cefepime and Bacteremia

To present systematic recommendations for carbapenem-sparing therapy against extended-spectrum β-lactamases (ESBLs) Enterobacteriaceae bloodstream infections (BSIs) derived from a critical review of clinical data.. A systematic literature search using PubMed and MEDLINE databases (January 1, 2012, to June 30, 2017) was performed using key MESH terms: ESBL or extended-spectrum β-lactamases and bacteremia or bloodstream infection with piperacillin/tazobactam, ciprofloxacin, levofloxacin, cefepime, cephamycins, carbapenem, doripenem, meropenem, and ertapenem. References within articles of interest were also evaluated.. All English language trials were considered, and results were limited to clinical efficacy trials. Articles were screened by title and abstract for inclusion.. Studies comparing noncarbapenem versus carbapenem therapy for ESBL BSIs were critically analyzed to identify heterogeneity among studies. Data abstracted included empirical or definitive therapy, patient population, dosing, source of infection and severity, infectious etiology, and outcome.. Completely sparing carbapenem therapy cannot be justified among patients with ESBL BSIs. Determining the source of infection is critical to identify patients for whom carbapenem-sparing therapy is appropriate.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Cefepime; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; Humans

This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase.. Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems.. PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014).. Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding.. Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Carbapenems; Cefepime; Cephalosporins; Enterobacteriaceae Infections; Humans; Quinolones; Serratia Infections; Survival Analysis; Treatment Outcome

Bloodstream infections (BSI) are among the most frequent complications in neutropenic cancer patients and, if caused by Gram-negative rods, are associated with high mortality. Thus, fever during neutropenia warrants prompt empirical antibiotic therapy which should be active against the most frequent Gram-negatives. In the last decade, there has been a worldwide increase in multidrug resistant (MDR) strains. In these cases, the traditional choices such as oral therapy, ceftazidime, cefepime, piperacillin-tazobactam, or even carbapenems, might be ineffective. Therefore novel de-escalation approach has been proposed for patients who are at high risk for infections due to MDR bacteria. It consists of starting antibiotics which cover the most probable resistant strain but it is narrowed down after 72 hours if no MDR pathogen is isolated. With increasing bacterial resistance, the benefit of fluoroquinolone prophylaxis during prolonged neutropenia remains to be confirmed. Antibiotic stewardship and infection control programs are mandatory in every cancer center.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Disease Management; Drug Resistance, Bacterial; Febrile Neutropenia; Fluoroquinolones; Gram-Negative Bacteria; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pre-Exposure Prophylaxis; Risk Factors

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

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

In-vitro studies with cefpirome or cefepime prove that both agents are highly active against Gram-negative bacilli and Gram-positive cocci. They possess a broader spectrum of activity than ceftazidime. In clinical trials cefpirome at doses ranging from 1 g to 2 g b.i.d. was compared to ceftazidime at a dose ranging from 1 g to 2 g b.i.d. or 2 g t.i.d. Cefepime at a dose of 2 g b.i.d. was compared to ceftazidime at a dose of 2 g t.i.d. Both cefpirome and cefepime were found to be as effective as ceftazidime in patients with septicemia. These new compounds are a valuable addition to the range of drugs available for empiric treatment of serious bacterial infections.

Topics: Bacteremia; Bacteria; Bacterial Infections; Cefepime; Cefpirome; Cephalosporins; Clinical Trials as Topic; Humans; In Vitro Techniques; Microbial Sensitivity Tests

In a multicenter, observational, propensity-score-weighted cohort of 249 adults with uncomplicated Pseudomonas aeruginosa bacteremia, patients receiving short-course (median, 9 days; interquartile range [IQR], 8-10) therapy had a similar odds of recurrent infection or death within 30 days as those receiving longer courses (median, 16 days; IQR, 14-17).

Topics: Aged; Bacteremia; Cefepime; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa

We assessed the influence of current cefepime minimal inhibitory concentration (MIC) breakpoints and the maximal cefepime dose on treatment outcomes in patients with bacteremia caused by cefepime-susceptible Pseudomonas aeruginosa.. Adult patients hospitalized between July 2010 and June 2014 with a positive blood culture for cefepime-susceptible P. aeruginosa and receipt of cefepime as the primary therapy throughout the course were reviewed. Cefepime Etest. A cefepime MIC of 4 mg/L may predict an unfavorable outcome among patients with serious infections caused by P. aeruginosa, even the MICs still within the CLSI susceptibility breakpoint.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Dose-Response Relationship, Drug; Female; Hospitals; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Treatment Outcome

Bacterial resistance is of growing concern in haematology wards. As the inappropriate administration of empirical antibacterial may alter survival, we studied risk factors for resistance to our usual empirical first-line antibacterial therapy, cefepime.. We retrospectively studied 103 first episodes of bacteraemia recorded in our haematology department over 2.5 years. Risk factors for cefepime-resistance were identified by multivariate logistic regression with backward selection (P < 0.05). A scoring system for predicting cefepime-resistance was built on independent factor, with an internal validation by the bootstrap resampling technique.. 38 (37%) episodes were due to Gram-negative bacteria. Fifty (49%) were due to bacteria resistant to cefepime. Cefepime resistance was significantly associated with a decreased survival at day 30 (P < 0.05). Three risk factors were independently associated with cefepime-resistance: acute lymphoblastic leukaemia; ≥18 days since hospital admission; and receipt of any β-lactam in the last month. Patients with ≥2 of these risk factors had a probability of 86% (CI 95%, 25 to 100%) to carry a cefepime-resistant strain.. Using our scoring system should reduce the indication of very broad antibacterial regimens in the empirical, first-line treatment of febrile hematology patients in more than 80% of the cases.

Topics: Adult; Aged; Bacteremia; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Hospital Departments; Humans; Male; Microbial Sensitivity Tests; Middle Aged

Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance.. This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis.. In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods.. We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Ciprofloxacin; Drug Administration Schedule; Female; Fever; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

Various dosing strategies for cefepime have been developed in an effort to maximize pharmacodynamic exposure of this agent against gram-negative infections. An assessment of cefepime dosing strategies is warranted given recent reports of poorer treatment outcomes associated with cefepime compared with other antibiotics, particularly in patients infected with gram-negative organisms with elevated MICs.. The aims of this study were to compare the efficacy of cefepime IV at a dose of 1 g q8h (adjusted based on renal function) with those of other appropriate antimicrobials in the treatment of gramnegative pulmonary and bloodstream infections and to identify risk factors for treatment failure.. This single-center, open-label, prospective, observational study was conducted at a tertiary care center (Barnes-Jewish Hospital, St. Louis, Missouri). Isolates from infections in adult patients with bacteremia or pulmonary infection caused by Pseudomonas aeruginosa, Enterobacter aerogenes, Enterobacter cloacae, or Citrobacter freundii were assessed in a noninterventional manner. Infections were identified using an electronic notification system. Patients receiving appropriate monotherapy against the studied isolate within 24 hours of culture attainment were stratified into 1 of 3 cohorts according to treatment outcome, as follows: treatment success (resolution of initial fever or elevated white blood cell count to normal values plus the presence of repeat negative cultures from the initial site or below the quantitative definition for infection), improvement (treatment success without repeat negative cultures), or treatment failure (persistent or repeat positive cultures for the original organism at the infected site despite appropriate and adequate antimicrobial therapy, lack of resolution in fever or leukocytosis, switch to an alternative antibiotic, or the addition of another antibiotic with gram-negative coverage after > or =3 days of the initial regimen, relapse of infection within 14 days, or mortality attributable to the index infection). Multivariate regression analysis was used to examine risk factors associated with treatment failure.. Data from 120 patients (56.7% male; mean age, 62.2 years) were analyzed. Treatment failure occurred in 48.6% (36/74) of patients who received cefepime versus 32.6% (15/46) of those who received other antibiotics; this difference was not statistically significant. The proportion of patients with markers of increased severity of illness (intensive care unit [P = 0.005] and mechanical ventilation [P = 0.002]) was significantly greater in the cefepime group compared with the group that received other antibiotics. Multivariate logistic regression identified infection with Pseudomonas aeruginosa (adjusted odds ratio [AOR], 1.40 [95% CI, 1.01-2.00]) and mechanical ventilation (AOR, 7.08 [95% CI, 1.80-31.3]) as being associated with treatment failure in patients who received cefepime. Mechanical ventilation (AOR, 3.97 [95% CI, 1.47-11.1]) and neutropenia (AOR, 5.26 [95% CI, 1.28-20.0]) were independent predictors of treatment failure among all patients studied.. Based on these results in this small cohort, the efficacy of this cefepime dosing strategy (1 g q8h) appeared to be similar to that of other antimicrobials.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Citrobacter freundii; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Risk Factors; Severity of Illness Index; Treatment Outcome

The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve (AUIC=area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration (AUC0-24/MIC) and time above the minimum inhibitory concentration (T>MIC) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime. Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospective, randomised, clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia, lower respiratory tract infection or complicated urinary tract infection. The relationships between the pharmacodynamic parameters and outcomes were examined. Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime, there were significant differences in the pharmacodynamic analysis. Patients with an AUIC> or =250 had significantly greater clinical cure (79% vs. 33%; P=0.002) and bacteriological eradication (96% vs. 44%; P<0.001) than patients with an AUIC<250. Patients with T>MIC of 100% had significantly greater clinical cure (82% vs. 33%; P=0.002) and bacteriological eradication (97% vs. 44%; P<0.001) than patients with T>MIC of <100%. Both microbiological and clinical cure rates were suboptimal in patients receiving cefepime or ceftazidime for the treatment of serious infections if the AUIC was <250 or T>MIC was <100%.

