cefepime and Klebsiella-Infections

To review the efficacy of cefepime for use in infections caused by extended-spectrum beta-lactamase (ESBL)-producing organisms.. A PubMed literature search (May 2000 to June 2017) was performed using the keyword. All human, English language studies evaluating cefepime use for the treatment of ESBL-producing. Studies assessing the use of cefepime for ESBL infections are few, and clinical studies are limited by design and sample size. The largest pharmacokinetic/pharmacodynamic study, a Monte Carlo simulation using data from the U.S. SENTRY antimicrobial surveillance program, evaluating cefepime use for infections due to ESBL-producing organisms found a 95% to 100% probability of target attainment with traditional cefepime dosing regimens. Most clinical studies found that patients treated with cefepime empirically and definitively had higher rates of mortality than those treated with carbapenems. However, in concordance with other studies reporting minimum inhibitory concentration (MIC) data, lower MICs were associated with lower mortality.. Cefepime should be avoided for empiric treatment of suspected ESBL infections and should only be considered for definitive treatment if the MIC ≤1 µg/mL. However, the site and severity of infection, local resistance patterns, and patient-specific risk factors should also help guide antimicrobial selection.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

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

Clinical treatment for blaKPC-positive Klebsiella pneumoniae isolates is challenging because the recommended antibiotic options are limited and are extraordinarily expensive. This study aimed to explore a new therapy for infection caused by KPC-producing K. pneumoniae.. Patients with blaKPC-positive K. pneumoniae infection, were prospectively screened and were categorised into two groups: patients in the study group received a combination-based therapy of cefepime and amoxicillin/clavulanic acid and the control group received tigecycline-based therapy. The pathogen clearance rate, 28-day mortality and cost of the antibiotic treatment were compared between the two groups. Moreover, the checkerboard microdilution method was performed to determine the synergy between cefepime and amoxicillin/clavulanic acid in vitro.. Twenty-six and 25 cases were enrolled in the study and control groups. The mortality and the overall pathogen clearance rate showed no significant differences (P=0.311 and P=0.447). Both the total cost and the portion of the cost not covered by insurance were higher for the control group compared to the study group (both P<0.001). Consistently, synergy (65.4%) and partial synergy (26.9%) were the main effects.. In contrast to the currently recommended tigecycline-based therapy, cefepime and amoxicillin/clavulanic acid combination was an effective and economical option to KPC-KP infection in China.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Tigecycline

We conducted a randomized, prospective, open comparison to evaluate the efficacy and safety of cefepime and ceftazidime in the treatment of hospitalized patients with suspected gram-negative bacteremia. Twenty-eight patients with signs and symptoms of sepsis were prospectively randomized to receive cefepime (13 patients) or ceftazidime (15 patients). Cultures of blood obtained at entry into the study were positive for 24 (85.7%) of 28 patients. Eight patients had two or more positive pretreatment blood cultures, and the remaining 16 had one positive pretreatment blood culture. The most commonly isolated blood pathogen was Escherichia coli. Eleven of 13 patients treated with cefepime and 12 of 15 patients treated with ceftazidime were clinically cured. Adverse effects attributable to therapy with the study drugs were minimal in both groups of patients and included rash, headache, nausea, and diarrhea. Our results suggest that cefepime is an efficacious and well tolerated as is ceftazidime in the treatment of hospitalized patients with documented gram-negative bacteremia.

Topics: Aged; Bacteremia; Cefepime; Ceftazidime; Cephalosporins; Drug Eruptions; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prospective Studies; Safety

Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L.. This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours.. Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016).. Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

Urinary tract infections (UTIs) and bacterial resistance to antibiotics is global health problem and a threat to public health in many countries.. The study aimed to determine the prevalence of MDR Escherichia coli and Klebsiella pneumoniae in UTI patients.. The midstream urine samples of 120 patients were collected and cultured as described by the protocols at the respective sample collection sites on MacConkey Blood agar. Samples were tested by using the fully automated VITEK 2 Compact system for Gram-negative identification and detection of antimicrobial susceptibility of microorganisms.. The most prevalent pathogen was E. coli, which was found in 82 (68.3%) urine samples, followed by K. pneumonia, found in 38 (31.7%) urine samples. As far as antibiotic resistance is concerned, E. coli isolates were found to be highly resistant for ceftriaxone (89.0% of the isolates), ampicillin (86.6%), levofloxacin (82.9%), cefotaxime (79.3%), aztreonam (74.4%), ceftazidime (68.3%) and gentamicin, piperacillin, and trimethoprim-sulfamethoxazole, 54.9 and 53.7%, respectively. The E. coli isolates were found to be relatively less resistant to imipenem (2.4%), cefepime (34.1%), and ciprofloxacin (35.4%). For K. pneumonia isolates, high resistance rates were observed for piperacillin (81.6%), levofloxacin (78.9%), ampicillin (76.3%), cefotaxime (73.7%), trimethoprim-sulfamethoxazole (71.1%), ceftazidime (65.8%), gentamicin (63.2%), cefepime (50.0%), and aztreonam (44.7%). However, moderate resistance rates were detected for these were found to be less resistant for imipenem (13.2%), ceftriaxone (31.6%), and ciprofloxacin (36.8%).. E. coli and K. pneumoniae from the clinical isolates displayed high resistance to many antibiotics in UTI patients.

Topics: Ampicillin; Anti-Bacterial Agents; Aztreonam; Cefepime; Ceftazidime; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Piperacillin; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88-42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65-21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30-31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003-0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02-0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cefepime; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged

Resistance to ceftazidime-avibactam due to mutations in KPC genes has been reported both

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Boronic Acids; Cefepime; Ceftazidime; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections

Klebsiella pneumoniae is a well-known pathogen and contributes to different types of infection. To investigate the antibiotic resistance profiles and prevalence of class I, II, and III integrons among clinical isolates of K. pneumoniae, a total of 142 non-duplicate clinical isolates were collected. Antibiotic susceptibility was assessed using Kirby-Bauer disk diffusion method and Clinical and Laboratory Standards Institute (CLSI) guidelines. Polymerase chain reaction (PCR) method was used to identify class I, II and III integrons. The isolates were mostly resistant against streptomycin (62 strains, 43.7 %) and ceftriaxone (42 strains, 29.6 %). Twenty-six (18.3%) isolates were found to be multi-drug resistant (MDR). Class I and II integrons were detected in 65 isolates (45.8%) and 1 (0.7%) isolate, respectively. The findings of this study revealed that the prevalence of streptomycin-resistant isolates is high, and its use must be restricted. Also, our results revealed that class I integrons are widely prevalent in clinical isolates of K. pneumoniae and a significant association was observed between resistance against imipenem, ciprofloxacin, gentamicin and streptomycin and the presence of integrons, necessitating appropriate infection control programs.

