cefepime and Gram-Positive-Bacterial-Infections

Cefepime is a broad-spectrum cephalosporin with enhanced coverage against Gram-positive and Gram-negative bacteria. We did a systematic review of randomised trials that compared cefepime with another beta-lactam antibiotic, alone or with the addition of a non-beta-lactam antibiotic to both study groups. We searched Central, PubMed, Embase, Lilacs, new US Food and Drug Administration drug applications, conference proceedings, and references of the included studies. Two reviewers independently did the search and data extraction. 57 trials were included. All-cause mortality-the primary outcome-was higher with cefepime than other beta-lactams (risk ratio [RR] 1.26 [95% CI 1.08-1.49]). Sensitivity analyses by the trials' methodological quality revealed higher RRs for trials reporting adequate allocation-sequence generation (1.52 [1.20-1.92]) and allocation concealment (1.36 [1.09-1.70]). Baseline risk factors for mortality were similar. No significant differences between groups in treatment failure, superinfection, or adverse events were found. This Review provides evidence and offers possible explanations for increased mortality among patients treated with cefepime in randomised trials.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Randomized Controlled Trials as Topic

Monotherapy with ceftazidime, cefepime, imipenem or meropenem for the empiric treatment of febrile neutropenia appears as effective as the combination therapy involving aminoglycosides. However, empiric therapy with a combination of a beta-lactam plus an aminoglycoside is a reasonable decision under circumstances where Gram negative sepsis is very likely. Monotherapy is usually associated with a modest rate of response in infections caused by Gram positive organisms. In about 30% of the patients, a glycopeptide will be added at some point, because the response to the initial therapy is not considered optimal.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefepime; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Meropenem; Neutropenia; Sepsis; Thienamycins

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Topics: Adolescent; Adult; Cefepime; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; India; Leukemia, Myeloid, Acute; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tigecycline

In phase 3 clinical trials for ceftobiprole treatment of complicated skin and skin structure infections, 1,219 gram-positive and 276 gram-negative aerobic baseline pathogens were identified. Ceftobiprole inhibited all staphylococcal isolates, including methicillin-resistant strains, at MICs of

Topics: Anti-Bacterial Agents; Cephalosporins; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Skin Diseases, Bacterial; Staphylococcus

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 purpose of this phase II trial was to evaluate the efficacy and safety of cefepime monotherapy in patients with neutropenia expected to last more than 7 days. Sixty-nine patients with neutropenia (<0.5 x 10(9)/1) were randomized during 94 episodes of fever to receive either cefepime monotherapy (n=76) or combination therapy with trimethoprim/sulfamethoxazole plus amikacin (TMP/SMZ plus AMI, n=18). A successful response to cefepime was seen in 31/76 (41%) episodes, with 10/36 (28%) in microbiologically documented infections, 3/4 (75%) in clinically documented infections and 18/36 (50%) in fever of unknown origin. No patient in either treatment group died due to the presenting infection. One patient in the cefepime group discontinued treatment due to a rash. Susceptibility testing of blood isolates by E-test strip showed low MIC values to cefepime for most isolates. It is concluded that cefepime monotherapy appeared both safe and effective as empirical therapy in patients with febrile neutropenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cefepime; Cephalosporins; Female; Fever; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia

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

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

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

Topics: Aged; Anti-Bacterial Agents; Brain Abscess; Cefepime; Gram-Positive Bacterial Infections; Humans; Male; Mastoiditis; Metronidazole; Otitis Externa; Peptostreptococcus; Temporal Lobe