Topics: Aged; Anti-Bacterial Agents; APACHE; Area Under Curve; Bacteremia; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Endpoint Determination; Escherichia coli; Female; Humans; Klebsiella; Male; Microbial Sensitivity Tests; Predictive Value of Tests; Pseudomonas aeruginosa; Renal Insufficiency; Sepsis; Treatment Outcome

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

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

We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Cefepime; Cephalosporins; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Male; Neutropenia; Time Factors; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Empiricism; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Meropenem; Neoplasms; Neutropenia; Therapeutic Equivalency; Thienamycins; Treatment Outcome

A multicenter open randomized trial was conducted to compare cefepime monotherapy with cefepime/amikacin combination (dual) therapy in treating febrile neutropenic patients with hematologic disorders. Among the 189 evaluable patients, 5.8% had microbiologically and 10.6% had clinically documented infections. Excellent response was seen in 32.6% and 45.7% of monotherapy and dual therapy recipients, respectively, at day 3 (P=.065). At day 3, patients with neutrophil counts of <500/ mu L receiving dual therapy had a better response than did those receiving monotherapy (45% vs. 27.6%; P=.024). The same was true for patients with leukemia. Adverse events were minimal, and early death was observed in 7 patients in the dual therapy group and 5 patients in the monotherapy group. Overall, cefepime monotherapy is as effective as dual therapy for the initial treatment of febrile neutropenic patients. Further study is warranted for patients with severe neutropenia and leukemia who may benefit from dual therapy.

Topics: Amikacin; Antineoplastic Agents; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Immunocompromised Host; Japan; Leukemia; Male; Neutropenia; Opportunistic Infections

The bactericidal activity of beta-lactams is time-dependent, and the time spent above the MIC (T > MIC) is the best predictor of efficacy. A prospective, randomized, open-label study was conducted in intensive care unit (ICU) patients with gram-negative rod infections to compare the efficacy of cefepime given as a continuous versus an intermittent infusion. Of the 18 patients included to date, 14 had severe pneumonia and four bacteremia. All patients received amikacin, 15 mg/kg/d, and cefepime, 4 g/d. Patients were randomized to cefepime administration as a continuous infusion (Group 1, n = 9) or as an intermittent infusion (Group 2, n = 9, 2 g every 12 h). No significant differences were found between the two groups for age, sex, initial infection, IGS II score (46 vs 48, NS) or the MIC of the gram-negative organism. Mechanical ventilation and hospital stay durations, recovery rates, and pharmacokinetic parameters (24-h AUIC, 12-h AUIC, T > MIC, and T > 5 x MIC) were compared in the two groups using the chi-square and Mann-Whitney tests. P values < 0.05 were considered statistically significant. There were no significant differences for mechanical ventilation duration, recovery rate, hospital stay duration (34 vs 36 days, NS), 24-h AUIC (624 vs 473, NS), or the 12-h AUIC (235 vs 238, NS). There were two interesting findings: T > MIC was significantly (P < 0.05) higher in Group 1 (23.84 +/- 0.2) than in Group 2 (20.7 +/- 3), and T > 5 x MIC was also significantly (P < 0.01) higher in Group 1 (23.61 +/- 0.6) than in Group 2 (16.6 +/- 6). Although clinical outcomes were similar in the two groups, it is reasonable to assume that the longer time spent with a cefepime level above the MIC in the continuous infusion group was associated with a more stable bactericidal effect.

Topics: Bacteremia; Cefepime; Cephalosporins; Critical Care; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged

Cefepime (Maxipime) was used in the management of 22 patients at the age of 18 to 73 years with the surgical sepsis syndrome (SAPS > 15). In 16 patients surgical sepsis was due to pancreatitis, appendititis, abdominal wound or trauma or complications after planned surgical interventions on the organs of the abdominal cavity. In the other 6 patients surgical sepsis was due to inflammatory processes in soft tissues after minor trauma. In 10 patients (group 1) cefepime was used after the pathogen verification and antibioticogram examination. In 12 patients (group 2) the antibiotic was used in the empirical therapy as the first line drug after the patients acceptance from another unit when the pathogen nature was obscure. Cefepime was administered intravenously in a dose of 2.0 g twice daily for 7 to 10 days in combination with metronidazole in a dose of 0.5 g thrice daily. After 5-6 days of the treatment the patients of group 1 were switched to the cefepime intramuscular regimen. The lethality totaled 18 per cent (4 patients). Three of them were from group 2. The patients died of progressive polyorgan insufficiency. It is characteristic that in no cases cefepime induced septic shock due to the endotoxin escape. No septicopyemia was as well observed even in the patients with verified bacteremia due to Staphylococcus aureus.

Topics: Adolescent; Adult; Aged; Bacteremia; Cefepime; Cephalosporins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Middle Aged; Severity of Illness Index; Surgical Wound Infection; Systemic Inflammatory Response Syndrome

An open label, randomized comparative study was conducted to evaluate the safety and efficacy of cefepime, in comparison with ceftazidime, in the treatment of adult hospitalized Chinese patients with severe bacterial infections. Forty patients with severe infections including septicemia, urinary tract infection and bacterial pneumonia were randomly assigned to receive treatment with cefepime (2 g intravenously every 12 h) or ceftazidime (2 g intravenously every 8 h). The cefepime group (20 evaluable patients) and ceftazidime group (16 evaluable patients) were comparable with respect to age, sex, underlying diseases and distribution of infection type. In both groups urinary tract infection was the most common type of infection and Escherichia coli was the most common etiologic microorganism. The rates of satisfactory clinical response were similar in the cefepime and ceftazidime groups (95 versus 93.7%; 95% confidence interval: -0.14 - 0.17, P = 0.87). The bacteriological response rates of the cefepime and ceftazidime groups did not differ significantly (88.9 versus 85.7%; 95% confidence interval: -0.30 - 0.36, P = 0.85). Both cefepime and ceftazidime were well tolerated, with similar incidence of side effects. The results of this study suggest that cefepime is as safe and effective as ceftazidime for the treatment of serious infections in adult hospitalized Chinese patients.

Topics: Asian People; Bacteremia; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Humans; Pneumonia, Bacterial; Taiwan; Urinary Tract Infections

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fever; Gastrointestinal Diseases; Gram-Negative Bacteria; Gram-Positive Bacteria; Hematologic Neoplasms; Humans; Male; Neutropenia; Skin Diseases, Bacterial; Soft Tissue Infections; Urinary Tract Infections

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

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

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

Since infection develops in significant numbers of hospitalized patients, the problem of resistance to third-generation cephalosporins is of increasing concern. We evaluated the efficacy of cefepime 1 g bd as treatment for acute, moderately severe bacterial infection in 239 hospitalized patients (mean age 60 years). Of these patients, 204 were evaluated clinically for urinary tract infection (UTI) (n = 90), lower respiratory tract infection (LRTI) (n = 70), skin and soft tissue infection (S/STI) (n = 12) and bacteraemia which was associated with either UTI or LRTI (n = 32) but not included in the previously mentioned UTI and LRTI groups. Amongst the pathogens isolated (36 Gram-positive, 150 Gram-negative), the most predominant species were Escherichia coli in UTI and bacteraemia (n = 81), Streptococcus pneumoniae in LRTI and bacteraemia (n = 23), Haemophilus influenzae in LRTI (n = 16), Pseudomonas aeruginosa (n = 4) and Enterobacter cloacae (n = 2) in S/STI. The mean duration of treatment was 8.5 days and was the same for the 204 clinically evaluable patients. Overall, the clinical cure rate for cefepime was 94% (191/204). Pathogen eradication was achieved in 93% (185/199) of infections. Of the patients with associated bacteraemia, the clinical cure rate was 97% (31/32) and 94% (16/17) of the pathogens were eradicated. Cefepime therapy was well-tolerated. Treatment was discontinued in eight patients (3%) because of local intolerance and in five patients (2%) because of drug-related adverse events (rash, headache and pruritus). Cefepime 1 g bd is as safe and effective as other parenteral cephalosporins for the treatment of acute bacterial UTI, LRTI and S/STI, including those cases with associated bacteraemia. The bd dosing schedule and reported lack of cross-resistance with other cephalosporins against some species of aerobic Gram-negative bacilli make cefepime an attractive treatment option in hospitalized patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Bacteria; Bacterial Infections; Cefepime; Cephalosporins; Female; Freeze Drying; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Powders; Respiratory Tract Infections; Skin Diseases, Infectious; Therapeutic Equivalency; Urinary Tract Infections

