Meropenem Group Research Articles

Evaluation of a pharmacokineticpharmacodynamic approach using software to optimize the carbapenem antibiotic regimen.

Meropenem (MEPM) and doripenem (DRPM), whose antipseudomonal activity is more potent than that of other carbapenem antimicrobials, were used in the study. Monte Carlo simulation of drug concentrations was performed to develop an administration plan for MEPM and DRPM that takes into account the pharmacokinetics (PK)-pharmacodynamics (PD) of MEPM and DRPM and the renal function of each patient. Drug administration plans were proactively applied to patients with pneumonia to determine the usefulness of the method by assessing treatment efficacy and safety. Patients with healthcareassociated pneumonia and an indication for MEPM or DRPM chemotherapy underwent drug administration in accordance with the MEPM and DRPM treatment plan developed by the PK-PD software applications. The primary efficacy endpoints were the clinical and bacteriological efficacy of the drugs agains pneumonia. The safety of the antimicrobials was assessed based on abnormal laboratory findings and the seizure disorders in accordance with the criteria for safety evaluation of antimicrobial agents. This study examined 12 and 11 patients in the MEPM and DRPM group, respectively; however, 3 DRPM patients were excluded due to the administration of anti-methicillin-resistant Staphylococcus aureus drugs after the initiation of DRPM treatment. MEPM and DRPM drug administration was determined to be safe and effective in all patients. The present results suggest that the Monte Carlo simulation-based PK-PD software is an effective tool for planning individualized antimicrobial chemotherapy with carbapenem in accordance with the PK-PD theory of antimicrobials. It is also possible to propose safe and effective drug administration plans for patients with healthcare-associated pneumonia.

Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI)

Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours or meropenem (1 g) every 8 hours intravenously for 4-14 days. The prospectively defined objectives were to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (24-32 days from start of therapy) in the microbiological intent-to-treat (primary) and microbiologically evaluable (secondary) populations using a noninferiority margin of 10%. Microbiological outcomes and safety were also evaluated. Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, -4.2%; 95% confidence interval [CI], -8.91 to .54) and secondary (94.2% [259/275] vs 94.7% [304/321]; weighted difference, -1.0%; 95% CI, -4.52 to 2.59) endpoints, meeting the prespecified noninferiority margin. In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 95.8% (23/24) and 88.5% (23/26) in the ceftolozane/tazobactam plus metronidazole and meropenem groups, respectively, and 100% (13/13) and 72.7% (8/11) in patients with CTX-M-14/15 ESBLs. The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%); the most common AEs in either group were nausea and diarrhea. Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in adult patients with cIAI, including infections caused by multidrug-resistant pathogens. NCT01445665 and NCT01445678.

Doripenem Versus Meropenem As the First-Line Empirical Therapy in High-Risk Febrile Neutropenic Patients with Hematological Malignancy: A Randomized, Controlled Trial