Ventilator-associated pneumonia (VAP) occurs in up to 25% of mechanically ventilated patients, with an associated mortality up to 50%. Early diagnosis and appropriate empiric antibiotic coverage of VAP are crucial. Given the multitude of noninfectious clinical and radiographic anomalies within trauma patients, microbiology from bronchioalveolar lavage (BAL) is often needed. Empiric antibiotics are administered while awaiting BAL culture data. Little is known about the effects of these empiric antibiotics on patients with negative BAL microbiology if a subsequent VAP occurs during the same hospital course.. This is a retrospective chart review of intubated trauma patients undergoing BAL for suspected pneumonia over a 3-y period at a Level 1 trauma center. All patients with suspected VAP undergoing a BAL receive empiric antibiotics. If microbiology data are negative at 72 h, all antibiotics are stopped; however, if the BAL returns with ≥10(5) colony-forming units per milliliter, the diagnosis of VAP is confirmed. We divided patients into three groups. Group 1 consisted of patients in whom the initial BAL was positive for VAP. Group 2 consisted of patients with an initial negative BAL, who subsequently developed VAP at a later point in the hospital course. Group 3 consisted of patients with negative BAL who did not develop a subsequent VAP.. We obtained 499 BAL specimens in 185 patients over the 3-y period. A total of 14 patients with 23 BAL specimens initially negative for VAP subsequently developed VAP later during the same hospital stay. These patients did not have an increase in the hospital length of stay, intensive care unit days, ventilator days, or mortality compared with those who had a positive culture on the first suspicion of VAP. There was a significant increase in the percentage of Enterobacter (21% versus 8%) and Morganella (8% versus 0%) as the causative organism in these 14 patients when the VAP occurred. Furthermore, the profile of the top two organisms in each group changed. Enterobacter (21%) and Pseudomonas (17%) were the principal organisms in the initial BAL-negative group, whereas the two predominant strains in the initial positive BAL group were methicillin-sensitive Staphylococcus aureus (21%) and Haemophilus influenza (11%). Interestingly, methicillin-resistant S. aureus remained the third most common organism in both groups. Empiric antibiotics also did not seem to induce the growth of multidrug-resistant organisms, and there was no increased rate of secondary infections such as Clostridium difficile.. Ventilator-associated pneumonia remains a significant cause of morbidity and mortality in mechanically ventilated trauma patients. The diagnosis and treatment of VAP continue to be challenging. Once clinically suspected, empiric coverage decreases morbidity and mortality. Our data demonstrate that patients who receive empiric coverage exhibit a significantly different microbiologic profile compared with those who had an initial positive BAL culture. Initial empiric antibiotics in BAL-negative patients were not associated with an increase in multidrug-resistant organisms, hospital, or intensive care unit length of stay, ventilator days, and mortality or secondary infections.

Topics: Acetamides; Anti-Bacterial Agents; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Penicillanic Acid; Piperacillin; Pneumonia, Ventilator-Associated; Retrospective Studies; Tazobactam; Treatment Outcome; Vancomycin; Wounds and Injuries

Proper dosing of specific antibiotics in morbidly obese patients has been studied inadequately. However, these data are beneficial as this patient population is at an increased risk to develop postoperative infections. Cefepime is an antibiotic used for the treatment of both gram-positive and especially gram-negative infections; administration of the appropriate dose in the morbidly obese population is crucial. We therefore examined the pharmacokinetics of cefepime in patients with body mass index >40 kg/m(2). Ten morbidly obese patients, with a mean [±SD] estimated glomerular filtration rate of 108.4 ± 34.6 mL/min, undergoing elective weight loss surgical procedures were administered cefepime in addition to standard prophylactic cefazolin and studied. Serial serum cefepime concentrations were analyzed after dosing using a validated high performance liquid chromatography method. Pharmacokinetics and duration above the minimum inhibitory concentration (MIC) were determined using a protein binding value of 15% and a MIC threshold of 8 μg/mL. Mean free cefepime concentrations for t = 30, 120, and 360 min were 69.6, 31.6, and 9.2 μg/mL, respectively. The dosing interval was calculated to maintain the free concentration above the MIC (fT > MIC) for 60% of the interval. This was determined to be 10.12 h, including time for infusion. There was no toxicity. Based on this analysis, an increased dose of 2 g every 8 h is necessary to maintain an adequate fT > MIC throughout the dosing interval. Further studies are necessary to determine the efficacy of this regimen in the settings of active infections and critical illness.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Surgical Wound Infection; Treatment Outcome

Topics: Aged; Aneurysm, False; Anti-Bacterial Agents; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cefepime; Cephalosporins; Drug Therapy, Combination; Echocardiography; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Endocarditis, Bacterial; Enterococcus; Gram-Positive Bacterial Infections; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Male; Mitral Valve; Mitral Valve Insufficiency; Tricuspid Valve Insufficiency; Vancomycin

