cefepime and Pneumonia--Bacterial

On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other beta-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials.. We performed meta-analyses using trial- and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method.. The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21).. In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Cephalosporins; Child; Child, Preschool; Clinical Trials as Topic; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neutropenia; Pneumonia, Bacterial; Skin Diseases, Bacterial; Survival Analysis; Urinary Tract Infections; Young Adult

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

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

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Bronchopneumonia; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Therapy, Combination; Humans; Inhalation; Injections, Intravenous; Lung Diseases; Pneumonia, Bacterial; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin

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

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

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

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

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

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

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cefoperazone; Drug Therapy, Combination; Female; Haemophilus Infections; Healthcare-Associated Pneumonia; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pseudomonas Infections; Sulbactam; Treatment Outcome

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

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

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

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

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

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

To evaluate the therapeutic effects and safety of cefepime (Maxipime) and sulbactam/cefoperazone (sulperazone) on moderate and severe respiratory infection in children.. Totally 100 children hospitalized for pneumonia were randomized equally into 2 groups, namely group A with maxipime treatment at the dose of 50 mg/kg given intravenously twice daily, and group B with sulperazone treatment at 50-100 mg/kg given intravenously twice a day. The therapeutic effects and safety of both medications were observed.. In maxipime group, 44 of the 50 cases were cured with complete elimination of the symptoms and signs, and obvious therapeutic effect was achieved in 5 cases with significant improvement or resolution of the majority of symptoms and signs. One case failed to respond favorably to the treatment, with the overall efficacy rate of 98% without incidence of adverse effects. In sulperazone group, 40 of the 50 cases were cured, 6 showed significant improvement, and 4 failed to respond to the treatment, with the rate of 92%. One patient complained of rashes during sulperazone treatment, which disappeared the next day without sulperazone withdrawal. Significant difference was not noted between the groups (chi(2)=2.43, P>0.05).. Both maxipime and sulperazon are effective and safe for application in children with moderate and severe respiratory infections.

Topics: Anti-Bacterial Agents; Cefepime; Cefoperazone; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Pneumonia, Bacterial; Sulbactam

An open-label, randomized study was conducted to evaluate the safety and efficacy of cefepime versus ceftazidime in the treatment of severe bacterial infections, including septicemia, urinary tract infection, bacterial bronchitis, bacterial pneumonia, and intraabdominal infection. Fifty-two patients with severe infections were eligible and prospectively randomized to receive cefepime (26 patients) or ceftazidime (26 patients) during a 15-month period. Forty-two patients were evaluable (24 in the cefepime group and 18 in the ceftazidime group). Most (86%) of the patients had urinary tract infections and the most commonly isolated pathogen was Escherichia coli (79%). Satisfactory clinical response rates of 71% and 61%, and bacteriological eradication rates of 87.5% and 89% were achieved for the cefepime and ceftazidime groups, respectively. Two patients treated with cefepime died, one from superinfection and one from suspected paraneoplastic syndrome. Cultures of the blood obtained at entry into the study were positive in 19 (45%) of the 42 evaluable cases. In the cefepime group, a patient with Salmonella paratyphi A septicemia was cured, which has not been previously reported. Adverse effects attributable to therapy were minimal in both groups of patients, and none required discontinuation or dose reduction. In conclusion, these results suggest that cefepime is as efficacious and well tolerated as ceftazidime in the treatment of severe bacterial infections, such as septicemia, urinary tract infection, bacterial bronchitis, bacterial pneumonia, and intraabdominal infection.

Topics: Adolescent; Aged; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Pneumonia, Bacterial; Taiwan; Treatment Outcome; Urinary Tract Infections