BACKGROUND: Febrile neutropenia (FN) is often observed in cases of hematological malignancy such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). Carbapenem antibiotics having a potent and broad antimicrobial activity against both gram-positive and gram-negative bacteria including Pseudomonas aeruginosa, are good candidates as the first-line therapy drug in high-risk FN patients. In the IDSA guideline 2010 on the use of antimicrobial agents in FN, mono-therapy with an anti-pseudomonal beta-lactam, such as piperacillin-tazobactam, cefepime or carbapenem [only meropenem (MEPM) and imipenem-cilastatin], is recommended as an empirical therapy for high-risk FN patients. Doripenem (DRPM) is a newer carbapenem with few data available as for the efficacy and safety in the setting of FN patients. Therefore, we conducted a randomized, cooperative group, open-label trial comparing DRPM (1.0 g every 8 hours) with MEPM (1.0 g every 8 hours) as the first-line empirical antibacterial therapy for high-risk FN patients with hematological malignancy including AML, ALL and high-risk MDS.PATIENTS and METHODS: One hundred and forty-six hospitalized high-risk FN patients with hematological malignancy (AML 76, ALL 43, APL 13, MDS-AML 9, MDS-RAEB 5 cases) during or after chemotherapy were randomized to each drug group (DRPM: n=73, MEPM: n=73). The study drug was started to administer as a mono-therapy and continued at least for 5 days without drug toxicity, and the efficacy and safety were evaluated.RESULTS: The overall response rate at 7 days in DRPM and MEPM group were not significantly different (DRPM: 67.6%, MEPM: 52.9%, respectively, P=0.098). Both the resolution of fever by mono-therapy at day 3 to 5 (DRPM: 56.9%, MEPM: 47.0%, respectively, p=0.26), and survival at day 30 (DRPM: 98.4%, MEPM: 98.5%, respectively, p=0.312) were not significantly different in the two groups. The frequency of cases needed for anti-MRSA agent and antifungal agent were a little less often in DRPM rather than in MEPM group [DRPM: 36.9%, MEPM: 50.0% (p=0.185), DRPM: 26.1%, MEPM: 32.3% (p=0.535), respectively]. Only grade 1-2 adverse events were observed in both groups (liver dysfunction, renal dysfunction, diarrhea and rash), and they were less often in DRPM group significantly (DRPM: 29.8%, MEPM: 40.8%, respectively, p=0.046). These adverse events were clinically acceptable in the two groups, and most of patients could continue the treatment by both study drugs.CONCLUSIONS: Our clinical study suggested that DRPM had the non-inferiority of efficacy in comparison with MEPM as the first-line empirical therapy in high-risk FN patients with hematological malignancy, and both drugs could be generally well tolerated. DisclosuresNo relevant conflicts of interest to declare.

The effect of borneol on the concentration of meropenem in rat brain and blood

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. The aim of the present study is to investigate the effect of borneol on the concentration of meropenem in rat brain and blood and to find the potential relationships of the combined use of medicine and traditional Chinese medicine. Analysis of meropenem in the dialysates was achieved using the microdialysis technique and HPLC. At 40 min after the administration of an intraperitoneal injection of meropenem, the concentration of meropenem in brain in borneol+meropenem group was 2.25 (0.35) μg ml− 1, which was significantly higher than that in meropenem group [1.20 (0.12) μg ml− 1; P < 0.01]. Within 80 min of drug administration, the AUCbrain/AUCblood (area under the curve, AUC) in the borneol+meropenem group was 1.2 times that of the meropenem group. Borneol can increase the concentration of meropenem in the cerebrospinal fluid, but has no influence on its blood concentration. This study represents a successful application of the microdialysis technique, which is an effective method for the study of pharmacokinetics of meropenem.

Effect of meropenem with or without immunoglobulin as second‐line therapy for pediatric febrile neutropenia

Meropenem (MEPM) is widely used for treatment of febrile neutropenia. There have been many reports on MEPM for pediatric febrile neutropenia showing success rates of approximately 50-75%. Although i.v. immunoglobulin (IVIG) is widely used for treatment of infection with antibiotics, there has been no report on the efficacy of IVIG for pediatric febrile neutropenia. This prospective randomized study was therefore carried out to clarify the usefulness of MEPM with or without IVIG as second line-therapy for pediatric febrile neutropenia. A total of 61 pediatric patients with 146 episodes were judged to have failure of first-line therapy (August 2008-April 2010: cefozopran vs cefepime; April 2010-April 2012: cefepime vs piperacillin/tazobactam) for febrile neutropenia, and were randomized to MEPM and MEPM + IVIG groups. MEPM with or without IVIG as second-line therapy was effective in 68.1% of a total of 144 episodes. Success rates in the MEPM and MEPM + IVIG groups were 66.3% and 70.5%, respectively. Furthermore, success rates for patients with IgG <500 mg/dL were 62.5% in the MEPM group and 81.3% in the MEPM + IVIG group. This result, however, was not statistically significant, possibly because of the small sample size. MEPM is effective and safe for second-line treatment of febrile episodes in neutropenic pediatric patients. Moreover, IVIG is effective for patients with low serum IgG.

Use of topical meropenem in management of hospital acquired Pseudomonas ocular infections

We report a case series of four eyes of four patients where resistant strains of Pseudomonas aeruginosa in nosocomial ocular infections were treated with topical meropenem with a successful outcome. Pseudomonas infections are known to be very fulminant. We observed strains of P. aeruginosa in four eyes resistant to all routine drugs such as fluoroquinolones, aminoglycosides and cephalosporins. Three eyes presented with infective corneal ulcers and one eye had endophthalmitis. Culture sensitivity of corneal scrape and aqueous tap respectively of each patient showed P. aeruginosa (Gram-negative bacilli) sensitive to carbapenem (meropenem and imipenem) group of drugs. These patients were treated with a topical meropenem 50 mg/ml once in an hour and responded dramaticaly and we could salvage all eyes. Topical meropenem 50 mg/ml, which is not routinely used in ocular infections is thus an effective drug for management of hospital acquired resistant Pseudomonas ocular infections.

Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial

Avibactam, a novel non-β-lactam β-lactamase inhibitor, restores the in vitro activity of ceftazidime against class A, C and some class D β-lactamase-producing pathogens, including those commonly associated with complicated intra-abdominal infections (cIAIs). This randomized, active-controlled, double-blind, Phase II trial (NCT00752219) aimed to evaluate the safety and efficacy of ceftazidime/avibactam plus metronidazole compared with meropenem in hospitalized patients with cIAI. Adults with confirmed cIAI requiring surgical intervention and antibiotics were randomized 1 : 1 to receive intravenously either (i) 2000 mg of ceftazidime plus 500 mg of avibactam plus a separate infusion of 500 mg of metronidazole or (ii) 1000 mg of meropenem plus placebo every 8 h for a minimum of 5 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 2 weeks after the last dose of study therapy. Overall, 101 patients received ceftazidime/avibactam plus metronidazole; 102 received meropenem. The median duration of treatment was 6.0 and 6.5 days, respectively. Favourable clinical response at the TOC visit in the ME population was observed in 91.2% (62/68) and 93.4% (71/76) of patients in the ceftazidime/avibactam plus metronidazole and meropenem groups, respectively (observed difference: -2.2%; 95% CI: -20.4%, 12.2%). The incidence of treatment-emergent adverse events was similar for ceftazidime/avibactam plus metronidazole (64.4%) and meropenem (57.8%). Ceftazidime/avibactam plus metronidazole was effective and generally well tolerated in patients with cIAI, with a favourable clinical response rate in the ME population of >90%, similar to that of meropenem.

Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis

Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial. To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43). Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure. clinicaltrials.gov Identifier: NCT00534287.

A Comparative Analysis of Meropenem and Doripenem in Febrile Patients with Hematologic Malignancies: a Single-Center Retrospective Study

Many patients with hematologic malignancies show immunosuppression and/or neutropenia, and are at a high risk of developing a serious infection that would require empiric therapy with broad-spectrum antibiotics. However, a thorough comparison of the efficacies of different carbapenems has not been carried out. To compare the efficacies of meropenem (MEPM) and doripenem (DRPM) in febrile patients with hematologic neoplasms, we retrospectively reviewed data of 149 consecutive febrile patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome (MDS) who were treated empirically with MEPM or DRPM. The duration from the start of carbapenem administration to decline of fever was not significantly different between the MEPM and DRPM groups (median, 3 versus 4 days; P = 0.79). Multivariate analysis showed that a diagnosis of MDS and the use of liposomal amphotericin-B or voriconazole are statistically significant risk factors for sustained fever. In conclusion, MEPM and DRPM showed similar efficacies in febrile patients with acute leukemia and MDS.