Topics: Anti-Bacterial Agents; Cefepime; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Female; Guidelines as Topic; Humans; Integrons; Klebsiella Infections; Klebsiella pneumoniae; Male; Polymerase Chain Reaction; Pseudomonas aeruginosa; Streptomycin

An 83-year-old man, presenting decreased renal function (estimated glomerular filtration rate 21 mL/min/1.73 m), was treated for a bone and joint infection (on a trans-metatarsal right foot amputation) caused by Klebsiella Pneumonia sensitive to cefepime. The starting dose (1 g bid) was based on recommendations for patients presenting severe infections. One week after treatment initiation, the patient developed neurotoxicity, exhibiting extremely high plasma cefepime concentrations. Based on TDM, the dose was reduced by 8 times the original dose. This case report highlights the importance of therapeutic drug monitoring for cefepime, especially in patients presenting altered renal functions, as typical recommendations are estimated for standard patients.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Drug Monitoring; Glomerular Filtration Rate; Humans; Kidney; Kidney Function Tests; Klebsiella Infections; Klebsiella pneumoniae; Male; Neurotoxicity Syndromes

Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy.. A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy.. A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37).. Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.

Topics: Aged; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Case-Control Studies; Cefepime; Ciprofloxacin; Colombia; Drug Resistance, Multiple, Bacterial; Endemic Diseases; Female; Genotype; Humans; Kaplan-Meier Estimate; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Male; Meropenem; Middle Aged; Phenotype; Prospective Studies; Risk Factors; Survival Analysis; Urinary Catheters

Klebsiella pneumoniae is an important multi-drug-resistant Gram-negative pathogen, associated with nosocomially acquired infections. This study aimed to determine the genotypic and phenotypic characterization of Klebsiella pneumoniae isolates and to correlate the antibiotic resistance with the presence of virulence genes revealed by molecular genotypic testing in Riyadh, Saudi Arabia.. About 23 Klebsiella pneumoniae isolates were collected from various specimen types. Identification of the organisms was carried out. Antimicrobial susceptibility performed against 12 antibiotics. The DNA was isolated and purified then genotypic confirmation was done through polymerase chain reactions (PCR) to detect TEM, SHV, CTX-M, IMP and KPC genes. PCR products were sequenced and aligned with GenBank sequences.. Out of 23 isolates of K. pneumoniae, the majority (43.5%) was from tracheal aspirate. The percentage of females (65.2%) was more than males (34.8%). The highest isolates prevalence was found in the age group of >58 (39.1%). About 100% of isolates were resistant to cefotaxime, ceftriaxone, ceftazidime, cefepime and ampicillin and 91.3% were sensitive to amikacin and Imipenem. Most isolates were SHV-9 gene positive (52.2%). It was found that tested isolates had 99-100% similarity when compared to GenBank sequences.. There was a preponderance of SHV-9 gene which suggests dissemination of the gene in the tested isolates.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; DNA, Bacterial; Female; Genetic Variation; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Saudi Arabia; Virulence

OXA-48 is an Ambler class D β-lactamase that hydrolyses penicillin and imipenem but has poor hydrolytic activity against cephalosporins. However, very few clinical experiences of treating extended-spectrum β-lactamase (ESBL)-negative OXA-48 producers with cephalosporins have been published.. The aim of this study was to report clinical experience of infections due to ESBL-negative OXA-48-producing Klebsiella pneumoniae (K. pneumoniae) treated with cephalosporins.. A retrospective study was conducted at Vall d'Hebron University Hospital, in Barcelona (Spain). It reviewed all microbiological isolates of OXA-48-producers that did not co-produce ESBL from May 2014 to May 2017, and included only clinical strains of patients treated with a cephalosporin for ≥72h.. From the 75 isolations of OXA-48 producers, there were 17 isolations of ESBL-negative OXA-48-producing K. pneumoniae. Three patients were treated with cephalosporins with successful outcomes: a pneumonia in a neutropenic patient treated with cefepime and amikacin; an acute focal nephritis of a renal graft treated with ceftriaxone; and an intrabdominal post-surgical infection treated with cefepime in combination with tigecycline at the beginning, and ciprofloxacin afterwards.. Cephalosporins could be an alternative treatment in selected patients with ESBL-negative OXA-48-producing K. pneumoniae infections, especially to avoid carbapenem use. However, it remains unknown if they should be given in combination.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefepime; Ceftriaxone; Cephalosporins; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Nephritis; Retrospective Studies; Spain

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Hospitalization; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Penicillanic Acid; Piperacillin; Tazobactam; Treatment Outcome; Young Adult

In this study, we investigated the frequency of isolates included in the susceptible-dose dependent (SDD) category, according to the Clinical and Laboratory Standards Institute guidelines, carrying bla

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Genes, Bacterial; Humans; Inactivation, Metabolic; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Typing; Practice Guidelines as Topic

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Aztreonam; Bacterial Proteins; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Prospective Studies; Young Adult

This retrospective study was conducted to evaluate clinical outcomes of bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities in febrile neutropenic children. Clinical characteristics, prognosis, and antibiotic susceptibilities were reviewed and compared between febrile neutropenic children with bacteremia caused by ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K. pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing strains, were diagnosed. There was no significant factor associated with bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in 85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli and K. pneumoniae bacteremia, occurred. The complication and mortality rates were not significantly different between the two groups. Antibiotic susceptibility rates were significantly lower in the ESBL group than in the non-ESBL group in most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all the isolates and 90.5% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam or cefepime in combination with aminoglycoside. In conclusion, the ESBL group did not show a significantly unfavorable outcome, and empirical therapy with piperacillin/tazobactam or cefepime in combination with aminoglycoside might be more useful for febrile neutropenic children, instead of β-lactam monotherapy in institutions with high prevalence of ESBL-producing E. coli and K. pneumoniae.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporins; Child; Escherichia coli; Escherichia coli Infections; Febrile Neutropenia; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Extended-spectrum β-lactamase (ESBL)-producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes.. This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL-producing Escherichia coli or Klebsiella pneumoniae, each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression.. Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior β-lactam-/β-lactamase-inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL-producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3).. Prior antimicrobial therapy, particularly with β-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Case-Control Studies; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Michigan; Middle Aged; Retrospective Studies; Risk Factors

Antibiotics not only support to alleviate the infections but also facilitate to avert the multiplication of microbes. Due to the irrational use of antibiotics, the resistance of antibiotics has been augmented which results may increase in morbidity and mortality with the span of time. World renowned regulatory bodies like Food and Drug Administration (FDA), Center of Disease Control and Prevention (CDC), and World Health Organization (WHO) vigorously advocate the surveillance of the resistance of antibiotics. During the present study by Kirby-Bauer disk diffusion method 141 clinical isolates of Staphylococcus aureus (n=47, 33.34%), Escherichia coli (n=54, 38.3%), Proteus species (n=26, 18.4%), and Klebsiella pneumoniae (n=14, 9.92%) are evaluated against cefepime and cefpirome which comes of fourth generation cephalosporin. It has been found that cefpirome has better bactericidal activity than cefepime against E. coli and K. pneumoniae while cefepime has been possessed better antibacterial activity against S. aureus and Proteus species which were isolated from respiratory tract infections, blood stream infection, intra-abdominal and urinary tract infections, and skin and soft tissue infections. K. pneumoniae, E. coli, Proteus species, and S. aureus were 34.8%, 26.3%, 11.3%, and 37.7% resistance against cefepime respectively. S. aureus, E. coli, K. pneumoniae, Proteus species has shown 41.4%, 21.7%, 17.6%, and 8.9% resistance against cefpirome correspondingly.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cefpirome; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pakistan; Proteus; Proteus Infections; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Urinary Tract Infections

Klebsiella pneumoniae is an important pathogen, increasingly notorious for its ability to become resistant to antimicrobial agents. This study sought to characterize trends in antimicrobial susceptibility rates for K. pneumoniae causing bacteremias across the United States (U.S.) Veterans Healthcare Administration (VHA) from 2007 through 2013 utilizing a national clinical database. K. pneumoniae grew in 9,235 blood cultures from 8,414 patients. Nationally, ampicillin-sulbactam, ceftazidime, cefepime, ertapenem, fluoroquinolones, and amikacin demonstrated statistically significant susceptibility rate increases against K. pneumoniae in the 2010-2013 period versus the 2007-2009 period. No antimicrobial agent had a statistically significant nationwide susceptibility rate decrease. Of the 126 antibiotic-organism pairs tested among 9 U.S. regions, 18 demonstrated statistically significant susceptibility rate increases while 6 demonstrated statistically significant susceptibility rate decreases. The East North Central (eight agents), Mid-Atlantic (five agents), and South Atlantic (four agents) regions demonstrated statistically significant susceptibility rate increases for multiple antimicrobial agents. Of the 70 antibiotic-organism pairs tested among 5 different medical center complexity levels, 11 antibiotics demonstrated statistically significant susceptibility rate increases and 1 demonstrated a statistically significant rate decrease. Extended-spectrum β-lactamase production did not significantly change over the study period across an available nationwide representation of 31 facilities (10.6% in 2007-2009 vs. 9.21% in 2010-2013, p=0.17). The South Atlantic and Mid-Atlantic regions had the highest prevalence of extended-spectrum ß-lactamase production in the two periods, respectively. The recent trend of generally increasing susceptibility rates for K. pneumoniae bloodstream isolates in this nationwide U.S. VHA study contrasts from other U.S. health system reports demonstrating increasing trends of antimicrobial resistance.

Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Cefepime; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Ertapenem; Fluoroquinolones; Gene Expression Regulation, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sulbactam; United States; United States Department of Veterans Affairs

We studied 68 ESBL-producing Klebsiella pneumoniae strains isolated in Lebanon, determined their profile of resistance to antibiotics, and identified 6 ESBL genes.. The susceptibility to antibiotics was determined by the disk diffusion method. The MIC of carbapenems and cefepime was determined by the agar dilution method. ESBL genes were detected by PCR.. A percentage of 88.2% and 86.7% of isolates carried the SHV and CTX-M gene respectively; combinations of more than 1 gene of resistance were detected in several isolates. Five strains were resistant to carbapenems; 4/5 carried the OXA-48 gene.. Our study revealed the emergence of K. pneumoniae ESBL (+) strains carrying several types of genes involved in this phenotype; we also identified carbapenem-resistant strains due to the OXA-48 gene, which are a real threat for public health, especially in Lebanon.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Colony Count, Microbial; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Lebanon; Microbial Sensitivity Tests; Organ Specificity; Substrate Specificity

In this study, the efficacy of ceftaroline fosamil was compared with that of cefepime in an experimental rabbit meningitis model against two Gram-negative strains (Escherichia coli QK-9 and Klebsiella pneumoniae 1173687). The penetration of ceftaroline into inflamed and uninflamed meninges was also investigated. Both regimens were bactericidal, but ceftaroline fosamil was significantly superior to cefepime against K. pneumoniae and E. coli in this experimental rabbit meningitis model (P < 0.0007 against K. pneumoniae and P < 0.0016 against E. coli). The penetration of ceftaroline was approximately 15% into inflamed meninges and approximately 3% into uninflamed meninges.

Topics: Animals; Anti-Bacterial Agents; Cefepime; Ceftaroline; Cephalosporins; Disease Models, Animal; Escherichia coli; Klebsiella Infections; Klebsiella pneumoniae; Meninges; Meningitis, Escherichia coli; Permeability; Rabbits; Treatment Outcome

In this study the efficacy of doripenem, a new broad-spectrum carbapenem, was tested against an Escherichia coli strain and a Klebsiella pneumoniae strain in an experimental animal model. The comparator was cefepime monotherapy.. The rabbit meningitis model was used in this study and the penetration of doripenem through uninflamed and inflamed meninges was determined.. Doripenem, injected three times (75 mg/kg), led to serum peak levels around 100 mg/L and trough levels around 5 mg/L, resulting in a penetration rate of 14% through inflamed meninges and 7% through uninflamed meninges. Against K. pneumoniae, doripenem was slightly but not significantly more efficacious than cefepime over 8 h (5.40 ± 1.37 log(10) cfu/mL versus 3.59 ± 0.89 log(10) cfu/mL for cefepime). Also against the E. coli strain doripenem was slightly superior to the comparator (5.55 ± 0.87 log(10) cfu/mL versus 3.80 ± 1.10 log(10) cfu/mL for cefepime), although the difference was not significant.. Doripenem is a potential monotherapy for the treatment of meningitis due to Gram-negative microorganisms.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Cefepime; Cephalosporins; Disease Models, Animal; Doripenem; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Meningitis, Bacterial; Rabbits; Treatment Outcome

Klebsiella pneumoniae is a gram-negative, non-motile, facultative anaerobe belonging to the Enterobacteriaceae family of the γ-Proteobacteria class in the phylum Proteobacteria. Multidrug resistant K. pneumoniae have caused major therapeutic problems worldwide due to emergence of extended-spectrum β-lactamase producing strains. Two-component systems serve as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions including antibiotic stress.. In the present study, we investigated the role of an uncharacterized cpxAR operon in bacterial physiology and antimicrobial resistance by generating isogenic mutant (ΔcpxAR) deficient in the CpxA/CpxR component derived from the hyper mucoidal K1 strain K. pneumoniae NTUH-K2044. The behaviour of ΔcpxAR was determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment and deletion resulted in higher sensitivity to bile, osmotic and acid stresses. The ΔcpxAR was more susceptible to β-lactams and chloramphenicol than the wild-type strain, and complementation restored the altered phenotypes. The relative change in expression of acrB, acrD, eefB efflux genes were decreased in cpxAR mutant as evidenced by qRT-PCR. Comparison of outer membrane protein profiles indicated a conspicuous difference in the knock out background. Gel shift assays demonstrated direct binding of CpxR(KP) to promoter region of ompC(KP) in a concentration dependent manner.. The Cpx envelope stress response system is known to be activated by alterations in pH, membrane composition and misfolded proteins, and this systematic investigation reveals its direct involvement in conferring antimicrobial resistance against clinically significant antibiotics for the very first time. Overall results displayed in this report reflect the pleiotropic role of the CpxAR signaling system and diversity of the antibiotic resistome in hyper virulent K1 serotype K. pneumoniae NTUH-K2044.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; Base Sequence; beta-Lactam Resistance; Blotting, Western; Cefepime; Cephalosporins; Chloramphenicol; Computational Biology; DNA, Bacterial; Electrophoretic Mobility Shift Assay; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Operon; Osmotic Pressure; Oxidative Stress; Protein Kinases; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Bacterial; RNA, Messenger; Sequence Homology, Amino Acid

We evaluated the efficacy of NXL104, a novel β-lactamase inhibitor, in combination with ceftazidime (CAZ) in two murine infection models (septicemia and thigh infection). We chose two KPC-producing Klebsiella pneumoniae strains (VA-361 and VA-406) showing MICs of CAZ of ≥256 μg/ml. Septicemia was induced by the intraperitoneal injection of KPC-producing K. pneumoniae followed 30 min later by a single subcutaneous treatment with CAZ alone or CAZ-NXL104 in ratios of 2:1, 4:1, 8:1, and 16:1. In this model, the median effective doses for 50% (ED(50)) of the animals for CAZ alone versus VA-361 and VA-406 were 1,578 and 709 mg/kg of body weight, respectively. When combined with NXL104 at 2:1, 4:1, 8:1, and 16:1 ratios, the CAZ ED(50)s for VA-361 and VA-406 were reduced to 8.1 and 3.5 mg/kg, 15.1 and 3.8 mg/kg, 16.9 and 7.2 mg/kg, and 29.5 and 12.1 mg/kg, respectively. For thigh infection, neutropenia was induced by the intraperitoneal injection of cyclophosphamide at days -4 and -1 preinfection. Infection was established by the intramuscular injection of KPC-producing K. pneumoniae into the right thigh. Mice were treated 1.5 h postinfection with either CAZ alone or CAZ-NXL104 at constant ratios of 4:1. When thighs were removed at 24 h postinfection, a >2-log CFU reduction was observed for mice treated with CAZ-NXL104 at doses of ≥128:32 mg/kg. In contrast, CAZ doses of ≥1,024 mg/kg were unable to reduce the numbers of CFU. Despite resistance to CAZ and possessing a complex β-lactamase background, NXL104 combined with CAZ proved to be very effective in murine models of infection due to contemporary highly resistant KPC-producing K. pneumoniae isolates.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Disease Models, Animal; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Sepsis

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

OmpK35 and OmpK36 are the major outer membrane porins of Klebsiella pneumoniae. In this study, a virulent clinical isolate was selected to study the role of these two porins in antimicrobial resistance and virulence. The single deletion of ompK36 (ΔompK36) resulted in MIC shifts of cefazolin, cephalothin, and cefoxitin from susceptible to resistant, while the single deletion of ompK35 (ΔompK35) had no significant effect. A double deletion of ompK35 and ompK36 (ΔompK35/36) further increased these MICs to high-level resistance and led to 8- and 16-fold increases in the MICs of meropenem and cefepime, respectively. In contrast to the routine testing medium, which is of high osmolarity, susceptibility tests using low-osmolarity medium showed that the ΔompK35 mutation resulted in a significant (≥ 4-fold) increase in the MICs of cefazolin and ceftazidime, whereas a ΔompK36 deletion conferred a significantly (4-fold) lower increase in the MIC of cefazolin. In the virulence assays, a significant (P < 0.05) defect in the growth rate was found only in the ΔompK35/36 mutant, indicating the effect on metabolic fitness. A significant (P < 0.05) increase in susceptibility to neutrophil phagocytosis was observed in both ΔompK36 and ΔompK35/36 mutants. In a mouse peritonitis model, the ΔompK35 mutant showed no change in virulence, and the ΔompK36 mutant exhibited significantly (P < 0.01) lower virulence, whereas the ΔompK35/36 mutant presented the highest 50% lethal dose of these strains. In conclusion, porin deficiency in K. pneumoniae could increase antimicrobial resistance but decrease virulence at the same time.

