meropenem and Shock--Septic

Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required to compensate the increased volume of distribution, regardless of impaired organ function. An additional loading dose may be required when CRRT is initiated due to steady-state equilibrium breakage driven by clearance variation. From day 2, dosing must be adjusted to CRRT settings and residual renal function. Therapeutic drug monitoring of beta-lactams may be regarded as a useful tool to daily individualize dosing and to ensure optimal antibiotic exposure.

Topics: Anti-Bacterial Agents; beta-Lactams; Ceftriaxone; Critical Illness; Humans; Meropenem; Piperacillin; Renal Replacement Therapy; Shock, Septic; Thienamycins

Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT.. This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety.. This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT.. Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .

Topics: Adolescent; Adult; Anti-Bacterial Agents; Critical Illness; Humans; Meropenem; Prospective Studies; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic

Topics: Anti-Bacterial Agents; Critical Illness; Dose-Response Relationship, Drug; Humans; Length of Stay; Meropenem; Organ Dysfunction Scores; Sepsis; Shock, Septic

To evaluate the effect of direct hemoperfusion with polymyxin B immobilized cartridge (DHP-PMX) on meropenem pharmacokinetics in critically ill patients with sepsis requiring continuous venovenous hemofiltration (CVVH).. After intravenous infusion of 1 g meropenem over 3 h repeated every 8 h for at least 3 doses, 2 serial blood and ultrafiltration fluid samples were collected: one over a dose interval of meropenem with DHP-PMX therapy; and the other on the following day over a dose interval of meropenem with no DHP-PMX therapy. Meropenem concentrations were measured by high performance liquid chromatography. Pharmacokinetic parameters of meropenem and extraction ratio of DHP-PMX were calculated.. No significant effect of DHP-PMX on meropenem pharmacokinetics was observed among severe sepsis/septic shock patients during CVVH treatment.. Clinical Trial Registry detail: NCT registry: 02413541 (First registered March 3, 2015, last update October 16, 2017).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Female; Hemoperfusion; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Meropenem; Middle Aged; Polymyxin B; Prospective Studies; Shock, Septic; Treatment Outcome

To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock.. Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277.. Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CLCR) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CLCR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h.. In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Models, Theoretical; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Shock, Septic; Tandem Mass Spectrometry; Thienamycins; Young Adult

The antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock. We compared the pharmacokinetic, clinical, and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients.. Patients admitted to the Intensive Care Unit (ICU) with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous (n = 25) or intermittent groups (n = 25). The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations for the first and third dosing periods (steady state) were also measured.. Clinical success was similar in both the continuous (64%) and intermittent (56%) groups (P = 0.564); the rates of microbiological eradication and superinfection (81.8% vs. 66.7% [ P = 0.255] and 4% vs. 16% [ P = 0.157], respectively) showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group (7.6 vs. 9.4 days; P= 0.035), where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first (Cmax: 19.8 mg/L vs. 51.8 mg/L, P= 0.000; Cmin: 11.2 mg/L vs. 0.5 mg/L, P= 0.000) and third dosing periods (Cmax: 12.5 mg/L vs. 46.4 mg/L, P= 0.000; Cmin: 11.4 mg/L vs. 0.6 mg/L, P= 0.000). For medium-susceptibility pathogens, continuous infusion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group.. Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous infusion may be more optimal against intermediate-susceptibility pathogens.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Intensive Care Units; Male; Meropenem; Middle Aged; Pilot Projects; Prospective Studies; Sepsis; Shock, Septic; Thienamycins

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

Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes.. To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis.. A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022.. Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304).. The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events.. All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients).. In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28.. ClinicalTrials.gov Identifier: NCT03452839.

Topics: Anti-Bacterial Agents; Critical Illness; Double-Blind Method; Female; Humans; Hypersensitivity; Male; Meropenem; Middle Aged; Monobactams; Sepsis; Shock, Septic

The aim of this prospective cohort study was to evaluate the therapeutic target attainment of 3-hour extended infusion of meropenem in patients with septic burns in the early and late periods of septic shock.. Meropenem serum levels were determined by liquid chromatography from blood samples collected within 48 hours (early period) of therapy and 10 to 14 days afterward (late period). Pharmacokinetic properties were investigated by noncompartmental analysis, and the therapeutic target was defined as 100% of the time above the MIC (100%fT> MIC).. Fifteen patients with 90 measured meropenem concentrations were included. Throughout the entire course of antimicrobial therapy, the therapeutic target was attained against gram-negative pathogens with an MIC ≤ 2 mg/L. Pathogens with intermediate susceptibility to meropenem were only covered in the early phase of therapy.. Higher-dose regimens or continuous infusions may be necessary to guarantee antimicrobial coverage of meropenem against less sensitive pathogens in patients with septic burns.