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

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

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

The role of piperacillin/tazobactam for treatment of serious infections due to AmpC-producing organisms remains debatable, particularly in immunocompromised patients.. This was a retrospective cohort study in immunocompromised patients that investigated the effect of definitive treatment with either piperacillin/tazobactam versus cefepime or carbapenems for bacteraemia caused by cefoxitin-non-susceptible Enterobacterales. The primary endpoint was a composite of clinical and microbiological failure. A logistic regression model was constructed to assess the impact of definitive treatment choice on the primary endpoint.. A total of 81 immunocompromised patients with blood cultures positive for cefoxitin-non-susceptible Enterobacterales were included for analysis. There was more microbiological failure in the piperacillin/tazobactam arm compared with the cefepime/carbapenem arm (11.4% versus 0.0%, P = 0.019). Definitive treatment with cefepime or a carbapenem was associated with a decreased odds of clinical or microbiological failure (OR 0.303, 95% CI 0.093-0.991, P = 0.048) when controlling for baseline characteristics.. In immunocompromised patients with bacteraemia due to cefoxitin-non-susceptible Enterobacterales, definitive treatment with piperacillin/tazobactam was associated with an increased risk of microbiological failure and higher odds of clinical or microbiological failure compared with cefepime or carbapenems.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Cefepime; Cefoxitin; Citrobacter freundii; Enterobacter aerogenes; Enterobacter cloacae; Humans; Microbial Sensitivity Tests; Morganella morganii; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Serratia marcescens

Carbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated.. We conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed.. Seventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999).. Targeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

Topics: Adult; Aged; Bacteremia; Carbapenems; Cefepime; Humans; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

Catheter-related bacteriemia by Cupriavidus spp. is a rare condition with very few cases reported in the literature. Most of them occurred in immunocompromised patients.. To report a case of recurrent catheter-related bacteriemia by Cupriavidus pauculus in an immunocompromised infant in order to analyze possible therapeutic options, especially in relation to the need or not for central venous catheter (CVC) removal.. 22-month-old infant with B-cell acute lymphoblas tic leukemia (ALL) in reinduction phase, CVC carrier. He presented to the Emergency Room with fever without focus on examination. Blood tests were performed (without increase of acute phase reactants) and differential blood cultures (peripheral and CVC). He was hospitalized and empirical antibiotic therapy was started with intravenous fourth-generation cephalosporin (cefepime). After 24 hours, blood cultures were positive for Cupriavidus pauculus, growing first in the CVC culture. We maintained cefepime, adding catheter lock therapy with ciprofloxacin. Afterward, the infection was resolved, allowing us to keep the CVC. Seven months later, in the context of fever, Cupriavidus pauculus was again identified in CVC blood culture. We decided this time to remove the catheter, in addition to the administration of intravenous cefepime. The patient has not presented new episodes nine months after de removal of the CVC.. Catheter-related bacteremia by Cupriavidus is a rare condition in children that usually occurs in immunocompromised patients. Catheter lock therapy associated with systemic antibiotics could be a safe option in patients with difficult CVC re moval. However, if persistent colonization of the CVC is suspected, it may be necessary to remove it.

Topics: Bacteremia; Cefepime; Central Venous Catheters; Child; Cupriavidus; Gram-Negative Facultatively Anaerobic Rods; Humans; Infant; Male

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

Heteroresistance to antibiotic agents can lead to diagnostic and therapeutic failures; however, to date, cefepime heteroresistance (FEP-HR) in Pseudomonas aeruginosa (P. aeruginosa) bacteraemia has not been characterised. The primary goal of this study was to investigate the molecular epidemiology, mechanisms and risk factors for cefepime-heteroresistant P. aeruginosa bacteraemia over approximately 6 years in Southwest China.. A high prevalence (57.3%) of heteroresistance to cefepime was observed during the study period, and these FEP-HR isolates were not clonally related. Mechanistic studies revealed that AmpC hyperproduction contributed to the development of this phenomenon. In addition, patients with advanced age, haematological malignancies, central venous catheters, and previous cephalosporin therapy were identified as independent risk factors for acquiring FEP-HR P. aeruginosa bacteraemia. Furthermore, patients infected with FEP-HR were generally at a greater risk for an adverse prognosis compared with those with non-FEP-HR. More importantly, characterisation of three successive P. aeruginosa isolates recovered from the same patient revealed that heteroresistance can act as an intermediate stage during the evolution from susceptibility to full resistance in patients undergoing antibiotic therapy for prolonged periods.. These findings emphasised the necessity of antimicrobial stewardship programs in clinical settings, as well as the need for some rapid screening methods for detecting this phenomenon.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; China; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

AmpC β-lactamases are found in Enterobacter species, Serratia species, Citrobacter freundii, Providencia species and Morganella morganii ('ESCPM'). Carbapenems are commonly used to treat severe 'ESCPM' infections. Carbapenem-sparing agents are needed because of increasing carbapenem resistance worldwide. Use of cefepime and piperacillin-tazobactam has limited supportive clinical data. We evaluated the efficacy of non-carbapenems vs. carbapenems in 'ESCPM' bacteraemia.. A retrospective cohort study was conducted on patients with 'ESCPM' bacteraemia. Primary outcome was 30-day mortality. Analyses were performed on patients who received carbapenems vs. piperacillin-tazobactam or cefepime monotherapy as empirical and definitive therapy. Propensity score for carbapenem therapy was adjusted for in multivariate analyses for 30-day mortality.. A total of 241 patients were included. The most common bacterium isolated was Enterobacter species (58.1%). Common sources were urinary (22.8%) and vascular lines (22.0%). Carbapenems (28.6%) and piperacillin-tazobactam (28.6%) were the commonest empirical antibiotics. Carbapenems (54.8%) and cefepime (23.7%) were the most common definitive antibiotics. Median Pitt bacteraemia score was 1 (interquartile range [IQR], 0-2). Overall, 30-day mortality was 12.9%. Adjusted multivariate analyses for empirical and definitive antibiotic treatment models yielded risk factors for 30-day mortality, including higher Pitt bacteraemia score (empirical: adjusted OR [aOR] 1.21 for each point increase, 95% confidence interval [CI]:1.01-1.45; definitive: aOR 1.33 for each point increase, 95% CI:1.06-1.69) and age (empirical: aOR 1.04 for each year increase, 95% CI:1.01-1.08). Empirical piperacillin-tazobactam (aOR 0.29, 95% CI:0.07-1.27) and definitive cefepime (aOR 0.65, 95% CI:0.12-3.55) were not associated with 30-day mortality.. Compared with carbapenem therapy, empirical piperacillin-tazobactam and definitive cefepime were not associated with 30-day mortality in 'ESCPM' bacteraemia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cefepime; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

We investigated the treatment outcomes before and after the addition of amikacin to cefepime monotherapy as an initial empirical antibiotic treatment in pediatric cancer patients with febrile neutropenia.. This was a retrospective historical cohort study. The subjects were pediatric cancer patients who visited the emergency room at the Samsung Medical Center, Seoul, Korea, due to chemotherapy-induced febrile neutropenia, between January 2011 and December 2016. Since September 2014, the empirical antimicrobial treatment regimen for febrile neutropenia was changed from high-dose cefepime monotherapy to combination therapy of adding a single dose of amikacin.. Two hundred twenty-five bacteremia episodes in 164 patients were reported during the study period. Bacteremia caused by cefepime-resistant Gram-negative bacteria was observed in 16% of patients before September 2014 and in 21% of the patients after September 2014 (P = 0.331). Use of appropriate empirical antibiotic treatments increased from 62% to 83% following addition of amikacin to cefepime treatment (P = 0.003). The duration of fever was shorter in the cefepime plus amikacin group than in the cefepime group (22 vs. 34 hours, P = 0.014); however, rates of septic shock and pediatric intensive care unit hospitalizations were not significantly different between the 2 groups (septic shock, both 7%, P = 0.436; pediatric intensive care unit 3% vs. 1%, P = 0.647).. We observed no additional benefit of amikacin addition to high-dose cefepime monotherapy. Therefore, adding amikacin to cefepime monotherapy in conditions where cefepime-resistant Gram-negative bacteremia amounts to 20% or less may not be justified.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteremia; Cefepime; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Neoplasms; Retrospective Studies; Treatment Outcome