Topics: Animals; Bacterial Proteins; Cefepime; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Genetic Complementation Test; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Sequence Data; Phagocytosis; Porins; Sequence Analysis, DNA; Thienamycins; Virulence

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Enzyme Inhibitors; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Aged; beta-Lactamases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Renal Dialysis; Republic of Korea

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

The aim of this research is to evaluate the recent changes in microorganisms causing spontaneous bacterial peritonitis in cirrhotic patients, antibiotic resistance, and response to empirical cephalosporin therapy. A total of 218 patients with ascites secondary to cirrhosis were enrolled. Parenteral cefotaxime or cefepime was given to patients who had a neutrophil count of 250/mm(3) or more or a positive bacterial culture of ascitic fluid. Antibiotic failure was defined by an absence of clinical improvement and an insufficient decrease in neutrophil count of ascites (<25% of initial value) by the third day of therapy. Of all the patients, 44.6% had culture-negative neutrocytic ascites, 24.8% had spontaneous bacterial peritonitis, and 10.1% had monomicrobial nonneutrocytic bacterascites. Growth in culture was observed in 76 patients (34.9%). The two most common isolated bacteria were Escherichia coli (33.8%) and coagulase-negative Staphylococcus (CoNS; 19.7%). The two cephalosporins were effective against E. coli (82%) and but not against CoNS (44%), while levofloxacin showed reasonable activity against both E. coli (71%) and CoNS (90%) in vitro. We confirmed a recent increased incidence of spontaneous bacterial peritonitis caused by Gram-positive bacteria. Levofloxacin seems to be a good alternative treatment for patients with uncomplicated spontaneous ascites infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Bacterial Infections; Cefepime; Cefotaxime; Cephalosporins; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Levofloxacin; Liver Cirrhosis; Male; Microbial Sensitivity Tests; Middle Aged; Neutrophils; Ofloxacin; Peritonitis; Pneumococcal Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections

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

This study was performed to determine the local etiologic pattern of blood culture isolates and antibiotic resistance in febrile neutropenic patients with hematological malignancies.. A total of 142 blood culture isolates from febrile neutropenic patients admitted to our hematology unit were examined, particularly for the detection of cefepime resistance, because cefepime, a fourth-generation cephalosporin, has been used in our unit as initial therapy for febrile neutropenia.. Among all isolates, 67 (47.2%) were Gram-positive bacteria, the majority of which were fully sensitive to vancomycin. Gram-negative bacteria accounted for 68 (47.9%) of the isolates. Cefepime resistance was seen in 24 (35.3%) of the Gram-negative isolates, and had significantly increased in 2007. The cefepime-resistant isolates primarily consisted of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Approximately 60% of the cefepime-resistant isolates were extended-spectrum β-lactamase (ESBL)-producing organisms. Molecular analysis showed the predominant emergence of CTX-M types. Most of the cefepime-resistant isolates were resistant to third- and various fourth-generation cephalosporins, while having a high susceptibility to carbapenems, particularly meropenem.. Cefepime resistance was often detected in the blood culture isolates from febrile neutropenic patients. This result suggests that therapeutic strategies for febrile neutropenia should be modified based on the local antibiotic resistance patterns.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporin Resistance; Cephalosporins; Escherichia coli; Escherichia coli Infections; Fever; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Klebsiella Infections; Klebsiella pneumoniae; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections

A negative extended-spectrum β-lactamase (ESBL) phenotypic confirmation test result obtained after a positive ESBL screening test result but which was cefepime-susceptible (NCPSCS) using the Clinical and Laboratory Standards Institute (CLSI) methods has been observed among isolates of Escherichia coli and Klebsiella spp. in the antimicrobial surveillance program in Shanghai, China. Among isolates collected from Huashan Hospital in 2005, NCPSCS strains were observed in 2.5% of 433 E. coli isolates and in 1.2% of 562 Klebsiella spp. isolates. We then selected 11 E. coli isolates and seven Klebsiella spp. NCPSCS isolates. Transmission electron microscopy (TEM), SHV, plasmid-borne AmpC, and CTX-M type ESBL genes were detected by the polymerase chain reaction (PCR) method. We found that all except two K. pneumoniae strains of NCPSCS isolates producing ESBL and AmpC harbored a plasmid-borne CMY-2 or DHA-1 type AmpC enzyme. The majority of NCPSCS E. coli and K. pneumoniae strains from Shanghai harbor plasmid-borne AmpC enzyme, and we recommend that, when NCPSCS strains are identified, further work such as the PCR detection of ESBL genes is necessary to determine whether they will produce ESBLs. The ESBL-positive strains should be reported as resistant to cefepime according to the CLSI guidelines.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; China; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Plasmids; Polymerase Chain Reaction

Carbapenem-resistant Klebsiella strains carrying Klebsiella pneumoniae carbapenemases (KPC) are endemic to New York City and are spreading across the United States and internationally. Recent studies have indicated that the KPC structural gene is located on a 10-kb plasmid-borne element designated Tn4401. Fourteen Klebsiella pneumoniae strains and one Klebsiella oxytoca strain isolated at a New York City hospital in 2005 carrying either bla(KPC-2) or bla(KPC-3) were examined for isoforms of Tn4401. Ten of the Klebsiella strains contained a 100-bp deletion in Tn4401, corresponding to the Tn4401a isoform. The presence of this deletion adjacent to the upstream promoter region of bla(KPC) in Tn4401a resulted in a different -35 promoter sequence of TGGAGA than that of CTGATT present in isoform Tn4401b. Complete sequencing of one plasmid carrying bla(KPC) from each of three nonclonal isolates indicated the presence of genes encoding other types of antibiotic resistance determinants. The 70.6-kb plasmid from K. pneumoniae strain S9 carrying bla(KPC-2) revealed two identical copies of Tn4401b inserted in an inverse fashion, but in this case, one of the elements disrupted a group II self-splicing intron. In K. pneumoniae strain S15, the Tn4401a element carrying bla(KPC-2) was found on both a large 120-kb plasmid and a smaller 24-kb plasmid. Pulsed-field gel electrophoresis results indicate that the isolates studied represent a heterogeneous group composed of unrelated as well as closely related Klebsiella strains. Our results suggest that endemic KPC-positive Klebsiella strains constitute a generally nonclonal population comprised of various alleles of bla(KPC) on several distinct plasmid genetic backgrounds. This study increases our understanding of the genetic composition of the evolving and expanding role of KPC-producing, healthcare-associated, gram-negative pathogens.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; DNA Transposable Elements; Drug Resistance, Bacterial; Hospitals, Urban; Humans; Isoenzymes; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Microbial Sensitivity Tests; New York City; Plasmids; Transposases

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Molecular Sequence Data; Poland

A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; beta-Lactamases; Carboxylic Ester Hydrolases; Cefotaxime; Cefuroxime; Cephalosporins; Cephalothin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; India; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillins; Sequence Analysis, DNA; Sequence Homology, Amino Acid