Cases of sepsis with bacteriemia detected in the S. P. Botkin State Clinical Hospital within 2000-2007 were analysed. The sources of the bacteriemia, the etiological pattern of the pathogens and their susceptibility to antibacterials were estimated. The study enrolled 256 patients with sepsis. The antibiotic susceptibility of 227 isolates from the blood samples was tested. More than a half of the infection sources was detected in the organs of the respiratory tract and abdominal cavity. All the grampositive pathogens were susceptible to vancomycin and linesolid. The overwhelming majority of the enterococcal isolates proved to be susceptible to carbapenem and cefepim.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Drug Resistance, Microbial; Enterobacteriaceae; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals; Humans; Linezolid; Male; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Retrospective Studies; Russia; Sepsis; Vancomycin

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Clinical Trials as Topic; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans

Carnobacterium divergens clinical isolates BM4489 and BM4490 were resistant to penicillins but remained susceptible to combinations of amoxicillin-clavulanic acid and piperacillin-tazobactam. Cloning and sequencing of the responsible determinant from BM4489 revealed a coding sequence of 912 bp encoding a class A beta-lactamase named CAD-1. The bla(CAD-1) gene was assigned to a chromosomal location in the two strains that had distinct pulsed-field gel electrophoresis patterns. CAD-1 shared 53% and 42% identity with beta-lactamases from Bacillus cereus and Staphylococcus aureus, respectively. Alignment of CAD-1 with other class A beta-lactamases indicated the presence of 25 out of the 26 isofunctional amino acids in class A beta-lactamases. Escherichia coli harboring bla(CAD-1) exhibited resistance to penams (benzylpenicillin and amoxicillin) and remained susceptible to amoxicillin in combination with clavulanic acid. Mature CAD-1 consisted of a 34.4-kDa polypeptide. Kinetic analysis indicated that CAD-1 exhibited a narrow substrate profile, hydrolyzing benzylpenicillin, ampicillin, and piperacillin with catalytic efficiencies of 6,600, 3,200, and 2,900 mM(-1) s(-1), respectively. The enzyme did not interact with oxyiminocephalosporins, imipenem, or aztreonam. CAD-1 was inhibited by tazobactam (50% inhibitory concentration [IC(50)] = 0.27 microM), clavulanic acid (IC(50) = 4.7 microM), and sulbactam (IC(50) = 43.5 microM). The bla(CAD-1) gene is likely to have been acquired by BM4489 and BM4490 as part of a mobile genetic element, since it was not found in the susceptible type strain CIP 101029 and was adjacent to a gene for a resolvase.

Topics: Amino Acid Sequence; beta-Lactams; Chromosomes, Bacterial; Cloning, Molecular; Electrophoresis, Gel, Pulsed-Field; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant, Newborn; Kinetics; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillin Resistance; Penicillinase; Sequence Alignment; Sequence Analysis, DNA; Substrate Specificity

Between 1 September 2005 and 30 June 2006, 19 medical centers collected 4,180 isolates recovered from clinical specimens from patients in intensive care units (ICUs) in Canada. The 4,180 isolates were collected from 2,292 respiratory specimens (54.8%), 738 blood specimens (17.7%), 581 wound/tissue specimens (13.9%), and 569 urinary specimens (13.6%). The 10 most common organisms isolated from 79.5% of all clinical specimens were methicillin-susceptible Staphylococcus aureus (MSSA) (16.4%), Escherichia coli (12.8%), Pseudomonas aeruginosa (10.0%), Haemophilus influenzae (7.9%), coagulase-negative staphylococci/Staphylococcus epidermidis (6.5%), Enterococcus spp. (6.1%), Streptococcus pneumoniae (5.8%), Klebsiella pneumoniae (5.8%), methicillin-resistant Staphylococcus aureus (MRSA) (4.7%), and Enterobacter cloacae (3.9%). MRSA made up 22.3% (197/884) of all S. aureus isolates (90.9% of MRSA were health care-associated MRSA, and 9.1% were community-associated MRSA), while vancomycin-resistant enterococci (VRE) made up 6.7% (11/255) of all enterococcal isolates (88.2% of VRE had the vanA genotype). Extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae occurred in 3.5% (19/536) and 1.8% (4/224) of isolates, respectively. All 19 ESBL-producing E. coli isolates were PCR positive for CTX-M, with bla CTX-M-15 occurring in 74% (14/19) of isolates. For MRSA, no resistance against daptomycin, linezolid, tigecycline, and vancomycin was observed, while the resistance rates to other agents were as follows: clarithromycin, 89.9%; clindamycin, 76.1%; fluoroquinolones, 90.1 to 91.8%; and trimethoprim-sulfamethoxazole, 11.7%. For E. coli, no resistance to amikacin, meropenem, and tigecycline was observed, while resistance rates to other agents were as follows: cefazolin, 20.1%; cefepime, 0.7%; ceftriaxone, 3.7%; gentamicin, 3.0%; fluoroquinolones, 21.1%; piperacillin-tazobactam, 1.9%; and trimethoprim-sulfamethoxazole, 24.8%. Resistance rates for P. aeruginosa were as follows: amikacin, 2.6%; cefepime, 10.2%; gentamicin, 15.2%; fluoroquinolones, 23.8 to 25.5%; meropenem, 13.6%; and piperacillin-tazobactam, 9.3%. A multidrug-resistant (MDR) phenotype (resistance to three or more of the following drugs: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) occurred frequently in P. aeruginosa (12.6%) but uncommonly in E. coli (0.2%), E. cloacae (0.6%), or K. pneumoniae (0%). In conclusion, S. aureus (MSSA and MRSA), E.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Canada; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Population Surveillance

