meropenem and Sepsis

The antibiotic meropenem is commonly administered to patients with sepsis and septic shock. The aim of this study was to conduct a meta-analysis to evaluate the clinical efficacy and safety of continuous compared to intermittent meropenem infusion for the treatment of sepsis. Electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were researched to collect clinical trials comparing continuous and intermittent infusion of meropenem in patients with sepsis. After data extraction and quality assessment of the included studies, Stata v. 12.0 software (Stata Corporation LLC, College Station, USA) was used for a meta-analysis of mortality, clinical cure, microbiological eradication, and safety. Seven studies with a total of 1,191 participants met the inclusion criteria and were included in the meta-analysis. The meta-analysis showed that continuous meropenem infusion was superior to intermittent infusion in terms of mortality (combined risk ratio (RR) = 0.66, 95% confidence interval (95% CI) = 0.46-0.98, p = 0.03), clinical cure rate (combined RR = 1.15, 95% CI = 1.02-1.30, p = 0.026) and microbiological eradication (combined RR = 1.20, 95% CI = 1.01-1.42, p = 0.04), although it may increase the incidence of some adverse events (AEs). Compared with intermittent dosing, administration of meropenem antibiotics through continuous infusion in patients with sepsis is associated with decreased hospital mortality, increased clinical cure rates and greater microbiological eradication. Further high-quality studies should be conducted to confirm our findings.

Topics: Anti-Bacterial Agents; China; Humans; Infusions, Intravenous; Meropenem; Sepsis

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used.

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Computer Simulation; Critical Illness; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Renal Replacement Therapy; Sepsis; Tazobactam; Thienamycins

The objective of this study was to describe the microbiological characteristics of an extensively drug-resistant (XDR) isolate of Morganella morganii obtained from a patient with sepsis of urinary origin and to describe the patient's clinical characteristics. We further aimed to perform a literature review of the situation in Latin America regarding Gram-negative bacillus (GNB) carriers of New Delhi metallo-β-lactamase (NDM-1) and qnr genes and current reports on the treatment of infections caused by XDR enterobacteria, with particular attention to colistin-resistant isolates.. The patient's clinical data were obtained from his medical history. Microbiological identification and susceptibility testing were done using the VITEK 2 Compact System. Resistance genes were detected by PCR and sequencing.. Blood and urine cultures grew an M. morganii isolate (Mm4232) harboring NDM-1 and qnrD1. The patient was treated successfully with fosfomycin and double doses of meropenem. There are no previous reports of the use of fosfomycin and meropenem to treat infections by XDR enterobacteria harboring NDM-1 carbapenemase.. This is the first report of qnrD1 in South America. We consider that this report could be helpful to physicians implementing treatments for infections caused by XDR GNB, including colistin-carbapenem-resistant GNB.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Fosfomycin; Humans; Male; Meropenem; Morganella morganii; Sepsis; South America; Thienamycins; Young Adult

Wegener's granulomatosis (WG) is a chronic, multisystemic disease of unknown etiology characterized by necrotizing vasculitis and granulomatous inflammation. WG primarily involves the upper and lower respiratory tract and kidneys, but it may also affect multiple other organs or tissues, including the gastrointestinal system.. Gastrointestinal involvement is an extremely rare manifestation of this disease. Moreover, during the course of WG, intestinal perforation is extremely rare in patients with gastrointestinal involvement. To our knowledge, only 13 WG cases with intestinal perforation have been reported in the English language literature as of September 2011.. We herein present the case of a 47-year-old male patient with WG who was diagnosed with multiple ileal perforations and ileovesical fistulae. The exact pathogenesis of intestinal perforation in WG is not fully understood. However, early surgical intervention and appropriate management with immunosuppressive therapy can be important to lifesaving measures. A review of 13 cases reported in the English language literature is also discussed, together with the pathogenesis of this serious complication.

Topics: Anti-Bacterial Agents; Cyclophosphamide; Fatal Outcome; Granulomatosis with Polyangiitis; Humans; Ileal Diseases; Immunosuppressive Agents; Intestinal Fistula; Intestinal Perforation; Male; Meropenem; Middle Aged; Prednisolone; Sepsis; Thienamycins; Urinary Bladder Fistula

To compare meropenem with ciprofloxacin for treatment of gram-negative bacilli sepsis in penicillin-allergic patients in the intensive care unit (ICU) to determine if increased anaphylaxis risk with meropenem precluded its use when weighed against risks of inactive therapy with ciprofloxacin.. A decision model constructed from probability distributions from the literature and data from a local ICU antibiogram. A probabilistic sensitivity analysis was performed to evaluate uncertainty in variable estimates by using one-way analyses, two-way analyses, and Monte Carlo simulation.. Microbiologic activity of treatment, anaphylaxis according to treatment regimen, curability of infection according to patient morbidity status, risk of superinfection, and recovery from gram-negative bacilli sepsis were the variables modeled. Effectiveness was defined by long-term survival and was modeled as life-years (LYs) and quality-adjusted life-years (QALYs) gained according to treatment group. Base case results were the incremental differences between the average effectiveness of each strategy calculated from the Monte Carlo simulation. Mean LYs and QALYs gained with meropenem were 9.9 (95% confidence interval [CI] 8.9-10.8) and 5.9 (95% CI 4.8-6.7), respectively. Mean LYs and QALYs gained with ciprofloxacin were 8.9 (95% CI 8.1-9.6) and 5.3 (95% CI 4.4-6.3), respectively. The incremental difference in effectiveness-or average benefit expected by selecting meropenem over ciprofloxacin-was 1.0 LY (95% CI 0.3-1.7 LYs) and 0.6 QALY (95% CI 0.2-1.1 QALYs) favoring meropenem.. Use of empiric meropenem over ciprofloxacin may be justified in patients in the ICU who are allergic to penicillin.

Topics: Anaphylaxis; Anti-Bacterial Agents; Ciprofloxacin; Decision Trees; Drug Hypersensitivity; Gram-Negative Bacterial Infections; Humans; Meropenem; Penicillins; Quality-Adjusted Life Years; Sepsis; Survival Analysis; Thienamycins

In this study, we report the case of a 2.5-day-old neonate with septicemia and meningitis due to Plesiomonas shigelloides. Culture of the cerebrospinal fluid showed Gram-negative rods, although the glucose, protein and leukocyte counts were normal. The patient was treated with meropenem and survived without any sequelae, although we were not able to identify the source of the infection. In addition, ten previously reported cases of this infection are reviewed.

Topics: Adult; Anti-Bacterial Agents; Cerebrospinal Fluid; Female; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Meningoencephalitis; Meropenem; Plesiomonas; Sepsis; Thienamycins; Treatment Outcome

Melioidosis is an infectious disease caused by the soil-associated Gram-negative bacterium Burkholderia pseudomallei. This review summarizes the evidence underlying current antibiotic regimens and discusses future strategies to reduce mortality.. Although simple rapid diagnostics exist, they rely on the availability of direct specimen and are not commercially available. Serological tests and nucleic acid detection are not sufficiently specific or sensitive for routine clinical use. Since the original trials defining setting the standard of care as ceftazidime, no antibiotic regimens have been shown to be superior in comparative trials, but ongoing trials are evaluating the efficacy of meropenem (in intensive treatment) and (TMP-SMX) (for eradication treatment).. In endemic areas, empiric antibiotics should include agents active against melioidosis as well as the other common causes of severe sepsis. It is likely that future improvements in mortality will be the result of efforts to improve on the early recognition and management of severe sepsis generally.

Topics: Anti-Bacterial Agents; Burkholderia pseudomallei; Ceftazidime; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Melioidosis; Meropenem; Sensitivity and Specificity; Sepsis; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

Fusobacterium necrophorum, an anaerobic, gram-negative rod, belongs to the physiological flora of the oropharynx. It causes Lemierre's syndrome characterized by oropharyngeal infection, septic thrombophlebitis of the neck, in particular of the internal jugular vein, and metastatic abscesses, predominantly in the lungs. Rarely, and mainly in children, it causes meningitis. Here we report the clinical course of a 25-year-old woman with F. necrophorum meningitis. She presented with incomplete, right third nerve palsy. Within a few days, she developed fever, meningism and progressive reduction of vigilance. Cerebrospinal fluid analysis showed typical signs of bacterial meningitis. After the identification of F. necrophorum, the antibiotic treatment was changed to meropenem, which led to continuous improvement of the clinical symptoms. Due to persistent signs of inflammation in the CSF, metronidazole was added to the antibiotic regime. This case report demonstrates that F. necrophorum should always be considered in the diagnostic workup of bacterial meningitis in adults.

Topics: Adult; Anti-Bacterial Agents; Blood Glucose; Cerebrospinal Fluid Proteins; Diagnosis, Differential; Drug Therapy, Combination; Female; Fusobacterium necrophorum; Humans; Lactic Acid; Leukocyte Count; Lung Abscess; Meningitis, Bacterial; Meropenem; Metronidazole; Oculomotor Nerve Diseases; Otitis Media; Pharyngitis; Sepsis; Syndrome; Thienamycins

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

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

As resistance to antibiotics is increasing among microbes, rational use of these drugs is important both in the community and in hospitals. Many infections with resistant microorganisms may be fatal. For a long time, carbapenems have been the last resort for treatment of resistant microorganisms. Unfortunately, resistance to these drugs is increasing. It appears that use of higher doses of antibiotics may help in some cases. However, the potential harm caused by higher doses is a problem. In this primary study, higher doses of meropenem, a common carbapenem, were found to be safe.