Evaluation of doripenem in an experimental model of resistant Pseudomonas aeruginosa pneumonia

Sir, In a previous study we demonstrated that doripenem, the most recently approved carbapenem, exhibited antimicrobial activity similar to that of imipenem or meropenem in an experimental rabbit model of susceptible Pseudomonas aeruginosa pneumonia. Mutational inactivation of oprD is known to be the main mechanism of imipenem resistance in the absence of acquired carbapenemase. Although oprD inactivation also increases the MICs of meropenem and doripenem, clinical resistance to these drugs is thought to require additional mechanisms. In this work we compared the efficacy of doripenem versus imipenem or meropenem against a resistant oprD-inactive strain of P. aeruginosa in an experimental model. The experimental rabbit model of pneumonia has been described previously. The bacterial strain was a DoprD PAO1, which is resistant to carbapenems after inactivation of OprD porin, a carbapenem-specific transport porin. This strain was provided by courtesy of Professor P. Plesiat, Besancon, France. MICs of meropenem, doripenem and imipenem were 8, 1 and 16 mg/L, respectively. Antibiotics were delivered through a venous catheter, with changing infusion rates determined by computer-controlled electric pumps, in order to simulate the pharmacokinetics observed in human serum. Animals were randomly assigned to four groups: (i) controls (no treatment); (ii) meropenem group [computer-controlled syringe-pump infusion to simulate a human equivalent (HE) dosage of meropenem of 1 g three times daily]; (iii) doripenem group (simulating an HE dosage of doripenem of 0.5 g three times daily); and (iv) imipenem group (simulating an HE dosage of imipenem of 1 g three times daily). Evaluation of infection was performed at the end of treatment (2 days). The spleen and both lungs from each animal were weighed and homogenized in 1 mL of saline buffer and used for quantitative cultures on agar for 24 h at 378C. Viable counts after 24 h of incubation were expressed as the mean+SD log10 cfu/g of lung. Spleen culture results were expressed quantitatively (positive or negative). From each animal, plasma antibiotic concentrations were determined by a microbioassay to obtain a pharmacokinetic analysis. Selection of variants resistant in vivo to doripenem, meropenem or imipenem was evaluated by spreading undiluted homogenates on agar plates that contained the appropriate antibiotic at a concentration of 4-fold the MIC. Bacterial counts were determined after 48 h of incubation at 378C. Quantitative variables were compared using one-way analysis of variance. This analysis was completed with a post hoc Bonferroni test. Proportions (percentages) were compared using Fisher’s exact test. P,0.05 was considered statistically significant. Animals were treated in accordance with institutional policies and the guidelines stipulated by the animal welfare committee. The Committee of Animal Ethics of the University of Nantes approved all animal experimentation in this study. Mean pulmonary bacterial loads were 3.1+1.3, 2.6+0.4 and 2.8+0.7 log10 cfu/g for meropenem, doripenem and imipenem, respectively, compared with 5.9+0.8 log10 cfu/g for control animals. The results of these pulmonary bacterial counts are shown in Figure 1; they were significantly lower in the treated animals compared with the controls (P,0.05), but were similar between the different antibiotic regimens. The proportions of positive versus negative spleen cultures for controls, meropenem, doripenem and imipenem were 4/3, 3/4, 1/6 and 2/7, respectively; they were not statistically different. No resistant mutants were isolated from any of the post-treatment biological samples.

Comparative evaluation of intratracheal colistimethate sodium, imipenem, and meropenem in BALB/c mice with carbapenem-resistant Acinetobacter baumannii pneumonia

The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB). A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 10⁷ colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25μl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined. A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs. Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.

