas aeruginosa was biphasic with a decreasing resistance rate for the first 5 days of hospitalisation and an increase for days 6-30. A different biphasic pattern occurred in Escherichia coli regarding amoxicillin-clavulanic acid resistance: odds/day increased for the first 7 days of hospitalisation and then remained stable for days 8-30. In the adjusted models epidemiological characteristics such as age, ward type, hospital type and linguistic region were identified as relevant co-variables for the resistance rates. The contribution of these confounders was specific to the individual species/antibiotic resistance models.. Resistance rates do not follow a dichotomic pattern (early versus late nosocomial) as suggested by current hospital-acquired pneumonia treatment guidelines. Duration of hospitalisation rather appears to have a more complex and non-linear relationship with bacterial resistance in hospital-acquired pneumonia, also depending on host and environmental factors.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Enterobacter; Escherichia coli; Female; Hospitalization; Humans; Klebsiella pneumoniae; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Oxacillin; Pneumonia; Pseudomonas aeruginosa; Respiratory System; Retrospective Studies; Staphylococcus aureus; Streptococcus pneumoniae

There is direct link between overutilisation or abuse of antibiotics and Pseudomonas aeruginosa resistance rates, but other factors may also influence the resistance rate. This study aimed to observe changes in P. aeruginosa resistance rates in patients with hospital-acquired infections (HAIs) following a period of cefepime unavailability in an ICU.. The study was designed as a retrospective observational analysis of trends in antibiotic utilisation and density of antibiotic resistance. It covered only P. aeruginosa isolates causing HAIs obtained from patients aged >18years. Isolates taken <48h after admission to the ICU and duplicate isolates were excluded. The effects of cefepime withdrawal from prescribing during the 2-year period on P. aeruginosa resistance density trends were also followed.. During the study period (2009-2016), a total of 318 non-duplicate P. aeruginosa isolates causing HAIs in the ICU were collected. The predominant anatomical localisation of these infections (nearly 95%) was the lungs (pneumonia), surgical sites and urinary tract (69.18%, 18.24% and 6.92%, respectively). The isolates showed a lower resistance density (per/1000 PDs) in the last year (2016) compared with the first year of observation (2009) for all monitored antibiotics, with a peak in 2011. Although a decreasing trend of resistance density was recorded for all examined drugs, statistical significance was noted only for imipenem, meropenem and piperacillin/tazobactam (P<0.05) CONCLUSIONS: Temporary withdrawal of cefepime in a hospital resulted in a significant decrease in the density of P. aeruginosa isolates resistant to imipenem, meropenem, piperacillin/tazobactam, ceftazidime and cefepime.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Cefepime; Cross Infection; Drug Utilization; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Young Adult

The spread of antibiotic resistance is rapidly threatening the effectiveness of antibiotics in the clinical setting. Many infections are being caused by known and unknown pathogenic bacteria that are resistant to many or all antibiotics currently available. Empedobacter falsenii is a nosocomial pathogen that can cause human infections. E. falsenii Wf282 strain was found to be resistant to many antibiotics, including carbapenems and colistin. Whole-genome shotgun sequencing of the strain was performed, and distinct features were identified. A novel metallo-β-lactamase, named EBR-2, was found, suggesting a potential role of E. falsenii as a reservoir of β-lactamases and other resistance determinants also found in its genome. The EBR-2 protein showed the highest catalytic efficiency for penicillin G as compared to meropenem and ampicillin and was unable to hydrolyze cefepime. The results described in this work broaden the current understanding of the role of β-lactamases in the Flavobacteriaceae family and suggest that E. falsenii Wf282 may be a reservoir of these novel resistance determinants.

Topics: Amino Acid Sequence; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae; Genome, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Penicillin G; Thienamycins

Carbapenems resistance is a growing phenomenon and a threat to public health because of the reduced therapeutic options for resistant infections.. A retrospective case-control study was conducted in 2 tertiary-care hospitals in Medellín, Colombia. Fifty patients infected with ertapenem-resistant enterobacteriaceae were compared with a control group consisting of 100 patients with infections caused by ertapenem susceptible enterobacteriaceae. A multivariate logistic regression model was used to identify factors that best explain ertapenem-resistant enterobacteriaceae infections.. The factors associated with ertapenem-resistant enterobacteriaceae infections were prior exposure to carbapenems (adjusted OR 3.43; 95% IC 1.08-10.87) and prior exposure to cefepime (adjusted OR 6.46; 95% IC 1.08-38.38).. Prior exposure to antibiotics is the factor that best explains the ertapenem-resistant enterobacteriaceae infection in this population, highlighting the importance of antimicrobial stewardship programs in hospitals.

Topics: Aged; Antimicrobial Stewardship; beta-Lactam Resistance; Carbapenems; Case-Control Studies; Cefepime; Colombia; Cross Infection; Diagnosis-Related Groups; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Female; Humans; Logistic Models; Male; Middle Aged; Retrospective Studies; Risk Factors; Tertiary Care Centers

To study the distribution characteristics and drug resistance of non-fermenting bacterial infection in intensive care unit (ICU) at a tertiary hospital during seven consecutive years, and to provide evidence for rational use of antibiotics in ICU.. A retrospective analysis was conducted. The related data about non-fermentative bacteria obtained from clinical specimens, collected from lower respiratory tract, blood, urine, bile and other secretions of ICU patients admitted to Binzhou Medical University Hospital from January 2009 to December 2015 were retrospectively analyzed. The distribution characteristics and drug resistance of non-fermentative bacteria, and isolation rate of multiple drug resistance (MDR) strains were analyzed.. 2 672 strains of nonfermentative bacteria were isolated during seven consecutive years, accounting for 57.9％ gram negative (G-) bacilli (2 672/4 613),and 35.2％ of all bacteria (2 672/7 587).The top five were Acinetobacter baumannii (38.4％),Pseudomonas aeruginosa (34.6％),Onion burkholderia cepacia (9.9％),Stenotrophomonas maltophilia (6.2％),and Pseudomonas fluorescens (5.6％).Non-fermentative bacteria were mainly isolated from the lower respiratory tract (60.9％).Isolation of the non-fermentative bacteria accounted for over 50％ of G-bacilli during seven consecutive years, and the isolation rate of the top five types of bacteria showed no obvious change, while positive rate of Acinetobacter baumannii showed a tendency to increase (obviously from 26.5％ in 2009 to 50.2％ in 2015),and a lowering trend of positive rate of Onion burkholderia cepacia,Stenotrophomonas maltophilia, and Pseudomonas fluorescens was obvious (from 15.6％,10.6％,13.0％ in 2009 to 5.6％,7.4％,1.4％ in 2015 respectively) was observed. The isolation rate of Pseudomonas aeruginosa was stable (about 30％) during seven consecutive years. The drug susceptibility results showed that the resistant rates of Acinetobacter baumannii against imipenem, meropenem, aminoglycosides and third-generation cephalmsporins were all higher than 70％,while its resistant rate to cefoperazone-sulbactam was relatively lower (40.2％-68.1％)with relatively higher sensitivity rate (23.6％-46.0％).In contrast, the resistant rates of Pseudomonas aeruginosa against antibiotics were low,while the sensitivity rate to fourth-generation cephalmsporins cefepime (58.3％-87.7％)and third-generation cephalmsporins was high (ceftazidime:55.6％-79.3％,piperacillin-tazobactam:62.5％-86.2％,cefoperazone-sulbactam:46.0％-89.8％).From 2009 to 2015,the incidence of MDR strains of Acinetobacter baumannii showed an obvious increasing tendency (from 68.0％ to 84.1％);in contrast, the incidence of MDR strains of Pseudomonas aeruginosa did not show an obviously increase in incidence from 2009 to 2012,on the other hand, it showed a decreasing tendency from a peak 68.6％ in 2012 to 23.5％ in 2015.. The isolation rate of non-fermentative bacteria was high and the drug resistance situation was serious. Therefore,it is important to grasp the knowledge regarding distribution characteristics, drug resistance and variation of non-fermentative bacteria in ICU. It is not only beneficial for both rational use of antibiotics, improve efficacy but also helpful in reducing the emergence of drug resistance stains.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cefoperazone; Cephalosporins; Cross Infection; Drug Resistance; Drug Resistance, Bacterial; Gram-Negative Bacteria; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Retrospective Studies; Thienamycins

We investigated an increase in Clostridium difficile infection (CDI) among pediatric oncology patients.. CDI cases were defined as first C difficile positive stool tests between December 1, 2010, and September 6, 2012, in pediatric oncology patients receiving inpatient or outpatient care at a single hospital. A case-control study was performed to identify CDI risk factors, infection prevention and antimicrobial prescribing practices were assessed, and environmental sampling was conducted. Available isolates were strain-typed by pulsed-field gel electrophoresis.. An increase in hospital-onset CDI cases was observed from June-August 2012. Independent risk factors for CDI included hospitalization in the bone marrow transplant ward and exposure to computerized tomography scanning or cefepime in the prior 12 weeks. Cefepime use increased beginning in late 2011, reflecting a practice change for patients with neutropenic fever. There were 13 distinct strain types among 22 available isolates. Hospital-onset CDI rates decreased to near-baseline levels with enhanced infection prevention measures, including environmental cleaning and prolonged contact isolation.. C difficile strain diversity associated with a cluster of CDI among pediatric oncology patients suggests a need for greater understanding of modes and sources of transmission and strategies to reduce patient susceptibility to CDI. Further research is needed on the risk of CDI with cefepime and its use as primary empirical treatment for neutropenic fever.

Topics: Adolescent; Anti-Bacterial Agents; Case-Control Studies; Cefepime; Cephalosporins; Child; Child, Preschool; Clostridioides difficile; Clostridium Infections; Cross Infection; Feces; Female; Hospitalization; Hospitals; Humans; Infant; Infection Control; Male; Medical Oncology; Pediatrics; Risk Factors; Young Adult

Multidrug-resistant bacterial pathogens are becoming a significant problem worldwide. Acinetobacter baumannii and Pseudomonas aeruginosa are problematic multidrug-resistant pathogens. This multicenter study in Vietnam determined the level of resistance to antimicrobial agents used to treat A baumannii and P aeruginosa infections in this country.. Five medical centers in Vietnam provided 529 P aeruginosa and 971 Acinetobacter species (904 A baumannii) isolates from patients with hospital-acquired or ventilator-associated pneumonia from 2012 to 2014. A central laboratory verified identification of the isolates and performed susceptibility testing using Clinical and Laboratory Standards Institute methods.. Resistance to cephalosporins, β-lactam/β-lactamase inhibitors, carbapenems, and fluoroquinolones was >90% against A baumannii. Aminoglycosides had only slightly better activity, with amikacin resistance >80%. Only colistin (MIC90, ≤0.25 mg/L) and tigecycline (MIC90, 4 mg/L) had appreciable activity against A baumannii. Similar activity was observed among the β-lactams tested against P aeruginosa. Cefepime demonstrated the highest activity (60.1% susceptible), which was similar to doripenem (58.6% susceptible), the most active carbapenem tested. Amikacin was the most active aminoglycoside tested against P aeruginosa, with susceptibility of 81.7% compared with tobramycin (58.0%) and gentamicin (56.5%). Fluoroquinolones had limited activity against P aeruginosa with susceptibility to ciprofloxacin (55.0%). All P aeruginosa isolates had colistin MIC values ≤2 mg/L.. The data from this 3-year longitudinal study in Vietnam demonstrate that 2 of the most common nonfermentative gram-negative pathogens associated with hospital-acquired and ventilator-associated pneumonia are significantly resistant to most of the available treatment options and require combination therapies unless new antimicrobial agents become available.

Topics: Acinetobacter baumannii; Amikacin; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactams; Carbapenems; Cefepime; Cephalosporins; Cross Infection; Doripenem; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Gentamicins; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Tigecycline; Vietnam

Topics: Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Confusion; Cross Infection; Electroencephalography; Humans; Male; Status Epilepticus

Resistance to all β-lactams is emerging among Pseudomonas aeruginosa (PA) clinical isolates. Aztreonam and cefepime act synergistically in vitro against AmpC overproducing PA isolates. The objective of this study was to evaluate the clinical efficacy of this treatment in ICU patients infected with multidrug-resistant PA.. Retrospective study (2 years, 2 ICUs) in a tertiary university hospital. Inclusion criteria were proven infection with evidence of a bacterial strain of PA resistant to all β-lactams and treated with the association of at least aztreonam plus cefepime. Treatment was considered effective for pneumonia using CPIS scores at the end of treatment and for other infections, using the SOFA score and signs of infection improvement at the end of treatment. Infectious episodes were classified as cure or failure.. Thirteen patients were included (10 nosocomial pneumonia, 3 nosocomial intra-abdominal infections). The median [25th-75th percentiles] admission SAPS2 score was 54 [51-69] and the median SOFA score at the beginning of infection was 7 [4-8]. The median CPIS scores for pneumonia at the beginning and end of treatment were 9 [7-10.5] and 2 [0.75-5.5]. The duration of treatment with the combination of aztreonam plus cefepime was 14 days [9.5-16]. Nine episodes were classified as cures and 4 as failures, indicating a clinical efficacy of 69.2%. Overall mortality was 38.5%.. These data suggest that the association of cefepime plus aztreonam could be an attractive alternative in the treatment of infections with multidrug-resistant PA to all β-lactams with a clinical efficacy rate of 69%.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Aztreonam; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Critical Care; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pilot Projects; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies

Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are frequently isolated pathogens in the hospital setting, and antimicrobial resistance among these organisms is on the rise. In an attempt to meet the challenge of gram-negative resistance, new therapies, including ceftolozane/tazobactam (C/T), were recently approved by the Food and Drug Administration, and others are in late-stage development. The purpose of this study is to describe the in vitro potency of C/T and other parenteral antimicrobials against a geographically diverse population of E coli, K pneumoniae, and P aeruginosa collected in US hospitals.. In 2013 to 2014, 44 hospitals provided nonduplicate, nonurine isolates of E coli (n = 1306), K pneumoniae (n = 1205), and P aeruginosa (n = 1257) from adult inpatients. MICs for C/T and 11 other antimicrobials were determined with broth microdilution methods.. The carbapenems, C/T, and colistin displayed the highest percentage of susceptibility and lowest MIC90 against the Enterobacteriaceae, followed by piperacillin/tazobactam (TZP), cefepime, tobramycin, aztreonam, ceftriaxone, and ciprofloxacin. C/T displayed the greatest potency (MIC90 = 2 mg/L) and 97% susceptibility of all compounds against P aeruginosa. In addition, C/T was highly active against P aeruginosa that were nonsusceptible to the carbapenems or TZP or were multidrug resistant and extended-spectrum β-lactamase-producing Enterobacteriaceae.. This national survey reported high levels of nonsusceptibility to antimicrobials among both Enterobacteriaceae and P aeruginosa. In contrast, many of these resistant pathogens were susceptible to C/T. These data highlight the enhanced potency of C/T and its potential utility for commonly encountered gram-negative nosocomial pathogens.

Topics: Adult; Anti-Infective Agents; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Enterobacteriaceae; Escherichia coli; Hospitals; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Pseudomonas aeruginosa; Tazobactam; United States

To investigate the spectrum and antimicrobial resistance of major pathogensthat causing nosocomial infections in China, 2013.. Nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 13 teaching hospital around China were collected. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The CLSI M100-S23 criteria were used for interpretation.. Of all cases, 1 022 cases were from BSI, 683 from HAP and 674 from IAI.Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI while Acinetobacter baumanii (34.6%) and Pseudomonas aeruginosa were dominated in HAP. Tigecycline, imipenem and meropenem exhibited high potency against Enterobacteriaceae and the susceptibilities rates were 95.6%, 94.2%and 95.2% respectively. Enterobacteriaceae demonstrated high resistance against cephalosporins (52.3%) and fluoroquinolones (38.9%) but were susceptible to β-lactam+inhibitor. Of all the Enterobacteriaceae, 30.5% were ESBLs positive and 4.3% were carbapenem resistant. Acinetobacter baumanii showed low susceptibilities to the microbial agents except for tigecycline (90.5%) and colistin (100%). The rate of carbapenem resistant Acinetobacter baumanii was 76.6%. Amikacin, ciprofloxacin, cefepime and piperacillin/tazobactam showed high antibacterial activity against Pseudomonas aeruginosa with susceptible rate 88.5%, 77.6%, 72.7% and 64.5% respectively. The resistant rate to imipenem and meropenem were 42.1% and 32.2%. All Staphylococcus aureus (166 strains) were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. MRSA accounted for 46.9% of all the Staphylococcus aureus. The prevalence of MRSA in IAI (55.2%) and HAP (54.4%) were higher that that in BSI (35.0%). No Enterococcus strains were found resistant to tigecycline, linezolid and daptomycin. VRE was found in Enterococcus faecium, accounting for 1.9% of all Enterococcus faecium strains.. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are the most common pathogens causing nosocomial infections. Nosocomial pathogens showed high susceptibilities against tigecycline. For ESBLs-producing Enterobacteriaceae strains, β-lactam+Inhibitor show high antibacterial activities. Vancomycin, teicoplanin and linezolid exhibit high potency to Staphylococcus aureus and Enterococcus.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefepime; Cephalosporins; China; Cross Infection; Hospitals, Teaching; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline; Vancomycin

OprD loss and hyperexpression of AmpC, MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were evaluated among 120 Pseudomonas aeruginosa isolates collected during 2012 in U.S. hospitals and selected based on ceftazidime MIC values (1 to >32 μg/ml). AmpC derepression (10-fold greater than that with the control) and OprD loss (decreased/no band) were the most prevalent resistance mechanisms: 47.5 and 45.8% of the isolates were considered positive, respectively. Elevated expression of the efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was observed in 32.5, 8.3, 0.0, and 28.4% of the isolates, respectively. A total of 21 different combinations of resistance mechanisms were noted, and the most prevalent included AmpC derepression with OprD loss with and without efflux hyperexpression (38 and 10 isolates, respectively). A total of 26 isolates had no changes in the resistance mechanisms tested and had lower MIC values for all β-lactams or β-lactam/β-lactamase inhibitor combinations analyzed. OprD loss had a strong correlation with elevated MIC results for imipenem and meropenem (median MIC values of 8 and 4 μg/ml, respectively), with all combinations displaying OprD loss also displaying elevated median MIC values for these carbapenems (4 to >8 μg/ml). AmpC expression levels were greater in isolates displaying elevated cefepime, ceftazidime, or piperacillin-tazobactam MIC values (≥4, ≥4, and ≥16 μg/ml, respectively). Isolates displaying derepressed AmpC had ceftolozane-tazobactam MIC values ranging from 1 to 16 μg/ml. No strong correlation was noticed with MIC values for this β-lactam/β-lactamase inhibitor combination and OprD loss or hyperexpression of efflux systems. Two KPC-producing isolates were detected among 16 isolates displaying ceftolozane-tazobactam MIC values of ≥8 μg/ml.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Gene Expression Regulation, Bacterial; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Porins; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Aged; Aged, 80 and over; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

A nosocomial outbreak of multi-drug-resistant Acinetobacter calcoaceticus-A. baumannii (MDR-ACB) complex infection occurred in a newly constructed building at a 2,500-bed tertiary medical center in Taiwan.. An investigation was carried out by molecular approaches to trace the bacteria. Antimicrobial susceptibilities, risk factors, and the occurrence of nosocomial MDR-ACB infections were investigated. From January to December 2009, 53 patients were infected with MDR-ACB, and 23 environmental surveys were performed in two surgical intensive care units (ICUs) within the new building. Forty-two clinical isolates were obtained from patients and 22 samples from nine environmental surveys.. Forty clinical isolates (95.2%) and 18 environmental samples (81.8%) were positive for MDR-ACB of type A, the predominant outbreak strain. This strain was identical to that isolated in an outbreak in the old hospital in 2006, as proved by repetitive extragenic palindromic-based polymerase chain reaction and pulsed-field gel electrophoresis. Although the outbreak isolates contained blaOXA-23-like and blaOXA-51-like genes, analysis of the antimicrobial susceptibilities demonstrated increases in resistance to cefepime and imipenem-cilastatin in MDR-ACB isolated in the later outbreak.. Not only patients or healthcare workers, but also medical equipment, might have carried the predominant outbreak strain from the old district to the new building. Therefore, even in a new environment, infection control programs must be enforced continually, and healthcare providers must be educated repeatedly to prevent recurrent outbreaks of MDR-ACB infection in the hospital setting.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Cefepime; Cephalosporins; Chi-Square Distribution; China; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Care; Cross Infection; Disease Outbreaks; Drug Combinations; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Microbial Sensitivity Tests; Public Health Surveillance; Retrospective Studies

Acinetobacter baumannii is characterized by strictly aerobic, gram-negative, nonmotile, nonlactose-fermenting, oxidase-negative, catalase-positive coccobacilli, and the combination of its environmental resilience and its rapid development of resistance to multiple classes of antimicrobials renders it a successful nosocomial pathogen.. The aim of this study was to identify specific risk factors and outcome of nosocomial pneumonia because of carbapenem-resistant Acinetobacter baumannii (CRAB).. The retrospective study, set in a 1,500-bed referral and tertiary care hospital, was conducted to analyze the clinical and microbiologic data of patients with nosocomial pneumonia because of Acinetobacter baumannii (A baumannii) from January 2006 to December 2011. Comparisons were made between patients with CRAB pneumonia and patients with carbapenem-susceptible A baumannii (CSAB) pneumonia. Only the first isolation of A baumannii was considered.. A total of 145 patients with CSAB pneumonia and 97 patients with CRAB pneumonia was included. Among these patients, the independent risk factors for acquiring CRAB pneumonia were Acute Physiology and Chronic Health Evaluation II (APACHE II) score (>20) at admission, systemic illnesses (chronic respiratory disease and cerebrovascular accident), presence of excess noninvasive or invasive devices (mechanical ventilation), and ever used antibiotics within 28 days (carbapenem and cefepime). The patients with CRAB pneumonia had higher mortality rate than CSAB pneumonia. Multivariate analysis showed that, among patients with A baumannii pneumonia, APACHE II score (>20) at pneumonia onset, infections with other microorganisms, and inappropriate therapy were independently associated with 28-day mortality.. Patients with CRAB pneumonia have a higher mortality rate than those with CSAB pneumonia. The nosocomial occurrence of CRAB pneumonia is strongly related to systemic illnesses, APACHE II score, mechanical ventilation, and ever used antibiotics within 28 days.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pneumonia; Retrospective Studies; Risk Factors