The safety and efficacy of cefepime empiric monotherapy compared with standard broad-spectrum combination therapy for hospitalized adult patients with moderate to severe community-acquired bacterial infections were evaluated. In an open-label, multicenter study, 317 patients with an Acute Physiology and Chronic Health Evaluation (APACHE II) score ranging from >5 to =19 were enrolled with documented pneumonia (n=196), urinary tract infection (n=65), intra-abdominal infection (n=38), or sepsis (n=18). Patients were randomly assigned 1:1 to receive cefepime 1 to 2 g IV twice daily or three times a day or IV ampicillin, cephalothin, or ceftriaxone +/-aminoglycoside therapy for 3 to 21 days. For both treatment groups, metronidazole, vancomycin, or macrolide therapy was added as deemed necessary. The primary efficacy variable was clinical response at the end of therapy. Two hundred ninety-six (93%) patients met evaluation criteria and were included in the efficacy analysis. Diagnoses included the following: 180 pneumonias (90 cefepime, 90 comparator), 62 urinary tract infections (29 cefepime, 33 comparator), 37 intra-abdominal infections (19 cefepime, 18 comparator), and 17 sepses (8 cefepime, 9 comparator). At the end of therapy, overall clinical success rates were 131/146 (90%) for patients treated with cefepime vs 125/150 (83%) for those treated with comparator (95% confidence interval [CI]: -2.6% to 16.3%). The clinical success rate for patients with community-acquired pneumonia, the most frequent infection, was 86% for both treatment groups. Among the patients clinically evaluated, 162 pathogens were isolated and identified before therapy. The most commonly isolated pathogens were Escherichia coli (n=49), Streptococcus pneumoniae (n=29), Haemophilus influenzae (n=14), and Staphylococcus aureus (n=11). Bacteriologic eradication/presumed eradication was 97% for cefepime vs 94% for comparator-treated patients. Drug-related adverse events were reported in 16% of cefepime patients and 19% of comparator patients. In conclusion, cefepime had higher cure rates compared with broad-spectrum combination therapy as an initial empiric treatment for hospitalized patients with moderate to severe community-acquired infections, including urinary tract infections, intra-abdominal infections, and sepsis.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Cefepime; Cephalosporins; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Peritonitis; Pneumonia, Bacterial; Prospective Studies; Sepsis; Severity of Illness Index; South America; Treatment Outcome; Urinary Tract Infections

An open, randomized, multicentre clinical trial was conducted to compare the efficacy and safety of cefepime 2 g iv bd (2 g tds daily in cases of Pseudomonas aeruginosa pneumonia) with cefotaxime 2 g iv tds, in the empirical treatment of bacterial pneumonia in HIV-infected patients. The primary end-point was effectiveness after 3-5 days of treatment, taking success to be when the study drug was continued during this period of time. Clinical and bacteriological responses at end of treatment (EOT) were also evaluated. Analyses of the intention-to-treat population (n = 160) and the as-per-protocol groups (n = 150) were carried out. Treatment groups were comparable with regard to sex, age, HIV status and degree of severity of pneumonia. The primary end-point for cefepime was considered successful for the intention-to-treat and as-per-protocol groups in 85.7% and 93.5% of cases, respectively, and for cefotaxime, in 77.6% and 80.8% of cases, respectively (P = 0.22 and P = 0.02). In the as-per-protocol group, cefotaxime treatment was independently related to failure at the primary end-point. A satisfactory clinical response in the intention-to-treat population was observed in 83.3% of cefepime and 82.9% of cefotaxime patients. Bacteriological cure was obtained in 100% of evaluable cefepime and 93.4% of evaluable cefotaxime patients at EOT. Safety of the study drugs was comparable in both treatment groups. Cefepime 2 g iv bd was at least as effective and as well tolerated as cefotaxime 2 g iv tds in the treatment of bacterial pneumonia in HIV-infected patients.

Topics: Adult; Cefepime; Cefotaxime; Cephalosporins; Empiricism; Female; HIV Infections; Humans; Male; Pneumonia, Bacterial; Treatment Outcome

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

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

In a prospective, multicentre double-blind trial, 151 patients over the age of 65 years were randomly assigned to receive either cefepime 2 g every 12 h for a minimum of 3 days and up to 14 days or ceftriaxone 1 g every 12 h for a minimum of 3 days and up to 14 days. Antibiotics were maintained until 48 h after fever had resolved; no other antibiotics were permitted. The average age in each group exceeded 77 years and significant co-morbidity was found in the majority of patients. The mean total duration of therapy was 5.8+/-2.4 days for the cefepime group and 6.7+/-2.7 days for the ceftriaxone group (P = 0.06). The clinical success rate at the end of therapy was 79.1% with cefepime and 75.4% with ceftriaxone (P = 0.62). At the end of follow-up, 91.7% of the cefepime-treated patients and 86.5% of the ceftriaxone patients had a satisfactory clinical response (P = 0.38). In 35 bacteriological evaluable patients, potential pathogens were eradicated in all but one patient receiving cefepime. Seven patients in each group died during the study period but in each case the death was unrelated to study drug. The commonest side-effect was diarrhoea (cefepime, five patients; ceftriaxone, two patients). The clinical and microbiological efficacy of cefepime is similar to that of ceftriaxone in elderly patients with community-acquired pneumonia requiring hospitalization. Cefepime is an appropriate choice for the treatment of community-acquired respiratory tract infections in the elderly.