Continuous Epileptiform Discharges in Patients Treated With Cefepime or Meropenem

To test the hypothesis that treatment with cefepime hydrochloride leads to higher incidence of periodic epileptiform discharges compared with treatment with other β-lactams. Data from hospital pharmacy databases of patients treated with cefepime or meropenem during a 42-month period (from January 1, 2007, through June 30, 2010) were retrospectively crossed with data from the electroencephalography database for the same period. Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. Patients who underwent electroencephalographic testing while taking cefepime or meropenem were selected. Only electroencephalographic tests performed during the antibiotic treatment period were considered. Matches were compared with nurses' medication records to ensure that the antibiotic considered was effectively given. Proportions of patients with continuous epileptiform discharges in the 2 groups were compared using the Fisher exact test. A total of 1120 patients were treated with cefepime and 1572 patients with meropenem. Electroencephalographic testing was performed during treatment in 59 patients treated with cefepime and 80 treated with meropenem (5.26% vs 5.08%, P = .85). Continuous epileptiform discharges were present in 14 patients in the cefepime group and 3 in the meropenem group (1.25% vs 0.19%, P < .001). Blood creatinine concentration was elevated in 5 of the 17 patients (range, 1.5-4.2 mg/dL; reference range, 0.7-1.2 mg/dL), and liver enzyme levels were elevated in 5 patients. No patient had major electrolyte disturbances. Our study showed a prevalence of electroencephalographic test results with continuous epileptiform discharges in 14 of 1120 patients receiving cefepime (1.25%) but only 3 of 1572 patients receiving meropenem (0.19%). Contrary to the results of previous case series, these electroencephalographic patterns occurred, in most cases, in patients with normal renal function. These results suggest that cefepime may be an independent risk factor for periodic epileptiform discharges, which are associated with worse outcomes. This finding could provide a partial explanation for the higher mortality rates reported in patients treated with cefepime compared with other β-lactams.

Combined Meropenem and Linezolid as a Systemic Treatment for Postoperative Endophthalmitis

The aim of this study was to evaluate the antibiotic treatment of postoperative endophthalmitis with combined systemic meropenem and linezolid. A retrospective analysis of endophthalmitis treated with systemic meropenem and linezolid compared to conventional systemic antibiotics by evaluation of outcome and adverse effects was carried out. 26 patients with unilateral postoperative endophthalmitis with a systemic combination regimen of meropenem (2 g TID, mean duration of treatment 5.5 days) and linezolid (600 mg BID, mean duration of treatment 8.9 days) (group 1, mean follow-up time 140 days) were included in this study and compared to 45 postoperative endophthalmitis patients treated with conventional systemic antibiotics (group 2; mean follow-up time 320 days). In group 1, 69.2 % of eyes additionally received intravitreal amikacin and vancomycin (vs. 24.4 % in group 2; p < 0.001), in 92.3 % pars plana vitrectomy was performed (vs. 68.9 % in group 2, p = 0.047). Mean best corrected visual acuity improved from a baseline of 1.76 logMar for group 1 and 1.83 logMar for group 2 to 0.91 logMar (p = 0.0001) and 0.90 logMar (p < 0.0001), respectively, at the end of the follow-up, revealing no significant differences between the two groups at any time point (p > 0.05). Ocular complications were observed in 34.6 % of eyes in group 1 (vs. 37.8 % in group 2; p > 0.05). Adverse drug effects occurred significantly more frequently in group 1 (26.9 % vs. 4.4 % p = 0.02). In spite of the reported better penetration through the blood-ocular barrier and the broader antibacterial spectrum of meropenem and linezolid, no benefit in outcome was found in the present study. In contrast, adverse effects and costs of the combination regimen were significantly higher.