Doripenem, a 1beta-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (microg/ml) were established by broth microdilution. By MIC(90), doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, < or =0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC(90) of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum beta-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC(90)/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC(90) = 2, 89.1%S) was twice as active by MIC(90) as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including beta-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of beta-lactam resistance.

Topics: Anti-Bacterial Agents; Carbapenems; Doripenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; United States

In contrast to expanded-spectrum cephalosporins, beta-lactam-beta-lactamase inhibitor combinations such as piperacillin-tazobactam have rarely been associated with vancomycin-resistant Enterococcus (VRE) colonization and infection. In mice, piperacillin-tazobactam has sufficient antienterococcal activity to inhibit the establishment of colonization during treatment, but this effect has not been confirmed in human patients. We prospectively evaluated the acquisition of rectal colonization by VRE among intensive care unit patients receiving antibiotic regimens containing piperacillin-tazobactam versus those receiving cefepime, an expanded-spectrum cephalosporin with minimal antienterococcal activity. Rectal swabs were obtained weekly and were cultured for VRE. For 146 patients with a negative rectal swab for VRE prior to therapy, there was no significant difference in the frequency of VRE acquisition between patients receiving piperacillin-tazobactam- and cefepime-containing regimens (19/72 [26.4%] and 23/74 [31.1%], respectively; P = 0.28). Of the 19 patients who acquired VRE in association with piperacillin-tazobactam, 10 (53%) developed the new detection of VRE during therapy. Patients initiated on treatment with cefepime-containing regimens were significantly more likely than those initiated on treatment with piperacillin-tazobactam-containing regimens to have received antibiotic therapy in the prior 30 days (55/74 [74.3%] and 22/72 [30.6%], respectively; P < 0.001). These findings suggest that piperacillin-tazobactam- and cefepime-containing antibiotic regimens may be associated with the frequent acquisition of VRE in real-world intensive care unit settings. Although piperacillin-tazobactam inhibits the establishment of VRE colonization in mice when exposure occurs during treatment, our data suggest that this agent may not prevent the acquisition of VRE in patients.

Topics: Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Culture Media; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Rectum; Vancomycin Resistance

The activities of several tricyclic heteroaryl isothiazolones (HITZs) against an assortment of gram-positive and gram-negative clinical isolates were assessed. These compounds target bacterial DNA replication and were found to possess broad-spectrum activities especially against gram-positive strains, including antibiotic-resistant staphylococci and streptococci. These included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-nonsusceptible staphylococci, and quinolone-resistant strains. The HITZs were more active than the comparator antimicrobials in most cases. For gram-negative bacteria, the tested compounds were less active against members of the family Enterobacteriaceae but showed exceptional potencies against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. Good activity against several anaerobes, as well as Legionella pneumophila and Mycoplasma pneumoniae, was also observed. Excellent bactericidal activity against staphylococci was observed in time-kill assays, with an approximately 3-log drop in the numbers of CFU/ml occurring after 4 h of exposure to compound. Postantibiotic effects (PAEs) of 2.0 and 1.7 h for methicillin-susceptible S. aureus and MRSA strains, respectively, were observed, and these were similar to those seen with moxifloxacin at 10x MIC. In vivo efficacy was demonstrated in murine infections by using sepsis and thigh infection models. The 50% protective doses were

Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Quinolones; Thiazoles

A contemporary collection of 12737 strains from pediatric patients (<18 years) isolated over a 7-year period (1998-2004) from 52 sentinel hospitals in North America was tested to determine the comparative antimicrobial potency of broad-spectrum parenteral cephalosporins and selected comparator agents. Most of the strains (84.1%) were isolated from blood stream or respiratory tract infections. The rank order of the top 10 pediatric pathogens analyzed was Streptococcus pneumoniae (15.5%) >Haemophilus influenzae (14.6%) >Staphylococcus aureus (13.8%) >Moraxella catarrhalis = coagulase-negative staphylococci (8.0%) >Escherichia coli (7.8%) >Pseudomonas aeruginosa (5.2%) >Klebsiella spp. (4.8%) >Enterococcus spp. (4.7%) > beta-hemolytic streptococci (4.4%). Both cefepime and ceftriaxone (MIC(90), 1 microg/mL; 93.9% and 93.7% susceptible, respectively) were highly active against S. pneumoniae. However, the S. pneumoniae strains showed reduced susceptibility to ceftazidime (56.6%), as well as penicillin (56.6%) < trimethoprim-sulfamethoxazole (57.1%) < erythromycin (66.2%) < tetracycline (71.4%). beta-Hemolytic streptococci showed 100.0% susceptibility to penicillin, cefepime, and ceftriaxone. Cefepime and ceftriaxone exhibited high activity against oxacillin (methicillin)-susceptible S. aureus, (MIC(90), 4 microg/mL; 100.0% and 99.8% susceptible, respectively), whereas ceftazidime (MIC(90), 16 microg/mL) was active against only 86.7% of strains. H. influenzae strains showed complete susceptibility to cefepime, ceftriaxone, and levofloxacin (MIC(90), < or =0.5 microg/mL; 100.0%), and 34.0% of H. influenzae and 99.2% of M. catarrhalis strains produced beta-lactamase. Although the 3 cephalosporins tested (cefepime, ceftriaxone, and ceftazidime) were very active (98.6-99.6% susceptible) against E. coli, cefepime (99.0% susceptible) was slightly more active than ceftriaxone and ceftazidime (96.4% and 95.1% susceptible, respectively) against Klebsiella spp. Cefepime was also the most active beta-lactam agent tested against Enterobacter spp. (MIC(90), 2 microg/mL; 99.3% susceptible), whereas the susceptibility rates of other broad-spectrum beta-lactams (ceftriaxone, ceftazidime and piperacillin-tazobactam) were significantly lower (78.4-81.5%). Against P. aeruginosa, imipenem and piperacillin-tazobactam showed the highest susceptibility rates (94.4% and 93.3%, respectively), whereas imipenem and cefepime showed the lowest resistance rates (1.4% and 2.3%, respectively)

Topics: Adolescent; Anti-Bacterial Agents; Cefepime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; North America; Sentinel Surveillance

Infections are a leading cause of morbidity and mortality in hemodialysis patients. Still, due to altered pharmacokinetics and potential toxic sideeffects, safe and efficient antibiotic therapy in dialysis patients remains a major challenge. We reviewed our experience with intermittent administration of betalactam antibiotics for treatment of severe infections in hemodialysis patients. A total of 81 episodes of infection in 45 patients was assessed. All patients were treated with betalactam antibiotics (cefepime in 11 episodes, cefpirom in 33 episodes, piperacillin in 9 episodes, amoxicillin in 18 episodes, ceftazidime in 10 episodes, respectively). All antibiotics were given post hemodialysis 3x per week. Treatment was considered efficient in case of a significant decrease in CRP in addition to clinical response. Overall treatment success rate was 85% (69 episodes of infection). The decrease of CRP was 52% (6.9 +/- 5.8 to 3.3 +/- 4.9 mg/dl; p = 0.00003). The mean duration of treatment was 19 +/- 13 days. Treatment was generally well tolerated. We conclude, that severe infections in hemodialysis patients can be treated safely and efficiently with an empiric therapy with betalactam antibiotics. Intermittent administration, potentially allowing ambulatory treatment, is possible.