Topics: Aged; Aged, 80 and over; Cefepime; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Double-Blind Method; Female; Humans; Male; Pneumonia, Bacterial; Prospective Studies; Treatment Outcome

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

Patients with bacterial pneumonia often are treated empirically with parenteral broad-spectrum antimicrobials intended to cover potential gram-negative and gram-positive pathogens. However, beta-lactamase-mediated resistance has developed to many of these antimicrobials, particularly third-generation cephalosporins, and has led to the development of fourth-generation agents that are relatively beta-lactamase stable. The purpose of these studies was to compare the efficacy and safety of the fourth-generation agent, cefepime, with that of the third-generation agent, ceftazidime, in the treatment of hospitalized patients with moderate-to-severe bacterial pneumonia. A total of 336 (97 evaluable) patients were enrolled in an open-label study, and 99 (23 evaluable) patients were enrolled in a blinded study of patients with lower respiratory tract infections (LRTI) including pneumonia. Patients were randomized to receive either cefepime 1 g every 12 hours or ceftazidime 1 g every 8 hours given as an intravenous infusion over 30 minutes. Efficacy analysis included the evaluable patients while the safety analysis included all patients. The results in the open-label study were as follows: In patients with pneumonia, clinical response was satisfactory in 58 (85%) of 68 patients in the cefepime group and 21 (72%) of 29 patients in the ceftazidime group. Bacteriologic eradication occurred for 75 (93%) of 81 pathogens and 30 (94%) of 32 pathogens isolated from the 68 cefepime-treated patients and 29 ceftazidime-treated patients, respectively. The results in the blinded study were as follows: In patients with pneumonia, clinical response was satisfactory in 12 (80%) of 15 cefepime patients and in 7 (88%) of 8 ceftazidime patients, and the bacteriologic eradication rates were 85% (17/20 pathogens) and 73% (8/11 pathogens) isolated from the 15 cefepime-treated patients and the eight ceftazidime-treated patients, respectively. Among the most frequent adverse events in both groups were nausea, diarrhea, vomiting, and abdominal pain. Similar adverse events were noted in the 99 patients in the blinded study. These studies indicate that the efficacy and safety of cefepime administered at 1 g twice daily is comparable to that of ceftazidime administered at 1 g three times daily for treatment of hospitalized patients with pneumonia caused by susceptible pathogens.

Topics: Acute Disease; Aged; Canada; Cefepime; Ceftazidime; Cephalosporins; Double-Blind Method; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Puerto Rico; United States

WCK 5222 combines cefepime with zidebactam, a β-lactam enhancer that binds PBP2 and inhibits class A and C β-lactamases. The efficacy of human-simulated bronchopulmonary exposures of WCK 5222 against MDR Pseudomonas aeruginosa was investigated in a neutropenic murine pneumonia model.. Nineteen MDR isolates of P. aeruginosa (cefepime MICs ≥64 mg/L) were studied. MICs of zidebactam and WCK 5222 ranged from 4 to 512 mg/L and from 4 to 32 mg/L, respectively. Dosing regimens of cefepime and zidebactam alone and in combination that achieved epithelial lining fluid (ELF) exposures in mice approximating human ELF exposures after doses of 2 g of cefepime/1 g of zidebactam every 8 h (1 h infusion) were utilized; controls were vehicle-dosed. Lungs were intranasally inoculated with 107-108 cfu/mL bacterial suspensions. Mice were dosed subcutaneously 2 h after inoculation for 24 h, then lungs were harvested.. In vitro MIC was predictive of in vivo response to WCK 5222 treatment. Mean±SD changes in bacterial density at 24 h compared with 0 h controls (6.72±0.50 log10 cfu/lungs) for 13 isolates with WCK 5222 MICs ≤16 mg/L were 1.17±1.00, -0.99±1.45 and -2.21±0.79 log10 cfu/lungs for cefepime, zidebactam and WCK 5222, respectively. Against these isolates, zidebactam yielded >1 log10 cfu/lungs reductions in 8/13, while activity was enhanced with WCK 5222, producing >2 log10 cfu/lungs reductions in 10/13 and >1 log10 cfu/lungs reductions in 12/13. Among isolates with WCK 5222 MICs of 32 mg/L, five out of six showed a bacteriostatic response.. Human-simulated bronchopulmonary exposure of WCK 5222 is effective against MDR P. aeruginosa at MIC ≤16 mg/L in a murine pneumonia model. These data support the clinical development of WCK 5222 for pseudomonal lung infections.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Cefepime; Cephalosporins; Cyclooctanes; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Healthy Volunteers; Humans; Lung; Mice; Microbial Sensitivity Tests; Neutropenia; Piperidines; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Specific Pathogen-Free Organisms

Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment.. To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance.. Retrospective, single-center study.. Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups.. In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Topics: Aged; Anti-Bacterial Agents; Cefepime; Enterobacter; Enterobacteriaceae Infections; Ertapenem; Female; Humans; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Expression; Hospitalization; Humans; Isoenzymes; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Plasmids; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Retrospective Studies; Tazobactam; United States

Cupriavidus pauculus is an emerging organism causing infections in immunocompromised and immunocompetent patients. We report a C.pauculus pneumonia case susceptible to cefepime in an infant with end-stage renal failure. To our knowledge, this is the first case report of C. pauculus causing respiratory infections in the Gulf Cooperation Council.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cupriavidus; Gram-Negative Bacterial Infections; Humans; Infant; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Saudi Arabia

Many antibiotics have no effect on Gram-positive and Gram-negative microbes, which necessitates the prescription of broad-spectrum antimicrobial agents that can lead to increased risk of antibiotic resistance. These pathogens constitute a further threat because they are also resistant to numerous beta-lactam antibiotics, as well as other antibiotic groups. This study retrospectively investigates antimicrobial resistance in hospitalized patients suffering from pneumonia triggered by Gram-negative Serratia marcescens or Proteus mirabilis.. The demographic and clinical data analyzed in this study were obtained from the clinical databank of the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, for inpatients presenting with pneumonia triggered by S. marcescens or P. mirabilis from 2004 to 2014. An antibiogram was conducted for the antibiotics utilized as part of the management of patients with pneumonia triggered by these two pathogens.. Pneumonia was caused by Gram-negative bacteria in 115 patients during the study period from January 1, 2004, to August 12, 2014. Of these, 43 (37.4 %) hospitalized patients [26 males (60.5 %, 95 % CI 45.9 %-75.1 %) and 17 females (39.5 %, 95 % CI 24.9 %-54.1 %)] with mean age of 66.2 ± 13.4 years had pneumonia triggered by S. marcescens, while 20 (17.4 %) patients [14 males (70 %, 95 % CI 49.9 %-90.1 %) and 6 females (30 %, 95 % CI 9.9 %-50.1 %)] with a mean age of 64.6 ± 12.8 years had pneumonia caused by P. mirabilis. S. marcescens showed an increased antibiotic resistance to ampicillin (100 %), ampicillin-sulbactam (100 %), and cefuroxime (100 %). P. mirabilis had a high resistance to tetracycline (100 %) and ampicillin (55 %). S. marcescens (P < 0.0001) and P. mirabilis (P = 0.0003) demonstrated no resistance to cefepime in these patients with pneumonia.. S. marcescens and P. mirabilis were resistant to several commonly used antimicrobial agents, but showed no resistance to cefepime.

Topics: Aged; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cefepime; Cephalosporins; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Female; Germany; Hospital Mortality; Hospitals, University; Humans; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Pneumonia, Bacterial; Proteus Infections; Proteus mirabilis; Retrospective Studies; Serratia Infections; Serratia marcescens