Meropenem monotherapy is as effective as and safer than imipenem to treat brain abscesses

The efficacy of carbapenems versus cefotaxime (8 g/day) + metronidazole (1.5–2 g/day) [combined standard chemotherapy (CSC)] for the treatment of brain abscess was compared. Fifty-nine adult patients with brain abscesses received either imipenem or meropenem (3–4 g/day) or CSC for a mean of 5 weeks, in addition to neurosurgery in most cases. Cure was obtained in 84.7% of cases; 42/47 (89.4%) on carbapenems [18/22 (81.8%) on imipenem versus 24/25 (96.0%) on meropenem] and 8/12 (66.7%) on CSC ( P = 0.06). Seven patients with multiple abscesses were treated with imipenem (1 died; cure rate 85.7%), five with meropenem (all survived; cure rate 100%) and five with CSC (2 died; cure rate 60%) ( P < 0.4). Neurosurgery was performed in 43/59 cases (72.9%); 17 (77.3%) in the imipenem group, 21 (84.0%) in the meropenem group and 5 (41.7%) in the CSC group ( P = 0.02). There was no significant difference in the rate of relapse requiring re-intervention. Treatment with meropenem was associated with a lower mortality than CSC ( P = 0.026). Seizures were observed only with carbapenems [8/22 (36.4%) for imipenem versus 2/25 (8.0%) for meropenem; P = 0.03]. Carbapenems were more effective than CSC for treatment of brain abscesses. Because meropenem induced significantly fewer seizures than imipenem with at least the same clinical efficacy, the former appears to be a better choice to treat this infection.

Assessment of an Alternative Meropenem Dosing Strategy Compared with Imipenem‐Cilastatin or Traditional Meropenem Dosing After Cefepime Failure or Intolerance in Adults with Neutropenic Fever

To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem-cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia. Retrospective, single-center cohort study. 1250-bed urban academic medical center. One hundred twenty-seven adults with neutropenic fever who received either imipenem-cilastatin or meropenem; imipenem-cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem. Of the 127 patients, 40 received imipenem-cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem-cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in-hospital mortality (5% vs 7% vs 7%), and 30-day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively. The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem-cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.

Early Antibiotic Treatment for Severe Acute Necrotizing Pancreatitis

In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved. A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe. One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo. Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days. Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization. Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476). This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.

EXPERIENCE WITH CEFEPIME VERSUS MEROPENEM AS EMPIRIC MONOTHERAPY FOR NEUTROPENIA AND FEVER IN PEDIATRIC PATIENTS WITH SOLID TUMORS

A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.

Empirical antimicrobial monotherapy in patients after high‐dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial

We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.

Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone-sulbactam against Acinetobacter baumannii strains in terms of bactericidal efficacy and resistance selection

BackgroundWe compared imipenem, meropenem and cefoperazone-sulbactam against hospital originated A. baumannii strains in terms of bactericidal efficacy and selection of resistant mutants during treatment in a rat thigh abscess model.MethodsA total of 18 strains were inoculated in 54 animals (one strain for three animals). Randomly selected 10 among these 18 strains were inoculated in another 10 rats as the control group. Imipenem, meropenem and cefoperazone-sulbactam were the antibiotics compared. After four days of treatment, Wistar albino rats (200 to 250 g) were sacrificed and the abscess materials were processed for mean colony counts and for the presence of resistant mutants.ResultsThe mean CFUs per gram (mean ± (std. deviation) [×104]) of the abscess were: 9,14 (25,24), 2,11 (3,78), 1,20 (1,70) in the imipenem (n = 17), meropenem (n = 18) and cefoperazone-sulbactam (n = 17) groups, respectively. The differences were not significant. On the other hand, no resistant mutant was detected in abscess materials.ConclusionThis study indicated; first, cefoperazone-sulbactam is comparable to carbapenems in bactericidal efficacy in this particular abscess model and second, emergence of resistance due to spontaneous mutations is not at least a frequent phenomenon among A. baumannii.

Meropenem Plus Amikacin Versus Piperacillin-Tazobactam Plus Netilmicin as Empiric Therapy for High-Risk Febrile Neutropenia in Children

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received iv meropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1–30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p= .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group.Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.