Topics: Anti-Bacterial Agents; Cross Infection; Humans; Meropenem; Pilot Projects; Sepsis

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

The aim of this study was to emulate the MERINO trial of piperacillin-tazobactam vs meropenem for the definitive treatment of bloodstream infection (BSI) caused by ceftriaxone-nonsusceptible E coli or Klebsiella spp.. Data from an observational study of BSI and a randomised controlled trial of a rapid diagnostic in BSI were used to emulate the MERINO trial. The primary outcome of the emulated trial was 28-day mortality after blood culture. Outcomes were compared using logistic regression adjusted for propensity score for emulated intervention.. Of the 6,371 observational study and RCT participants, 1,968 had a bloodstream infection with E. coli or Klebsiella spp. of which 121 met the eligibility criteria. In the emulated trial, a total of 14/82 patients (17.1%) allocated to piperacillin-tazobactam met the primary outcome compared with 6/39 (15.4%) in the meropenem group (unadjusted odds ratio 1.13 (95% CI 0.40 to 3.21)). After adjustment for propensity score, the odds ratio increased to 1.31 (95% CI 0.40 to 4.26). This difference is in the same direction but of a smaller magnitudethan observed in the MERINO trial, where 30-day mortality was met by 23/187 patients (12.3%) in the piperacillin-tazobactam and 7/191 (3.7%) in the meropenem group (unadjusted odds ratio of 3.69 (95% CI 1.48 to 10.41)).. The mortality rate in an emulated trial population was more than double the mortality rate in the MERINO trial. The methodology used attempts to address the concern that previous results could be explained by biases such as selection bias and uncontrolled confounding and provides information on how a trial such as the MERINO trial may have performed in the NHS.

Topics: Anti-Bacterial Agents; Escherichia coli; Humans; Meropenem; Piperacillin, Tazobactam Drug Combination; Sepsis

Bloodstream infections (BSIs) adversely affect clinical outcome in children with cancer. Over 1 decade, this retrospective cohort study describes pathogen distribution in BSIs and antimicrobial susceptibility against empirical antibiotics frequently prescribed in children with cancer. The antibiotic efficacy was evaluated through the determination of minimal inhibitory concentrations for piperacillin-tazobactam and meropenem and by disk diffusion for remaining antibiotics. From 2004 to 2013, 398 BSIs occurred in 196 children with cancer (median age: 5.4 y), resulting in 457 bacteria. Overall, 266 (58.2%) were Gram-positive, and 191 (41.8%) were Gram-negative with a significant Gram-positive increase over time (P=0.032). Coagulase-negative staphylococci (74, 16.2%), viridans group streptococci (67, 14.7%), Escherichia coli (52, 11.4%), and Staphylococcus aureus (39, 8.5%) were the most common pathogens. Susceptibility to piperacillin-tazobactam (95.9%, P=0.419) and meropenem (98.9%, P=0.752) was stable over time, and resistance was observed among viridans group streptococci against piperacillin-tazobactam (18%) and meropenem (7%) and among Enterobacterales against piperacillin-tazobactam (3%). Vancomycin showed 98% Gram-positive activity, gentamicin 82% Gram-negative activity and ampicillin, cefotaxime, and cefuroxime were active in 50%, 72%, and 69% of pathogens, respectively, and BSI-related mortality was 0%. In conclusion, over 1 decade, we report an increase in Gram-positive BSIs, and stable, low-resistance rates against currently recommended empirical antibiotics, piperacillin-tazobactam and meropenem.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Neoplasms; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

The optimal treatment for extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae bloodstream infections has yet to be defined. Retrospective studies have shown conflicting results, with most data suggesting the non-inferiority of beta-lactam-beta-lactamase inhibitor combinations compared with carbapenems. However, the recently published MERINO trial failed to demonstrate the non-inferiority of piperacillin-tazobactam to meropenem. The potential implications of the MERINO trial are profound, as widespread adoption of carbapenem treatment will have detrimental effects on antimicrobial stewardship in areas endemic for ESBL and carbapenem-resistant bacteria. Therefore, we believe that it is justified to re-examine the comparison in a second randomised controlled trial prior to changing clinical practice.. PeterPen is a multicentre, investigator-initiated, open-label, randomised controlled non-inferiority trial, comparing piperacillin-tazobactam with meropenem for third-generation cephalosporin-resistant. The study is approved by local and national ethics committees as required. Results will be published, and trial data will be made available.. ClinicalTrials.gov Registry (NCT03671967); Israeli Ministry of Health Trials Registry (MOH_2018-12-25_004857).

Topics: Anti-Bacterial Agents; beta-Lactamases; Canada; Cephalosporins; Enterobacteriaceae; Humans; Israel; Italy; Meropenem; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Sepsis

Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients.. Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio).. Tertiary and University hospitals.. 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h).. The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group.. The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

Topics: Anti-Bacterial Agents; Critical Care; Critical Illness; Humans; Meropenem; Sepsis

Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli.. This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected.. Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024.. The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390 . Registered on 23 January 2020.

Topics: Adult; Anti-Bacterial Agents; Australia; beta-Lactamases; Cephalosporins; Clostridioides difficile; Escherichia coli; Humans; Italy; Lebanon; Meropenem; Microbial Sensitivity Tests; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Saudi Arabia; Sepsis; Singapore; Spain; Tazobactam

Neutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty.. If the trial demonstrates non-inferiority of early switching to oral antibiotics, with potential benefits for patient quality of life and resource savings, this finding will have significant implications for the routine clinical management of those with low-risk neutropenic sepsis.. ISRCTN: 84288963. Registered on the 1 July 2015. https://doi.org/10.1186/ISRCTN84288963. EudraCT: 2015-002830-35.

Topics: Administration, Intravenous; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ciprofloxacin; Cost-Benefit Analysis; Drug Administration Schedule; Equivalence Trials as Topic; Humans; Meropenem; Multicenter Studies as Topic; Neoplasms; Neutropenia; Piperacillin; Pragmatic Clinical Trials as Topic; Quality of Life; Sepsis; Tazobactam; Treatment Outcome

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

β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis.. The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 RCT to compare continuous infusion with standard intermittent infusion of β-lactam antibiotics in critically ill patients with sepsis. The study will be conducted in about 70 intensive care units (ICUs) in Australia, New Zealand, the United Kingdom, Belgium and selected other countries, from 2018 to 2021.. BLING III will recruit 7000 critically ill patients with sepsis being treated with one of two β-lactam antibiotics (piperacillin-tazobactam or meropenem) to receive the β-lactam antibiotic by either continuous or intermittent infusion.. The primary outcome is allcause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 after randomisation, new acquisition, colonisation or infection with a multiresistant organism or Clostridium difficile diarrhoea up to 14 days after randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation and duration of renal replacement therapy up to 90 days after randomisation.. The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis.. ClinicalTrials.gov Registry (NCT03213990).

Topics: Anti-Bacterial Agents; Australia; beta-Lactams; Critical Illness; Drug Administration Schedule; Humans; Infusions, Intravenous; Meropenem; New Zealand; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Treatment Outcome; United Kingdom

Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking.. To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS).. Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed.. A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome.. Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

Topics: Anti-Bacterial Agents; Europe; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Meningitis, Bacterial; Meropenem; Monte Carlo Method; Neonatal Sepsis; Sepsis

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

Patients admitted to intensive care unit (ICU) with Klebsiella pneumoniae infections are characterized by high mortality. The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens.. Twenty-seven consecutive patients were included in the study. Meropenem was administered as 3-h intravenous (i.v.) infusions at doses of 1-2 g every 8 or 12 h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography (HPLC) method, and a population pharmacokinetics analysis was performed using NONMEM software. Meropenem plasma disposition was simulated for extended (3 h; 5 h) or continuous i.v. infusions, and the following parameters were calculated: time during which free drug concentrations were above minimum inhibitory concentration (MIC) (fT > MIC), free minimum plasma concentrations above 4× MIC (fCmin > 4× MIC), probability of target attainment (PTA), and cumulative fraction of response (CFR).. Gender and severity of sepsis affected meropenem clearance, whose typical population values ranged from 6.22 up to 12.04 L/h (mean ± standard deviation (SD) value, 9.38 ± 4.47 L/h). Mean C min value was 7.90 ± 7.91 mg/L, suggesting a high interindividual variability. The simulation confirmed that 88 and 97.5 % of patients achieved effective C min > 4× MIC values after 3- and 5-h i.v. infusions of meropenem 2 g × 3/day, respectively. On the contrary, the same total daily doses reached the target C min > 4× MIC values in 100 % of patients when administered as continuous i.v. infusions.. Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets.

Topics: Adult; Aged; Anti-Bacterial Agents; Critical Illness; Cross Infection; Female; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Models, Biological; Sepsis; Thienamycins

Meropenem is a carbapenem antibiotic commonly used in critically ill patients to treat severe infections. The available pharmacokinetic (PK) data has been mostly obtained from healthy volunteers as well as from clinical studies addressing selected populations, often excluding the elderly and also patients with renal failure. Our aim was to study PK of meropenem in a broader population of septic critically ill patients.. We characterized the PK of meropenem in 15 critically ill patients during the first 36 hrs of therapy. Aditionally, whenever possible, we collected a second set of late plasma samples after 5 days of therapy to evaluate PK intra-patient variability and its correlation with clinical course.Patients received meropenem (1 g every 8 hrs IV). Drug plasma profiles were determined by high-performance liquid chromatography. The PK of meropenem was characterized and compared with clinical parameters.. Fifteen septic critically ill patients (8 male, median age 73 yrs) were included. The geometric mean of the volume of distribution at the steady state (Vss)/weight was 0.20 (0.15-0.27) L/kg. No correlation of Vss/weight with severity or comorbidity scores was found. However the Sequential Organ Failure Assessment score correlated with the Vss/weight of the peripheral compartment (r2 = 0.55, p = 0.021). The median meropenem clearance (Cl) was 73.3 (45-120) mL/min correlated with the creatinine (Cr) Cl (r2 = 0.35, p = 0.033).After 5 days (N = 7) although Vss remained stable, a decrease in the proportion of the peripheral compartment (Vss2) was found, from 61.3 (42.5-88.5)% to 51.7 (36.6-73.1)%. No drug accumulation was noted.. In this cohort of septic, unselected, critically ill patients, large meropenem PK heterogeneity was noted, although neither underdosing nor accumulation was found. However, Cr Cl correlated to meropenem Cl and the Vss2 decreased with patient's improvement.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Female; Humans; Male; Meropenem; Middle Aged; Sepsis; Thienamycins