Acquired factor V deficiency (AFVD) caused by Factor V (FV) inhibition is a rare event, characterized by prolonged prothrombin time and activated partial thromboplastin time. To date, various factors were reported as triggers for developing FV inhibitor. Clinical symptoms range from asymptomatic to life-threatening bleeding. Case Report and Conclusions: Here, we report an 84-year-old Japanese male on hemodialysis due to renal failure who developed subcutaneous hemorrhage after administration of cefepime (CFPM) to treat bacteremia. Deficient FV activity (< 1.0%) was identified and AFVD with FV inhibitor titer of 9 BU/mL was diagnosed. Although the patient had multiple risks for developing FV inhibitor, CFPM was thought to be the major culprit in this case. After the diagnosis, oral prednisolone (30 mg/day) was initiated, but the patient died of respiratory/cardiac failure, unrelated to AFVD.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood Coagulation Tests; Cefepime; Factor V; Factor V Deficiency; Fatal Outcome; Hemorrhage; Humans; Male; Renal Dialysis

The quantitative importance of active antimicrobial treatment relative to other modifiable and non-modifiable risk factors for mortality has not been well defined in the literature. Here we quantify the impact of active antimicrobial treatment on mortality relative to other disease modifiers in patients with Gram-negative bloodstream infection (GNBSI). Patients with at least one positive blood culture who were treated with ≥24 h of cefepime for GNBSI were included in the study. To examine in-hospital survival, a full primary model and a base model with the least significant covariate from the primary model were established. Relative importance of covariates was calculated using percentages of difference in log-likelihood values when each covariate was iteratively added to the base model. A total of 154 unique patients with GNBSI were included. The primary model included active cefepime therapy (P = 0.004), normalised days to positive culture (P = 0.091), intensive care unit (ICU) at time of treatment (P = 0.001), modified Acute Physiology and Chronic Health Evaluation (APACHE) II score on day zero (P = 0.025), history of leukaemia (P = 0.008) and prior immunosuppressive therapy (P = 0.088). Active antimicrobial therapy displayed a relative importance of 32.2%, which was second to ICU residence at the time of culture. Amongst all covariates in the model, active antimicrobial therapy was the only modifiable variable and contributed significantly to in-hospital survival in acutely ill patients with GNBSI.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Risk Factors

Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed.. Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected.. Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week.. BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Candidemia; Cefepime; Coinfection; Dengue; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Hospitals; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Mortality; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Staphylococcal Infections; Streptococcus; Taiwan

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Gram-Negative Bacteria; Humans; Meropenem; Probability; Sepsis; Tazobactam

Topics: Bacteremia; Cefepime; Gram-Negative Bacteria; Humans; Meropenem; Piperacillin; Sepsis; Tazobactam

Infections in humans by Raoultella spp. are rare and the effect that Raoultella spp. might have as a human pathogen is currently unknown. A clinical case is presented of catheter-related bacteraemia caused by Raoultella ornithinolytica, treated successfully with applied antibiotic therapy (intravenous cefepime and sealed the catheter with amikacin).

Topics: Aged; Amikacin; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Catheter-Related Infections; Cefepime; Combined Modality Therapy; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Equipment Contamination; Female; Humans; Pancreatic Neoplasms; Postoperative Complications

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Cefepime; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Daptomycin; Endocarditis, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Staphylococcal Infections; Vancomycin

The quantitative impact of severity of illness on pharmacodynamic thresholds is poorly defined. We used a robust cefepime outcomes cohort and previously identified pharmacodynamic breakpoints of 68% [pharmacokinetic (PK) model 1] and 74% (PK model 2) to probe interactions and relationships with modified Acute Physiology and Chronic Health Evaluation (mAPACHE) II scores. When the time that serum concentration remains above the minimum inhibitory concentration during the dosing interval (fT

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Serum; Severity of Illness Index; Survival Analysis; Time Factors; Treatment Outcome

BACKGROUND Aspergillus terreus is an evolving opportunistic pathogen, and patients with A. terreus often have poor outcomes due to its intrinsic resistance to several systemic antifungal agents. Here we present a unique case of intracranial abscesses of A. terreus in a patient with recurrent angiosarcoma, complicated by development of tension pneumocephalus. CASE REPORT A 67-year old gentleman with history of scalp angiosarcoma with wide excision two years prior presented to the hospital for left arm clumsiness, altered mental status, and low-grade fever. Staphylococcus aureus and Proteus mirabilis bacteremia was detected, and Computed Tomography (CT) of the head showed right frontal lobe abscesses. He was started on steroids, intravenous vancomycin and cefepime, and was eventually discharged. He presented to the hospital again due to persistent and worsening symptoms. MRI showed progression of the brain lesions, and surgical biopsy and culture of lesions revealed A. terreus and gram-positive cocci. He was started on trimethroprim/sulfamethoxazole and voriconazole and symptoms improved. On post-op day four, he acutely decompensated with total loss of left arm strength; MRI demonstrated tension pneumocephalus. Conservative management was undertaken with continuous supplemental oxygen. Serial x-ray imaging over the next week demonstrated resolution of the pneumocephalus, and the patient was able to regain all proximal lower and upper extremity strength. CONCLUSIONS Never before has a case of A. terreus been associated with angiosarcoma or tension pneumocephalus in the literature. Proper identification and prompt diagnosis of species is crucial in the immunocompromised patient. Tension pneumocephalus should be included in the differential diagnosis of nontraumatic hemiparesis for emergent evaluation and management.

Topics: Aged; Anti-Bacterial Agents; Aspergillosis; Aspergillus; Bacteremia; Brain Abscess; Cefepime; Cephalosporins; Disease Progression; Drug Combinations; Drug Therapy, Combination; Glucocorticoids; Hemangiosarcoma; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Pneumocephalus; Proteus mirabilis; Skin Neoplasms; Staphylococcus aureus; Sulfamethizole; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim; Vancomycin; Voriconazole

The United States Clinical and Laboratory Standards Institute recently elected not to revise ceftazidime and cefepime Pseudomonas aeruginosa minimum inhibitory concentration (MIC) susceptibility breakpoints but rather recommended specific dosage regimens to correspond to breakpoints. This study's objective was to examine mortality of low and high MIC P. aeruginosa isolates in bacteremic patients treated with cefepime or ceftazidime. Data were gathered through a Veterans Health Administration national administrative database for veterans with P. aeruginosa blood cultures who received cefepime or ceftazidime. Seventy-four patients in the low MIC (≤2 μg/mL) group and 29 patients in the high (4-8 μg/mL) MIC group were included. Independent baseline variables associated with 30-day all-cause mortality were determined through multivariate analysis to calculate propensity scores and perform matching. All-cause 30-day mortality was not statistically significant between the 2 resultant propensity score-matched groups (17.2% mortality in the low MIC group versus 27.6% in the high MIC group; P=0.34). Data suggested that P. aeruginosa bacteremia episodes where the cephalosporin MIC = 8 μg/mL may have higher mortality, however this may be reflective of higher propensity scores. Our study suggests that it is reasonable to designate a cefepime or ceftazidime MIC ≤8 μg/mL as susceptible for P. aeruginosa bacteremia infections, but potential suboptimal outcomes in episodes for which the P. aeruginosa MIC is 8 μg/mL may need further investigation.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Ceftazidime; Cephalosporins; Female; Humans; Male; Microbial Sensitivity Tests; Multivariate Analysis; Propensity Score; Pseudomonas aeruginosa; Pseudomonas Infections

We determined the correlation between Etest and BMD MICs with bactericidal activity in MSSA blood isolates. Ceftriaxone was bactericidal in 36% and 9% of isolates exposed to the Etest and BMD MIC, respectively. With the sub-optimal activity of ceftriaxone, the Etest MIC may be a conservative method in identifying clinical utility.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Ceftaroline; Ceftriaxone; Cefuroxime; Cephalosporins; Cephalothin; Disk Diffusion Antimicrobial Tests; Humans; Oxacillin; Staphylococcus aureus

Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients with acute leukemia. However, fluoroquinolone use has been associated with development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum β-lactamase producing gram-negative bacilli. Due to a presumed risk of multi-drug resistance associated with fluoroquinolone prophylaxis, patients admitted to our hospital with neutropenic fever receive empiric carbapenem therapy until cultures are negative for 72 h or identification of an organism. Our study seeks to identify the incidence of multi-drug-resistant organism colonization and bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate duration of empiric carbapenem therapy. A retrospective review of adult patients with acute leukemia receiving a fluoroquinolone as outpatient infection prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic fever was completed. Surveillance and blood cultures were reviewed for antibiotic resistance. Duration of empiric carbapenem therapy was reviewed. One hundred patients and 177 admissions for neutropenic fever were included. Six patients harbored a piperacillin-tazobactam-resistant organism found during routine surveillance. Among these patients, two bacteremias were identified, one of which was a piperacillin-tazobactam-resistant organism. Five bacteremias were identified among 83 patients with negative surveillance cultures. Among the bloodstream infections, five organisms isolated were fluoroquinolone resistant. No cefepime-resistant organism was isolated on surveillance or bloodstream cultures. Adherence to the institution guideline of narrowing antibiotics after 72 h of negative cultures occurred in only 13% of neutropenic fever cases. The average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4 days. Our findings show that among our patient population, there is a low risk of bacteremia with a piperacillin-tazobactam-resistant or cefepime-resistant organism. However, prompt de-escalation of carbapenem therapy needs to be reiterated within hospital practice.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Female; Fluoroquinolones; Humans; Leukemia; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Post-Exposure Prophylaxis; Random Allocation; Retrospective Studies; Risk Factors; Young Adult

Infection 'is a common complication in children with hematological malignancies' during febrile neutropenia. '. The aim of this study was to' evaluate common bacterial and fungal pathogens in children with hematological malignancies during febrile neutropenia in single center Egyptian study. '. This study was carried out on 90' children with hematological malignancies during febrile neutropenia including 54 with ALL, 27 with AML and 9 with NHL with their ages ranging from 2.5- 13 years and mean age value of 5.5 ± 3.5. Complete blood count, BM aspiration, and blood and throat cultures were done for all patients.. Positive bacterial growth was found in 54 cultures (30%) including 42 blood cultures and 12 throat cultures with significantly higher Gram negative bacterial growth. Staphylococcus aurous and Pseudomonas aeruginosa were the most common Gram positive and negative organisms respectively. Cefepime was the most effective antibiotic against isolated bacterial growth where 80% of Gram negative bacterial growth was sensitive to it, 20% showed intermediate response and no Gram negative Cefepime resistance was recorded. On the other hand, 62.5% of Gram positive organisms was sensitive to it, 25% showed intermediate response and Gram positive Cefepime resistance was found in 12.5%. Ampicillin sulbactam 'was the most effective antibiotic against Gram positive' organisms with 100% sensitivity. Positive fungal growth was found in 36 cultures (20%) including 30 throat cultures and 6 blood cultures and all fungal isolates were candida. Amphotericin was active against 100% of fungal isolates, while resistance to Fluconazole and Voriconazole was found in 25% and 33.33% respectively.. 'Gram negative is still more common than gram positive' infections and fungal infection is also a common cause of fever in patients with hematological malignancies during neutropenia and must be taken in consideration in every case of febrile neutropenia.

Topics: Adolescent; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Blood Cell Count; Candida; Cefepime; Cephalosporins; Child; Child, Preschool; Egypt; Febrile Neutropenia; Female; Fungi; Gram-Negative Bacteria; Hematologic Neoplasms; Humans; Male; Pharynx; Pseudomonas aeruginosa; Staphylococcus aureus

To identify the clinical characteristics and risk factors for mortality of patients with cefepime-resistant Pseudomonas aeruginosa (FRPa) bacteremia.. This retrospective study analyzed adult patients with FRPa bacteremia hospitalized between January 2006 and December 2011.. Seventy eight patients (46 male, 32 female; mean age: 72.2 ± 14.1 years) were included. Of them, 46 (59.0%) had ventilator use and 45 (57.7%) had intensive care unit stay. All the bacteremia episodes were health-care associated or hospital acquired, and 55.1% of FRPa blood isolates were multidrug resistant. The sources of bacteremia were identified in 42 patients (53.8%), with pneumonia being the most common one (28/42; 66.7%). The mean interval between admission and the sample date of the first FRPa-positive blood culture was 45.8 ± 52.6 days. The mean Pittsburgh bacteremia score was 5.0 ± 3.4. The 15-day and 30-day mortality rates were 50.0% and 65.4%, respectively. Patients (41; 52.6%) on appropriate antibiotic therapy within 72 hours of the first FRPa-positive blood culture had a higher 30-day survival rate than those without (48.8% vs. 18.9%, p = 0.011 by log-rank test). Multivariate analyses revealed that a higher Pittsburgh bacteremia score was an independent risk factor for either 15-day (p = 0.002) or 30-day mortality (p = 0.010), and appropriate antibiotic therapy within 72 hours was an independent protecting factor for either 15-day (p = 0.049) or 30-day mortality (p = 0.017).. FRPa bacteremia had a high mortality rate. The disease severity and appropriate antimicrobial therapy within 72 hours of positive blood culture were related to the patients' outcome.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Female; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Severity of Illness Index; Survival Analysis

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

Predicted and observed failures at higher cefepime MICs have prompted the Clinical and Laboratories Standards Institute (CLSI) to lower the susceptible breakpoint for Enterobacteriaceae to ≤2mg/L, with dose-dependent susceptibility at 4-8mg/L, while the susceptibility breakpoint for nonfermentative organisms remain unchanged at ≥8mg/L. The contribution of increasing cefepime MIC to mortality risk in the setting of aggressive cefepime dosing is not well defined. Patients who were treated with cefepime for Gram-negative blood stream infections (GNBSIs), including both Enterobacteriaceae and nonfermentative organisms, were screened for inclusion in this retrospective cohort study. Demographic and microbiologic variables were collected, including pathogen, cefepime MIC, dosage, and interval. The objective was to define a risk-adjusted mortality breakpoint for cefepime MICs. Secondarily, we looked at time to death and length of stay (LOS) postculture. Ninety-one patients were included in the analysis. Overall, 19 patients died and 72 survived. Classification and Regression Tree analysis identified an inhospital mortality breakpoint at a cefepime MIC between 2 and 4mg/L for patients with a modified Acute Physiology and Chronic Health Evaluation II score ≤16.5 (4.2% versus 25%, respectively). Multivariate logistic regression revealed increased odds of mortality at a cefepime MIC of 4mg/L (adjusted odds ratio [aOR] 6.47; 95% confidence interval [CI] 1.25-33.4) and 64mg/L (aOR 6.54, 95% CI 1.03-41.4). Those with cefepime MICs ≥4mg/L experienced a greater median intensive care unit LOS for survivors (16 versus 2days; P=0.026). Increasing cefepime MIC appears to predict inhospital mortality among patients who received aggressive doses of cefepime for GNBSIs, supporting a clinical breakpoint MIC of 2mg/L.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Cohort Studies; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Survival Analysis; Treatment Outcome

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

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 μg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Diabetes Complications; Diabetes Mellitus; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Gene Expression; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Neoplasms; Renal Insufficiency, Chronic; Retrospective Studies; Severity of Illness Index; Survival Analysis; Treatment Outcome

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

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

There are controversies regarding the association of cefepime therapy with increased mortality among patients with infections caused by Gram-negative bacteria (GNB). We evaluated the effect of cefepime on the mortality of patients with GNB bloodstream infections (BSIs).. A prospective cohort study was conducted in adult patients with creatinine ≤1.5 mg/dL who received empirical therapy with cefepime for at least 48 h for BSIs caused by GNB. The outcome was hospital mortality. Potential clinical predictors, including a high-dose regimen (2 g every 8 h), were assessed.. One hundred and thirteen patients were included. Most (78.8%) isolates had low cefepime MICs (≤0.25 mg/L). The overall hospital mortality was 35.4% [25.6% (10/39) and 40.5% (30/74) in patients receiving high-dose and usual-dose cefepime, respectively (P = 0.17)]. In a Cox regression model adjusted for cefepime MIC and propensity score, a high-dose regimen was independently associated with lower mortality rates [adjusted hazard ratio (aHR) 0.41; 95% CI 0.18-0.91; P = 0.029] while presentation with severe sepsis or septic shock was independently associated with higher mortality rates (aHR 4.10; 95% CI 1.78-9.40; P = 0.001). A trend to lower mortality rates was also found in the subgroup analysis of patients who had not switched antibiotic during therapy after adjustment for the latter variables.. High-dose cefepime therapy was associated with lower mortality rates in patients with GNB BSIs, even for GNB with low cefepime MICs.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Drug Substitution; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Risk Factors; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Ciprofloxacin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin; Treatment Failure

Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy.. We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia ≥1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems.. Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for ≥1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P < .01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI, .58-3.98; P = .39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI, .19-1.40; P = .19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses.. Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefepime; Cephalosporins; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Survival Analysis; Treatment Outcome

Intensive chemotherapy for pediatric acute myeloid leukemia incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear.. In the current study, among 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children's Research Hospital, the authors retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, as well as on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (group A). The protocol was then amended to administer intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (group B).. There were 334 infectious episodes. Patients in group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia; P = .0003 and .001, respectively) compared with patients in group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not found to be different between the 2 groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs none in group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures.. Outpatient intravenous antibiotic prophylaxis is feasible in children with acute myeloid leukemia and reduces the frequency of documented infection but not of febrile neutropenia. Despite the emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored.

Topics: Administration, Oral; Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Candidiasis; Cefepime; Cephalosporins; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Ciprofloxacin; Consolidation Chemotherapy; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Incidence; Induction Chemotherapy; Infant; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Neoplasm Staging; Nose; Outpatients; Rectum; Retrospective Studies; Treatment Outcome; Vancomycin; Young Adult

This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies.. The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB.. A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome.. There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.

Topics: Adult; Age Factors; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Febrile Neutropenia; Female; Hematologic Neoplasms; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Streptococcal Infections; Viridans Streptococci

To report the first case of Rhizobium radiobacter bacteremia in a critically ill trauma patient.. A 36-year-old female trauma patient hospitalized at The Regional Medical Center at Memphis developed bacteremia due to Rhizobium radiobacter on hospital day 9. The central line catheter tip culture from the same hospital day was negative. No source for the R radiobacter bacteremia was identified. Empirical and definitive antibiotic therapy consisted of cefepime 2 g intravenously every 8 hours for at total of 8 days. On completion of antibiotics, the patient demonstrated clinical resolution by immediate defervescence and gradual normalization of her white blood cell count. She demonstrated microbiologic success of therapy with negative blood cultures on hospital days 22, 34, 45, and 61. She was discharged on hospital day 80.. Rhizobium species are common soil and plant pathogens that rarely cause infections in humans. Previous reports of Rhizobium infections have been in immunocompromised patients; generally those with cancer or HIV infection. Intravenous catheters have commonly been cited as the source of infection. The trauma patient in this case constitutes a unique presentation of R radiobacter bacteremia when compared with other case reports. Her indwelling catheter was not the source of her infection, and her only identifiable risk factor for R radiobacter infection was hospitalization. However, she did possess potential reasons for development of an infection with an unusual organism such as R radiobacter. Potential immune modulating therapies included blood transfusions, opioid analgesics, benzodiazepines, general anesthetics, and surgical procedures. Finally, trauma itself has been associated with some degree of immunosuppression. All these issues may have placed the patient in this case at risk of an opportunistic infection like R radiobacter.. Based on this case, R radiobacter may be considered a potential pathogen causing bacteremia in critically ill trauma patients.

Topics: Adult; Agrobacterium tumefaciens; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Critical Illness; Female; Humans; Opportunistic Infections; Treatment Outcome; Wounds and Injuries

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae isolates are important clinical pathogens. In addition, the efficacy of cefepime for such infections is controversial.. We performed a retrospective study of monomicrobial bacteremia caused by ESBL producers at 2 medical centers between May 2002 and August 2007. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) in a propensity score-matched analysis to assess therapeutic effectiveness. The 30-day crude mortality is the primary endpoint.. A total of 178 patients were eligible for the study. Patients who received cefepime (n = 17) as definitive therapy were more likely to have a clinical failure (odds ratio [OR] 6.2; 95% confidence interval [CI], 1.7-22.5; P = .002), microbiological failure (OR 5.5; 95% CI, 1.3-25.6; P = .04), and 30-day mortality (OR 7.1; 95% CI, 2.5-20.3; P < .001) than those who received carbapenem therapy (n = 161). Multivariate regression revealed that a critical illness with a Pitt bacteremia score ≥ 4 points (OR 5.4; 95% CI, 1.4-20.9; P = .016), a rapidly fatal underlying disease (OR 4.4; 95% CI, 1.5-12.6; P = .006), and definitive cefepime therapy (OR 9.9; 95% CI, 2.8-31.9; P < .001) were independently associated with 30-day crude mortality. There were 17 case-control pairs in the propensity scores matched analysis. The survival analysis consistently found that individuals who received cefepime therapy had a lower survival rate (log-rank test, P = .016).. Based on the current Clinical and Laboratory Standards Institute susceptible breakpoint of cefepime (minimum inhibitory concentration ≤ 8 μg/mL), cefepime definitive therapy is inferior to carbapenem therapy in treating patients with so-called cefepime-susceptible ESBL-producer bacteremia.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Case-Control Studies; Cefepime; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Treatment Outcome

Despite many years of clinical experience with cefepime, data regarding the outcome of patients suffering from bloodstream infections (BSIs) due to Enterobacter cloacae (Ecl) are scarce. To address the gap in our knowledge, 57 Ecl responsible for 51 BSIs were analysed implementing phenotypic and molecular methods (microarrays, PCRs for bla and other genes, rep-PCR to analyse clonality). Only two E. cloacae (3.5%) were ESBL-producers, whereas 34 (59.6%) and 18 (31.6%) possessed inducible (Ind-Ecl) or derepressed (Der-Ecl) AmpC enzymes, respectively. All isolates were susceptible to imipenem, meropenem, gentamicin and ciprofloxacin. Der-Ecl were highly resistant to ceftazidime and piperacillin/tazobactam (both MIC₉₀≥256 μg/mL), whereas cefepime retained its activity (MIC₉₀ of 3 μg/mL). rep-PCR indicated that the isolates were sporadic, but Ecl collected from the same patients were indistinguishable. In particular, three BSIs initially due to Ind-Ecl evolved (under ceftriaxone or piperacillin/tazobactam treatment) into Der-Ecl because of mutations or a deletion in ampD or insertion of IS4321 in the promoter. These last two mechanisms have never been described in Ecl. Mortality was higher for BSIs due to Der-Ecl than Ind-Ecl (3.8% vs. 29.4%; P=0.028) and was associated with the Charlson co-morbidity index (P=0.046). Using the following directed treatments, patients with BSI showed a favourable treatment outcome: cefepime (16/18; 88.9%); carbapenems (12/13; 92.3%); ceftriaxone (4/7; 57.1%); piperacillin/tazobactam (5/7; 71.4%); and ciprofloxacin (6/6; 100%). Cefepime represents a safe therapeutic option and an alternative to carbapenems to treat BSIs due to Ecl when the prevalence of ESBL-producers is low.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporins; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Genotype; Hospitals, University; Humans; Infections; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Survival Analysis; Switzerland; Tertiary Care Centers; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Chronic Disease; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome

Extended-spectrum-β-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio [OR], 2.17; 95% confidence interval [CI], 0.98 to 4.78), presence of a central-line catheter prior to positive culture (OR, 2.33; 95% CI, 0.77 to 7.03), presence of a rapidly fatal condition at the time of admission (OR, 5.13; 95% CI, 2.13 to 12.39), and recent prior hospitalization (OR, 1.92; 95% CI, 0.83 to 4.09). When carbapenems were added as empirical therapy to the predictor model, there was a trend between empirical carbapenem therapy and decreased mortality (OR, 0.61; 95% CI, 0.26 to 1.50). When added to the model, receipt of empirical cefepime alone (n = 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was as

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporins; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies

The patient is a 54-year-old man with severe thermal burn injury involving 45.5% of the total body-surface area, complicated with bacteremia caused by Pseudomonas aeruginosa with a cefepime MIC of 8 µg/ml. The plasma concentrations of cefepime 1 g every 6 h measured by validated high performance liquid chromatography were 25.8 µg/ml at 1 h and 6.28 µg/ml at 5 h after infusion, and 3.9 µg/ml before the infusion, when creatinine clearance was increased to 136 ml/min by vigorous fluid replacement. The pharmacokinetic-pharmacodynamic analyses in the one-compartment model with use of the Sawchuk-Zaske method revealed marked increase in the volume of distribution (28.9 l), total clearance (10.7 l/h), and shortening of plasma half- life (1.79 h) of cefepime, with time >MIC and 24-h area under the concentration-time-curve being 58% and 358, respectively. These pharmacokinetic parameters of cefepime quantified in the patient estimated a time >MIC of 87% if administered every 4 h. P. aeruginosa, however, was successfully eradicated without revision of the dosing regimen of cefepime. Decrease in creatinine clearance by correction of the fluid imbalance and wound closure by skin graft surgery likely contributed to the restoration of fluid shift, resulting in normal disposition of cefepime and favorable clinical outcome of the patient.