Pneumonia is a severe infection that causes high morbidity and mortality rate worldwide. It is caused by Klebsiella pneumoniae, which generally causes upper respiratory tract infection. In case of such type of infection, levels of oxidant and antioxidant become imbalanced, which may contribute to lung injury. The present study was planned to evaluate the status of oxidant and antioxidant enzyme activities in plasma and lung tissue of pneumonia-infected rats model. Animals were randomly distributed into 3 groups of 8 rats each: groups I (control, normal saline treated), II (infected group), and III (infected + treated group). The findings showed that there was significant increase (P < .001) in body temperature along with decreased body weight in the infected group as compared to the control group. Similarly, all the activities of antioxidant enzymes (superoxide dismutase [SOD], catalase) were significantly decreased along with increased malonaldialdehyde (MDA) levels in plasma and lung tissue of the infected group as compared to the control group. These enzyme activities along with MDA levels were improved and came back near to normal level after administration of cefepime plus amikacin (potentox) for 7 days in group III. These studies concluded that fixed-dose combination of potentox improved oxidant and antioxidant levels in pneumonia infection.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Antioxidants; Catalase; Cefepime; Cephalosporins; Drug Therapy, Combination; Klebsiella Infections; Klebsiella pneumoniae; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Pneumonia, Bacterial; Rats; Rats, Wistar; Superoxide Dismutase

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Female; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids

Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the beta-lactamase bla KPC-2 gene was located on a novel Tn3-based transposon, Tn4401. Tn4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the beta-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, ISKpn6 and ISKpn7. Tn4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn4401a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn4401b, which was found in the Colombian isolates. In all isolates tested, Tn4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn4401 is likely at the origin of carbapenem-hydrolyzing beta-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.

Topics: Base Sequence; beta-Lactamases; beta-Lactams; Cloning, Molecular; Colombia; DNA Transposable Elements; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA; United States

An outbreak of cephalosporin-resistant Klebsiella pneumoniae occurred in a neonatal intensive care unit in São Paulo, Brazil. Of the 10 pulsotypes identified during the outbreak and follow-up periods, nine produced CTX-M-2 or its new variant CTX-M-59 and one produced SHV-5. bla(CTX-M-2/59) genes were located on closely related plasmids that were transferable.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Brazil; Cephalosporins; Disease Outbreaks; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Polymerase Chain Reaction

The presence of plasmid-mediated quinolone resistance genes [i.e., qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA] was evaluated among 42 bla(KPC)-containing Klebsiella pneumoniae isolates collected in the eastern United States. One isolate carried the bla(KPC-3) and qnrB19 genes on the same conjugative plasmid, whereas another carried the bla(KPC-3) and qnrA1 genes on separate plasmids.

Topics: Aged; Bacterial Proteins; Base Sequence; beta-Lactamases; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Genes, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Plasmids; Quinolones; United States

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

Topics: Adult; Anti-Bacterial Agents; Belgium; beta-Lactamases; beta-Lactams; Carbapenems; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Plasmids

A clinical strain of Klebsiella pneumoniae was found to possess the chromosomal gene bla(SHV-56), encoding a new inhibitor-resistant beta-lactamase with a pI of 7.6. SHV-56 is derived from SHV-11 by the single substitution K234R. This mutation therefore evidences a new critical site for inhibitor resistance among SHV enzymes.

Topics: Aged; Amino Acid Substitution; Base Sequence; beta-Lactam Resistance; beta-Lactamases; DNA Primers; DNA, Bacterial; Female; Genes, Bacterial; Humans; Isoelectric Point; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Mutagenesis, Insertional; Recombinant Proteins

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

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

Carbapenem resistance due to KPC has rarely been observed outside the United States. We noticed a sharp increase in carbapenem-resistant Klebsiella pneumoniae strains possessing KPC in Tel Aviv Medical Center from 2004 to 2006. Sixty percent of the isolates belonged to a single clone susceptible only to gentamicin and colistin and carried the bla(KPC-3) gene, while almost all other clones carried the bla(KPC-2) gene. This rapid dissemination of KPC outside the United States is worrisome.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Hospitals; Humans; Israel; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Molecular Epidemiology

This study was designed to compare cefepime exposures with microbiological outcomes in ESBL and non-ESBL infections and determine the pharmacodynamic profiles associated with successful outcome.. Cefepime pharmacodynamic exposures of unbound drug [time above MIC (fT>MIC), minimal concentration over MIC (fC(min)/MIC), and area under the curve over MIC (fAUC/MIC)] for 18 patients with ESBL and non-ESBL infections were determined by using a published population pharmacokinetic model. Classification and regression tree analysis was used to identify pharmacodynamic breakpoints that predicted eradication. A 5000-patient Monte Carlo Simulation was conducted to estimate the probability of target attainment for the goal pharmacodynamic exposures.. Eradication was 80% when fT>MIC was 50% compared with 0% when T>MIC was less than 50% (p<0.05). The median fC(min)/MIC ratio for ESBL group was statistically lower than that for the non-ESBL group (1.54 versus 138, p<0.001). Regardless of ESBL production, all pathogens were eradicated when fC(min)/MIC>7.6 and only 33.3% were eradicated when fC(min)/MIC< or =7.6 (p<0.05). Pharmacodynamic exposures of 50% fT>MIC and fAUC/MIC>1654 were also predictive of eradication. While conventional dosage regimens of 2g q 12h and q 8h failed to achieve adequate target attainment, 4 g continuous infusion and 2g q 6-8h prolonged infusion could attain more than 90% of target attainment at the MIC of 2 microg/ml for the breakpoint of fCmin/MIC=7.6.. Microbiological eradication in patients receiving cefepime was best predicted by fCmin/MIC ratio greater than 7.6 regardless of the presence of an ESBL. Continuous or prolonged infusion regimens provided the greatest probability of attaining this exposure.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Case-Control Studies; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals, Urban; Humans; India; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

The in vivo activities of imipenem, meropenem, and cefepime were studied in a model of rat pneumonia caused by a plasmid-mediated AmpC beta-lactamase ACT-1-producing Klebsiella pneumoniae strain (K. pneumoniae strain 12) and a derivative porin-deficient mutant (K. pneumoniae strain 12dp). No differences between these activities were seen with K. pneumoniae 12. Only meropenem showed an activity slightly better than that of imipenem with K. pneumoniae 12dp.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Colony Count, Microbial; Imipenem; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Plasmids; Pneumonia, Bacterial; Porins; Rats; Rats, Wistar; Thienamycins; Treatment Outcome