The study aimed to characterize the pharmacokinetics (PK) of four β-lactams (piperacillin, ceftazidime, cefepime, and meropenem) in patients comedicated with amikacin (AMK), and to confirm the predictive performance of AMK data, obtained from therapeutic drug monitoring (TDM), on these PK, using a population modeling approach.. Serum samples were collected in 88 critically ill septic patients. For each β-lactam, the covariate model was optimized using renal function. Furthermore, predictive performance of AMK concentrations and PK parameters was assessed on β-lactam PK.. A two-compartment model with first-order elimination best fitted the β-lactam data. Results supported the superiority of AMK concentrations, over renal function and AMK PK parameters, to assess the β-lactam PK.. The study confirmed the significant link between the exposure to AMK and to β-lactams, and presented population models able to guide β-lactam dosage adjustments using renal biomarkers or TDM-related aminoglycoside data.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Amikacin; Anti-Bacterial Agents; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Critical Illness; Drug Monitoring; Female; Humans; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Models, Biological; Piperacillin; Sepsis; Thienamycins; Tissue Distribution; Treatment Outcome

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

Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates. We compared the steady-state pharmacokinetics (PK) of meropenem given as a short (30-min) or prolonged (4-h) infusion to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates to define the appropriate dosing regimen for a phase 3 efficacy study. Short (n = 9) or prolonged (n = 10) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, and 12 h after the 4th to 7th doses of meropenem, blood samples were collected. Meropenem concentrations were measured by ultrahigh-performance liquid chromatography. PK analysis was performed with WinNonlin software, and modeling was performed with NONMEM software. A short infusion resulted in a higher mean drug concentration in serum (C(max)) than a prolonged infusion (89 versus 54 mg/liter). In all but two patients in the prolonged-infusion group, the free serum drug concentration was above the MIC (2 mg/liter) 100% of the time. Meropenem clearance (CL) was not influenced by postnatal or postmenstrual age. In population PK analysis, a one-compartment model provided the best fit and the steady-state distribution volume (V(ss)) was scaled with body weight and CL with a published renal maturation function. The covariates serum creatinine and postnatal and gestational ages did not improve the model fit. The final parameter estimates were a V(ss) of 0.301 liter/kg and a CL of 0.061 liter/h/kg. Meropenem infusions of 30 min are acceptable as they balance a reasonably high C(max) with convenience of dosing. In very-low-birth-weight neonates, no dosing adjustment is needed over the first month of life.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Enterocolitis, Necrotizing; Female; Gram-Negative Bacteria; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Infusions, Intravenous; Male; Meropenem; Models, Statistical; Pneumonia; Sepsis; Software; Thienamycins

Late onset neonatal sepsis (LOS) with the mortality of 17 to 27% is still a serious disease. Meropenem is an antibiotic with wide antibacterial coverage. The advantage of it over standard of care could be its wider antibacterial coverage and thus the use of mono-instead of combination therapy.. NeoMero-1, an open label, randomised, comparator controlled, superiority trial aims to compare the efficacy of meropenem with a predefined standard of care (ampicillin + gentamicin or cefotaxime + gentamicin) in the treatment of LOS in neonates and infants aged less than 90 days admitted to a neonatal intensive care unit.A total of 550 subjects will be recruited following a 1:1 randomisation scheme. The trial includes patients with culture confirmed (at least one positive culture from normally sterile site except coagulase negative staphylococci in addition to one clinical or laboratory criterion) or clinical sepsis (at least two laboratory and two clinical criteria suggestive of LOS in subjects with postmenstrual age < 44 weeks or fulfilment of criteria established by the International Pediatric Sepsis Consensus Conference in subjects with postmenstrual age ≥ 44 weeks). Meropenem will be given at a dose of 20 mg/kg q12h or q8h depending on the gestational- and postnatal age. Comparator agents are administered as indicated in British National Formulary for Children. The primary endpoint measured at the test of cure visit (2 days after end of study therapy) is graded to success (all baseline symptoms and laboratory parameters are resolved or improved with no need to continue antibiotics and the baseline microorganisms are eradicated and no new microorganisms are identified and the patient has received allocated treatment for 11 ± 3 days with no modification) or a failure (all remaining cases). Secondary outcome measures include comparison of survival, relapse rates or new infections by Day 28, clinical response at Day 3 and end of therapy, duration of hospitalisation, population pharmacokinetic analysis of meropenem and effect of antibiotics on mucosal colonisation and development of antibacterial resistance.The study will start recruitment in September 2011; the total duration is of 24 months.. EudraCT 2011-001515-31.

Topics: Anti-Bacterial Agents; Clinical Protocols; Humans; Infant; Infant, Newborn; Length of Stay; Meropenem; Sepsis; Thienamycins

To compare the plasma and subcutaneous tissue concentration-time profiles of meropenem administered by intermittent bolus dosing or continuous infusion to critically ill patients with sepsis and without renal dysfunction, and to use population pharmacokinetic modelling and Monte Carlo simulations to assess the cumulative fraction of response (CFR) against Gram-negative pathogens likely to be encountered in critical care units.. We randomized 10 patients with sepsis to receive meropenem by intermittent bolus administration (n = 5; 1 g 8 hourly) or an equal dose administered by continuous infusion (n = 5). Serial subcutaneous tissue concentrations were determined using microdialysis and compared with plasma data for first-dose and steady-state pharmacokinetics. Population pharmacokinetic modelling of plasma data and Monte Carlo simulations were then undertaken with NONMEM.. It was found that continuous infusion maintains higher median trough concentrations, in both plasma (intermittent bolus 0 versus infusion 7 mg/L) and subcutaneous tissue (0 versus 4 mg/L). All simulated intermittent bolus, extended and continuous infusion dosing achieved 100% of pharmacodynamic targets against most Gram-negative pathogens. Superior obtainment of pharmacodynamic targets was achieved using administration by extended or continuous infusion against less susceptible Pseudomonas aeruginosa and Acinetobacter species.. This is the first study to compare the relative concentration-time data of bolus and continuous administration of meropenem at the subcutaneous tissue and plasma levels. We found that the administration of meropenem by continuous infusion maintains higher concentrations in subcutaneous tissue and plasma than by intermittent bolus dosing. Administration by extended or continuous infusion will achieve superior CFR against less-susceptible organisms in patients without renal dysfunction.

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Critical Illness; Female; Humans; Male; Meropenem; Middle Aged; Models, Statistical; Monte Carlo Method; Plasma; Pseudomonas Infections; Sepsis; Subcutaneous Tissue; Thienamycins; Treatment Outcome

Clinical efficacy of Ronem preparation was studied in injured persons, suffering deep burns. High efficacy of the preparation in an acute period of the burn disease was established concerning the reduction in severity of the syndrome of systemic inflammatory answer clinical signs, the infection complications prophylaxis, microbal sensibilization lowering and preservation of natural detoxication systems on subcompensation level.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Burns; Female; Humans; Male; Meropenem; Middle Aged; Sepsis; Thienamycins; Trauma Severity Indices; Treatment Outcome; Young Adult

To evaluate and compare the pharmacokinetic profiles of imipenem and meropenem in a population of critically ill patients with sepsis to find possible differences that may help in selecting the most appropriate drug and/or dosage in order to optimise empiric antimicrobial therapy.. This was a single-centre, randomised, nonblind study of the pharmacokinetics of both intravenous imipenem 1g and meropenem 1g in 20 patients admitted to an intensive care unit with sepsis in whom antimicrobial therapy was indicated on clinical grounds. Patients were divided into two groups: group I received intravenous imipenem 1g plus cilastatin 1g, and group II received intravenous meropenem 1g over 30 minutes. Peripheral blood samples were collected at 0, 0.5 (end of infusion), 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hours after the first dose and were centrifuged for 10 minutes at 4 masculineC. Urine samples were collected during the 8 hours after antimicrobial administration at 2-hour intervals: 0-2, 2-4, 4-6 and 6-8 hours. The total volume of urine was recorded; the serum and urine samples were immediately frozen and stored at -80 masculineC until assayed. Pharmacokinetic analysis was carried out through computerised programs using the least-square regression method and a two-compartment open model. Statistical differences were evaluated by means of one-way ANOVA.. The following pharmacokinetic differences between the two drugs were observed: the imipenem mean peak serum concentration was significantly higher than for meropenem (90.1 +/- 50.9 vs 46.6 +/- 14.6 mg/L, p < 0.01); the area under the serum concentration-time curve was significantly higher for imipenem than for meropenem (216.5 +/- 86.3 vs 99.5 +/- 23.9 mg . h/L, p < 0.01), while the mean volume of distribution and mean total clearance were significantly higher for meropenem than for imipenem (25 +/- 4.1 vs 17.4 +/- 4.5L, p < 0.01 and 191 +/- 52.2 vs 116.4 +/- 42.3 mL/min, p < 0.01, respectively).. The more favourable pharmacokinetic profile of imipenem compared with meropenem in critically ill patients with sepsis might balance the possibly greater potency demonstrated in vitro for meropenem against Gram-negative strains. Hence, the clinical efficacy of the two carbapenems depends mostly on their correct dosage.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Critical Illness; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sepsis; Thienamycins

Melioidosis, an infection due to Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We reviewed our experience with meropenem in the treatment of severe melioidosis in 63 patients over a 6-year period. Outcomes were similar to those of ceftazidime-treated patients (n = 153) despite a deliberate selection bias to more-unwell patients receiving meropenem. The mortality among meropenem-treated patients was 19%. One patient had a possible drug fever associated with the use of meropenem. We conclude that meropenem (1 g or 25 mg/kg every 8 h intravenously for >/=14 days) is an alternative to ceftazidime and imipenem in the treatment of melioidosis. The use of meropenem may be associated with improved outcomes in patients with severe sepsis associated with melioidosis.