Topics: Amoxicillin; Anti-Bacterial Agents; beta-Lactams; C-Reactive Protein; Cefepime; Ceftazidime; Cephalosporins; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Piperacillin; Renal Dialysis; Treatment Outcome

We evaluated the antimicrobial spectrum and potency of cefepime and selected comparators agents against clinical bacterial strains collected in North America over a 6-year period (1998-2003). Isolates were consecutively collected from bloodstream (44%), respiratory tract (41%), urinary tract (6%), and skin/soft tissue (5%) infections in 48 medical centers. Isolates were susceptibility tested by reference broth microdilution methods in a central laboratory. Oxacillin-resistant staphylococci and enterococci were excluded from the analysis. Imipenem (MIC90 = 1 microg/mL, 99.9% susceptible) was the most active compound tested against Enterobacteriaceae (22860 isolates tested) followed by cefepime (MIC90 = 0.25 microg/mL, 99.5% susceptible) > amikacin (99.4% susceptible) > ceftriaxone (95.6% susceptible) > aztreonam (95.1% susceptible). Among comparators, the lowest susceptibility rate for Enterobacteriaceae was observed with ciprofloxacin (92.8% susceptible). Imipenem was also the most active compound against ESBL-producing Klebsiella spp. and Escherichia coli (99.3% and 100% susceptible, respectively), followed by amikacin (81.4% and 97.2% susceptible, respectively) and cefepime (92.5% and 93.8% susceptible, respectively). Cefepime activity against Pseudomonas aeruginosa (85.2% susceptible) was similar to that of imipenem (86.9% susceptible). Against oxacillin-susceptible Staphylococcus aureus, cefepime (MIC90 = 4 microg/mL, 100.0% susceptible) was 4-fold more active than ceftazidime (MIC90 = 16 microg/mL, 86.4% susceptible) and showed a higher susceptibility rate than ciprofloxacin (93.2% susceptible). Cefepime was the most active compound tested against Streptococcus pneumoniae (MIC90 = 1 microg/mL, 97.4% susceptible), ranked after gatifloxacin and levofloxacin (99.2% susceptible). The activity of cefepime remained stable during the study period evaluated with the susceptibility rates varying from 99.3% to 99.8% among the Enterobacteriaceae and 84.4% to 88.4% among P. aeruginosa isolates. In summary, cefepime has retained broad activity and spectrum against Enterobacteriaceae, P. aeruginosa, and Gram-positive cocci (except oxacillin-resistant staphylococci and enterococci) isolated from North American medical centers in the 1998-2003 period. Continued resistance surveillance is critical to monitor the effectiveness of widely used parenteral antimicrobial agents such as cefepime.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; North America

In this study, we evaluated the current effectiveness of 11 beta-lactam antibiotics for treatment of orofacial odontogenic infections by determining the antimicrobial susceptibility of the major pathogens. The antimicrobial susceptibilities of viridans streptococci (n = 47), Peptostreptococcus (n = 67), Porphyromonas (n = 18), Fusobacterium (n = 57), black-pigmented Prevotella (n = 59) and non-pigmented Prevotella (n = 47) isolated from pus specimens of 93 orofacial odontogenic infections to penicillin G, cefmetazole, flomoxef, cefoperazone, cefoperazone/sulbactam, ceftazidime, cefpirome, cefepime, cefoselis, imipenem and faropenem were determined using the agar dilution method. Penicillin G, most cephalosporins, imipenem and faropenem worked well against viridans streptococci, Peptostreptococcus, Porphyromonas and Fusobacterium. Penicillin G and most cephalosporins, including fourth-generation agents, were not effective against beta-lactamase-positive Prevotella, though they were effective against beta-lactamase-negative strains. Cefmetazole, cefoperazone/sulbactam, imipenem and faropenem expressed powerful antimicrobial activity against beta-lactamase-positive Prevotella. In conclusion, penicillins have the potential to be first-line agents in the treatment of orofacial odontogenic infections. Most of the other beta-lactam antibiotics, including fourth-generation cephalosporins, were not found to have greater effectiveness than penicillins. In contrast, cefmetazole, cefoperazone/sulbactam, imipenem and faropenem were found to have greater effectiveness than penicillins.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteroidaceae Infections; beta-Lactams; Cefepime; Cefmetazole; Cefoperazone; Cefpirome; Ceftazidime; Ceftizoxime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Fusobacterium; Fusobacterium Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Lactams; Microbial Sensitivity Tests; Mouth Diseases; Penicillin G; Penicillins; Peptostreptococcus; Porphyromonas gingivalis; Prevotella; Streptococcal Infections; Streptococcus; Sulbactam

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

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

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

Topics: Bacterial Infections; Cefepime; Cefpirome; Cephalosporins; Gram-Negative Aerobic Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests