meropenem and Multiple-Organ-Failure

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.

Topics: Aged; Anti-Bacterial Agents; Aza Compounds; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Meropenem; Middle Aged; Moxifloxacin; Multiple Organ Failure; Quinolines; Sepsis; Shock, Septic; Survival Analysis; Thienamycins; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactams; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multiple Organ Failure; Thienamycins

Topics: Animals; Anti-Bacterial Agents; Bunyaviridae Infections; Female; Humans; Meropenem; Middle Aged; Multiple Organ Failure; Orthobunyavirus; Thienamycins; Tick-Borne Diseases; Ticks; Treatment Outcome; Vancomycin

Melioidosis is an endemic disease in southeast Asia and northern Australia, caused by Burkholderia pseudomallei. A typhoon-related outbreak occurred in southern Taiwan in July 2005. High mortality in melioidosis associated with bacteremic pneumonia and septic shock. We report a patient with life-threatening melioidosis who developed rapid progression of bacteremic pneumonia with acute respiratory distress syndrome, septic shock and multiple organ dysfunction and was successfully treated with recombinant human activated protein C (rhAPC) and meropenem. Although rhAPC has been reported to reduce the mortality of severe septic shock caused by various pathogens, to our best knowledge, this is the first reported case of rhAPC application in life-threatening melioidosis.

Topics: Anti-Bacterial Agents; Burkholderia pseudomallei; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Male; Melioidosis; Meropenem; Middle Aged; Multiple Organ Failure; Pneumonia, Bacterial; Protein C; Recombinant Proteins; Respiratory Distress Syndrome; Shock, Septic; Thienamycins

Meropenem is a carbapenem antibiotic with a broad antibacterial spectrum of activity. Its main route of elimination is through the kidneys, with 63% of the drug excreted unchanged in the urine. Meropenem clearance is diminished in renal impairment; therefore, doses need to be adjusted in patients with varying degrees of renal function. An appropriate dose of meropenem for patients undergoing continuous venovenous hemodiafiltration (CVVHDF) is unknown. We evaluated the pharmacokinetics of meropenem in a patient with fulminant meningococcemia undergoing CVVHDF. Meropenem concentrations in serial venous, arterial, and ultrafiltrate samples after a 1 g intravenous dose were measured using high-performance liquid chromatography (HPLC). Meropenem clearance was found to be 129.36 mL/min and 141.29 mL/min for every 8- and 12-hour dosing, respectively. Trough levels were above the MIC90 for Neisseria meningitidis and most anaerobic pathogens. We recommend that meropenem 1 g intravenously every 12 hours be used as the initial dose in patients undergoing CVVHDF. Differences between meropenem clearance during CVVHDF and other forms of renal replacement therapy are discussed.

Topics: Adult; Bacteremia; Carbapenems; Chromatography, High Pressure Liquid; Hemodiafiltration; Humans; Male; Meningococcal Infections; Meropenem; Multiple Organ Failure; Thienamycins