Topics: Adolescent; Adult; Aged; Ceftazidime; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Male; Melioidosis; Meropenem; Middle Aged; Prospective Studies; Sepsis; Thienamycins; Treatment Outcome

Prophylactic antibiotics are helpful in decreasing the incidence of septic complications in acute pancreatitis. The aim of this study was to compare the efficacy of meropenem, a new carbapenem antibiotic, with that of imipenem, which is the standard prophylactic treatment in patients with severe acute pancreatitis.. One hundred seventy-six patients with necrotizing pancreatitis were prospectively randomized to prophylactic treatment with 0.5 g meropenem t.i.d. intravenously or 0.5 g imipenem q.i.d. intravenously. The occurrence of infection of pancreatic necrosis, rate of extrapancreatic infections, systemic and local complications, need for surgery, mortality rate, and length of hospitalization were recorded for each group. When a septic complication of pancreatic necrosis was suspected, fine needle aspiration with cultures of the sample was performed. Surgery was performed in cases of verified infected necrosis.. No difference was observed between patients treated with meropenem and those treated with imipenem in terms of incidence of pancreatic infection (11.4% versus 13.6%) and extrapancreatic infections (21.6% versus 23.9%) and clinical outcome. Meropenem is as effective as imipenem in preventing septic complications of patients with severe acute pancreatitis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Pancreatitis, Acute Necrotizing; Prospective Studies; Sepsis; Thienamycins; Time Factors; Treatment Outcome

The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14 critically ill patients with sepsis. Patients with creatinine clearance (CrCl) higher than 50 ml/min received 1 g meropenem three times daily (Group I) and patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily (Group II). Meropenum concentrations in plasma were determined by high performance liquid chromatography with UV detection. The pharmacokinetic parameters differed between the two groups as follows, Group I, maximal concentration 56.3 +/- 19.1 microg/ml; trough concentration 3.3 +/- 2.5 microg/ml; elimination half life 2.5 +/- 1.2 h; clearance (Cl) 155.8 +/- 40.6 ml/min; MRT 2.2 +/- 0.4 h; steady state volume of distribution (V(ss)) 21.7 +/- 5.7 l, and AUC(-8) 119.4 +/- 32.6 microg/ml h. Group II, maximal concentration 71.1 +/- 5.1 microg/ml; trough concentration 3.4 +/- 1.8 microg/ml; elimination half life 3.9 +/- 1.6 h; Cl 77.7 +/- 15.8 ml/min; MRT 3.5 +/- 0.6 h; V(ss), 17.1 +/- 2.1 l, and AUC(0-12) 230.2 +/- 43.3 microg/ml h. The most frequently isolated bacteria from blood and wound infections were Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli; their meropenem minimal inhibitory concentrations (MICs) ranged from 0.064 to 3.0 mg/l. In most cases the pharmacodynamic parameters, measured as T>MIC index, were higher than 75%. In both groups, patients with susceptible pathogens (MIC<1 mg/l) had meropenem plasma levels which exceeded the MIC for the whole dosing interval. When pathogens were highly resistant (A. baumanii or P. aeruginosa) the T>MIC indices were lower.

Topics: Aged; Creatinine; Critical Illness; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sepsis; Thienamycins

The efficacy and safety profile of meropenem were analyzed according to data collected from hospitalized pediatric patients aged 4 days to 20 years who had serious bacterial infections and were treated in a major teaching hospital in Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and 53 for safety. The satisfactory clinical response rate was 57% in lower respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract infection, osteomyelitis, and central nervous system infection, 83% in skin and soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%) patients experienced adverse events related to meropenem. The most commonly observed adverse reactions were elevated hepatic enzymes (7.5%), increased alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem-related seizure, withdrawal, or death. The results of this study suggested that meropenem is well tolerated even in young infants, and is effective in treating serious childhood bacterial infection. However, this study also identified a proportion of hospitalized pediatric patients with isolates that were resistant to meropenem. The trends in meropenem resistance among nosocomially acquired bacteria should be monitored closely.

Topics: Adult; Bacterial Infections; Child; Drug Evaluation; Female; Humans; Infant, Newborn; Male; Meropenem; Prospective Studies; Respiratory Tract Infections; Sepsis; Thienamycins; Treatment Outcome

Topics: Abdomen; Acute Disease; Adult; APACHE; Female; Humans; Male; Meropenem; Middle Aged; Peritonitis; Sepsis; Surgical Procedures, Operative; Thienamycins; Time Factors

Meropenem and imipenem are beta-lactam antibiotics of the carbapenem group. Carbapenems have bactericidal activity against a broad spectrum of bacteria, including most gram-positive cocci, gram-negative bacilli and anaerobes. Experience in using meropenem in Chinese patients has not been previously reported.. Meropenem (2 g daily) and imipenem/cilastatin (2 g daily) were compared in an open, randomized, prospective study on the treatment of hospitalized Chinese septic patients. All participants (male or female) were hospitalized with a diagnosis of sepsis. All patients were randomly allocated to one of the two treatment groups: the meropenem group or the imipenem/cilastatin group. Clinical status was evaluated daily during treatment and at the end of therapy or when treatment was withdrawn. Patients were checked every day for potential side-effects, according to subjective and objective symptoms.. Fifty-three patients were enrolled in the study; 50 were evaluated for clinical efficacy and 27 patients were evaluated for bacteriologic efficacy. The most frequent clinical diagnoses were pneumonia and urinary tract infection. The predominant pathogens were Pseudomonas aeruginosa, Escherichia coli and Enterobacter cloacae. There were 31 pathogens isolated from 27 patients. A single pathogen was identified in 23 patients, and two pathogens were isolated from four patients. Satisfactory clinical outcome (excellent and good) was 84% in the meropenem group and 76% in the imipenem/cilastatin group. Satisfactory bacteriologic response was 80% in the meropenem group and 75% in the imipenem/cilastatin group. Transiently elevated liver enzymes were the most common side-effect. One patient treated with imipenem/cilastatin experienced a seizure during the study, while another patient treated with meropenem withdrew due to urticaria.. The efficacy and safety data presented in this report indicate that meropenem was well tolerated and appeared to be as effective as standard monotherapy with imipenem in bacteremic patients. Meropenem and imipenem/cilastatin were highly effective for the treatment of bacteremia in Chinese patients and only mild or negligible side-effects were noted.

Topics: Adult; Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Sepsis; Thienamycins

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Critical Illness; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Middle Aged; Pneumonia; Sepsis; Thienamycins

Meropenem was used in the treatment of 15 newborns (8 preterm) with sepsis, pneumonia or meningitis by intravenous infusion of 15-20 mg/kg daily divided to 3 equal doses. Clinical improvement was achieved in all the cases. No side effects were recorded.

Topics: Bacterial Infections; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Infant, Premature, Diseases; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Sepsis; Thienamycins

In a multicenter, randomized, open comparison of meropenem to ceftazidime as empiric treatment of severe acute infections, 185 children (1 mo-15 years old, mean 65.4 mo) were enrolled. Meropenem (20 mg/kg t.i.d. i.v.) was given to 98 and ceftazidime (10-30 mg/kg t.i.d. i.v.) to 87 children, generally for 5 to 10 days (mean: 6.9 for meropenem and 7.5 for ceftazidime). Clinical response was evaluated at the beginning and at the end of therapy and 4 weeks later (follow-up). Clinical response was deemed satisfactory at the end of therapy in 96.7% of the patients treated with meropenem and in 95.3% of those who received ceftazidime without any statistically significant difference. One relapse occurred in a meropenem-treated patient at the follow-up clinical assessment. The baseline infecting organism was eradicated or presumed eradicated at the end of therapy in 14/16 patients treated with meropenem and in 14/15 treated with ceftazidime. The incidence of drug-related adverse events (mostly a slight increase in liver enzymes) was 9.2% in the meropenem group and 4.6% in the ceftazidime group. Our data show that meropenem is as effective as ceftazidime in the empiric treatment of severe infections in infants and children.

Topics: Adolescent; Bacterial Infections; Ceftazidime; Cephalosporins; Child; Child, Preschool; Drug Monitoring; Hospitalization; Humans; Infant; Infant, Newborn; Liver; Meropenem; Respiratory Tract Infections; Sepsis; Skin Diseases, Infectious; Thienamycins; Treatment Outcome; Urinary Tract Infections

A multicentre, open, randomised, parallel group study was carried out to assess the efficacy and safety of meropenem monotherapy versus the combination of ceftazidime plus amikacin in the treatment of serious bacterial infections. Adult, hospitalised patients (n = 237) were included if they had infections at one or more of the following sites: lower respiratory tract (89 community-acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated), skin and skin structures (n = 8), or septicaemia (n = 29). Patients were randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43, 93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs 23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in each treatment group experienced adverse events, the most frequent being transient elevations in serum transaminases. Seven patients in the meropenem group and eight patients in the ceftazidime plus amikacin group died during the study period from reasons unrelated to study medication, and seven patients (five meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events. Empirical monotherapy with meropenem is as well tolerated and as effective as the combination of ceftazidime plus amikacin in the treatment of serious infections.

Topics: Adolescent; Adult; Aged; Amikacin; Bacterial Infections; Carbapenems; Ceftazidime; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Drug Tolerance; Hospitalization; Humans; Meropenem; Middle Aged; Respiratory Tract Infections; Sepsis; Thienamycins; Time Factors; Treatment Outcome; Urinary Tract Infections

Meropenem is a new broad spectrum carbapenem antibiotic which can be administered as monotherapy for serious infections. The efficacy and safety of meropenem was compared with that of ceftazidime (alone or in combination with amikacin) in 153 patients with septicaemia who were enrolled into identical, prospective, randomised studies. Forty-five patients with infections arising from the urinary or lower respiratory tracts were given either meropenem 500 mg or ceftazidime 250-1000 mg intravenously every 8 h; 108 patients with more serious infections were given meropenem 1 g or ceftazidime 2 g every 8 h +/- amikacin 15 mg/kg/day. Overall, 71 patients received meropenem, 47 ceftazidime and 35 ceftazidime plus amikacin. Comparable clinical response rates were achieved in the meropenem and ceftazidime/amikacin groups (92% vs 94% at the end of therapy respectively). Furthermore, a satisfactory bacteriological response was obtained in all evaluable patients. The most common pathogens isolated were Escherichia coli, Streptococcus pneumoniae and Pseudomonas aeruginosa. Relapse occurred in one patient in the ceftazidime/amikacin group, who had a mixed infection of E. coli and P. aeruginosa. There were no relapses in the meropenem group. Both treatments were well tolerated and only one patient had to withdraw from the trial because of an adverse effect (rash associated with ceftazidime). In conclusion, these data confirm that meropenem monotherapy is well tolerated and is as effective as ceftazidime (alone or combined with amikacin) in the empirical treatment of septicaemia. It should prove to be a useful addition to the drugs currently available for this life-threatening disease.

Topics: Adult; Aged; Amikacin; Carbapenems; Ceftazidime; Drug Therapy, Combination; Drug Tolerance; Hospitalization; Humans; Meropenem; Middle Aged; Sepsis; Thienamycins; Treatment Outcome

Treatment of neonatal peritonitis and sepsis is challenging. Following infection, neutrophils elaborate neutrophil extracellular traps (NETs)-extracellular lattices of decondensed chromatin decorated with antimicrobial proteins. NETs, however, can augment pathogenic inflammation causing collateral damage. We hypothesized that NET inhibition would improve survival in experimental neonatal infectious peritonitis.. We induced peritonitis in 7 to 10-day-old mice by intraperitoneal injection with cecal slurry. We targeted NETs by treating mice with neonatal NET-Inhibitory Factor (nNIF), an endogenous NET-inhibitor; Cl-amidine, a PAD4 inhibitor; DNase I, a NET degrading enzyme, or meropenem (an antibiotic). We determined peritoneal NET and cytokine levels and circulating platelet-neutrophil aggregates. Survival from peritonitis was followed for 6 days.. nNIF, Cl-amidine, and DNase I decreased peritoneal NET formation and inflammatory cytokine levels at 24 h compared to controls. nNIF, Cl-amidine, and DNase I decreased circulating platelet-neutrophil aggregates, and NET-targeting treatments significantly increased survival from infectious peritonitis compared to controls. Finally, nNIF administration significantly improved survival in mice treated with sub-optimal doses of meropenem even when treatment was delayed until 2 h after peritonitis induction.. NET inhibition improves survival in experimental neonatal infectious peritonitis, suggesting that NETs participate pathogenically in neonatal peritonitis and sepsis.. 1. Neutrophil extracellular trap formation participates pathogenically in experimental neonatal infectious peritonitis. 2. NET-targeting strategies improve outcomes in a translational model of neonatal infectious peritonitis. 3. NET inhibition represents a potential target for drug development in neonatal sepsis and infectious peritonitis.

Topics: Animals; Animals, Newborn; Cytokines; Deoxyribonuclease I; Extracellular Traps; Meropenem; Mice; Mice, Inbred C57BL; Neutrophils; Peritonitis; Sepsis

Creatinine clearance (CCr) and pharmacokinetic parameters are markedly affected by pathophysiological changes in patients with sepsis. However, only a few reports have assessed renal function in patients with sepsis using the measured CCr. Furthermore, the administration regimen has not been sufficiently evaluated using a population PK (PPK) model across renal function broad ranges. Therefore, this study was performed to construct a meropenem PPK model for patients with sepsis using the measured CCr and evaluate the optimized meropenem dosing regimen based on the CCr.. Patients with sepsis who received intravenous meropenem at the Showa University Hospital were enrolled in this prospective observational study. The PPK model was constructed using blood samples and clinical information of patients. The probability of target attainment (PTA) indicates the likelihood of achieving 50% time above the minimum inhibitory concentration (% T > MIC) based on 10,000 virtual patients using Monte Carlo simulations. The PTA for each meropenem regimen was 50% T > MIC based on different renal functions using the Monte Carlo simulation.. One hundred samples were collected from 31 patients. The final PPK model incorporating the measured CCr as a covariate in CL displayed the best fit. The recommended dosing regimen to achieve a PTA of 50% T > MIC of 4 mcg/mL was 1 g every 8 hours as a 3-hour prolonged infusion for patients with CCr 85-130 mL/min and 1 g every 8 hours as an 8-hour continuous infusion for patients with CCr ≥ 130 mL/min.. This model precisely predicted meropenem concentrations in patients with sepsis by accurately evaluating renal function using the measured CCr. Extended dosing was demonstrated to be necessary to achieve a PTA of 50% T > MIC for patients with CCr ≥ 85 mL/min. Meropenem effectiveness can be maximized in patients with sepsis by selecting the appropriate dosing regimen based on renal function and the MIC.

Topics: Anti-Bacterial Agents; Creatinine; Critical Illness; Humans; Meropenem; Microbial Sensitivity Tests; Sepsis; Thienamycins

The investigation on antibiotic stewardship in neonatal intensive care unit in China is scarce. This study aimed to analyze the effect of a comprehensive 2-year antibiotic stewardship in a level 4 NICU. During this baseline period from October 1st 2017 to October 1st 2019, continuation of empirical antibiotic therapy for ruled-out sepsis courses was beyond 72 h and for pneumonia was more than 7 days. Meropenem or vancomycin was used even if they were not the only bacterial sensitive antibiotics. The intervention period was from October 2nd 2019 to August 23rd 2021. Three areas for quality improvement were targeted in our center: discontinuation of antibiotic use in ruled-out sepsis within 72 h, treatment duration for culture-negative pneumonia less than 7 days, and vancomycin or meropenem was not used unless the cultured bacteria was only susceptible to them. The total antibiotic consumption decreased from 791.1 to 466.3 days of therapy per 1000 patient days from baseline to intervention period. Antibiotics were stopped within 72 h for 47.48% patients with rule-out sepsis and within 7 days for 75.70% patients with pneumonia compared with 11.56% and 37.69% during the baseline period respectively. The prevalence of multi-drug resistance bacteria decreased from 67.20 to 48.90%. The total use rate of meropenem or vancomycin decreased from 7.6 to 1.8%. Our quality improvement approach on antibiotic strategy significantly reduced antibiotic use and prevalence of multi-drug resistance bacteria in our NICU.

Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Meropenem; Sepsis; Vancomycin

Critically ill patients with sepsis are predisposed to physiological changes that can reduce the probability of achieving target antibiotic exposures. Precision dosing software programs may be used to improve probability of obtaining these target exposures.. To quantify the accuracy of a precision dosing software program for predicting antibiotic concentrations as well as to assess the impact of using software predictions on actual dosing adjustments.. The software program ID-ODS was used to predict concentrations for piperacillin, meropenem and vancomycin using patient covariate data with and without the use of therapeutic drug monitoring (TDM) data. The impact of these predictions on actual dosage adjustments was determined by using software predicted concentrations versus measured concentrations.. Software predictions for piperacillin and meropenem exhibited large bias that improved with the addition of TDM data (bias improved from -28.8 to -2.0 mg/L for piperacillin and -3.0 to -0.1 mg/L for meropenem). Dosing changes using predicted concentrations of piperacillin and meropenem with TDM data versus measured concentrations were matched on 89.2% (107/120) and 71% (9/69) occasions, respectively. Although vancomycin predictions demonstrated good accuracy with and without TDM, these findings were limited by our small sample size.. These data demonstrate that precision dosing software programs may have scope to reasonably predict antibiotic concentrations in critically ill patients with sepsis. The addition of TDM data improves the predictive performance of the software for all three antibiotics and the ability to anticipate the correct dose change required.

Topics: Anti-Bacterial Agents; Critical Illness; Drug Monitoring; Humans; Meropenem; Piperacillin; Sepsis; Software; Vancomycin

Topics: Anti-Bacterial Agents; Child, Preschool; Clostridium symbiosum; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Male; Meropenem; Sepsis; Sulbactam

To evaluate the association between early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI).. Early and cumulative achievement of fT

Topics: Adult; Anti-Bacterial Agents; beta-Lactams; Critical Illness; Humans; Meropenem; Microbial Sensitivity Tests; Middle Aged; Piperacillin, Tazobactam Drug Combination; Sepsis

This paper is to explore the composition and antibiotic resistance of pathogens isolated from blood cultures of patients with bloodstream infection (BSI) in the intensive care unit (ICU).. A retrospective study has been performed to identify the pathogens isolated from blood cultures of 147 patients with BSI in the ICU of our Hospital over 12 years (January 2008 to December 2019). The antibiotic resistance and susceptibility of the isolates were tested.. Among the 152 pathogens isolated from positive blood cultures, 61.84% were Gram-positive bacteria, 34.87% were Gram-negative bacteria, and 3.29% were fungi. The most frequently isolated pathogens were coagulase-negative Staphylococci, Staphylococcus aureus, and Escherichia coli. The pathogen distributions remained stable over 12 years. Gram-positive cocci were highly susceptible to vancomycin, linezolid, and teicoplanin. Extended-spectrum β-lactamase-producing pathogens were highly susceptible to amikacin, imipenem, meropenem, and polymyxin B. Acinetobacter were relatively sensitive to amikacin, trimethoprim-sulfamethoxazole, and polymyxin, whereas Pseudomonas aeruginosa were sensitive to amikacin, gentamicin, levofloxacin, imipenem, meropenem, and ciprofloxacin, with resistance rates less than 30%.. Gram-positive bacteria were the dominant pathogens isolated from blood cultures of ICU-BSI patients and were susceptible to vancomycin, linezolid, and teicoplanin. The antibiotic susceptibility of Gram-negative bacteria varies greatly. Our results provide important information to guide the treatment decisions in the management of ICU-BSIs.