Topics: Anti-Bacterial Agents; Burns; Critical Illness; Humans; Infusions, Intravenous; Meropenem; Microbial Sensitivity Tests; Prospective Studies; Shock, Septic; Thienamycins

Topics: Anti-Bacterial Agents; Ciprofloxacin; Humans; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Shock, Septic

Antibiotics may trigger alterations in mitochondrial function, which has been explored in cells culture, and in animal model of sepsis. This study sought to evaluate whether antibiotic therapy affects mitochondrial bioenergetics in a 68-patients clinical study. We studied mitochondrial respiratory rates at two time points: the first day of antibiotic administration and three days after. The Δbasal, ΔCI, ΔCII respiration, and ΔBCE respiratory rates were not different between patients administered with polymyxin, vancomycin, amoxicillin-clavulanate, and azithromycin compared to those who were not administered. Specific beta-lactams are associated with specific modifications in mitochondrial respiratory endpoints - patients who used meropenem had higher delta C2 values compared to those who did not (p = 0.03). Patients who used piperacillin-tazobactam had lower delta C1 (p = 0.03) values than those who did not, but higher delta C2 values (p = 0.02). These mitochondrial metabolic signatures in isolated lymphocytes challenges the proposed effects of antibiotics in mitochondrial bioenergetics of cell cultures, but at current status have an uncertain clinical significance.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; beta-Lactams; Clavulanic Acid; Energy Metabolism; Humans; Lymphocytes; Meropenem; Mitochondria; Piperacillin, Tazobactam Drug Combination; Polymyxins; Prospective Studies; Shock, Septic; Vancomycin

Topics: Critical Illness; Cytokines; Humans; Meropenem; Sepsis; Shock, Septic

Topics: Animals; Anti-Bacterial Agents; Inflammation; Kidney; Liver; Meropenem; Rats; Shock, Septic

To determine if aztreonam as initial empiric treatment of adult septic shock is associated with increased mortality compared to the use of anti-pseudomonal beta-lactam agents.. This was a multicenter, retrospective cohort study of 582 adult emergency department patients admitted to 12 acute care facilities within a single health system from January 2014 to December 2017 with septic shock receiving either aztreonam or an anti-pseudomonal beta-lactam for empiric treatment and discharged with an infection-related ICD-9 or ICD-10 code. The primary endpoint was in-hospital mortality.. Initial exposure to aztreonam was associated with increased hospital mortality compared to treatment with an anti-pseudomonal beta-lactam agent (22.7% vs. 12.9%, OR = 1.98, 95% CI: 1.27-3.11). When adjusted for APACHE II score, the treatment group effect on mortality remained statistically significant (OR = 1.74, 95% CI: 1.08-2.80). Aztreonam use was also associated with increased utilization of aminoglycosides (28.9% vs. 12.4%, p < 0.0001) and fluoroquinolones (50.5% vs. 25.8%, p < 0.01). There was no difference in hospital or intensive care unit length of stay in surviving patients between the two groups.. Compared to anti-pseudomonal beta-lactams, empiric treatment with aztreonam is associated with increased mortality and greater antibiotic exposure among patients with acute septic shock. These findings suggest that treatment with anti-pseudomonal beta-lactams should be prioritized over allergy avoidance whenever feasible.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; APACHE; Aztreonam; beta-Lactams; Cefepime; Cohort Studies; Drug Hypersensitivity; Female; Fluoroquinolones; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Shock, Septic

The SEP-1 measures have tied financial reimbursement to the treatment of patients with severe sepsis and septic shock. The purpose of this study was to assess the impact of a SEP-1 initiative on the utilization of broad-spectrum combination therapy (BSCT) in the emergency department (ED).. This was an IRB-approved, retrospective evaluation of adult patients who received vancomycin plus an antipseudomonal beta-lactam for a urinary tract infection (UTI) or skin or soft tissue infection (SSTI) in the ED. The primary outcome was the proportion of patients in which use of BSCT was considered appropriate based on clinical criteria. Secondary outcomes included door to antibiotic order time, door to administration time, proportion of patients continued on BSCT upon admission, duration of BSCT, and in-hospital mortality.. A total of 400 patients were included in the analysis. Following SEP-1 implementation, appropriate use of BSCT decreased by 12%, with 54% of patients in the pre-SEP-1 group meeting clinical criteria compared to 42% in the post-SEP-1 group (p = 0.028). In the subgroup of patients with a suspected UTI the appropriate use of BSCT declined by 25% (40% vs 15%, p = 0.005). The median door to first antibiotic administration time was not significantly different between groups (63 min vs 61 min, p = 0.091).. The implementation of the SEP-1 mandated measures was associated with an increase in the unnecessary use of BSCT. Additionally, no difference was seen in time to antibiotic administration. The results of this study demonstrate the negative impact that the SEP-1 mandate may have on antimicrobial utilization within the ED.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Cefepime; Centers for Medicare and Medicaid Services, U.S.; Early Diagnosis; Early Medical Intervention; Emergency Service, Hospital; Female; Guideline Adherence; Hospital Mortality; Hospitalization; Humans; Male; Medical Overuse; Meropenem; Middle Aged; Patient Care Bundles; Piperacillin, Tazobactam Drug Combination; Reimbursement Mechanisms; Retrospective Studies; Sepsis; Shock, Septic; Soft Tissue Infections; Time-to-Treatment; United States; Urinary Tract Infections; Vancomycin

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Computer Simulation; Humans; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Piperacillin; Prospective Studies; Pseudomonas aeruginosa; Shock, Septic

A 62-year-old man with diabetes mellitus and a two-day history of fever and dyspnea presented at our hospital. He was diagnosed with community-acquired pneumonia (CAP), septic shock, and respiratory failure. Sputum Gram staining revealed Gram-negative coccobacilli. Based on the Gram staining findings and history, Acinetobacter baumannii was considered as one of the causative organisms of his CAP. Consequently, he was successfully treated with the initial administration of meropenem. We suggest that A. baumannii should be considered as one of the possible causative organisms of CAP based on a fulminant clinical course, and the presence of Gram-negative coccobacilli.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteriological Techniques; Community-Acquired Infections; Dyspnea; Fever; Gentian Violet; Humans; Male; Meropenem; Middle Aged; Phenazines; Pneumonia, Bacterial; Respiratory Insufficiency; Shock, Septic; Sputum; Staining and Labeling

Topics: Anti-Bacterial Agents; Boronic Acids; Chromatography, High Pressure Liquid; Continuous Renal Replacement Therapy; Humans; Male; Meropenem; Middle Aged; Shock, Septic; Tandem Mass Spectrometry; Treatment Outcome

Gram-negative organisms (GNOs) have increasing resistance rates to levofloxacin at Virginia Commonwealth University Health System (VCUHS), where levofloxacin is the most common agent added to provide double coverage of gram-negative infections. The goal of this study was to determine the adequacy of empiric gram-negative coverage for septic patients at our institution.. A retrospective review of patients admitted to VCUHS, from January 1, 2014, to December 31, 2014, with a diagnosis of sepsis, severe sepsis, or septic shock and documented infection, was performed to determine the adequacy of various empiric antibiotic combinations.. Of 219 patients who met the inclusion criteria, 56% of patients received monotherapy and 21% of patients received combination therapy (2 antibiotics) covering GNOs. GNOs (84%) were susceptible to piperacillin-tazobactam. When used in combination with cefepime and meropenem, levofloxacin did not increase coverage. However, levofloxacin provided an 8% increase in coverage and gentamicin provided an additional 13% increase in coverage, respectively, when used in combination with piperacillin-tazobactam.. Among septic patients at VCUHS, gentamicin provided increased gram-negative coverage when compared with levofloxacin. Although susceptibility to piperacillin-tazobactam alone was relatively low, the combination of piperacillin-tazobactam and gentamicin provided nearly equivalent coverage to meropenem and gentamicin.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Gram-Negative Bacteria; Humans; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis; Shock, Septic; Virginia; Young Adult