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

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

Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state. Additionally, clinical outcomes for 33 patients with Gram-negative bacterial pneumonia who received cefepime monotherapy were determined. The free minimum concentration (fCmin) to MIC ratio for each patient was determined by conditioning the validated pharmacokinetic model using patient-specific creatinine clearance (CLCr), dosing regimen and cefepime MIC of the organism isolated, and was subsequently correlated with clinical failure. Classification and regression tree (CART) analysis was used to determine the most significant drug exposure breakpoint. Mean±S.D. CLCr and cefepime Cmin in the 12 patients were 87.5±21.2mL/min and 6.2±3.8mg/L, respectively. In comparison, the Cmin predicted by the pharmacokinetic model was 5.8mg/L using a CLCr of 90mL/min. MICs of organisms ranged from 0.5mg/L to 8mg/L. Percent time free drug above MIC of 100% was achieved in 32/33 patients, but 12 patients experienced clinical failure. CART analysis determined patients with an fCmin/MIC≥2.1 had a significantly lower risk of clinical failure (OR=0.11, 95% CI 0.02-0.67; P=0.017). The fCmin/MIC ratio is a useful predictor of clinical failure in Gram-negative bacterial pneumonia. The clinical utility of fCmin/MIC in therapeutic drug monitoring should be further explored.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Creatinine; Female; Humans; Male; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged; Plasma; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

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

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

Ventilator-associated pneumonia is the first or second most commonly diagnosed nosocomial infection in the PICU. Centers for Disease Control diagnostic criteria include clinical signs or symptoms in conjunction with a "positive" tracheal aspirate, defined as more than 10 colony-forming units/mL of bacteria on quantitative culture and/or more than 25 polymorphonuclear neutrophils per low-power field on Gram stain. We hypothesized that tracheal aspirate cultures and Gram stains would not correlate with clinical signs and symptoms and would therefore not distinguish between colonization and infection.. Prospective observational study.. PICU in an academic tertiary care center.. Children intubated more than 48 hours.. Sequential tracheal aspirate quantitative cultures and Gram stains in conjunction with daily collection of concordant clinical signs and symptoms.. Time since intubation correlated strongly (p < 0.001) with the proportion of positive (> 10 colony-forming units/mL) tracheal aspirate quantitative cultures, but Centers for Disease Control-defined clinical signs or symptoms of ventilator-associated pneumonia, either singly or in combination, did not. Use of in-line suction catheters versus new, sterile catheters to obtain tracheal aspirates was associated with significantly greater proportion of positive tracheal aspirate bacterial cultures (p < 0.001). Most subjects had more than 25 polymorphonuclear neutrophils per low-power field on Gram stain; polymorphonuclear neutrophils on Gram stain correlated with positive bacterial culture (p = 0.04). Seventy-seven percent of the bacterial isolates detected in positive quantitative cultures were "pathogens." Antibiotic use at the time tracheal aspirates were obtained was associated with a lower frequency of positive quantitative cultures only with antibiotic regimens that included cefepime.. Positive bacterial cultures of tracheal aspirates increase rapidly after intubation and usually include bacteria considered to be pathogens. Tracheal aspirate cultures and Gram stains do not appear to distinguish between infection and colonization. Antibiotic regimens that include cefepime decrease the frequency of positive cultures, but the significance of this is unclear.

Topics: Anti-Bacterial Agents; Catheters; Cefepime; Cephalosporins; Child, Preschool; Colony Count, Microbial; Female; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Intubation, Intratracheal; Male; Neutrophils; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Prospective Studies; Respiration, Artificial; Time Factors; Trachea

The aim of this study was to compare the bactericidal activity of cefepime plus amikacin against experimental pneumonia induced by a stably derepressed cephalosporinase-producing Enterobacter cloacae strain in immunocompetent and leucopenic rats.. Sixty Wistar rats were used. Leucopenia was induced in half of them by a single intravenous administration of 30 mg/kg cyclophosphamide, while the remaining rats received the same volume of saline. All rats were infected 96 h later by tracheal instillation of 8 log(10) colony-forming units of E. cloacae. Twelve rats (6 immunocompetent and 6 leucopenic) were sacrificed 6 h later to assess the initial bacterial burden to the lungs. Then, the remaining 48 rats received a combination of 60 mg/kg cefepime twice a day and 25 mg/kg amikacin once a day given intraperitoneally or the same volume of saline. Six rats per group (leucopenic or not, treated or not) were sacrificed 12 and 30 h after therapy started.. Spontaneous bacterial clearance with time was observed only in immunocompetent rats. Compared to untreated animals, antibiotic administration induced a decrease in lung bacterial titres in immunocompetent and leucopenic rats. The difference was statistically significant only in leucopenic rats.. The use of leucopenic rats reduced spontaneous bacterial clearance in the lungs and increased the bactericidal effect of the antibiotic combination and ultimately the confidence in the reliability of the results.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Cefepime; Cephalosporinase; Cephalosporins; Cyclophosphamide; Drug Therapy, Combination; Enterobacter cloacae; Immunocompromised Host; Injections, Intraperitoneal; Leukopenia; Male; Models, Animal; Pneumonia, Bacterial; Rats; Rats, Wistar