Topics: Amikacin; Anti-Bacterial Agents; Blood Culture; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Intensive Care Units; Linezolid; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Sepsis; Teicoplanin; Tertiary Care Centers; Vancomycin

Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L.. This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours.. Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016).. Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases.. We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis.. A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

Topics: Bayes Theorem; Communicable Diseases; Female; Humans; Infant, Newborn; Klebsiella pneumoniae; Meropenem; Neonatal Sepsis; Perinatal Death; Pregnancy; Sepsis; South Africa; Vaccines

To demonstrate the feasibility of continuous infusion of meropenem-vaborbactam to optimize the treatment of carbapenem-resistant Enterobacterales.. Report of a case of a Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection comfirmed by whole genome sequencing and therapeutic drug monitoring (TDM) of meropenem.. A patient with augmented renal clearance (ARC) went into septic shock caused by an ST11 KPC-3-producing K. pneumoniae bloodstream infection that was successfully treated with a continuous infusion of meropenem-vaborbactam at a dosage of 1 g/1 g q4h as a 4-h infusion. TDM confirmed sustained concentrations of meropenem ranging from 8 to 16 mg/L throughout the dosing interval.. Continuous infusion of meropenem-vaborbactam was feasible. It could be appropriate for optimizing the management of critically ill patients with ARC, as it resulted in antibiotic concentrations above the minimum inhibitory concentration for susceptible carbapenem-resistant Enterobacterales (up to 8 mg/L) throughout the dosing interval.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Critical Illness; Drug Combinations; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Sepsis

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

Sepsis is the major cause of mortality across intensive care units globally, yet details of accompanying pathological molecular events remain unclear. This knowledge gap has resulted in ineffective biomarker development and suboptimal treatment regimens to prevent and manage organ dysfunction/damage. Here, we used pharmacoproteomics to score time-dependent treatment impact in a murine Escherichia coli sepsis model after administering beta-lactam antibiotic meropenem (Mem) and/or the immunomodulatory glucocorticoid methylprednisolone (Gcc). Three distinct proteome response patterns were identified, which depended on the underlying proteotype for each organ. Gcc enhanced some positive proteome responses of Mem, including superior reduction of the inflammatory response in kidneys and partial restoration of sepsis-induced metabolic dysfunction. Mem introduced sepsis-independent perturbations in the mitochondrial proteome that Gcc counteracted. We provide a strategy for the quantitative and organotypic assessment of treatment effects of candidate therapies in relationship to dosing, timing, and potential synergistic intervention combinations during sepsis.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Gram-Negative Bacterial Infections; Meropenem; Mice; Proteome; Sepsis

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the β-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate β-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed.

Topics: Anti-Bacterial Agents; Bacteremia; Cohort Studies; Hematologic Neoplasms; Humans; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sepsis

This study aimed to investigate the clinical characteristics, management and prognosis of Bacillus cereus sepsis in premature neonates. The clinical information of 8 premature neonates with B cereus sepsis who were treated in Shanghai Children Hospital from January 2015 to December 2019 was retrospectively collected from the medical records and analyzed. The neurodevelopment related conditions were collected at follow up visits at corrected age of 6 months and 12 months. Five patients developed meningitis, and cerebral magnetic resonance image showed abnormal in 5 patients. After treatment with meropenem and vancomycin, 1 patient died, and 7 patients survived and were smoothly discharged. At follow up visits, 1 patient was diagnosed with hydrocephalus and showed severely delayed neurodevelopment, 2 patients had mild delayed neurodevelopment, and the neurodevelopment was basically normal in remaining 4 patients. B cereus infection can cause severe complications of central nervous system, and affect neurodevelopmental outcome. Antibiotic treatment with meropenem and vancomycin is proven to be effective. Refreshing the central catheters is helpful for the prevention of B cereus sepsis and cerebral magnetic resonance image may be employed for the prognosis assessment.

Topics: Bacillus cereus; Child; China; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meropenem; Prognosis; Retrospective Studies; Sepsis; Vancomycin

Topics: Anti-Bacterial Agents; Escherichia coli; Humans; Meropenem; Pseudomonas aeruginosa; Sepsis

Topics: Anti-Bacterial Agents; Critical Illness; Humans; Meropenem; Sepsis

Topics: Anti-Bacterial Agents; Critical Illness; Humans; Meropenem; Sepsis

Bloodstream infection (BSI) caused by carbapenem-resistant P. aeruginosa (CRPA) has high mortality in hematopoietic stem cell transplant (HSCT) recipients. We performed MIC, checkerboard, time-kill assay, PFGE, PCR, and whole genome sequence and described the clinical outcome through Epi Info comparing the antimicrobial combination in vitro. Mortality was higher in BSI caused by CRPA carrying the lasB virulence gene. The isolates were 97% resistant to meropenem displaying synergistic effect to 57% in combination with colistin. Seventy-three percent of the isolates harbored bla

Topics: Adolescent; Adult; Anti-Bacterial Agents; Brazil; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Young Adult

We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient β-lactam concentrations.. In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold.. Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient β-lactam concentrations.. Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient β-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration.. NCT02820987.

Topics: Anti-Bacterial Agents; beta-Lactams; Critical Illness; Humans; Meropenem; Piperacillin; Prospective Studies; Sepsis

sepsis is defined as a systemic inflammatory host response syndrome (SIRS) to infection, commonly bacterial. The global prevalence of sepsis is 8.2% with a mortality rate of 25%, whilst in Tanzania the prevalence is 6.6%. Treatment of sepsis involves early initiation of antibiotics based on local sensitivity patterns. However, there is an increase in antimicrobial resistance to commonly used antibiotics. Hence to promote rational use of antibiotics, we aimed at establishing the etiology, local susceptibility patterns and outcome of children with sepsis aged 2 months to 15 years, admitted at Muhimbili National Hospital (MNH), Dar es Salaam.. a hospital based prospective cross sectional study was conducted among 245 participants who were consecutively recruited. A standardized structured questionnaire was used to collect information. Blood cultures and complete blood counts were done. Antimicrobial susceptibility was also done on positive cultures using disc diffusion method. Data were analyzed using SPSS version 20. Frequencies and proportions were used to summarize categorical data, whilst median and interquartile range was used to summarize continuous data. Student T test was used to compare means of data which were normally distributed and the differences in proportions were tested using Chi square test or Fisher's exact test. A p value of = 0.05 was considered to be statistically significant.. there was predominance of male participants (67.5%) with a median age was 2 years and an interquartile range (IQR) 10 months to 4 years. Culture positive sepsis was detected among 29.8% of the participants, and the common Gram-positive bacterial isolates were S. aureus (39.7%) Coagulase Negative Staphylococcus (CoNS) (35.6%) and Gram-negative isolates were E. coli (12.3%), Klebsiella spp (6.8%) and Pseudomonas aeruginosa (5.5%). All bacteria showed a high resistance to ampicillin (80%- 100%) followed by ceftriaxone (40 - 70%). All Pseudomonas aeruginosawere 100% resistant to ampicillin, gentamycin and ceftriaxone but were sensitive to amikacin. There was less than 40% resistance to co-amoxiclav, meropenem, ciprofloxacin, amikacin, and clindamycin. The overall case mortality rate from sepsis was 9.4%. Among children discharged 59.3% had prolonged hospital stay of more than 7 days. Age group 1 to 5 years, prior use of antibiotics, tachycardia, and leukocytosis were significantly associated with high mortality.. bacterial sepsis is prevalent at Muhimbili National Hospital contributing to 9.4% of mortality and a prolonged hospital stay of more than 7 days among 59.3% of the participants. Gram-positive bacteria were found to be predominant cause of sepsis, whereas both Gram-positive and Gram-negative bacteria had a high resistance to first and second line antimicrobials including: ampicillin, gentamycin, and ceftriaxone.

Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Child, Preschool; Ciprofloxacin; Clindamycin; Coagulase; Cross-Sectional Studies; Escherichia coli; Female; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitals; Humans; Infant; Male; Meropenem; Microbial Sensitivity Tests; Prospective Studies; Sepsis; Staphylococcus aureus; Tanzania

This experiment was carried out to provide a basis for the treatment of clinical bloodstream infections by analyzing the drug resistance characteristics and integrated gene distribution of Escherichia coli in bloodstream infections in elderly patients. For this aim, E. coli were collected for bacterial identification and drug sensitivity testing from bloodstream infections in elderly patients in the hospital from January 2016 to December 2019. ESBLs positive strains were assayed for genotypes and their integron carriage rates by PCR amplification. The characteristics and differences of various genotype rates were compared and analyzed. Results showed that a total of 230 E. coli strains were isolated. The detection rate of ESBLs-producing bacteria was 37.39 %. ESBLs-producing E. coli showed a high rate of resistance to cefepime, levofloxacin, cotrimoxazole, and ticarcillin/clavulanic acid (>40%). The resistance rate of 230 strains of E. coli to meropenem, minocycline, amikacin, gentamicin and cefoxitin was less than 20%. Among the ESBLs-producing E. coli in bloodstream infections in elderly patients, CTX-M-9 accounted for 27.91%, CTX-M-2 for 17.44%, and SHV for 13.95%. The detection rate of type I integrated genes was 41.30%, and type II and III integrated genes were not detected. ESBLs-producing genotyping-positive bacteria were detected with more than 50% of type I integrated genes. It was concluded that type I integrated genes in ESBLs-producing E. coli isolated from elderly patients carried resistance genes such as CTX-M-9 and CTX-M-2 aggravating multi-drug resistance in bacteria.

Topics: Aged; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefoxitin; Clavulanic Acid; Drug Resistance; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Integrons; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Sepsis; Ticarcillin; Trimethoprim, Sulfamethoxazole Drug Combination

To characterize one OXA-232-producing. Minimum inhibitory concentrations (MICs) were measured. Early detection of CRKP strains carrying chromosomal

Topics: Amikacin; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Chromosomes; Ciprofloxacin; DNA Transposable Elements; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Plasmids; Sepsis; Virulence; Virulence Factors; Whole Genome Sequencing

Neutrophil extracellular traps (NETs) clear pathogens but may contribute Q8 pathogenically to host inflammatory tissue damage during sepsis. Innovative therapeutic agents targeting NET formation and their potentially harmful collateral effects remain understudied.. We investigated a novel therapeutic agent, neonatal NET-Inhibitory Factor (nNIF), in a mouse model of experimental sepsis - cecal ligation and puncture (CLP). We administered 2 doses of nNIF (1 mg/ kg) or its scrambled peptide control intravenously 4 and 10 hours after CLP treatment and assessed survival, peritoneal fluid and plasma NET formation using the MPO-DNA ELISA, aerobic bacterial colony forming units (CFU) using serial dilution and culture, peritoneal fluid and stool microbiomes using 16S rRNA gene sequencing, and inflammatory cytokine levels using a multiplexed cytokine array. Meropenem (25 mg/kg) treatment served as a clinically relevant treatment for infection.. We observed increased 6-day survival rates in nNIF (73%) and meropenem (80%) treated mice compared to controls (0%). nNIF decreased NET formation compared to controls, while meropenem did not impact NET formation. nNIF treatment led to increased peritoneal fluid and plasma bacterial CFUs consistent with loss of NET-mediated extracellular microbial killing, while nNIF treatment alone did not alter the peritoneal fluid and stool microbiomes compared to vehicle-treated CLP mice. nNIF treatment also decreased peritoneal TNF-a inflammatory cytokine levels compared to scrambled peptide control. Furthermore, adjunctive nNIF increased survival in a model of sub-optimal meropenem treatment (90% v 40%) in CLP-treated mice.. Thus, our data demonstrate that nNIF inhibits NET formation in a translationally relevant mouse model of sepsis, improves survival when given as monotherapy or as an adjuvant with antibiotics, and may play an important protective role in sepsis.

Topics: Animals; Cytokines; Extracellular Traps; Meropenem; Mice; Neutrophils; Punctures; Receptor Protein-Tyrosine Kinases; RNA, Ribosomal, 16S; Sepsis

Increasing antibiotic resistance to WHO-recommended first- and second-line treatments of pediatric sepsis requires adaptation of prescribing guidelines. We discuss the potential and limitations of a weighted-incidence syndromic combination antibiogram (WISCA) as a practical tool for incorporating local microbiology data when assessing empiric coverage of commonly used antibiotics.. A brief questionnaire of 18 clinically significant isolates from pediatric blood cultures (Jan-Dec 2018) was sent to a global network of pediatric hospitals in July 2019. Weighted coverage estimates of non-antipseudomonal third-generation cephalosporins (3GC) and meropenem were estimated using Monte-Carlo simulation for each site reporting >100 isolates.. 52 hospitals in 23 countries in 5 WHO regions responded to the questionnaire; 13 sites met the sample size requirement. The most common isolates were. A WISCA is a data-driven, clinically intuitive tool that can be used to compare empiric antibiotic regimens for pediatric sepsis using existing large datasets. The estimates can be further refined using more complex meta-analytical methods and patient characteristics.

Topics: Anti-Bacterial Agents; Child; Escherichia coli; Humans; Incidence; Meropenem; Microbial Sensitivity Tests; Sepsis; Staphylococcus aureus

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

Meropenem, a broad-spectrum carbapenem, is frequently used to treat severe bacterial infections in critically ill children. Recommendations for meropenem doses in adult infections are available; however, few studies have been published regarding the use of meropenem in children with sepsis, especially in those receiving continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). We aimed to investigate the pharmacokinetic (PK) parameters of meropenem in children with sepsis receiving extracorporeal life support (ECLS).. This was a prospective observational clinical study of children with sepsis receiving ECMO or CRRT in the paediatric intensive care unit (PICU) of a children's hospital. The enrolled children received 20 mg/kg meropenem infusion over 1 hour, every 8 hours, and were grouped into children receiving ECMO, children receiving CRRT and children receiving neither ECMO nor CRRT. Plasma meropenem concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The key PK parameters were determined using the non-compartmental approach.. Twenty-seven patients were finally enrolled. The eCLCR of the CRRT group was lower than that of the ECMO group. The values of elimination half-life (t. No significant alterations in the PK parameters of meropenem occurred in children with sepsis administered ECMO and/or CRRT. Further investigations including PK modelling could provide evidence for appropriate meropenem dosing regimens during ECLS administration.

Topics: Anti-Bacterial Agents; Area Under Curve; Child; Child, Preschool; Creatinine; Critical Illness; Extracorporeal Membrane Oxygenation; Female; Half-Life; Humans; Infant; Male; Meropenem; Metabolic Clearance Rate; Prospective Studies; Sepsis

Topics: Administration, Intravenous; Animals; Anti-Bacterial Agents; Chromatography, Liquid; Drug Monitoring; Linear Models; Male; Meropenem; Microdialysis; Parenteral Nutrition, Total; Rabbits; Reproducibility of Results; Sensitivity and Specificity; Sepsis; Tandem Mass Spectrometry

To describe the population pharmacokinetics (PK) and probability of target attainment (PTA) of continuous infusion (CI) of meropenem in septic patients receiving renal replacement therapy (RRT).. Fifteen patients without RRT, 13 patients receiving sustained low-efficiency dialysis and 12 patients receiving continuous veno-venous haemodialysis were included. Population PK analysis with Monte Carlo simulations for different dosing regimens was performed. For minimum inhibitory concentration 2 mg/L was chosen. The target was set as 50% time ≥4× minimum inhibitory concentration.. The PK of meropenem was best described by a 1-compartment model with linear elimination. Serum creatinine, residual diuresis and time on RRT, with no difference between sustained low-efficiency dialysis and continuous veno-venous haemodialysis, were found to be significant covariates affecting clearance, explaining >20% of the clearance between subject variability. PTA analysis showed that in patients with RRT, 2 g/24 h, meropenem CI achieved a PTA of 95%. In patients without RRT, the target was achieved with 3 g/24 h CI or prolonged infusion of 1 g meropenem over 8 hours but not with bolus application of 1 g meropenem for 8 hours. Only 2 patients (both without RRT) had meropenem concentrations below the target level. However, approximately half of the patients with RRT receiving CI 3 g/24 h meropenem had toxic concentrations.. We found relevant PK variability for meropenem CI in septic patients with or without RRT, leading to a substantial risk for overdosing in patients with RRT. This finding highlights the strong demand for personalized dosing in critically ill patients.

Topics: Anti-Bacterial Agents; Continuous Renal Replacement Therapy; Humans; Hybrid Renal Replacement Therapy; Meropenem; Probability; Renal Replacement Therapy; Sepsis

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

Some strains of Bacteroides fragilis species are associated with diarrhea as a result of enterotoxin production (bft or fragilysin). Fragilysin is activated by C11 protease (fpn) and together with C10 protease (bfp) play a significant role in its invasiveness. The objectives of this study were to investigate the proportion of clinical isolates from extra-intestinal sources that are toxin producers and characterize the genes mediating toxin production. Clinical isolates submitted to our reference laboratory over the last 13 years were screened for toxin production using PCR technique. All stool isolates were excluded. The isolates were tested for their susceptibility to 8 antimicrobial agents by E test. Carbapenem resistance gene cfiA was detected by PCR.. A total of 421 B. fragilis isolates were viable. Out of these, bft was detected in 210 (49.9%) isolates. Of the 210 bft-positive isolates, 171 (81.4%), 33 (15.7%) and 6 (2.8%) harbored bft-1, bft-2, and bft-3 genes, respectively. Twenty (9.5%) of the bft-positive strains originated from bloodstream infections. Twenty-five, 20 and 9 strains harbored bfp-1, bfp-2 and bfp-3 gene, respectively. Two, 3, 4 bfp isotypes were detected simultaneously in some of strains. The resistance rates against amoxicillin-clavulanic acid was 32%, clindamycin 62%, cefoxitin 26%, imipenem 11%, meropenem 17%, metronidazole 4%, piperacillin 61% and tigecycline 14%. A chromosomally located cfiA gene that encode metallo-β-lactamase was identified in only 34 isolates (16.2%).. The prevalence of enterotoxin-producing B. fragilis was high among the extra-intestinal isolates. Metronidazole was the most active agent against all isolates. There was no statistically significance difference between resistance rates among bft-positive and bft-negative isolates except for clindamycin.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Toxins; Bacteroides fragilis; Bacteroides Infections; Cefoxitin; Clindamycin; Drug Resistance, Bacterial; Feces; Female; Humans; Imipenem; Kuwait; Male; Meropenem; Metronidazole; Microbial Sensitivity Tests; Piperacillin; Prevalence; Prospective Studies; Respiratory Tract Infections; Sepsis; Tigecycline; Wound Infection

The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD).. The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD.. The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97-134 points) and 19.5 points (IQR 18-21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined.. The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Anticoagulants; Chromatography, High Pressure Liquid; Citric Acid; Cohort Studies; Continuous Renal Replacement Therapy; Critical Illness; Female; Humans; Male; Meropenem; Middle Aged; Prospective Studies; Sepsis; Tandem Mass Spectrometry