Topics: Aged; Amikacin; Anti-Bacterial Agents; Chryseobacterium; Drug Therapy, Combination; Flavobacteriaceae Infections; Humans; Male; Meropenem; Rifampin; Shock, Septic; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Ciprofloxacin; Colistin; Cupriavidus; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Middle Aged; Shock, Septic; Treatment Outcome

Klebsiella pneumonia (K. pneumonia), primarily a hospital-acquired pathogen, can cause a variety of deep-seated infections with significant morbidities. However, in the current scenario of global rise in antibiotic abuse, unexpected infection could be caused by K. pneumoniae.. A 56-year-old male who presented with intermittent headache and low fever was admitted, he had transsphenoidal surgery for pituitary adenoma 3 years ago. Routine laboratory tests revealed an elevated WBC count of 10.12 × 10/L and C-reactive protein (CRP) 12.9 mg/L. computed tomography (CT) revealed the sellar region with suspicious hemorrhage.. The patient was initially diagnosed with acute residual tumor hemorrhage. But the consequent diagnose of Klebsiella pneumoniae purulent meningitis was made based on the cerebrospinal fluid lab test and cerebrospinal fluid (CSF) and blood culture, and CT scan.. Lumbar puncture examination was made and the antibiotics were adjusted to meropenem and vancomycin according to the antibiotic sensitivity test. But because of the patient's unstable vital signs, his family refuse further lateral ventricular drainage.. The infection was out of control and the patient died of spontaneous breath and heartbeat arrest.. Through this case, we could learn that any clue of suspicious intracranial infection should be carefully considered in the current scenario of global rise in antibiotic abuse. The manifestation of intermittent headache and mild fever could be potential signs of fatal infection, and prompt appropriate measures should be taken timely.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Fatal Outcome; Fever; Headache; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Shock, Septic; Thienamycins; Vancomycin

Sphingobacterium spiritivorum is a glucose non-fermenting Gram-negative rod, formerly classified as one of the Flavobacterium species. It is characterized by a large number of cellular membrane sphingophospholipids. Sphingobacterium species are ubiquitous and isolated from natural environments, such as soil and water. However, they rarely cause infections in humans. Only a limited number of cases have been reported in elderly and immunocompromised patients with underlying diseases and predisposing factors.. An 80-year-old Japanese man with chronic obstructive pulmonary disease and congestive heart failure visited the Kariya Toyota General Hospital, Aichi, Japan with the chief complaint of fever accompanied by chills and left leg pain. At initial presentation, he was distressed and dyspneic. He was febrile (38.8 °C), and his left foot was swollen with reddening and tenderness. We diagnosed him as having cellulitis, and he was hospitalized for antibiotic therapy. Initially, he was treated with intravenously administered cefazolin, but after the isolation of a glucose non-fermenting Gram-negative rod from blood cultures, we decided to switch cefazolin to intravenously administered meropenem on day 4, considering the antibiotic resistance of the causative organism. The causative organism was identified as S. spiritivorum on day 6. His condition gradually stabilized after admission. Meropenem was switched to orally administered levofloxacin on day 12. He was discharged on day 16 and treated successfully without any complications.. Although S. spiritivorum is rare, with limited cases isolated from cellulitis, it should be considered as a causative organism in elderly and immunocompromised patients with cellulitis. Blood cultures are the key to correct diagnosis and appropriate treatment.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Cellulitis; Gram-Negative Bacterial Infections; Heart Failure; Humans; Levofloxacin; Male; Meropenem; Pulmonary Disease, Chronic Obstructive; Shock, Septic; Sphingobacterium; Thienamycins; Treatment Outcome

Various complications are reported with Clostridium difficile infection (CDI), including fulminant CDI. Fulminant CDI is an underappreciated life-threatening condition associated with complications such as toxic megacolon and bowel perforation.. A 79-year-old woman presented to the Emergency Department with altered mental status. She was admitted and conservatively treated for a left thalamic hemorrhage. While hospitalized, she developed watery diarrhea due to Clostridium difficile. Although metronidazole was initiated, she developed altered mental status and septic shock. Abdominal x-ray study and computed tomography revealed a significantly dilatated colon and a massive pneumoperitoneum. She underwent subtotal colectomy with a 14-day course of intravenous meropenem. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that we must be aware of the complications that CDI may present and adequately consider surgical management because early diagnosis and surgical treatment is critical to reduce the mortality of fulminant CDI.