AmpC β-lactamases are clinically significant since these confer resistance to cephalosporins in the oxyimino group, 7-α methoxycephalosporins and are not affected by available β-lactamase inhibitors. In this study we looked for both extended spectrum β-lactamases (ESBL) and AmpC β-lactamases in Klebsiella pneumoniae clinical isolates.. One hundred consecutive, non-duplicate clinical isolates of K. pneumoniae collected over a period of one year (June 2008 - June 2009) were included in the study. An antibiotic susceptibility method was used with 10 antibiotics for Gram-negative infections which helped in screening for ESBL and AmpC β-lactamases and also in confirmation of ESBL production. The detection of AmpC β-lactamases was done based on screening and confirmatory tests. For screening, disc diffusion zones of cefoxitin <18 mm was taken as cefoxitin resistant. All cefoxitin resistant isolates were tested further by AmpC disk test and modified three dimensional test. Multiplex-PCR was performed for screening the presence of plasmid-mediated AmpC genes.. Of the 100 isolates of K. pneumoniae studied, 48 were resistant to cefoxitin on screening. AmpC disk test was positive in 32 (32%) isolates. This was also confirmed with modified three dimensional test. Indentation indicating strong AmpC producer was observed in 25 isolates whereas little distortion (weak AmpC) was observed in 7 isolates. ESBL detection was confirmed by a modification of double disk synergy test in 56 isolates. Cefepime was the best cephalosporin in synergy with tazobactam for detecting ESBL production in isolates co-producing AmpC β-lactamases. The subsets of isolates phenotypically AmpC β-lactamase positive were subjected to amplification of six different families of AmpC gene using multiplex PCR. The sequence analysis revealed 12 CMY-2 and eight DHA-1 types.. Tazobactam was the best β-lactamase inhibitor for detecting ESBL in presence of AmpC β-lactamase as this is a very poor inducer of AmpC gene. Amongst cephalosporins, cefepime was the best cephalosporin in detecting ESBL in presence of AmpC β-lactamase as it is least hydrolyzed by AmpC enzymes. Cefepime-tazobactam combination disk test would be a simple and best method in detection of ESBLs in Enterobacteriaceae co-producing AmpC β-lactamase in the routine diagnostic microbiology laboratories.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Humans; India; Klebsiella pneumoniae; Microbial Sensitivity Tests; Penicillanic Acid; Tazobactam

Previous antibiotic exposure is a risk factor for extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolation, but the optimal definition of previous antibiotic exposure remains unclear.. This was a retrospective, case-control study comparing 88 patients with ESBL-producing K pneumoniae (cases) and 88 patients with non-ESBL-producing K pneumoniae (controls). Three previous antibiotic exposure definitions were analyzed, including durations of 30, 60, and 90 days prior to organism isolation.. The mean cohort age was 63.6 ± 16.9 years, 43% were male, and 86% were black. In bivariate analysis, third-generation cephalosporins and cefepime were associated with ESBL-producing K pneumoniae isolation, and the odds ratios (OR) were significant regardless of previous antibiotic exposure definition. However, for fluoroquinolones and ampicillin/sulbactam, the ORs varied as a function of previous antibiotic exposure definition. In multivariate analysis, third-generation cephalosporin usage was a risk factor for ESBL-producing K pneumoniae isolation, whereas ampicillin/sulbactam usage was protective against these organisms, regardless of the time frame analyzed. Other independent predictors of ESBL-producing K pneumoniae included nursing home residence (OR, 9.30 [95% confidence interval: 3.69-23.43]) and hemodialysis (OR, 13.60 [95% confidence interval: 4.29-43.17]).. Prior use of third-generation cephalosporins, nursing home residence, and hemodialysis were independent risk factors for isolation of an ESBL-producing K pneumoniae regardless of the time frame analyzed.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Black or African American; Case-Control Studies; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Female; Fluoroquinolones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Michigan; Middle Aged; Multivariate Analysis; Nursing Homes; Odds Ratio; Renal Dialysis; Retrospective Studies; Risk Factors; United States

Antimicrobial resistance among microorganisms is a global concern. In 2003, a nationwide antibiotic restriction program (NARP) was released in Turkey. In this study we evaluated the effect of NARP on antibiotic consumption, antimicrobial resistance, and cost.. The data obtained from all of the four university hospitals, and one referral tertiary-care educational state hospital in Ankara. Antimicrobial resistance profiles of 14,233 selected microorganisms all grown in blood cultures and antibiotic consumption from 2001 to 2005 were analyzed retrospectively.. A negative correlation was observed between the ceftriaxone consumption and the prevalence of ceftriaxone resistant E.coli and Klebsiella spp. (rho:-0.395, p:0.332 and rho:-0.627, p:0.037, respectively). The decreased usage of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (rho:0.155, p:0.712 and rho:0.180, p:0.668, respectively for imipenem). Methicillin resistance rates of S.aureus were decreased from 44% to 41%. After two years of NARP 5,389,155.82 USD saving occurred.. NARP is effective in lowering the costs and antibiotic resistance.

Topics: Acinetobacter; Anti-Bacterial Agents; Cefepime; Ceftazidime; Ceftriaxone; Cephalosporins; Cost Savings; Cross Infection; Drug Costs; Drug Prescriptions; Drug Resistance, Bacterial; Drug Utilization; Escherichia; Health Policy; Hospitals; Humans; Imipenem; Klebsiella; Meropenem; Methicillin Resistance; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas; Staphylococcus aureus; Teicoplanin; Thienamycins; Turkey; Vancomycin

Cefepime neurotoxicity usually occurs in patients with renal impairment. The aim of this study was to evaluate the neurotoxicity of cefepime administered by continuous intravenous infusion during treatment of nosocomial infections in neurological patients with normal renal function.. This was an open pilot study of neurological patients with infections caused by cefepime sensitive bacteria. Patients had baseline neurological assessment and electroencephalogram (EEG). Cefepime plasma concentrations were determined 48 hours after infusion was initiated and at end of treatment (EOT).. Eleven patients were included. These were diagnosed with a brain tumor (9), cerebrovascular disease (1) and polyneuropathy (1). Infections were surgical site infection in 5, clinically defined nosocomial pneumonia in 4, and bacterial meningitis associated to postoperative CSF fistula in 2. Gram-negative organisms were isolated in 10 patients. Cefepime dose was 2 g/day in 9 patients and 4 g/day in 2. Mean cefepime plasma concentration at 48h was 13.6 ± 2.0 µg/mL (range 4.6 to 24.5 µg/mL), at EOT was 11.9 ± 1.8 µg/mL (range 3.0 to18.9 µg/mL ). EEG interpreted by two experts showed at baseline alpha background rhythm in 5 and theta-alpha rhythm in 6 patients. On EEG at EOT background rhythm was alpha in 4 and theta-alpha in 7, one patient presented isolated sharp and slow wave activity. No mental status changes or seizures occurred and all infections resolved.. Significant EEG change was observed in 1of 11 patients. A preserved mental status may correlate with cefepime safety in neurological patients with normal renal function during cefepime treatment.

Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Electroencephalography; Female; Humans; Infusions, Intravenous; Male; Mental Disorders; Microbial Sensitivity Tests; Middle Aged; Pilot Projects; Young Adult

Cefepime-induced thrombocytopenia is a rare adverse event (incidence <1.0%), based on data from clinical trials. However, there is limited post-marketing surveillance documentation on thrombocytopenia associated with cefepime. We describe a 45-year-old male who was admitted to the intensive care unit after allegedly being hit by a large metal bar in the right upper chest and shoulder. Rhabdomyolysis secondary to the trauma, pneumothorax, acute renal failure, and nosocomial sepsis were subsequently diagnosed. Four days after intravenous cefepime initiation, the patient developed thrombocytopenia with platelet count dropping from 102 × 10(3)/μL to 15 × 10(3)/μL. Cefepime was discontinued and the platelet count normalized to 140 × 10(3)/μL after 6 days. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between the patient's thrombocytopenia and cefepime therapy.. Although cefepime-induced thrombocytopenia is rare, clinicians should be alert to this potential adverse effect among critically ill patients.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefepime; Cephalosporins; Critical Illness; Cross Infection; Humans; Intensive Care Units; Male; Middle Aged; Pneumothorax; Rhabdomyolysis; Sepsis; Thrombocytopenia

The resistance mechanism of 49 Enterobacteriaceae isolates with decreased susceptibility to carbapenems collected from 2004 to 2008 at 16 teaching hospitals in China was investigated. Moderate- to high-level carbapenem resistance in most isolates was more closely associated with loss or decreased expression of both major porins combined with production of AmpC or extended-spectrum beta-lactamase enzymes, while KPC-2, IMP-4, and IMP-8 carbapenemase production may lead to a low to moderate level of carbapenem resistance in Enterobacteriaceae in China.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Genotype; Integrons; Microbial Sensitivity Tests; Phenotype; Population Surveillance; Porins; Reverse Transcriptase Polymerase Chain Reaction

A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate.