Topics: Anti-Bacterial Agents; Bacteremia; Burns; Cefepime; Cephalosporins; Humans; Male; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections

Melioidosis is an important disease in Asia and Australia. It is very rare in Venezuela. We describe the case of a 50-year-old diabetic patient with several episodes of right tibial osteomyelitis, left shoulder arthritis, sternal osteomyelitis, right parietal osteomyelitis, and subperiosteal abscess, followed by septic arthritis of the right knee. In all cases Gram stain smear showed Gram-negative bacilli. Culture yielded Burkholderia pseudomallei, susceptible to third- and fourth-generation cephalosporins, ciprofloxacin and aztreonam, and resistant to aminoglycosides. He developed sepsis syndrome. Blood cultures and culture of abscess and joint fluids also revealed B. pseudomallei. The patient was treated with ceftazidime and ciprofloxacin, then cefepime and trimethoprim-sulfamethoxazole. He was discharged with suppressive therapy consisting of oral doxycycline and trimethoprim-sulfamethoxazole, and follow-up has continued to date. At this time he remains asymptomatic. Melioidosis is an extremely rare disease in our country. To our knowledge, this is only the second case reported in Venezuela.

Topics: Anti-Bacterial Agents; Bacteremia; Burkholderia pseudomallei; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Drug Therapy, Combination; Humans; Male; Melioidosis; Microbial Sensitivity Tests; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

We used a retrospective cohort to evaluate the 28 day all-cause mortality in adult patients with Gram-negative bloodstream infection (BSI) who received cefepime therapy compared with those who received other β-lactam antibiotics with in vitro activity against aerobic Gram-negative bacilli.. We identified 398 adult patients who received β-lactam antibiotic monotherapy during hospitalization at Mayo Clinic hospitals in Rochester, MN, USA, for monomicrobial Gram-negative BSI from 1 January 2001 to 31 October 2006. After adjusting for the propensity to receive cefepime, multivariable Cox proportional hazard regression was used to compare the 28 day mortality in patients who were treated with cefepime with that in those who received other β-lactam antibiotics.. The median age of patients with Gram-negative BSI was 65 years (interquartile range 51-77) and 230 (58%) were male. Compared with patients who received other β-lactams, patients treated with cefepime were more likely to have cancer (59% versus 44%, P = 0.007) and immunocompromising conditions (55% versus 21%, P < 0.001). Patients who received cefepime were less likely to have community-acquired infection acquisition (18% versus 33%, P = 0.002) and urinary source of BSI (14% versus 23%, P = 0.04) than those treated with other β-lactam antibiotics. After adjusting for the propensity to receive cefepime and other covariates in the multivariable Cox model, cefepime therapy was not associated with an increased 28 day all-cause mortality (hazard ratio 0.99, 95% confidence interval 0.53-1.79, P = 0.97).. In adult patients with monomicrobial Gram-negative BSI, cefepime therapy was not associated with increased mortality when compared with other β-lactam antibiotics.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Cohort Studies; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States

Persistent bacteraemia arising from a case of post-operative mediastinitis as a result of a Proteus mirabilis isolate, possessing two class 1 integrons carrying bla(VIM-1) and aadA2 gene cassettes located on chromosomal and plasmidic DNA, respectively, is reported. Despite the in vitro susceptibility to carbapenems, meropenem therapy failed, whereas the patient responded to treatment with cefepime plus amikacin. To our knowledge, this is the first report of metallo-beta-lactamase production in a clinical isolate of P. mirabilis in Italy.

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Chromosomes, Bacterial; DNA, Bacterial; Humans; Integrons; Italy; Male; Meropenem; Plasmids; Proteus Infections; Proteus mirabilis; Surgical Wound Infection; Thienamycins; Treatment Failure; Treatment Outcome

Chryseobacterium species are a rare cause of human disease and are usually associated with indwelling devices or altered immune status. This is the first case to our knowledge, of Chryseobacterium indologenes bacteremia in a previously healthy infant. Chryseobacteria are pathogens resistant to the usual empiric treatments for neonatal or infantile septicemia.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Chryseobacterium; Female; Flavobacteriaceae Infections; Humans; Infant; Microbial Sensitivity Tests; Treatment Outcome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Enterobacter; Enterobacteriaceae Infections; Female; Fever; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Treatment Outcome

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 novel Klebsiella pneumoniae carbapenemase (KPC) variant, designated bla(KPC-5), was discovered in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate from Puerto Rico. Characterization of the upstream region of bla(KPC-5) showed significant differences from the flanking regions of other bla(KPC) variants. Comparison of amino acid sequences with those of other KPC enzymes revealed that KPC-5 was an intermediate between KPC-2 and KPC-4, differing from KPC-2 by a single amino acid substitution (Pro(103)-->Arg), while KPC-4 contained Pro(103)-->Arg plus an additional amino acid change (Val(239)-->Gly). Transformation studies with an Escherichia coli recipient strain showed differences in the properties of the KPC variants. KPC-4 and KPC-5 both had pIs of 7.65, in contrast with the pI of 6.7 for KPC-2. KPC-2 transformants were less susceptible to the carbapenems than KPC-4 and KPC-5 transformants. These data correlated with higher rates of imipenem hydrolysis for KPC-2 than for KPC-4 and KPC-5. However, KPC-4 and KPC-5 transformants had higher ceftazidime MICs, and the enzymes from these transformants had slightly better hydrolysis of this drug than KPC-2. KPC-4 and KPC-5 were more sensitive than KPC-2 to inhibition by clavulanic acid in both susceptibility testing and hydrolysis assays. Thus, KPC enzymes may be evolving through stepwise mutations to alter their spectra of activity.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; beta-Lactamases; Clavulanic Acid; Drug Resistance, Bacterial; Enzyme Inhibitors; Genetic Variation; Hydrolysis; Isoelectric Focusing; Klebsiella pneumoniae; Microbial Sensitivity Tests; Phenotype; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporins; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Neutropenia; Treatment Failure; Young Adult

Levofloxacin and tobramycin, alone and in combination with cefepime, were investigated for their in vitro activities and post-antibiotic effects (PAEs) on Pseudomonas aeruginosa.. The in vitro activities of tobramycin and levofloxacin in combination with cefepime were determined by microbroth chequerboard technique against six P. aeruginosa strains that were isolated from patients with bacteremia. The results were interpreted by fractional inhibitory concentration index. To determine the PAEs, P. aeruginosa strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation.. Three synergistic interactions were observed with cefepime-tobramycin and one with cefepime-levofloxacin combinations against tested strains.No antagonism was observed. Levofloxacin produced a PAE ranging from 1.9 to 4.5 h in a concentration-dependent manner. Similar PAEs were induced by tobramycin (ranging from 1.5 to 3.1 h). However, negative PAE values were obtained with cefepime. In combination, cefepime slightly reduced the PAE of tobramycin and levofloxacin against studied strains.. The finding of this study may have important clinical implications for the timing of doses during therapy with cefepime, levofloxacin and tobramycin alone and in combination.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Humans; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Pseudomonas aeruginosa; Time Factors; Tobramycin

Catheter-related blood stream infections (CRBSI) cause significant morbidity and mortality in patients with hematological malignancies. Previous studies have identified a predominance of gram-positive organisms causing CRBSI but they included both neutropenic and non-neutropenic patients with solid organ and hematological malignancies. The aim of our study was to evaluate the incidence and microbiological profile of CRBSIs in a specific cohort of patients with hematological malignancies in their non-neutropenic phase of illness.. A detailed retrospective review was done from January 2003 to December 2005 on all patients with hematological malignancies who had double-lumen non-antibiotic impregnated tunneled CVCs (Hickman catheters) inserted in our hospital to identify those fulfilling our criteria for CRBSI episodes.. Amongst 273 evaluable patients, 61 developed CRBSI on 70 occasions. In contrast to previous studies, there was a predominance of gram-negative infections (68%). The majority (73%) of initial CRBSI episodes required catheter removal within 7 days of onset. Vancomycin and cefepime was the most common initial antibiotic regimen used.. This study highlights the predominance of gram-negative infections in our cohort of non-neutropenic patients with underlying hematological malignancies who had Hickman catheters whose lines were not salvageable in the majority of cases. Empiric monotherapy with an antimicrobial agent with broad spectrum gram-negative cover needs to be given upfront pending results of the nature and sensitivity of organisms identified.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cefepime; Cephalosporins; Cohort Studies; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Incidence; Male; Middle Aged; Neutropenia; Retrospective Studies; Vancomycin; Victoria

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

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

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

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

In this study, we systematically investigated the resistance mechanisms to beta-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary beta-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactams; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Fluoroquinolones; Genotype; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Reverse Transcriptase Polymerase Chain Reaction