Topics: Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colectomy; Colon; Consciousness Disorders; Diarrhea; Female; Fever; Hemorrhage; Humans; Intestinal Perforation; Meropenem; Metronidazole; Pneumoperitoneum; Shock, Septic; Thienamycins; Tomography, X-Ray Computed

Topics: Anti-Bacterial Agents; Ciprofloxacin; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Infant; Meropenem; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Purpura; Shock, Septic; Skin Diseases, Bacterial; Thienamycins

Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80% fT>MIC. The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 μg/ml, the PTAs of 40% fT>MIC following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 μg/ml in immunocompromised hosts, the PTAs of 80% fT>MIC following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h were 84.32% and 94.72%, respectively. These findings indicated that the V of meropenem was greater and the CL of meropenem was lower than the values obtained in a previous study with healthy subjects. The maximum recommended dose, i.e., 2 g of meropenem every 8 h, may be required for treatment of life-threatening infections in this patient population.

Topics: Adult; Aged; Critical Illness; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Sepsis; Shock, Septic; Thienamycins

Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) and V = 33.00 · (weight/73)(2.07), where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), and V is the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (fu ) of drug above the MIC of the bacteria for 40% of dosing interval T (referred to as 40% of the ƒ uT >MIC), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒ uT >MIC was chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and inexpensive tool to help with titration of the meropenem dose and infusion time in this challenging population.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Renal Replacement Therapy; Shock, Septic; Thienamycins

Vibrio vulnificus is a rare but potential fatal bacterium that can cause severe infections. Wound infections, primary sepsis and gastroenteritis are the most common clinical features. Septic arthritis caused by V. vulnificus is an atypical presentation that has been reported in only two case reports; however, it has not been previously noted in Denmark. The authors report a case of septic arthritis caused by V. vulnificus in an immunocompromised patient. The disease progressed to severe sepsis and subsequent death within 10 h of admission.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Infectious; Cardiotonic Agents; Cefuroxime; Denmark; Dobutamine; Drug Resistance, Bacterial; Fatal Outcome; Humans; Male; Meropenem; Microbial Sensitivity Tests; Shock, Septic; Thienamycins; Vibrio Infections; Vibrio vulnificus

A 62-year-old man was scheduled for transurethral lithotripsy. Systemic shivering, vomiting and decreased blood pressure occurred after extubation. Blood gas analysis showed metabolic acidosis. After 45 minute observation, he became unconsciousness. He was reintubated. Elevated procalcitonin (PCT) and endotoxin activity assay (EAA) brought us to the diagnosis of severe septic shock. He was treated by a standard therapy conforming to early goal direct therapy and PMX-DHP with CHDF. He showed full recovery, and was discharged 9 days after the procedure. TUL is commonly performed, but it seldom leads to sepsis. We need to pay a careful attention peri- and postoperatively.

Topics: Anesthesia, General; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Hemodiafiltration; Hemoperfusion; Humans; Infusions, Intravenous; Kidney Calculi; Lithotripsy; Male; Meropenem; Middle Aged; Protein Precursors; Severity of Illness Index; Shock, Septic; Thienamycins; Treatment Outcome; Urethra

Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fanconi Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis.

Topics: Adenoviridae Infections; Animals; Anthracyclines; Anti-Bacterial Agents; Ataxia Telangiectasia Mutated Proteins; Autophagy-Related Protein 7; Cecum; DNA Damage; DNA Repair; Epirubicin; Fanconi Anemia Complementation Group D2 Protein; Inflammation; Inflammation Mediators; Injections, Intraperitoneal; Lung; Meropenem; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; Organ Specificity; Peritonitis; Respiratory Tract Infections; Sepsis; Shock, Septic; Thienamycins; Whole-Body Irradiation

Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum β-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of ≥ 30 kg/m(2)) treated with a broad-spectrum β-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m(2)) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in β-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of β-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient β-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of β-lactams should be continued in obese critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Case-Control Studies; Cefepime; Ceftazidime; Cephalosporins; Drug Monitoring; Enzyme Inhibitors; Female; Humans; Male; Meropenem; Middle Aged; Obesity; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Sepsis; Shock, Septic; Tazobactam; Thienamycins; Young Adult

A patient with septic shock due to extensively drug resistant (XDR) Pseudomonas aeruginosa was cured by optimizing the meropenem (MEM) regimen to obtain at least 40% of the time between two administrations in which drug levels were four times higher than the MIC of the pathogen. As the standard drug dose did not achieve these optimal concentrations, the MEM regimen was progressively increased up to 12 g/day (3 g every 6 h in a 3-h extended infusion), which eventually resulted in sepsis resolution. High MEM dosage may represent a valuable therapeutic option for infection due to multidrug-resistant (MDR) strains, and drug monitoring would allow rapid regimen adjustment in clinical practice.