Topics: Belgium; beta-Lactamases; Cephalosporinase; Cephalosporins; Cross Infection; Escherichia coli; Genes, Bacterial; Humans; Kinetics; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

We describe the activity of a novel cephalosporin, CXA-101 (FR26 4205), against a panel of highly resistant Pseudomonas aeruginosa isolates collected from U.S. hospitals. CXA-101 demonstrated increased potency against this population of resistant isolates, with activity that is 4- to 10-fold higher than that of comparator agents in each phenotypic category. The addition of tazobactam did not improve its activity. CXA-101 appears to be a promising addition to the category of antipseudomonal beta-lactams.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cephalosporins; Child; Child, Preschool; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Pseudomonas aeruginosa; Tazobactam; Young Adult

CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. We evaluated the activity of CXA-101 against a highly challenging collection of beta-lactam-resistant Pseudomonas aeruginosa mutants selected in vitro and after antipseudomonal treatment of intensive care unit (ICU) patients. The in vitro mutants investigated included strains with multiple combinations of mutations leading to several degrees of AmpC overexpression (ampD, ampDh2, ampDh3, and dacB [PBP4]) and porin loss (oprD). CXA-101 remained active against even the AmpD-PBP4 double mutant (MIC = 2 microg/ml), which shows extremely high levels of AmpC expression. Indeed, this mutant showed high-level resistance to all tested beta-lactams, except carbapenems, including piperacillin-tazobactam (PTZ), aztreonam (ATM), ceftazidime (CAZ), and cefepime (FEP), a cephalosporin considered to be relatively stable against hydrolysis by AmpC. Moreover, CXA-101 was the only beta-lactam tested (including the carbapenems imipenem [IMP] and meropenem [MER]) that remained fully active against the OprD-AmpD and OprD-PBP4 double mutants (MIC = 0.5 microg/ml). Additionally, we tested a collection of 50 sequential isolates that were susceptible or resistant to penicillicins, cephalosporins, carbapenems, or fluoroquinolones that emerged during treatment of ICU patients. All of the mutants resistant to CAZ, FEP, PTZ, IMP, MER, or ciprofloxacin showed relatively low CXA-101 MICs (range, 0.12 to 4 microg/ml; mean, 1 to 2 microg/ml). CXA-101 MICs of pan-beta-lactam-resistant strains ranged from 1 to 4 microg/ml (mean, 2.5 microg/ml). As described for the in vitro mutants, CXA-101 retained activity against the natural AmpD-PBP4 double mutants, even when these exhibited additional overexpression of the MexAB-OprM efflux pump. Therefore, clinical trials are needed to evaluate the usefulness of CXA-101 for the treatment of P. aeruginosa nosocomial infections, particularly those caused by multidrug-resistant isolates that emerge during antipseudomonal treatments.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cephalosporins; Cross Infection; Humans; Intensive Care Units; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections

From 2002 to 2008, there was a significant increase in extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli isolates in European intra-abdominal infections, from 4.3% in 2002 to 11.8% in 2008 (P < 0.001), but not for ESBL-positive Klebsiella pneumoniae isolates (16.4% to 17.9% [P > 0.05]). Hospital-associated isolates were more common than community-associated isolates, at 14.0% versus 6.5%, respectively, for E. coli (P < 0.001) and 20.9% versus 5.3%, respectively, for K. pneumoniae (P < 0.01). Carbapenems were consistently the most active drugs tested.

Topics: Abdomen; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae

To evaluate the change of extended spectrum beta-lactamase (ESBLs) Producing Klebsiella Pneumoniae (ESBLs-KPN) and Escherichia coli (ESBLs-ECO) causing nosocomial infection after antimicrobial intervention.. We regularly monitored the data on the yearly consumption [defined as daily dose (DDD) per 1 000 patient-days] of frequently used antibiotics from Dec. 2004 to Dec. 2007. From Jan. 2005 to Dec. 2007, we monitored the resistance of frequently used antibiotics and the timely integrative antimicrobial intervention was based on the outcome of antimicrobial resistance. We also monitored the isolation rate of ESBLs-KPN and ESBLs-ECO causing nosocomial infection. The departments studied were the experimental group and other comparable medical departments were the control group(ICU was excluded).. The isolation rate of ESBLs-KPN (43.90%) and ESBLs-ECO (45.83%) in the experimental group was higher than that in the control group (28.04% and 24.90%, respectively) before the intervention (P<0.05). The isolation rate of ESBLs-KPN decreased (from 26.47% to 17.65%) in the experimental group and that in the control group increased ( ESBLs-KPN: from 34.18% to 52.94%; ESBLs-ECO: from 47.13% to 63.78%) from 2005 to 2007 (P<0.05). The isolation rate of ESBLs-KPN and ESBLs-ECO in the experimental group was lower than that in the control group after the antimicrobial intervention (P<0.05). Usage of ceftazidime and cefoperazone/sulbactam and imipenem was reduced and the consumption of cefepime was increased in the experimental group (P<0.05). Consumption of ceftazidime and cefoperazone/sulbactam and cefepime was increased.. The prevalence of ESBLs-KPN and ESBLs-ECO may be decreased after the integrative antimicrobial intervention.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged

Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia.. Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) >or= 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis.. Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC >or= 50%) for the pathogens recovered in this study (MIC or= 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest.. These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr >or= 50 ml/minute infected by pathogens with cefepime MICs

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Europe; Female; Humans; Intensive Care Units; Male; Middle Aged; Monitoring, Physiologic; Pneumonia; Prospective Studies; Young Adult

Catheter related infections are reported as one of the most common source of nosocomial infections. Rhizobium radibacter infections are generally manifested by fever and leukocytosis. Here, a 14 months-old girl diagnosed as T (-) B (-) NK (+) severe combined immunodeficiency (SCID) is presented. She had received repeated (x3) unconditioned haploidentical hematopoetic stem cell transplantations. During the follow-up, she has been arised an asymptomatic infection with R. Radiobacter, which was isolated from central venous catheter and peripheral blood while she was clinically stable, free of symptoms, fever or leukocytosis. She was treated successfully with cefepime and amikacin and did not require catheter removal. So, it is once more clear that the blood cultures should be obtained on regular basis from all patients with an intravascular device, even they were asymptomatic.

Topics: Agrobacterium tumefaciens; Amikacin; Anti-Bacterial Agents; Blood; Catheter-Related Infections; Catheterization, Central Venous; Catheters; Cefepime; Cephalosporins; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Severe Combined Immunodeficiency; Stem Cell Transplantation

The mechanisms responsible for the increasing prevalence of colistin-only-sensitive (COS) Pseudomonas aeruginosa isolates in a Spanish hospital were investigated. Pulsed-field gel electrophoresis revealed that 24 (50%) of the studied isolates belonged to the same clone, identified as the internationally spread sequence type 235 (ST235) through multilocus sequence typing. In addition to several mutational resistance mechanisms, an integron containing seven resistance determinants was detected. Remarkably, the extended-spectrum beta-lactamase GES-1 and its Gly170Ser carbapenem-hydrolyzing derivative GES-5 were first documented to be encoded in a single integron. This work is the first to describe GES enzymes in Spain and adds them to the growing list of beta-lactamases of concern (PER, VIM, and OXA) detected in ST235 clone isolates.

Topics: Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Colistin; Cross Infection; Humans; Molecular Sequence Data; Pseudomonas aeruginosa

Intrahospital infections (IHI) and antibiotics resistance are the problems which exist in virtually all hospitals in the world. The main aim of the present research is establishing of epidemiological surveillance over occurrence of IHI at the Clinic for Gynaecology and Obstetrics at the University Clinical Center Tuzla and thus identifies: types of bacteria which cause IHI, types of infection according to anatomical localization and research resistance organisms causing of IHI on antimicrobial drugs. A study was implemented on all patients admitted to Clinic for Gynaecology and Obstetrics during the period of one year and who subsequently developed infection. Determination of intrahospital infections was done according to criteria defined by the Centres for Disease Control and Prevention from the United States. The results of our work have shown that both urinary tract infections and surgical site infections are the most frequent. As IHI causers the most found are gram-negative organisms (73,7%), such as Escherichia coli (29,8%), right after that Klebsiella pneumoniae (24,6%), Pseudomonas aeruginosa (14%) and Proteus mirabilis (5,3%) (p<0,05). Gram-positive organisms as causers of IHI are registered in 26,3% cases. Out of that Streptococcus species are isolated in 10,5% cases, Staphylococcus aureus (8,8%) and coagulasa negative staphylococci (7%) (p>0,05). High percent resistance of bacteria was evident to beta-lactams, aminoglycosids and cephalosporin's of third generation. Gram-positive organisms were 100% sensitive to vancomycin, while gram-negative organisms manifested the high percent of sensibility to imipenem and cefepime.

Topics: Anti-Bacterial Agents; Bosnia and Herzegovina; Cefepime; Cephalosporins; Cross Infection; Female; Humans; Imipenem; Klebsiella pneumoniae; Obstetrics and Gynecology Department, Hospital; Population Surveillance; Prevalence; Prospective Studies; Proteus mirabilis; Pseudomonas aeruginosa; Staphylococcus aureus; Streptococcus; Surgical Wound Infection; Urinary Tract Infections; Vancomycin

Cefepime (FEP) and ceftazidime (CAZ) are broad-spectrum cephalosporins that display similar MICs for wild-type Pseudomonas aeruginosa strains. Recently, P. aeruginosa isolates showing a discordance in susceptibility to CAZ and FEP have been noted at the Hospital de Bellvitge in Barcelona, Spain, and a clustering was suspected. During the study period (March to December 2007), 51 patients, particularly those in an intensive care units (ICUs) (n = 29 [57%]), infected or colonized with at least one P. aeruginosa non-FEP-susceptible and CAZ-susceptible (Fep(ns) Caz(s)) phenotype strain were detected. Twenty-three (45%) patients were infected, and the respiratory tract was the most frequent site of infection. Changes in the consumption of antimicrobials in the ICUs were observed over time: a progressive reduction in the levels of consumption of carbapenems (247 defined daily doses [DDD]/1,000 patient days to 66 DDD/1,000 patient days; P = 0.008), after restriction of its use in 2006, and an expected increase in the rate of piperacillin-tazobactam use (42 DDD/1,000 patient days in 2004 to 200 DDD/1,000 patient days in 2007; P < 0.001). Throughout the whole study period, only a single clone of a P. aeruginosa Fep(ns) Caz(s) phenotype strain was identified by pulsed-field gel electrophoresis analysis to be associated with the hyperexpression of MexXY-OprM and the production of an integron-borne PSE-1 ss-lactamase. In conclusion, we identified an epidemic P. aeruginosa clone of an Fep(ns) Caz(s) phenotype strain involving 51 patients, in particular, ICU patients. The combination of the overexpression of an efflux pump and PSE-1 ss-lactamase production is associated with the multidrug-resistant phenotype. The dominant use of a single class of antibiotics could have provided the selective pressure required for the emergence and spread of this P. aeruginosa strain.

Topics: Adult; Aged; Aged, 80 and over; Animals; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Drug Utilization; Female; Gene Expression; Genes, Bacterial; Hospitals; Humans; Integrons; Intensive Care Units; Male; Membrane Transport Proteins; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Spain

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Chromosomes, Bacterial; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Bacterial; Edetic Acid; Greece; Humans; Imipenem; Integrons; Isoelectric Focusing; Microbial Sensitivity Tests; Molecular Sequence Data; Sequence Analysis, DNA

The basis of the beta-lactam resistance of 39 multidrug-resistant Acinetobacter baumannii isolates recovered from hospitalized patients was studied. These isolates were collected from 2001 to 2005 at the Sahloul Hospital in Sousse, Tunisia. They belonged to two distinct clones. One clone that grouped 19 isolates produced a carbapenem-hydrolyzing oxacillinase, OXA-97, that differed from OXA-58 by a single amino acid substitution and conferred the same beta-lactam resistance profile as OXA-58. The bla(OXA-97) gene was located on plasmids that varied in size in 18 isolates and was chromosomally located in a single isolate. Cloning and sequencing identified genetic structures surrounding the bla(OXA-97) gene similar to those reported to be adjacent to the bla(OXA-58) gene. In addition, the novel ISAba8 element (which is of the IS21 family) was identified. This is the first report of the nosocomial spread of carbapenemase producers in A. baumannii isolates in Africa.

Topics: Acinetobacter baumannii; Africa; Bacterial Proteins; beta-Lactamases; Blotting, Southern; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Models, Genetic; Molecular Sequence Data; Polymerase Chain Reaction; Tunisia

The first outbreak of carbapenem-resistant Klebsiella pneumoniae isolates producing the plasmid-encoded carbapenem-hydrolyzing oxacillinase OXA-48 is reported. The 39 isolates belonged to two different clones and were collected at the University Hospital of Istanbul, Turkey, from May 2006 to February 2007, and they coproduced various beta-lactamases (SHV-12, OXA-9, and TEM-1 for clone A and CTX-M-15, TEM-1, and OXA-1 for clone B).

Topics: Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Models, Genetic; Turkey

We investigated the basis of the carbapenem resistance of 17 multidrug-resistant Acinetobacter baumannii clinical isolates collected from 2004 to 2005 at the Saint George University Hospital in Beirut, Lebanon. A. baumannii isolates were clonally related and were susceptible to colistin and trimethoprim-sulfamethoxazole, susceptible or intermediate to ampicillin-sulbactam and meropenem, and resistant to all other antimicrobials. Conjugation experiments demonstrated that resistance to imipenem could be transferred along with a plasmid containing the carbapenem-hydrolyzing oxacillinase bla(OXA-58) gene. The plasmid that we called pABIR was 29,823 bp in size and showed a novel mosaic structure composed of two origins of replication, four insertion sequence (IS) elements, and 28 open reading frames. The bla(OXA-58) gene was flanked by IS18 and ISAba3 elements at the 5' and 3' ends, respectively. The production of the carbapenem-hydrolyzing oxacillinase OXA-58 was apparently the only mechanism for carbapenem resistance in A. baumannii isolates causing the outbreak at the Lebanese Hospital.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Conjugation, Genetic; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Hospitals, University; Humans; Imipenem; Lebanon; Molecular Epidemiology; Molecular Sequence Data; Plasmids

A total of 49 unique clinical isolates of multidrug-resistant (MDR) Acinetobacter baumannii identified at a tertiary medical center in Pittsburgh, Pennsylvania, between August 2006 and September 2007 were studied for the genetic basis of their MDR phenotype. Approximately half of all A. baumannii clinical isolates identified during this period qualified as MDR, defined by nonsusceptibility to three or more of the antimicrobials routinely tested in the clinical microbiology laboratory. Among the MDR isolates, 18.4% were resistant to imipenem. The frequencies of resistance to amikacin and ciprofloxacin were high at 36.7% and 95.9%, respectively. None of the isolates was resistant to colistin or tigecycline. The presence of the carbapenemase gene bla(OXA-23) and the 16S rRNA methylase gene armA predicted high-level resistance to imipenem and amikacin, respectively. bla(OXA-23) was preceded by insertion sequence ISAba1, which likely provided a potent promoter activity for the expression of the carbapenemase gene. The structure of the transposon defined by ISAba1 differed from those reported in Europe, suggesting that ISAba1-mediated acquisition of bla(OXA-23) may occur as an independent event. Typical substitutions in the quinolone resistance-determining regions of the gyrA and parC genes were observed in the ciprofloxacin-resistant isolates. Plasmid-mediated quinolone resistance genes, including the qnr genes, were not identified. Fifty-nine percent of the MDR isolates belonged to a single clonal group over the course of the study period, as demonstrated by pulsed-field gel electrophoresis.

Topics: Academic Medical Centers; Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Base Sequence; beta-Lactamases; Cross Infection; DNA Primers; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Pennsylvania; Polymerase Chain Reaction

VIM-type metallo-betalactamases (MBLs) exhibit hydrolytic activity against most betalactam antibiotics, including carbapenems. So far, VIM-type-producing Klebsiella pneumoniae isolates had not been reported in Latin America.. In July 2005, a carbapenem-resistant Klebsiella pneumoniae was isolated from a urine sample collected from a 7-year-old girl hospitalized at the Hospital de Niños "J. M. de los Ríos" in Caracas, Venezuela. This strain was identified using conventional biochemical tests. The susceptibility analysis was conducted by disk diffusion, and MICs for Imipenem and Meropenem were performed by agar dilution. For the phenotypic detection of MBL we used the Imipenem-EDTA/SMA double-disk diffusion method. The hydrolytic activity against carbapenems was determined by the Masuda microbiological method. Purified protein was subjected to isoelectric focusing (IEF). Detection of antimicrobial resistance genes was performed by PCR amplification with specific VIM primers.. The strain showed resistance to most betalactam antibiotics, quinolones and amynoglicosides, but remained susceptible to Aztreonam and Cefepime. The use of phenotypic and microbiological methods detected the presence of a metallobetalactamase. By IEF we visualized three bands at pI 5.4, 7.6 and 7.9, corresponding to reduced-spectrum betalactamases, and a band at pI 5.8 that corresponded to the metallobetalactamase. PCR screening of bla genes revealed the presence of blaVIM, with an amplicon of 261 bp.. This is the first report of a MBL-mediated carbapenem-resistant Klebsiella pneumoniae in Latin America, which constitutes a public health concern in our region since their transference to other microorganisms with multiple antibiotic resistance mechanisms will increase the antimicrobial resistance problem.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Child; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Quinolones; Thienamycins; Urine; Venezuela

To define the pharmacokinetic behaviour of cefepime in neonates with severe nosocomial infections using a mixed effects model.. Thirty-one newborn infants were included in the study; 10 additional infants participated in the validation of the pharmacokinetic model. Cefepime CL and V were determined using an open monocompartmental model with first-order elimination. The influence of demographic and clinical characteristics on the model was evaluated. The non-linear mixed effect model (nonmem) program was used to determine the pharmacokinetic population model.. The mean corrected gestational age for infants participating in the construction and validation of the model were 35 and 33 weeks, respectively. Factors included in the final pharmacokinetic model were body surface area (BSA) and calculated CL(CR). The final population model was CL (L/h) = 0.457 BSA (m(2)) + 0.243 CL(CR) (L/h) and V(L) = 4.12 BSA (m(2)). This model explains 33.3% of the interindividual variability for CL and 12.8% for V. This model was validated in ten neonates with nosocomial infections by assessing the predictive capacity of plasma cefepime concentrations using a priori and Bayesian strategies.. The predictive performance of this population model for cefepime plasma concentrations was adequate for clinical purposes and can be used for individualizing cefepime therapy in newborn infants with severe infections. Cefepime plasma concentrations can be predicted based on BSA and calculated CL(CR). Cefepime therapy using a 250 mg/m(2) dose administered every 12 h is adequate to achieve plasma concentrations greater than 8 mug/mL during more than 60% of the dosing interval and is expected to be effective in the treatment of bloodstream infections caused by most gram negative organisms in newborn infants. A dose of 550 mg/m(2) would be required for the treatment of infections caused by Pseudomonas sp.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Female; Gestational Age; Humans; Infant, Newborn; Infusions, Intravenous; Intensive Care Units, Neonatal; Male; Mexico; Models, Biological; Nonlinear Dynamics

A Klebsiella pneumoniae strain resistant to third-generation cephalosporins was isolated in the eastern Netherlands. The strain was found to carry a novel extended-spectrum beta-lactamase, namely, SHV-31. The combination of the two mutations by which SHV-31 differs from SHV-1, namely, L35Q and E240K, had previously only been described in association with one or more additional mutations.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Isoelectric Focusing; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Netherlands; Plasmids

Of the 181 unduplicated Escherichia coli strains isolated in nine different hospitals in three Portuguese regions, 119 were extended-spectrum beta-lactamase (ESBL)-CTX-M producers and were selected for phenotype and genotype characterization. CTX-M producer strains were prevalent among community-acquired infections (56%), urinary tract infections (76%), and patients >/=60 years old (76%). In MIC tests, all strains were resistant to cefotaxime, 92% were resistant to ceftazidime, 93% were resistant to quinolones, 89% were resistant to aminoglycoside, and 26% were resistant to trimethoprim-sulfamethoxazole; all strains were sensitive to carbapenems, and 92% of the strains had a multidrug resistance phenotype. Molecular methods identified 109 isolates harboring a bla(CTX-M-15) gene, 1 harboring the bla(CTX-M-32) gene (first identification in the country), and 9 harboring the bla(CTX-M-14) gene. All isolates presented the ISEcp1 element upstream from the bla(CTX-M) genes; one presented the IS903 element (downstream of bla(CTX-M-14) gene), and none had the IS26 element; 85% carried bla(TEM-1B), and 84% also carried a bla(OXA-30). Genetic relatedness analysis based on pulsed-field gel electrophoresis defined five clusters and indicated that 76% of all isolates (from cluster IV) corresponded to a single epidemic strain. Of the 47 strains from one hospital, 41 belonged to cluster IV and were disseminated in three main wards. CTX-M-producing E. coli strains are currently a problem in Portugal, with CTX-M-15 particularly common. This study suggests that the horizontal transfer of bla(CTX-M) genes, mediated by plasmids and/or mobile elements, contributes to the dissemination of CTX-M enzymes to community and hospital environments. The use of extended-spectrum cephalosporins, quinolones, and aminoglycosides is compromised, leaving carbapenems as the therapeutic option for severe infections caused by ESBL producers.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Middle Aged; Portugal

Bloodstream infections (BSI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Predictive Value of Tests; Proteus mirabilis; Risk Factors; Survival Analysis; Treatment Outcome

Clinical isolates of Acinetobacter baumannii (n = 470) were collected during a 7-year period and investigated for the genetic determinants of resistance to expanded-spectrum beta-lactams. Thirty-one isolates produced the TEM-92 extended-spectrum beta-lactamase (ESBL) and were clonally related. This is the first report of A. baumannii producing a TEM-type ESBL.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Cross Infection; Humans; Italy; Microbial Sensitivity Tests

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

Topics: Bacteremia; Community-Acquired Infections; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae Infections; Gene Transfer, Horizontal; Humans; Infectious Disease Transmission, Professional-to-Patient; Integrons; Microbial Sensitivity Tests; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Sequence Analysis, DNA; Treatment Outcome

Seven bla(IMP-1)-harboring Acinetobacter sp. isolates and one Pseudomonas putida clinical isolate were recovered from hospitalized patients. All isolates possessed a class 1 integron, named In86, carrying the same cassette array [bla(IMP1), aac(6')-31, and aadA1], which was plasmid located in five of the isolates. This report describes the ability of nonfermentative nosocomial pathogens to acquire and disseminate antimicrobial resistance determinants.

Topics: Acinetobacter; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Base Sequence; Brazil; Codon, Terminator; Cross Infection; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Hospitals; Humans; Integrons; Microbial Sensitivity Tests; Molecular Sequence Data; Open Reading Frames; Plasmids; Pseudomonas putida; Transcription, Genetic

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; beta-Lactamases; Cross Infection; Humans; Plasmids; Portugal

Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all beta-lactams and were only susceptible to colistin. bla(OXA-23)-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the bla(OXA-23) carbapenemase gene. Analysis of the genetic context of bla(OXA-23) showed the presence of ISAba1 upstream of bla(OXA-23). All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a bla(OXA-51)-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of bla(OXA-66) for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated bla(OXA-58) carbapenemase gene, while one isolate of another clone (clone L) carried the bla(OXA-72) carbapenemase gene. Only 1 isolate of clone Q carried the bla(IMP-8) metallo-beta-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried bla(PER-1)-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA-23 carbapenemase in China.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Blotting, Southern; Carbapenems; China; Chloramphenicol; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Imipenem; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Rifampin; Sequence Analysis, DNA

All (236) Pseudomonas aeruginosa isolates resistant to imipenem and/or meropenem collected during a multicenter (127-hospital) study in Spain were analyzed. Carbapenem-resistant isolates were found to be more frequently resistant to all beta-lactams and non-beta-lactam antibiotics than carbapenem-susceptible isolates (P < 0.001), and up to 46% of the carbapenem-resistant isolates met the criteria used to define multidrug resistance (MDR). Pulsed-field gel electrophoresis revealed remarkable clonal diversity (165 different clones were identified), and with few exceptions, the levels of intra- and interhospital dissemination of clones were found to be low. Carbapenem resistance was driven mainly by the mutational inactivation of OprD, accompanied or not by the hyperexpression of AmpC or MexAB-OprM. Class B carbapenemases (metallo-beta-lactamases [MBLs]) were detected in a single isolate, although interestingly, this isolate belonged to one of the few epidemic clones documented. The MBL-encoding gene (bla(VIM-2)), along with the aminoglycoside resistance determinants, was transferred to strain PAO1 by electroporation, demonstrating its plasmid location. The class 1 integron harboring bla(VIM-2) was characterized as well, and two interesting features were revealed: intI1 was found to be disrupted by a 1.1-kb insertion sequence, and a previously undescribed aminoglycoside acetyltransferase-encoding gene [designated aac(6')-32] preceded bla(VIM-2). AAC(6')-32 showed 80% identity to AAC(6')-Ib' and the recently described AAC(6')-31, and when aac(6')-32 was cloned into Escherichia coli, it conferred resistance to tobramycin and reduced susceptibility to gentamicin and amikacin. Despite the currently low prevalence of epidemic clones with MDR, active surveillance is needed to detect and prevent the dissemination of these clones, particularly those producing integron- and plasmid-encoded MBLs, given their additional capacity for the intra- and interspecies spread of MDR.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Chromosomes, Bacterial; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Integrons; Molecular Epidemiology; Molecular Sequence Data; Mutation; Plasmids; Polymerase Chain Reaction; Porins; Pseudomonas aeruginosa; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Spain

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Cefepime; Ceftriaxone; Cephalosporins; Cross Infection; Drug Therapy, Combination; Drug Utilization; Homes for the Aged; Hospital Mortality; Hospitalization; Humans; Injections, Intramuscular; Nursing Homes; Pneumonia, Aspiration; Pneumonia, Bacterial; Survival Rate; Treatment Failure

This study evaluated the clinical and microbiological characteristics of 16 patients who were colonised or infected with 26 isolates of pan-drug-resistant Pseudomonas aeruginosa (PDRPA; intermediately-resistant or resistant to all cephalosporins, piperacillin-tazobactam, aztreonam, carbapenems, ciprofloxacin and aminoglycosides) in a university hospital during 1999-2002. All the isolates had colistin MICs < or = 4 mg/L, 19 (73%) isolates had bla(VIM-3), and 25 (96%) isolates had class I integrons (intI). Time-kill studies for two PDRPA blood isolates demonstrated synergism for cefepime-amikacin after 24 h. Pulsed-field gel electrophoresis analysis of the isolates revealed a polyclonal nature (12 pulsotypes), although clonal dissemination of PDRPA isolates among these patients was also present.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Taiwan

To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease.. Ten thousand-subject Monte Carlo simulation.. Research center.. None.. Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin. Prevalence of causative pathogens was based on the 2000 SENTRY Antimicrobial Surveillance Study, and minimum inhibitory concentration (MIC) values were obtained using the 2003 US MYSTIC database. The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated. Bactericidal targets were defined as 40% T>MIC for the carbapenems, 50% T>MIC for other beta-lactams, and an area under the curve (AUC)/MIC ratio of 125 for ciprofloxacin. A sensitivity analysis was performed using two alternate models to determine the impact of varying pathogen prevalence on target attainment.. Meropenem and imipenem provided high probabilities of achieving their bactericidal target of 40% T>MIC, with target attainments of 98% for all regimens. At the bactericidal end point of 50% T>MIC, cefepime 2 g every 8 hrs displayed the highest target attainment at 99.9%, followed by cefepime 2 g every 12 hrs, ceftazidime 2 g every 8 hrs, piperacillin/tazobactam 4.5 g every 6 hrs and 3.375 g every 6 hrs, cefepime 1 g every 12 hrs, and ceftazidime 1 g every 8 hrs with target attainments of 95.0%, 92.5%, 92.3%, 91.3%, 90.3%, and 67.9%, respectively. Ciprofloxacin presented the lowest probability of achieving its bactericidal target of an AUC/MIC ratio of 125, with target attainments of 54.7% and 12.0% when given as 400 mg every 8 hrs and 400 mg every 12 hrs, respectively.. Meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin/tazobactam have high probabilities of achieving adequate pharmacodynamic exposures when given for the empirical treatment of nosocomial pneumonia in the absence of methicillin-resistant S. aureus. Ceftazidime 1g every 8 hrs and ciprofloxacin produce low target attainment rates and will not likely result in high clinical success rates when given as monotherapy.

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Thienamycins

Microbiological and clinical monitoring for 3 years (from 2001 to 2003) confirmed high clinical and microbiological efficacy of cefepime (Maxipime, Bristol-Myers-Squibb) in the treatment of infectious complications in patients with solid tumors in an oncologic hospital. It should be noted, however, that high efficacy of cefepime and wide ranges of the indications to its use do not allow to consider it as an agent for the treatment of all possible complications in such patients. The drug is not active against enterococci, not always clinically sufficiently effective in the treatment of Pseudomonas aeruginosa infections, it is impossible to use cefepime in monotherapy of suspected anaerobic infections. Therefore, widespread uncontrolled use of cefepime should be prohibited. It should be prescribed strictly by the indications with the account of the pathogen susceptibility, the infection severity and the recommended doses and regimens. The use of cefepime is undoubtedly valid when other antimicrobials fail or when empirical antimicrobial therapy of severe cases is required, including those under intensive care.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Gram-Negative Bacteria; Humans; Neoplasms

Of 72 blood isolates of Enterobacter spp. collected over an 8-year period, 50% (36 of 72) were derepressed or partially derepressed AmpC mutants. The extended-spectrum beta-lactamase (ESBL) production rate was 43% (31 of 72 isolates), and 67.3% (31 of 46) of extended-spectrum cephalosporin-resistant strains produced ESBLs. Thus, a confirmatory test for ESBL production is necessary for extended-spectrum cephalosporin-resistant Enterobacter spp.

Topics: Anti-Infective Agents; beta-Lactamase Inhibitors; beta-Lactamases; Cefepime; Cephalosporin Resistance; Cephalosporins; Cross Infection; Enterobacter; Enterobacteriaceae Infections; Enzyme Inhibitors; Gene Frequency; Genes, Bacterial; Humans; Isoelectric Focusing; Microbial Sensitivity Tests; Mutation

The in vitro activities of new expanded spectrum of fourth-generation cephalosporins, cefepime and cefpirome, were compared with those of three third-generation cephalosporins, cefoperazone, ceftazidime, and ceftriaxone, that are commonly used in the treatment of serious infections caused by aerobic gram-negative bacteria. The agar dilution method described by the US National Committee for Clinical Laboratory Standards was used to determine the minimum inhibitory concentrations of antibiotics tested. 302 clinical isolates, representing a cross-section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa were tested. Cefepime was considerably more active than other antibiotics tested, against Klebsiella species and Enterobacter species, and demonstrated activity similar to ceftazidime against Pseudomonas aeruginosa. Ceftazidime was active against Pseudomonas aeruginosa but was less potent against Enterobacter species. Cefoperazone and ceftriaxone were less active than ceftazidime against Pseudomonas aeruginosa. Cefepime had slightly greater activity than cefpirome against the gram-negative bacteria tested. However, cefepime and cefpirome were found to be highly active against many resistant organisms that traditionally have been difficult to treat.

Topics: Cefepime; Cefpirome; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests

Cefepime has activity against many hospital-acquired Gram-negative pathogens resistant to earlier beta-lactam antibiotics. This study was designed to test whether preferential use of cefepime in a pediatric intensive care unit could reduce enteric colonization with antibiotic-resistant Gram-negative rods.. After a 6-month period of uncontrolled antibiotic use, cefepime was preferentially used during 2 years as treatment for nosocomial or serious community-acquired infection. Rectal swab specimens were obtained daily on every patient regardless of antibiotic exposure during the 6 months of uncontrolled antibiotic use and during the first and last 6 months of the 2 years of cefepime preference. The study outcome was rectal colonization with a facultative Gram-negative rod resistant to at least one of four antibiotics: cefepime; ceftazidime; gentamicin; or piperacillin-tazobactam.. The incidence of colonization by a resistant organism decreased only slightly during the first 6 months of cefepime use. By contrast, the number of antibiotic-resistant bacilli isolated from rectal swab specimens diminished from 27.6/100 patients during the baseline period to 12.9/100 patients by the last 6 months of the 2 years of cefepime preference (P < 0.01). The proportion of patients harboring at least one resistant organism decreased from 11.6% to 7.4% during the same time period (P < 0.01). A decrease in colonization with resistant organisms occurred for all the tested resistance phenotypes, including cefepime.. Cefepime may possess a low potential for promoting bacillary resistance in critically ill patients, suggesting that its preferential use might be a key element in limiting the presence of antibiotic resistance in the intensive care unit.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Child, Preschool; Colony Count, Microbial; Cross Infection; Drug Resistance, Microbial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units, Pediatric; Male; Microbial Sensitivity Tests; Sensitivity and Specificity