For commonly encountered gram-negative bacilli, a MIC of cefepime of 8 mug/ml or less was defined by the Clinical and Laboratory Standards Institute as "susceptible" prior to the commercial release of the antibiotic. We assessed 204 episodes of bacteremia caused by gram-negative organisms for which patients received cefepime (typically 1 to 2 g every 12 h) as the primary mode of therapy. The cefepime MIC breakpoint derived by classification and regression tree (CART) software analysis to delineate the risk of 28-day mortality was 8 microg/ml. Patients infected with gram-negative organisms treated with cefepime at a MIC of > or =8 microg/ml had a mortality rate of 54.8% (17/31 died), compared to 24.1% (35/145 died) for those treated with a cefepime MIC of <8 microg/ml. The rate of mortality for those treated with a cefepime MIC of 8 microg/ml was 56.3% (9/16 died), compared to 53.3% (8/15 died) for those treated with cefepime at a MIC of >8 microg/ml. A multivariable analysis including severity of illness indices showed that treating patients with bacteremia due to gram-negative organisms with a cefepime MIC of > or =8 microg/ml was an independent predictor of mortality (P < or = 0.001). There was no significant difference in outcome according to the dosage regimen utilized. Pharmacodynamic assessments that were presented previously would suggest that cefepime treatment (particularly a dosage of 1 g every 12 h) has a low probability of target attainment associated with successful in vivo outcome when the cefepime MIC is > or =8 microg/ml. It would appear reasonable, based on pharmacodynamic and clinical grounds, to lower the breakpoints for cefepime in countries where the cefepime dosage of 1 to 2 g every 12 h is the licensed therapy for serious infections, so that organisms with a cefepime MIC of 8 microg/ml are no longer regarded as susceptible to the antibiotic.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Survival Rate; Treatment Outcome

International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result.. The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003.. One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy.. Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Topics: Anti-Bacterial Agents; Bacteremia; Bacteria; Bacterial Infections; Catheterization; Cefepime; Cephalosporins; Drug Resistance; Equipment Contamination; Fever; Gentamicins; Hematologic Diseases; Hematologic Neoplasms; Hospitals, Urban; Humans; Laboratories, Hospital; Medical Audit; Microbial Sensitivity Tests; Neutropenia; New Zealand; Prospective Studies; Risk Assessment; Species Specificity

Topics: Aged; Anti-Bacterial Agents; Aortic Valve; Bacteremia; Cefepime; Cephalosporins; Echocardiography, Transesophageal; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Time Factors; Treatment Outcome

Antibiotic dependence in clinical isolates has been reported, albeit rarely, such as vancomycin-dependent enterococcus and beta-lactam-dependent Staphylococcus saprophyticus. We report herein a clinical isolate of beta-lactam-dependent Bacillus cereus. A 16-yr-old female was admitted on 8 September 2005 with neutropenic fever during chemotherapy following surgical removal of peripheral neuroectodermal tumor. She had had an indwelling chemoport since August 2004 and experienced B. cereus bacteremia three times during the recent 3-month period prior to the admission; the bacteremias were treated with cefepime-based chemotherapy. On hospital days 1 and 3, B. cereus was isolated from blood drawn through the chemoport. The isolates were resistant to penicillin, ceftriaxone, and erythromycin, and susceptible to vancomycin and ciprofloxacin. The isolate of hospital day 3 grew only nearby the beta-lactam disks including penicillin and ceftriaxone on disk diffusion testing. The beta-lactam-dependent isolate required a minimum of 0.064 microg/mL of penicillin or 0.023 microgram/mL of cefotaxime for growth, which was demonstrated by E test (AB Biodisk, Sweden). Light microscopy and transmission electron microscopy revealed a marked elongation of the dependent strain compared with the non-dependent strain. Prolonged therapy with beta-lactams in the patient with an indwelling intravenous catheter seemed to be a risk factor for the emergence of beta-lactam-dependence in B. cereus.

Topics: Adolescent; Anti-Bacterial Agents; Bacillaceae Infections; Bacillus cereus; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Female; Humans; Microbial Sensitivity Tests; Neutropenia; Risk Factors

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

Topics: Aged; Amikacin; Aorta; Aortic Aneurysm; Aortic Valve; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; Male; Neisseria elongata; Neisseriaceae Infections; Species Specificity; Ultrasonography

In a prospective observational study of 133 neutropenic episodes, interleukin (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53% and a specificity of 97% as a predictor of gram-negative bacteremia (GNB; positive predictive value, 73%; negative predictive value, 94%). The rates of early death differed significantly between patients with high and those with low IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever define a low-risk subgroup of patients who can safely be treated with monotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefepime; Cephalosporins; Drug Therapy, Combination; Fever; Gentamicins; Gram-Negative Bacterial Infections; Humans; Interleukin-8; Leukemia; Lymphoma; Male; Middle Aged; Netilmicin; Neutropenia; Predictive Value of Tests; Prospective Studies

We report a case of bacteremia due to Abiotrophia species in a patient with neutropenic fever and cancer who was receiving levofloxacin prophylaxis, followed by empirical therapy with cefepime; the organism was resistant to both antibiotics. We provide susceptibility data on 20 additional bloodstream isolates of Abiotrophia species.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Drug Resistance, Microbial; Fever; Gram-Positive Bacterial Infections; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Ofloxacin; Streptococcaceae

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Humans; Infant; Male; Neoplasms; Neutropenia; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome

Topics: Acute Disease; Aged; Bacteremia; Cefepime; Cephalosporins; Cholangiography; Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy; Cholecystitis; Enterobacteriaceae Infections; Gentamicins; Hafnia alvei; Humans; Liver Abscess; Male; Netilmicin; Suppuration; Treatment Outcome

We performed a prospective assessment of the current epidemiology of bacteraemia in cancer patients hospitalized in 70 different adult and paediatric haematology and oncology departments. Over a 1-month period, microbiologists from 54 hospitals collected clinical data relating to patients with at least one positive blood culture. In addition, all strains isolated were assessed for their in vitro susceptibility to three broad-spectrum cephalosporins suitable for empirical treatment in cancer patients: cefpirome, cefepime and ceftazidime. A total of 494 different strains were isolated from 1,038 blood cultures taken from 403 different patients. Seventeen strains were isolated from 13 patients with various nonmalignant diseases, and these cases were excluded from analysis. Overall, 330 (69.2%) of the strains were isolated in patients with haematological malignancy and 147 (30.8%), in patients with solid tumours. There was no difference in the distribution of the species involved in bacteraemia between patients with haematological malignancy and patients with solid tumours: coagulase-negative staphylococci were the leading pathogens (50.6% and 44.9%, respectively), followed by E. coli (11.2% and 12.2% respectively), S. aureus (6.3% vs 7.5%), streptococci (4.8% vs 5.4%) and P. aeruginosa (5.2% vs 4.8%). All other species accounted for less than 5% in both groups. There was no difference in the strain distribution with age (> or = 15 years vs < 15 years) or type of underlying disease. S. aureus and Enterobacteriaceae bacteraemia were more frequent in patients with end-stage disease, while oral streptococci, Enterobacteriaceae and P. aeruginosa infections were more frequent in patients who were severely neutropenic. Digestive tract decontamination was associated with increased frequency of oral streptococci and decreased frequency of Enterobacteriaceae infections. All three cephalosporins demonstrated similar activity against E. coli, while cefpirome and cefepime appeared to be more effective against other Enterobacteriaceae. Ceftazidime had better activity against P. aeruginosa. Cefpirome was the most effective against Gram-positive cocci, especially oral streptococci and methicillin-susceptible staphylococci.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Bacteria; Bacteriological Techniques; Cefepime; Cefpirome; Ceftazidime; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Opportunistic Infections; Prospective Studies

A total of 300 recent blood stream and pneumonia isolates of Pseudomonas aeruginosa from 32 different medical centers in the United States were used to assess the accuracy of the Vitek System (GNS-107 card) for cefepime, a new "fourth-generation" cephalosporin. The Vitek System test result was compared to the consensus of the three other methods (reference broth microdilution, disk diffusion, Etest (AB BIODISK, Solna, Sweden)); and 271 of 300 consensus category of susceptibility sets were unanimous. The Vitek System produced a 25.3% error rate (5.3% false resistance, 20.0% minor errors). A consistent trend toward higher MIC results with the Vitek System was observed that produced a 15.3 to 21.3% lower susceptible rate compared with the other susceptibility test methods. The consensus cefepime resistance rate was only 4.3% compared to 14.0% for the Vitek GNS-107 card. The error was reproducible on triplicate repeat testing. These results indicate an unacceptable rate of false resistance being produced by the Vitek System when testing cefepime against P. aeruginosa strains. Alternative methods are suggested for this broad-spectrum antipseudomonal cephalosporin.

Topics: Bacteremia; Cefepime; Cephalosporins; Evaluation Studies as Topic; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Reference Standards; Reproducibility of Results; Sensitivity and Specificity

Topics: Abscess; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Humans; Mutation; Pneumonia, Bacterial

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

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

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

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