Topics: Aged; Anti-Bacterial Agents; C-Reactive Protein; Drug Resistance, Multiple, Bacterial; Humans; Male; Meropenem; Microbial Sensitivity Tests; Norepinephrine; Obesity; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Shock, Septic; Thienamycins; Vasoconstrictor Agents

Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT.. This open, prospective study enrolled consecutive patients treated with CRRT and receiving either meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) or ceftazidime (CAZ). Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from samples taken before (t = 0) and 1, 2, 5, and 6 or 12 hours (depending on the β-lactam regimen) after the administration of each antibiotic. Series of measurements were separated into those taken during the early phase (< 48 hours from the first dose) of therapy and those taken later (> 48 hours).. A total of 69 series of serum samples were obtained in 53 patients (MEM, n = 17; TZP, n = 16; FEP, n = 8; CAZ, n = 12). Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp. for the recommended time in 81% of patients treated with MEM, in 71% with TZP, in 53% with CAZ and in 0% with FEP. Accumulation after 48 hours of treatment was significant only for MEM.. In septic patients receiving CRRT, recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP, FEP and CAZ; for these latter drugs, higher doses and/or extended infusions should be used to optimise serum concentrations.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Dose-Response Relationship, Drug; Female; Humans; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Prospective Studies; Pseudomonas aeruginosa; Renal Replacement Therapy; Shock, Septic; Thienamycins

Massive hemolysis secondary to sepsis caused by Clostridium perfringens is a rare entity but appears fairly often in the literature. In nearly all published reports, the clinical course is rapid and fatal. We describe the case of a 75-year-old woman with diabetes who was admitted with symptoms consistent with acute cholecystitis. Deteriorating hemodynamics and laboratory findings were consistent with intravascular hemolysis, coagulation disorder, and renal failure. Gram-positive bacilli of the Clostridium species were detected in blood along with worsening indicators of hemolysis. In spite of antibiotic and surgical treatment, hemodynamic support and infusion of blood products, the patient continued to decline and died in the postoperative recovery unit 14 hours after admission. Mortality ranges from 70% to 100% in sepsis due to Clostridium perfringens, and risk of death is greater if massive hemolysis is present, as in the case we report. Only a high degree of clinical suspicion leading to early diagnosis and treatment can improve the prognosis. This bacterium should therefore be considered whenever severe sepsis and hemolysis coincide.

Topics: Acute Kidney Injury; Aged; Anemia, Hemolytic; Anti-Bacterial Agents; Bacteremia; Blood Component Transfusion; Cholecystectomy; Cholecystitis; Clindamycin; Clostridium perfringens; Combined Modality Therapy; Delayed Diagnosis; Diabetes Complications; Emergencies; Fatal Outcome; Female; Gas Gangrene; Hemofiltration; Humans; Meropenem; Norepinephrine; Postoperative Complications; Shock, Septic; Thienamycins

Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum β-lactam concentrations when standard dosages are administered. Previous studies on β-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock.. Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration.. 80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 μg/mL), 45% for ceftazidime (MIC = 32 μg/mL), 34% for cefepime (MIC = 32 μg/mL), and 33% for piperacillin-tazobactam (MIC = 64 μg/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam.. Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Penicillanic Acid; Piperacillin; Prospective Studies; Sepsis; Shock, Septic; Tazobactam; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Early Diagnosis; Escherichia coli; Escherichia coli Proteins; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Shock, Septic; Thienamycins; Time Factors