(i) To develop a population pharmacokinetics (PK) model for cefepime in patients in intensive care units (ICUs). (ii) To assess the pharmacokinetic-pharmacodynamic profile of various cefepime dosing regimens and to assess their expected probability of target attainment (=PTA expectation value) against common ICU pathogens such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.. Thirteen ICU patients received cefepime 2 g 12 hourly intravenous (3 min). Twelve blood samples were taken on two occasions: (i) immediately after initial dose; and (ii) between days 3 and 6 after starting therapy. Population PK models were developed using NONMEM. Based on the final covariate model, Monte Carlo simulations were undertaken (n=1000) to simulate free-drug concentrations of cefepime for two administration methods: (i) intermittent bolus administration (IBA); and (ii) continuous infusion (CI). Concentration-time profiles were evaluated by the probability of achieving free-drug concentration above the MIC for >65% of the dosing interval. Finally, using local MIC distributions of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii the PTA expectation values for each dosing administration method were evaluated.. A three-compartment model with zero-order input best described the concentration-time data. The PTA expectation values for E. coli and K. pneumoniae were >90% in all CI doses but only when administered as 1 g every 6 h and higher daily doses for IBA. For the current treatment protocol, 2 g every 12 h, P. aeruginosa and A. baumannii achieved target concentrations of only 54% and 28%, respectively. For P. aeruginosa, a CI of at least 4 g/day was required to achieve a PTA expectation value>90% while for A. baumannii a 6 g/day CI only achieved a PTA expectation value of 75%.. When given as IBA or CI for E. coli and K. pneumoniae, cefepime should be successful in achieving the bactericidal target. For P. aeruginosa higher doses of cefepime (>4 g/day) are required to achieve the required PTA expectation value. Cefepime fails to achieve the bactericidal target even when administered at high doses, e.g. 6 g/day, for A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Administration Schedule; Escherichia coli; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Pseudomonas aeruginosa; Pseudomonas Infections

Patients with pyogenic liver abscesses often present to the emergency department with fever of unknown origin. After the appropriate clinical evaluation, cross-sectional imaging may be performed in the emergent setting to aid in localization of fever source. On computed tomography imaging, pyogenic liver abscesses may present as inflammatory masses in the liver, with Escherichia coli as the most common pathogen. We report an emerging hepatic pathogen as the cause, Klebsiella pneumoniae.

Topics: Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Abscess, Pyogenic; Male; Tomography, X-Ray Computed

To investigate the in vivo activities of ceftazidime and cefepime with susceptibility in vitro in rats with experimental pneumonia caused by extended-spectrum beta-lactamase-producing strain of Klebsiella pneumonia.. With intratracheal instillation method, 3 Klebsiella pneumonia strains isolated from this hospital were used to produce 3 groups of experimental model of pneumonia in rats. All the 3 strains showed resistant to cefotaxime and susceptible to piperacillin-tazobactam in vitro. To ceftazidime and cefepime, strain 1 was both susceptible. Strain 2 was susceptible to ceftazidime and resistant to cefepime. Strain 3 was resistant to ceftazidime and susceptible to cefepime. The three groups of rats were randomly assigned to one of the following five groups: one control group and four treatment groups. The efficacies were evaluated 96 hours later by the survival rate and the viable bacterial counts of the lungs (lg CFU/g).. Group 1: piperacillin-tazobactam, ceftazidime and cefepime significantly improved the survival rate (75.0%, 76.9%, 80.0%) and reduced the bacterial counts [(10.8 +/- 2.8), (11.1 +/- 3.2), (11.0 +/- 3.7) lg CFU/g] compared with cefotaxime and the control group [36.0%, 32.0%; (15.7 +/- 5.6), (16.0 +/- 5.5) lg CFU/g; P < 0.05]. Group 2: piperacillin-tazobactam, ceftazidime significantly improved the survival rate (79.2%, 73.1%) and reduced the bacterial counts [(10.7 +/- 2.3), (11.0 +/- 2.7) lg CFU/g] compared with cefotaxime and the control groups [42.3%, 33.3%; (15.5 +/- 5.4), (15.8 +/- 4.6) lg CFU/g; P < 0.05]. Group 3: the survival rate in piperacillin-tazobactam and cefepime groups (80.8%, 75.0%) were significantly higher and the bacterial counts in piperacillin-tazobactam [(10.4 +/- 2.4) lg CFU/g] were significantly lower compared with the cefotaxime and the control groups [37.5%, 34.6%; (14.2 +/- 5.6), (15.3 +/- 4.9) lg CFU/g; P < 0.05].. Cefepime and ceftazidime can reduce the mortality and the number of viable bacteria in rat pneumonia caused by some ESBL-producing Klebsiella pneumonia strains susceptible to either of them and their efficacies were similar to piperacillin-tazobactam.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Female; Klebsiella Infections; Klebsiella pneumoniae; Pneumonia, Bacterial; Rats; Rats, Sprague-Dawley

An investigation to determine the efficacy of cefepime in treating infections caused by extended spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumonia and Escherichia coli was performed. Retrospective chart reviews were conducted on patients who received cefepime and had an ESBL-producing E. coli or K. pneumoniae isolated from a clinical specimen. Among 13 patients with 15 episodes and 17 sites of infection, there were 12 episodic clinical cures, 1 clinical improvement, and 2 failures. Bacteriologic eradication of the infecting organism from the original clinical site was seen in 11 of the episodes with an additional presumed eradication. Cefepime is a potential alternative, in many cases, to the carbapenems for the treatment of infections caused by ESBL-producing bacteria.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Retrospective Studies

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Colony Count, Microbial; Guinea Pigs; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lung; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Porins; Thienamycins; Treatment Outcome

Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type beta-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1x, 2x, 4x, 6x, and 8x MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 mug/ml, respectively. DeltaT/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Disease Models, Animal; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Pneumonia, Bacterial; Porins; Treatment Outcome

A case of failure of cefepime treatment of a bloodstream infection with AmpC-producing Klebsiella pneumoniae is reported. The failure was attributed to extended-spectrum beta-lactamase (ESBL) acquisition by the isolate, possibly during therapy. Problems encountered with ESBL detection in AmpC-producing isolates are discussed.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Treatment Failure

To determine the affect of ESBL production among Klebsiella species and Escherichia coli on cefepime effectiveness.. This was a retrospective, case-controlled study comparing the clinical and microbiologic responses of patients receiving cefepime for ESBL producing Klebsiella species or E. coli from a non-urine source with matched controls receiving cefepime for non-ESBL strains. Cases with ESBLs were included if they received monotherapy and were clinically evaluable. Non-ESBL controls were matched in a 2:1 ratio based on age, infection site, intensive care unit (ICU) stay, pathogen species and date of hospitalization.. Ten patients receiving cefepime for ESBLs were matched to 20 controls. Most patients received cefepime 1g q12h. Patients receiving cefepime for an ESBL infection were 9.7 (95% CI: 1.4-68.8) and 28.5 (95% CI: 2.6-306.6) times as likely to have an unsuccessful clinical and microbiological response compared with those with a non-ESBL infection. The presence of an ESBL did not have a statistically significant effect on all cause or infection-related mortality.. These data indicate that ESBL production among non-urinary Klebsiella species and E. coli negatively affected cefepime effectiveness. Further studies are required to evaluate if higher doses of cefepime may improve responses in ESBLs that are initially susceptible.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Case-Control Studies; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome

The bactericidal activity of moxifloxacin alone and in combination with cefepime or piperacillin-tazobactam against clinical isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii was evaluated by using time-kill methods and antimicrobial concentrations of one-half and one times the MIC. Synergy was observed in 58 to 88% of the strains and resulted in bactericidal activity against 60 to 100% of the strains. Combinations including moxifloxacin demonstrated enhanced bactericidal activity compared with that of either agent tested alone.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Aza Compounds; Cefepime; Cephalosporins; Colony Count, Microbial; Drug Synergism; Enterobacter cloacae; Enterobacteriaceae Infections; Enzyme Inhibitors; Fluoroquinolones; Humans; Klebsiella Infections; Klebsiella pneumoniae; Moxifloxacin; Penicillanic Acid; Penicillins; Piperacillin; Quinolines; Tazobactam

In this study, we evaluated the performance of a new ESBL Etest configuration based on clavulanate synergy with cefepime compared with cefotaxime-clavulanate and ceftazidime-clavulanate ESBL Etest strips for the detection of extended-spectrum beta-lactamases (ESBL) in an Enterobacteriaceae strain collection, with special focus on Enterobacter spp.. Overall, a total of 54 clinical isolates of ESBL-producing Enterobacteriaceae species were evaluated: Enterobacter aerogenes (n=3), Enterobacter cloacae (n=10), Escherichia coli (n=10), Klebsiella oxytoca (n=3), Klebsiella pneumoniae (n=25) and Proteus mirabilis (n=3). To check Etest behaviour with resistance phenotypes similar to ESBL, our panel was expanded by six clinical isolates of K. oxytoca that were identified as putative producers of their chromosomal K1 beta-lactamase.. With this panel, ESBL Etest was 98% sensitive with cefepime-clavulanate, 83% with cefotaxime-clavulanate, and 74% with ceftazidime-clavulanate strips. Concentrating on Enterobacter spp., reliable ESBL detection could only be achieved by the new cefepime-clavulanate strip since it confirmed ESBL production in all strains (100% sensitivity) whereas only 4/13 (31%) of Enterobacter strains were positive using cefotaxime-clavulanate or ceftazidime-clavulanate strips. A limitation of using the new cefepime strip was less than optimal specificity with K1 phenotypes of K. oxytoca: among six strains, four isolates were scored false-positive by Etest strips containing cefepime-clavulanate.. The new Etest ESBL strip containing cefepime-clavulanate is a valuable supplement to current methods for detection of ESBLs. In our study collection, the cefepime-clavulanate strip was the best configuration for detection of ESBLs, particularly in Enterobacter spp.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Cefepime; Cephalosporins; Clavulanic Acid; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Klebsiella Infections; Klebsiella oxytoca; Phenotype

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

Topics: Acyclovir; Brain Abscess; Cefepime; Cephalosporins; Ethnicity; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Taiwan; Vancomycin

The in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.

Topics: Amikacin; Animals; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Drug Therapy, Combination; Imipenem; Kinetics; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Survival Analysis

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

Mice experimentally infected with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains were injected twice daily for three days with ceftazidime, cefepime, or imipenem (25, 50, or 100 mg/kg/injection). Treatment efficacy was based on five-day survival and on the spleen viable bacteria count 16 hours after the last treatment dose. Under these experimental conditions, ceftazidime showed some activity on strains with low levels of resistance to ceftazidime. Cefepime used in a dose of 50 or 100 mg per injection demonstrated good activity but was slightly less effective than imipenem.

Topics: Animals; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Colony Count, Microbial; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Spleen; Thienamycins

The in vivo activities of piperacillin-tazobactam and cefepime were compared with those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat model of intra-abdominal abscess with a strain of Klebsiella pneumoniae elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of ceftazidime, all of the antimicrobial agents significantly reduced bacterial counts within abscesses at the end of therapy compared with those in untreated controls. Residual viable cell counts (mean +/- standard deviation in log10 CFU/gram) were as follows: control, 8.76 +/- 0.97; ceftazidime, 8.00 +/- 0.76; piperacillin-tazobactam, 3.87 +/- 1.72; ticarcillin-clavulanate, 3.74 +/- 1.34; cefepime, 3.15 +/- 1.19; cefotaxime, 2.61 +/- 0.77; imipenem, 2.41 +/- 0.93. Imipenem was more effective than either of the inhibitor combinations (P < 0.05). Cefotaxime was unexpectedly effective given its poor in vivo activity against this organism in our earlier studies, which used a different dose and total duration of therapy (L. B. Rice, J. D. C. Yao, K. Klimm, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 35:1243-1244, 1991). These observations suggest that the effectiveness of cephalosporins in the treatment of experimental infections caused by extended-spectrum beta-lactamase-producing K. pneumoniae may be highly dependent on dosing regimens, even for a specific organism and site of infection.

Topics: Abdominal Abscess; Animals; beta-Lactamases; Cefepime; Cephalosporins; Drug Therapy, Combination; Enzyme Inhibitors; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Rats; Rats, Sprague-Dawley; Tazobactam

Increasing antimicrobial resistance has been reported for Klebsiella spp. and Enterobacter spp. The in-vitro activities of 14 antimicrobial agents against 656 clinical isolates of Klebsiella spp. and 630 isolates of Enterobacter spp. collected from seven cities in Canada were determined by microbroth dilution. There was no regional variation in the susceptibility patterns. Klebsiella spp. remain highly susceptible to most antimicrobials, only one isolate was resistant to third-generation cephalosporins. However, many isolates of Enterobacter spp. (> 16%) were resistant to the third-generation cephalosporins with marked cross-resistance to piperacillin (63.1%), piperacillin/tazobactam (44.9%), and aztreonam (76.6%). Gentamicin, tobramycin, imipenem, ciprofloxacin, cefepime, and cefpirome were consistently active against most isolates of Enterobacter spp. including those resistant to the third-generation cephalosporins.

Topics: Anti-Bacterial Agents; Canada; Cefepime; Cefpirome; Cephalosporins; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Humans; Klebsiella; Klebsiella Infections; Microbial Sensitivity Tests