Because results of pathogen identification are often lacking when antibiotic therapy is initiated, treatment must frequently be instituted on an empirical basis. The type of empirical therapy will depend on the anticipated pathogen spectrum and naturally also on the prevailing resistance patterns. Inadequate antibiotic therapy may not only be associated with increased overall treatment costs, but will also have adverse effects on mortality. The clinician is frequently faced with an overabundant variety of microbiological data and may fail to interpret them correctly. Therefore, the present study has attempted to "translate" the available microbiological resistance data, frequently presented in the form of percentage rates, into concrete patient numbers and thus illustrate the frequency of inadequate antibiotic therapy. For this purpose, "Indication Failure" (IF), "Cumulative Indication Failure" (CIF) and "Balanced Indication Failure" (BIF) have been calculated based on available microbiological data. For the indication "nosocomial pneumonia", calculations of the BIF show that only one out of 67 or one out of 63 patients is inadequately treated with a therapy with cefepime or imipenem, while one out of 25 patients is inadequately treated when using ceftazidime. However, it must be pointed out that these calculations only represent an interpretation of microbiological data and the success of antibiotic therapy will ultimately also depend on parameters such as the pharmacodynamic properties of an antibiotic or on the immunocompetence of the patient treated.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Drug Resistance, Multiple; Empiricism; Enterobacteriaceae Infections; Humans; Imipenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Treatment Failure

To determine the steady-state plasma and epithelial lining fluid concentrations of cefepime administered in continuous infusion in critically ill patients with severe bacterial pneumonia.. Prospective, open-label study.. An intensive care unit and research ward in a university hospital.. Twenty adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation were enrolled.. All subjects received a 30-min intravenous infusion of cefepime 2 g followed by a continuous infusion of 4 g over 24 hrs. The concentrations of cefepime in plasma and epithelial lining fluid were determined at steady state after 48 hrs of therapy with high performance liquid chromatography.. The mean +/- sd steady-state plasma and epithelial lining fluid concentrations of cefepime 4 g in continuous infusion were 13.5 +/- 3.3 microg/mL and 14.1 +/- 2.8 microg/mL, respectively, with a mean percentage penetration of cefepime into epithelial lining fluid of about 100%.. The administration of 4 g of cefepime in continuous infusion in critically ill patients with severe nosocomial pneumonia appears to optimize the pharmacodynamic profile of this beta-lactam by constantly providing concentrations in excess of minimal inhibitory concentration of most of susceptible organisms over the course of therapy in both serum and epithelial lining fluid.

Topics: Aged; Bronchoalveolar Lavage; Cefepime; Cephalosporins; Chromatography, High Pressure Liquid; Cross Infection; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitals, University; Humans; Infusions, Intravenous; Intensive Care Units; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Prospective Studies; Respiratory Mucosa

The incidence of extended-spectrum beta-lactamase (ESbetaL)-mediated resistance has increased markedly during the past decade. Risk factors for colonization with ESbetaL-producing Escherichia coli and Klebsiella species (ESbetaL-EK) remain unclear, as do methods to control their further emergence.. Case-control study.. Two hospitals within a large academic health system: a 725-bed academic tertiary-care medical center and a 344-bed urban community hospital.. Thirteen patients with ESbetaL-EK fecal colonization were compared with 46 randomly selected noncolonized controls.. Duration of hospitalization was the only independent risk factor for ESbetaL-EK colonization (odds ratio, 1.11; 95% confidence interval, 1.02 to 1.21). Of note, 8 (62%) of the patients had been admitted from another healthcare facility. In addition, there was evidence for dissemination of a single K oxytoca clone. Finally, the prevalence of ESbetaL-EK colonization decreased from 7.9% to 5.7% following restriction of third-generation cephalosporins (P = .51).. ESbetaL-EK colonization was associated only with duration of hospitalization and there was no significant reduction following antimicrobial formulary interventions. The evidence for nosocomial spread and the high percentage of patients with ESbetaL-EK admitted from other sites suggest that greater emphasis must be placed on controlling the spread of such organisms within and between institutions.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; beta-Lactam Resistance; Carrier State; Case-Control Studies; Cefepime; Cephalosporins; Cross Infection; Drug Therapy, Combination; Drug Utilization Review; Escherichia coli Infections; Feces; Female; Formularies, Hospital as Topic; Gentamicins; Hospitals, Community; Hospitals, Urban; Humans; Infection Control; Klebsiella Infections; Length of Stay; Male; Middle Aged; Pennsylvania; Prevalence; Risk Factors; Sulbactam

The aim of the study was to evaluate susceptibility of 976 bacterial isolates from nosocomial infections to cefepime and 9 other antibiotics used in the treatment of hospitalised patients. Bacterial strains were mainly derived from wound and soft tissue infections, sputum, abscesses and blood. The most prevalent etiologic agents were: Pseudomonas aeruginosa (18.7%), Escherichia coli (13.8%), Staphyloccocus aureus (9.7%, Acinetobacter baumannii (9.12%), Klebsiella pneumoniae (7.38%), Enterobacter cloacae (5.6%). The most susceptible to cefepime were strains of K. pneumoniae (98.62%), E. coli (98.52%) and E. cloacae (98.19%) including those producing extended spectrum beta-lactamases. The degree of susceptibility to cefepime was equal to that of imipenem. A. baumannii was the least susceptible species (67.42%). This study indicate that cefepime may play an important role in therapy of nosocomial infections in particular caused by Enterobacteriace.

Topics: Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests

Over a 3-year period, 67 patients of the Hospital of Pau (Pau, France), including 64 patients hospitalized in the adult intensive care unit (ICU), were colonized and/or infected by strains of Pseudomonas aeruginosa P12, resistant to all potentially active antibiotics except colistin. Most patients were mechanically ventilated and presented respiratory tract infections. Since cefepime and amikacin were the least inactive antibiotics by MIC determination, all ICU patients were treated with this combination, and most of them benefited. Cefepime-amikacin was found highly synergistic in vitro. Ribotyping and arbitrary primer-PCR analysis confirmed the presence of a single clonal isolate. Isoelectrofocusing revealed that the epidemic strain produced large amounts of the chromosomal cephalosporinase and an additional enzyme with a pI of 5.7, corresponding to PSE-1, as demonstrated by PCR and sequencing. Outer membrane protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the absence of a ca. 46-kDa protein, likely to be OprD, and increased production of two ca. 49- and 50-kDa proteins, consistent with the outer membrane components of the efflux systems, MexAB-OprM and MexEF-OprN. Thus, we report here a nosocomial outbreak due to multiresistant P. aeruginosa P12 exhibiting at least four mechanisms of beta-lactam resistance, i.e., production of the penicillinase PSE-1, overproduction of the chromosomal cephalosporinase, loss of OprD, and overexpression of efflux systems, associated with a better activity of cefepime than ceftazidime.

Topics: Adult; Amikacin; Bacterial Outer Membrane Proteins; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Ribotyping

Effective empiric treatment of pneumonia requires antibiotic coverage against gram-negative and gram-positive pathogens, including drug-resistant isolates. This study evaluated the efficacy of cefepime treatment in 20 patients with community-acquired pneumonia (CAP) and 21 patients with hospital-acquired pneumonia (HAP), and ceftazidime treatment in 20 patients with HAP. The mean age of patients was over 70 years. More than half of the patients had multiple lobe involvement. There was no significant difference in the severity of illness according to the acute physiology, age, chronic health evaluation (APACHE) III score between the HAP-cefepime and HAP-ceftazidime group. The most common bacteria isolated from sputum of patients with CAP were Streptococcus pneumoniae (n = 7), Klebsiella pneumoniae (n = 4), and Pseudomonas aeruginosa (n = 2). In patients with HAP, P. aeruginosa (n = 13), Acinetobacter baumannii (n = 11), Serratia marcescens (n = 6), K. pneumoniae (n = 5), Stenotrophomonas maltophilia (n = 5), Enterobacter cloacae (n = 3), Citrobacter spp. (n = 2), and Escherichia coli (n = 2) were isolated. The cure rates were 95%, 76%, and 60% in the CAP-cefepime group, the HAP-cefepime group, and the HAP-ceftazidime group, respectively. The increased rates of antimicrobial resistance commonly found among isolates causing CAP and HAP indicate that extended-spectrum antimicrobial agents, such as cefepime, would be more appropriate therapeutic agents.

Topics: Adult; Aged; Cefepime; Ceftazidime; Cephalosporins; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial

Pseudomonas aeruginosa is an important nosocomial pathogen. Resistance to certain beta-lactam antimicrobial agents among P. aeruginosa is increasing. The SENTRY Antimicrobial Surveillance Program was designed to employ a network of hospitals in the United States, Canada, Latin America, and Europe to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY results was to extract information on the current North American susceptibility pattern of P. aeruginosa for two antipseudomonal cephalosporins, ceftazidime, and cefepime. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory by using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of the 34, 530 North American bacterial isolates tested during 1997 and 1998, 2299 (6.7%) were P. aeruginosa. There were no substantial differences in regional rates of P. aeruginosa susceptibility to ceftazidime (range 78.8-81.9%) or cefepime (range 80.0-83.4%) The percentage of resistant isolates among the 1784 United States isolates was 13.3% for ceftazidime versus 7.1% for cefepime (p < 0.05). It is essential to continue surveillance of the in vitro efficacy of these and other beta-lactam agents against P. aeruginosa because of the clinical importance of these safe and broad-spectrum cephems used alone or in combination in current clinical practice.

Topics: Cefepime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Cross Infection; Databases, Factual; Humans; Microbial Sensitivity Tests; North America; Pseudomonas aeruginosa

The novel 4(th) generation cephalosporin FK037 was in vitro compared to cefepime and cefpirome on 563 multiresistant nosocomial isolates including methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Their time-kill effect was studied on MSSA, Escherichia coli, Klebsiella pneumoniae, and isolates of Enterobacter cross-resistant to cefotaxime, ceftriaxone, and to ceftazidime, their interaction with amikacin being also evaluated on the latter isolates. Results revealed that FK037 possessed a superior antistaphylococcal activity on MSSA isolates to both other compounds being however equal active to cefepime and cefpirome on multiresistant enterobacteriaceae. Synergy was documented between 4(th) generation cephalosporins and amikacin on K. pneumoniae and on Enterobacter spp. cross-resistant to 3(rd) generation cephalosporins. In the latter species 4(th) generation cephalosporins remained inactive. The presented results support the need of clinical studies with FK037 as monotherapy for nosocomial infections based on the local surveillance data of the level of antimicrobial resistance of each hospital.

Topics: Acinetobacter; Cefepime; Cefpirome; Ceftizoxime; Cephalosporins; Cross Infection; Enterobacteriaceae; Gram-Negative Bacteria; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Pseudomonas; Staphylococcus aureus; Stenotrophomonas

Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.