Our objective was to describe the pharmacokinetics of meropenem in the peritoneal fluid (PF) of six patients with severe peritonitis and septic shock and to relate measured concentrations to the minimum inhibitory concentration of bacteria. Microdialysis catheters were placed into the peritoneal space during surgery. Meropenem concentrations in plasma and in PF were analyzed using compartmental modeling. Meropenem areas under the concentration-time curve were lower in PF than in plasma (average ratio, 73.8+/-15%) because of degradation confirmed ex vivo. Compartment modeling with elimination from a peripheral compartment described the data adequately, and was used to simulate steady-state concentration profiles in plasma and PF during various dosing regimens. At the currently recommended dosing regimen of 1 g infused over 20 min every 8 h, PF concentrations of meropenem in patients with severe peritonitis associated with septic shock reach values sufficient for antibacterial effects against susceptible, but not always against intermediately susceptible, bacteria.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Female; Humans; Male; Meropenem; Microdialysis; Middle Aged; Peritonitis; Shock, Septic; Thienamycins; Tissue Distribution

A 25-year-old female was admitted to our intensive care unit with septic shock and multiorgan failure caused by extended-spectrum beta-lactamase-producing Escherichia coli originating from the right renal pelvis. A 16-day course of treatment with meropenem reversed the septic condition, but the infection recurred thereafter. The patient recovered fully after therapy was changed to tigecycline.

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Meropenem; Minocycline; Recurrence; Shock, Septic; Thienamycins; Tigecycline; Urinary Tract Infections

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

Reported here is the case of a patient with septic shock due to multidrug-resistant Acinetobacter baumannii, which developed after complicated acute pancreatitis with intra-abdominal abscess. Treatment with colistin methanesulphonate and high doses of meropenem were initiated, but since shock persisted, tigecycline was added to the regimen, resulting in successful resolution of the infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Minocycline; Pancreatitis, Acute Necrotizing; Shock, Septic; Thienamycins; Tigecycline; Treatment Outcome

Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is endemic in northern Australia and Southeast Asia. Risk factors for this infection have also been associated with functional neutrophil defects. Because of this, granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients with septic shock due to melioidosis in December 1998. We compared the mortality rates from before and after the introduction of G-CSF therapy at the Royal Darwin Hospital (Darwin, Australia) during the period of 1989-2002. The mortality rate decreased from 95% to 10% after the introduction of G-CSF. Risk factors, the duration of illness before presentation, and the severity of illness were similar in both groups. A smaller decrease in mortality among patients in the intensive care unit who did not have melioidosis was observed, suggesting that other changes in management did not account for the magnitude of the benefit seen. We conclude that G-CSF may have contributed to the reduction in the mortality rate among patients with septic shock due to melioidosis.

Topics: Adolescent; Adult; Burkholderia pseudomallei; Child; Female; Granulocyte Colony-Stimulating Factor; Humans; Intensive Care Units; Male; Melioidosis; Meropenem; Middle Aged; Shock, Septic; Thienamycins

The use of meropenem, a new antibiotic from the carbapenemic family, was analyzed in the treatment of all types of serious infections in patients in critical condition. The global clinical response was satisfactory in 85.4% of the 178 assessable cases, with no significant differences being found in the form of treatment (monotherapy or combination therapy with aminoglycosides and/or glycopeptides) or in the type of infection treated, although the patients that received three or more antibiotics had more treatment failure. In the case of pneumonia, a better clinical response was observed with the use of monotherapy (38/40, 95% vs. 38/47, 80.8%, p = 0.049). The microbiological response was satisfactory in 72.7% of the 110 assessable cases. Initial pathogens persisted in just 8.2% of the cases, with superinfection in 12.7% and colonization in 6.4%. Differences relating to the form of treatment or the area of infection were not detected. The severity of the patient's condition influenced the choice of the form of meropenem treatment (monotherapy or combined therapy). Such factors as the patient's severity, the presence of hypotension or shock, and the need for mechanical ventilation were indicators for the use of two or more antibiotics. The severity also influenced the use of a larger average daily dose, as well as the length of treatment. Adverse reactions were detected in 6 of the 178 (3.37%) assessable patients, with 4 cases of nephrotoxicity, and 2 of hepatotoxicity. Global mortality was 14%, while infection-related mortality was 8.43%.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; APACHE; Bacterial Infections; Child; Child, Preschool; Critical Illness; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Glycopeptides; Humans; Male; Meropenem; Middle Aged; Sepsis; Shock, Septic; Thienamycins