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Cefepime; Cephalosporins; Consciousness Disorders; Diabetic Nephropathies; Electroencephalography; Female; Humans; Pneumonia, Bacterial; Renal Dialysis; Status Epilepticus; Treatment Outcome; Uremia

Combination antimicrobial therapy is clinically used as a last-resort strategy to control multidrug-resistant bacterial infections. However, selection of antibiotics is often empirical, and conventional assessment of combined drug effect has not been correlated to clinical outcomes. Here, we report a quantitative method to assess combined killing of antimicrobial agents against 2 multidrug-resistant bacteria.. Combined time-kill studies were performed using clinically achievable concentrations for each 2-agent combination against clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. Bacterial burden observed at 24 h was mathematically modeled using a 3-dimensional response surface. Subsequently, a neutropenic murine pneumonia model with simulated clinical dosing exposures was used to validate our quantitative assessment of combined killing.. Different antimicrobial combinations were found to have varying efficacy against the multidrug-resistant bacteria. As predicted by our quantitative method, cefepime plus amikacin was found to be the most superior combination, which was evidenced by a reduction in tissue bacterial burden and prolonged survival of infected animals.. The consistency between the predictions of the mathematical model and in vivo observations substantiated the robustness of our quantitative method. These data highlighted a novel and promising method to guide rational selection of antimicrobial combination in the clinical setting.

Topics: Acinetobacter baumannii; Amikacin; Animals; Anti-Bacterial Agents; Cefepime; Cephalosporins; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Lung; Mice; Ofloxacin; Pneumonia, Bacterial; Polymerase Chain Reaction; Pseudomonas aeruginosa; Random Allocation; Survival Analysis

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

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

The aim of this study was to evaluate the epidemiology of bacterial and fungal pneumonia in lung transplant (LT) recipients and to assess donor-to-host transmission of these microorganisms.. We retrospectively studied all positive cultures from bronchoalveolar lavage (BAL) of 49 lung transplant recipients and their donors from August 2003 to April 2007.. There were 108 episodes of pneumonia during a medium follow-up of 412 days (range, 1-1328 days). The most frequent microorganisms were: Pseudomonas aeruginosa (n = 36; 33.3%), Staphylococcus aureus (n = 29; 26.8%), and Aspergillus spp. (n = 18; 16%). Other fungal infections were due to Fusarium spp., Cryptococcus neoformans, and Paracoccidioides brasiliensis. Of the 31 donors with positive BAL, 15 had S. aureus. There were 21 pretransplant colonized recipients (43%) and 16 of them had suppurative underlying lung disease. P. aeruginosa was the most frequent colonizing organism (59% of pretransplant positive cultures). There were 11 episodes of bacteremia and lungs were the source in 5 cases. Sixteen deaths occurred and 6 (37.5%) were due to infection. Statistical analyses showed association between pretransplant colonizing microorganisms from suppurative lung disease patients and pneumonias after lung transplantation (RR = 4.76; P = .04; 95% CI = 1.02-22.10). No other analyzed factor was significant.. Bacterial and fungal infections are frequent and contribute to higher mortality in lung transplant recipients. P. aeruginosa is the most frequent agent of respiratory infections. This study did not observe any impact of donor lung organisms on pneumonia after lung transplantation. Nevertheless, we demonstrated an association between pretransplant colonizing microorganisms and early pneumonias in suppurative lung transplant recipients.

Topics: Anti-Bacterial Agents; Antiviral Agents; Candidiasis; Cefepime; Cephalosporins; Cytomegalovirus Infections; Humans; Lung Transplantation; Mycoses; Patient Selection; Pneumonia; Pneumonia, Bacterial; Retrospective Studies

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

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

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

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

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

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

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

This study evaluated the pharmacodynamics of continuous infusion beta-lactams against pulmonary isolates of Gram-negative bacteria from patients managed in intensive care units (ICUs) in the USA. Multiple 10,000-patient Monte Carlo simulations were performed by integrating pharmacokinetic data from healthy individuals with 2408 MICs from the 2002 Intensive Care Unit Surveillance System database. These pharmacodynamic simulations suggested that continuous infusion regimens of cefepime, aztreonam, ceftazidime and piperacillin-tazobactam 13.5 g have the greatest likelihood of achieving pharmacodynamic targets against isolates of Enterobacteriaceae in the ICU. Beta-lactams are unlikely to achieve pharmacodynamic targets against Pseudomonas aeruginosa or Acinetobacter baumannii when administered as monotherapy.

Topics: Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Computer Simulation; Drug Combinations; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intensive Care Units; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; United States

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

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

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

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

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

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

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

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

Topics: Cefepime; Cephalosporins; Humans; Infusions, Intravenous; Lung; Pneumonia, Bacterial

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

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

The antibacterial activities of imipenem-cilastatin, meropenem-cilastatin, cefepime and ceftazidime against Enterobacter cloacae NOR-1, which produces the carbapenem-hydrolyzing beta-lactamase NmcA and a cephalosporinase, and against one of its in vitro-obtained ceftazidime-resistant mutant were compared by using an experimental model of pneumonia with immunocompetent rats. The MICs of the beta-lactams with an inoculum of 5 log(10) CFU/ml were as follows for E. cloacae NOR-1 and its ceftazidime-resistant mutant, respectively: imipenem, 16 and 128 microg/ml, meropenem, 4 and 32 microg/ml, cefepime, <0.03 and 1 microg/ml, and ceftazidime, 1 and 512 microg/ml. The chromosomally located cephalosporinase and carbapenem-hydrolyzing beta-lactamase NmcA were inducible by cefoxitin and meropenem in E. cloacae NOR-1, and both were stably overproduced in the ceftazidime-resistant mutant. Renal impairment was induced (uranyl nitrate, 1 mg/kg of body weight) in rats to simulate the human pharmacokinetic parameters for the beta-lactams studied. Animals were intratracheally inoculated with 8.5 log(10) CFU of E. cloacae, and therapy was initiated 3 h later. At that time, animal lungs showed bilateral pneumonia containing more than 6 log(10) CFU of E. cloacae per g of tissue. Despite the relative low MIC of meropenem for E. cloacae NOR-1, the carbapenem-treated rats had no decrease in bacterial counts in their lungs 60 h after therapy onset compared to the counts for the controls, regardless of whether E. cloacae NOR-1 or its ceftazidime-resistant mutant was inoculated. A significant decrease in bacterial titers was observed for the ceftazidime-treated rats infected with E. cloacae NOR-1 only. Cefepime was the only beta-lactam tested effective as treatment against infections due to E. cloacae NOR-1 or its ceftazidime-resistant mutant.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; beta-Lactamases; Carbapenems; Cefepime; Ceftazidime; Cephalosporins; Creatinine; Drug Resistance, Microbial; Enterobacter cloacae; Enterobacteriaceae Infections; Half-Life; Imipenem; Kidney Diseases; Male; Meropenem; Penicillinase; Pneumonia, Bacterial; Protein Binding; Rats; Rats, Wistar; Thienamycins; Uranyl Nitrate

The antibacterial activity of imipenem, cefepime and piperacillin-tazobactam alone or in combination with amikacin against a Pseudomonas aeruginosa strain producing an extended-spectrum beta-lactamase (PER-1) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected intratracheally with 8.0 +/- 0.4 log10 cfu of P. aeruginosa, and therapy was initiated 3 h later, by which time animal lungs showed bilateral pneumonia containing >7 log10 P. aeruginosa cfu/g of tissue. Since rats eliminate antibiotics much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. MICs determined using an inoculum of 4 log10 cfu/mL were as follows: imipenem, 1 mg/L; cefepime, 8 mg/L; piperacillin-tazobactam, 32 mg/L; and amikacin, 16 mg/L. A noticeable inoculum effect was observed with the four antimicrobial agents tested, which was greatest for cefepime and piperacillin-tazobactam. In-vitro studies indicated that imipenem was the beta-lactam with the greatest bactericidal effect and that amikacin was synergic only in combination with cefepime and imipenem. Cefepime and piperacillin-tazobactam alone failed to decrease bacterial counts in the rats' lungs 60 h after therapy onset, whereas imipenem and, to a lesser extent, amikacin significantly reduced the number of viable microorganisms. Combination of amikacin with any of the three beta-lactams tested was synergic, despite a high amikacin MIC for the infecting strain. These results paralleled our in-vitro data showing a marked inoculum effect for cefepime and piperacillin-tazobactam. Based on the results of this study, the best treatment for infections caused by this type of extended-spectrum beta-lactamase-possessing strain would be imipenem plus amikacin.

Topics: Amikacin; Animals; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Imipenem; Lung; Male; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Wistar

The activities of cefepime and amikacin alone or in combination against an isogenic pair of Enterobacter cloacae strains (wild type and stably derepressed, ceftazidime-resistant mutant) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected by administering 8.4 log10 cfu of E. cloacae intratracheally, and therapy was initiated 12 h later. At that time, the animals' lungs showed bilateral pneumonia and contained more than 7 log10 E. cloacae cfu/g tissue. Because rats eliminate amikacin and cefepime much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. In-vitro susceptibilities showed an inoculum effect with cefepime proportional to the bacterial titre against the two strains, but more pronounced with the stably derepressed mutant strain, whereas with bacterial concentrations of up to 7 log10 cfu/mL, no inoculum effect was observed with amikacin. In-vitro killing indicated that antibiotic combinations were synergic only at intermediate concentrations. At peak concentrations, the combination was merely as effective as amikacin alone. At trough concentrations, a non-significant trend towards the superiority of the combination over each antibiotic alone was noted. Moreover, cefepime was either bacteriostatic or permitted regrowth of the organisms in the range of antibiotic concentrations tested. Although each antibiotic alone failed to decrease bacterial counts in the lungs, regardless of the susceptibility of the strain used, the combination of both antibiotics was synergic and induced a significant decrease in the lung bacterial count 24 h after starting therapy when compared with tissue bacterial numbers in untreated animals or animals treated with either antibiotic alone. No resistant clones emerged during treatment with any of the antibiotic regimens studied.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Colony Count, Microbial; Creatinine; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Lung; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rats; Rats, Mutant Strains; Time Factors; Treatment Outcome

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

We developed an experimental model of pneumonia to evaluate the efficacy of new antibiotic regimens against Enterobacter cloacae. Rats were infected by administering 8.5 log10 cfu E. cloacae intratracheally, and therapy was initiated 24 h later. At that time, animals' lungs showed bilateral pneumonia containing more than 7 log10 cfu/g of tissue. Because rats eliminate amikacin and cefepime much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters in humans. Using this model, we compared the bactericidal activities of cefepime and amikacin alone or in combination against the same cefotaxime-susceptible E. cloacae strain. The MICs of cefepime and amikacin for this strain were 0.5 and 2 mg/L, respectively. In-vitro killing studies showed that antibiotic combinations were synergic only at intermediate concentrations. At peak concentrations, the combination was only as effective as amikacin alone. At trough concentrations, a non-significant trend towards the superiority of the combination over cefepime alone was found. In-vivo studies showed that each antibiotic alone failed to decrease bacterial counts in the lungs except at 6 h, whereas the combination of both antibiotics induced a significant decrease in the lung bacterial count 6, 12 and 24 h after the onset of therapy when compared with tissue bacterial numbers in untreated animals or animals treated with either antibiotic alone. In-vivo synergy between cefepime and amikacin was observed at the three time points studied. No resistant clones emerged during treatment with any of the antibiotic regimens studied.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Cefepime; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Drug Synergism; Enterobacter cloacae; Enterobacteriaceae Infections; Kidney; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rats; Rats, Wistar

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

We investigated broncho-alveolar distribution of cefepime (CFPM), a fourth generation cephem, using 38 BALF specimens from 19 serious pneumonia patients who underwent artificial respiratory system control. The mean broncho-alveolar CFPM level was 3.44 microgram/ml (5.34% of the mean peak blood level). We thus observed that the BALF level after a single dose of 1 g of CFPM exceeds the MIC90 of the drug against RTI causing bacteria such as Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophillus influenzae, Branhamella catarrhalis, coagulase-negative Staphylococcus, Pseudomonas aeruginosa and Staphylococcus aureus.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cefepime; Cephalosporins; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Respiratory System; Sputum