Topics: Amino Acid Sequence; Aztreonam; Bacterial Proteins; Base Sequence; beta-Lactamases; Cefepime; Cefotaxime; Cefoxitin; Ceftazidime; Ceftriaxone; Cephalosporins; Cephamycins; Cloning, Molecular; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; France; Hafnia; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Monobactams; Plasmids; Polymerase Chain Reaction

Comparative activity of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, imipenem and piperacillin/tazobactam against isolates from patients of pediatric intensive care units within October-December 1998 was studied. The isolates were identified with the Walkaway-40 System. The antibiotic susceptibility was evaluated by the E-test on the Mueller-Hinton II agar. The data were interpreted in accordance with the NCCLS. The number of the isolates totaled 100. Among them not more than 10 to 12 strains belonged to the same species. 92 per cent of the isolates was susceptible to cefepime and 70 to 75 per cent of the isolates were susceptible to the third generation cephalosporins. Piperacillin/tazobactam proved to be highly susceptible, the number of the isolates resistant and moderately resistant to it being 6 and 1 per cent respectively. The results showed that cefepime was intermediate between the third generation cephalosporins and carbapenems.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Cross Infection; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intensive Care Units, Pediatric; Microbial Sensitivity Tests

Topics: Acinetobacter; Acinetobacter Infections; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Humans; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Pseudomonas aeruginosa; Pseudomonas Infections; Turkey

Topics: Anti-Bacterial Agents; Bacteria; Cefepime; Cephalosporins; Colombia; Cross Infection; Hospitals, Teaching; Humans

Topics: Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Hydrolysis; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins

Cefepime, a new parenteral cephalosporin, was evaluated for its in vitro antibacterial activity in comparison with other broad-spectrum antibiotics against a total of 445 recently isolated microorganisms of nosocomial origin. Cefepime was highly active against all species of Enterobacteriaceae with minimum inhibitory concentrations (MIC90S) ranging from 0.25-8 micrograms/ml. Cefepime showed moderate activity against Acinetobacter spp (MIC50 and MIC90, 16 micrograms/ml) but its activity was superior to that of any drug tested, except imipenem. Against Pseudomonas aeruginosa its activity was comparable to that of ceftazidime and was greater than that of cefotaxime, aztreonam, ciprofloxacin and aminoglycosides. Of all the agents tested, imipenem was the most active compound. Cefepime was active against Staphylococcus aureus and coagulase-negative methicillin-susceptible staphylococci but it had no activity against methicillin-resistant staphylococci and enterococci.

Topics: Acinetobacter; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Enterobacteriaceae; Greece; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pseudomonas aeruginosa; Staphylococcus aureus

In vitro activities of cefepime and cefpirome against 96 isolates of Chryseobacterium indologenes and 21 of C. meningosepticum were determined by the agar dilution method. Overall, cefepime was more active than cefpirome against C. indologenes (MIC at which 50% of the isolates were inhibited [MIC50] and MIC90, 4 and 16 microg/ml, respectively, for cefepime and 8 and 128 microg/ml, respectively, for cefpirome). Both agents had poor potency against C. meningosepticum (MIC50 and MIC90, 64 and >256 microg/ml, respectively, for cefepime and 128 and >256 microg/ml, respectively, for cefpirome).

Topics: Cefepime; Cefpirome; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Flavobacterium; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests

The increasing prevalence of streptococci as causes of potentially fatal nosocomial bacteremia requires that antimicrobial agents used for empiric therapy in hospitalized patients include both pneumococci and viridans group streptococci as well as beta-hemolytic streptococci in their activity profile. In this study, the in vitro activity of cefepime, a new fourth-generation cephalosporin, was compared with other cephalosporins versus 197 nosocomial blood stream isolates of streptococci (20 Streptococcus pneumoniae, 104 viridans group, and 73 beta-hemolytic) isolated from patients at more than 30 medial centers from 1995 to 1997. Additional agents tested included penicillin, erythromycin, and vancomycin. Overall, cefepime inhibited 83% of the isolates at concentrations < or = 0.5 microgram/mL and 100% at < or = 8 micrograms/mL. By comparison, ceftazidime inhibited 35 and 88% of isolates at the same concentrations. Cefepime was approximately eightfold more potent than ceftazidime against S. pneumoniae, viridans group streptococci, and beta-hemolytic streptococci. Among the 42 isolates with penicillin MICs > 0.12 microgram/mL, 100% were inhibited by cefepime and only 48% by ceftazidime at < or = 8 micrograms/mL. The rank order of activity for all six agents against the 197 isolates was vancomycin > ceftriaxone > cefepime > penicillin > erythromycin > ceftazidime. Based on the results of the present study, cefepime and ceftriaxone were the superior cephalosporins in potency and spectrum for empiric coverage of patients at risk for streptococcal blood stream infections.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Ceftazidime; Ceftriaxone; Cephalosporins; Cross Infection; Erythromycin; Humans; Penicillins; Streptococcal Infections; Streptococcus; Vancomycin

The authors report a retrospective study of 35 patients treated with cefepime (Axepim). This patients were either hospitalized in a medical or in a surgical ICU or were febrile neutropenic patients. The non neutropenic group was put on cefepime for nosocomial pneumonia or miscellaneous sepsis. When recovered, Enterobacteriaceae were the most frequent pathogens. Clinical cure rate for the patients treated with cefepime was 83%. Cefepime is a safe and effective empirical treatment for serious infections and nosocomial infections in particular.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Cefepime; Cephalosporins; Cross Infection; Drug Therapy, Combination; Female; Fluoroquinolones; Glycopeptides; Hospitals, University; Humans; Injections, Intravenous; Lung Diseases; Male; Middle Aged; Neutropenia; Retrospective Studies; Sepsis

The in-vitro susceptibility 244 consecutive, non-duplicate clinical isolates of Pseudomonas aeruginosa cefepime and ceftazidime was studied. Using an agar dilution method to measure susceptibility, the antibiotics showed comparable activity. The Etest and two types of agar diffusion discs were compared with the reference agar dilution method, and showed an absolute interpretive agreement value of over 95%.

Topics: Cefepime; Ceftazidime; Cephalosporins; Colony Count, Microbial; Cross Infection; Diffusion; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Quality Control; Reference Standards; Reproducibility of Results

Cefepime is a new aminothiazolylacetamido cephalosporin with a wider spectrum and greater potency than many currently available cephalosporins. Since the blood culture isolates from patients of the study centre in Saudi Arabia are significantly more resistant to antimicrobial agents in clinical practice, we evaluated the in-vitro activity of cefepime and six other beta-lactam antibodies against 390 and 273 isolates of Gram-negative and Gram-positive bacteria, respectively. Cefepime had a broad spectrum of activity against the Enterobacteriaceae (MIC50 < 0.12 mg/L), Pseudomonas aeruginosa, Acinetobacter spp. and methicillin susceptible Staphylococcus aureus (MIC50 2.0 mg/L). The activity of cefepime was generally two-to four-fold greater than that of ceftazidime. Resistance to cefepime was most often encountered with Serratia spp. (45%), Citrobacter spp. (25%), Enterobacter cloacea (22%), and Stenotrophomonos mattophilia (45%). It had little or no activity against methicillin-resistant S. aureus and enterococci. Cefepime was highly active, with a spectrum better than ceftazidime against Gram-negative, and better than cephalothin against Gram-positive blood culture isolates.

Topics: Bacteremia; Bacteria; Cefepime; Cephalosporins; Cross Infection; Humans; Microbial Sensitivity Tests

The potency of cefepime, a parenteral aminothiazolyl methoxyimino cephalosporin, was assessed against 256 ceftazidime-resistant Gram-negative bacilli from five medical centers in the United States. In addition, cefepime activity was compared with that of ciprofloxacin and imipenem against 506 ceftazidime-resistant Gram-negative bacilli collected during an 11-medical-center international study. All US clinical isolates were susceptible (< or = 8 micrograms/ml) to cefepime except Enterobacter cloacae (94% susceptible) and Pseudomonas aeruginosa (19% susceptible). Enterobacteriaceae isolates from the 11-nation sample were > 80% cefepime susceptible with the exception of those from Brazil (48% susceptible) and Italy (55% susceptible). These international, enteric isolates were also very susceptible to ciprofloxacin (55%-100% susceptible) and imipenem (84%-100% susceptible). Nonenteric organisms (Pseudomonas, Xanthomonas, and Acinetobacter) from the same international locations had overall rates of susceptibility of 47% for ciprofloxacin, 28% for imipenem, and only 5% for cefepime. Cross-resistance between the broad-spectrum cephalosporins (cefepime or ceftazidime) with either imipenem or ciprofloxacin was incomplete. Cefepime appears to have a spectrum of use against a significant number of contemporary, ceftazidime-resistant Gram-negative bacillus isolates worldwide.

Topics: beta-Lactamases; Cefepime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Ciprofloxacin; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; International Cooperation; Microbial Sensitivity Tests

Topics: Cefepime; Cephalosporins; Cross Infection; Humans; Microbial Sensitivity Tests

The in vitro activity of a new parenteral cephalosporin cefepime (BMY 28142) was compared with that of ceftazidime, cefotaxime, piperacillin, imipenem, gentamicin, amikacin and ciprofloxacin against 173 recent multiresistant Pseudomonas aeruginosa isolates of nosocomial origin using an agar dilution technique with an inoculum of 10(4) CFU per spot. The activity of cefepime was comparable to that of ceftazidime, superior to that of cefotaxime, piperacillin, gentamicin and amikacin, but inferior to that of imipenem and ciprofloxacin. Cross-resistance of Pseudomonas aeruginosa to ceftazidime and cefepime occurred in nearly 50% of the cefepime resistant strains and 61.5% of the ceftazidime resistant strains respectively.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Pseudomonas aeruginosa

The in vitro activity of the new parenteral cephalosporin BMY-28142 was compared with that of cephalothin, cefoxitin, cefotaxime, ceftriaxone, moxalactam, aztreonam and ceftazidime, against a total of 374 recent multiresistant Gram-negative microorganisms of nosocomial origin. Against all species of Enterobacteriaceae resistant to the first- and second-generation cephalosporins, BMY-28142 had superior inhibitory activity than the newer beta-lactams tested, with intrinsic activity against E. coli and Pr. mirabilis slightly less than that of cefotaxime and ceftriaxone. BMY-28142 differed from the other beta-lactams mainly in being at least 16-fold more active against E. cloacae, while BMY-28142 and ceftazidime showed comparable activity against Ps. aeruginosa strains. Against strains of Ps. aeruginosa resistant to both BMY-28142 and amikacin, the combination of the two antibiotics proved to be synergistic in vitro.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests

The activity of three new antimicrobial agents [cefpirome (HR 810), BMY 28142, WIN 49375], and imipenem was compared to that of four currently available agents, ceftazidime, aztreonam, timentin and piperacillin, against 253 bacterial isolates from cancer patients. The activity of all four agents not yet in clinical use at our institution was significantly greater than that of the four antibiotics already in use.

Topics: Anti-Bacterial Agents; Cefepime; Cefpirome; Cephalosporins; Ciprofloxacin; Cross Infection; Fluoroquinolones; Gram-Negative Bacteria; Humans; Imipenem; Microbial Sensitivity Tests; Neoplasms; Quinolines; Thienamycins