Listeria monocytogenes is a foodborne pathogen which causes life-threatening septicemia and meningoencephalitis. Defective cell-mediated immunity is a well-known risk factor of human listeriosis. We herein present a case of 64-year-old Japanese woman with relapsed and refractory follicular lymphoma (FL). Salvage chemoimmunotherapy with cyclophosphamide, vincristine, prednisolone, and obinutuzumab was followed by obinutuzumab maintenance therapy, when a follow-up computed tomography scan revealed recurrent lymphadenopathy. One month later, the patient presented with fever and headache. L. monocytogenes was recovered from an anaerobic blood culture. Cerebrospinal fluid analysis confirmed the presence of meningoencephalitis. The invasive listeriosis was successfully treated with meropenem for three weeks. There were several predisposing factors of invasive listeriosis in our case. Cell-mediated immunity was severely impaired by prior cytotoxic chemotherapy and low-dose prednisolone. Use of a proton pump inhibitor facilitated entry of the microorganism into the host. Under these circumstances, patients with relapsed and refractory FL are susceptible to invasive listeriosis even if they avoid high-level contaminated food products. Of note, physical examination at initial presentation detected periorbital vesiculopustular eruptions with surrounding erythema. Cutaneous listeriosis is a rare but recurrent manifestation which might be occasionally overlooked. Skin eruptions should be carefully examined for early diagnosis.

Topics: Anti-Bacterial Agents; Female; Humans; Listeria monocytogenes; Listeriosis; Lymphoma, Follicular; Meningoencephalitis; Meropenem; Middle Aged; Sepsis

Beta-lactam anti-infective levels after standard dosing have been shown to be subtherapeutic when renal clearance is augmented.. To determine if piperacillin and meropenem are found to be in their therapeutic range in infected critically ill patients when administered by continuous intravenous infusion (CII) assisted by a therapeutic drug monitoring (TDM) report issued by the pharmacy service.. This prospective non-controlled intervention study evaluated septic patients in an intensive care unit. Patients received a loading dose of meropenem or piperacillin-tazobactam and the antibiotics were afterwards administered by CII. Blood concentrations were determined by high-performance liquid chromatography assays. The adequacy of β-lactam therapy in the cohort subjected to intervention was assessed by determining whether plasma levels during CII were >4 times the informed minimum inhibitory concentration during the first 96 hours of treatment.. A total of 124 patients were subject to TDM during antibiotic treatment but, for the analysis of the fulfilment of pharmacodynamic requirements, data from 31/124 (25%) were excluded. Of the whole cohort of treatment courses, 57/93 (61.3%) reached the target level. Plasma levels were adequate in 41/70 (58.6%) and 16/23 (69.6%) of the patients treated with piperacillin-tazobactam and meropenem, respectively. Globally, recommendations based on TDM results were followed in 35/93 (37.6%) of the treatment courses.. The results of the study show that, in critically ill patients with sepsis, there is a significant proportion of treatment courses where target levels are not reached even if the antibiotics are administered by CII and TDM support is provided by the pharmacy service. This TDM support should be offered on a real-time basis to be really useful.

Topics: Aged; Anti-Bacterial Agents; Cohort Studies; Critical Illness; Drug Monitoring; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis

Topics: Adult; Anti-Bacterial Agents; Bacterial Typing Techniques; Chromobacterium; Ciprofloxacin; Farmers; Humans; Male; Meropenem; Microbial Sensitivity Tests; Neisseriaceae Infections; Phylogeny; RNA, Ribosomal, 16S; Sepsis; Treatment Outcome; Wound Infection

In 2013 German infection surveillance guidelines recommended weekly colonization screening for multidrug-resistant (MDRO) or highly epidemic organisms for neonatal intensive care units (NICUs) and extended hygiene measures based on screening results. It remains a matter of debate whether screening is worth the effort. We therefore aimed to evaluate sepsis related outcomes before and after the guideline update.. The German Neonatal Network (GNN) is a prospective cohort study including data from extremely preterm infants between 22 + 0 and 28 + 6 gestational weeks born in 62 German level III NICUs.. Infants treated after guideline update (n = 8.903) had a lower mortality (12.5% vs. 13.8%, p = 0.036), reduced rates for clinical sepsis (31.4 vs. 42.8%, p <  0.001) and culture-proven sepsis (14.4% vs. 16.5%, p = 0.003) as compared to infants treated before update (n = 3.920). In a multivariate logistic regression analysis, nine pathogens of culture-proven sepsis were associated with sepsis-related death, e.g. Pseudomonas aeruginosa [OR 59 (19-180), p <  0.001)]. However, the guideline update had no significant effect on pathogen-specific case fatality, total sepsis-related mortality and culture-proven sepsis rates with MDRO. While the exposure of GNN infants to cefotaxime declined over time (31.1 vs. 40.1%, p <  0.001), the treatment rate with meropenem was increased (31.6 vs. 26.3%, p <  0.001).. The introduction of weekly screening and extended hygiene measures is associated with reduced sepsis rates, but has no effects on sepsis-related mortality and sepsis with screening-relevant pathogens. The high exposure rate to meropenem should be a target of antibiotic stewardship programs.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Cefotaxime; Female; Germany; Humans; Hygiene; Infant, Extremely Premature; Infant, Newborn; Intensive Care Units, Neonatal; Logistic Models; Male; Meropenem; Mortality; Multivariate Analysis; Population Surveillance; Practice Guidelines as Topic; Prospective Studies; Pseudomonas aeruginosa; Sepsis

Topics: Aged; Anti-Bacterial Agents; Critical Care Outcomes; Critical Illness; Drug Administration Schedule; Female; Hospital Mortality; Humans; Infusions, Intravenous; Intensive Care Units; Male; Meropenem; Microbial Sensitivity Tests; Proportional Hazards Models; Retrospective Studies; Sepsis

In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria.. We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to β-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS.. Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued.. Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Female; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Pneumonia, Ventilator-Associated; Sepsis; Surgical Wound Infection; Young Adult

Individualizing drug dosing regimens in critically ill patients on renal replacement therapy is a challenge to clinicians as guidelines are often imprecise and specific-validated pharmacokinetic software is unavailable.. A case of a septic patient on hemodialysis is presented, where a quick solution for antibiotic dose adjustment based on the application of pharmacokinetic principles was found.. The dose adjustment was made in two steps-the first step was to calculate total antibiotic clearance (using the formula: total drug clearance = dialysate flow rate × fraction of unbound drug in plasma + extrarenal clearance), and the second step was to calculate maintenance dose based on target plasma concentrations in steady-state (using the formula: maintenance dose = target plasma concentration × total drug clearance × dose interval).. After the doses of antibiotics were adjusted, the patient's condition gradually improved, with a drop in body temperature to normal values, a decrease in plasma levels of inflammatory parameters, and the emergence of spontaneous diuresis. The plasma concentration of vancomycin was within the recommended therapeutic range.. Specific pharmacokinetic software and measuring plasma concentrations of the drugs should be used for calculation of total drug clearance and dose adjustment whenever possible. However, if unavailable, basic pharmacokinetic formulas and principles could be successfully used instead to adjust the dose in critically ill patients on hemodialysis.

Topics: Aged; Anti-Bacterial Agents; Area Under Curve; Critical Illness; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Meropenem; Metabolic Clearance Rate; Renal Dialysis; Sepsis; Time Factors; Treatment Outcome; Vancomycin

Ecthyma gangrenosum is a cutaneous infection, most commonly occurring during sepsis evolution with Pseudomonas aeruginosa on an immunocompromised background. There have been rare case reports in previously healthy children and rarer are the cases with double etiology.. We present the case of a female Caucasian patient, aged 1 year and 8 months, who developed severe sepsis during flu evolution with predominant respiratory and cerebral manifestations. On admission, at skin level, there was noticed a necrotic coccygeal ulceration (with rapid increasing dimensions 0.5/0.5 cm in 24 hours), and with the transformation from a dry necrosis in a sphacelus at the periphery and progression of necrosis in depth.. The patient was diagnosed with ecthyma gangrenosum from which Pseudomonsa aeruginosa and Enterococcus faecalis were isolated from the samples that were harvested intraoperatively, decision that was taken considering the appearance of CT scan and the extremely rapid expansion of necrosis. Excisional debridement with necrectomy, lavage, and dressing being performed. The invasion of the fascia was excluded intraoperatively.. Treatment with Meropenem for 14 days was initiated, as well as amikacin and linezolid, the latter being replaced with teicoplanin for 14 days. Red blood cells transfusion, intravenous immunoglobulins, anticonvulsants were also administered.. Under treatment the evolution was favorable.. This case brings into discussion a double etiology of ecthyma gangrenosum, in a previously healthy child that occurred in the evolution of influenza. The evolution was favorable under broad-spectrum antibiotic treatment and surgical excision.

Topics: Anti-Bacterial Agents; Debridement; Ecthyma; Enterococcus faecalis; Female; Gram-Positive Bacterial Infections; Humans; Immunocompromised Host; Infant; Influenza, Human; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

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

Central venous catheter-associated bacteraemia caused by Nocardia species is very rare; the diagnosis of nocardiosis in patients with cancer is challenging because its clinical presentation is varied, sometimes mimicking metastases, and the high index of clinical suspicion is required for prompt institution of therapy. Herein, we report a case of nocardial sepsis with native aortic valve endocarditis in a patient with breast cancer in whom multidisciplinary team involvement and prompt initiation of therapy have led to successful outcome.

Topics: Amikacin; Anti-Bacterial Agents; Anticoagulants; Aortic Valve; Breast Neoplasms; Central Venous Catheters; Clopidogrel; Cough; Endocarditis, Bacterial; Fatigue; Female; Headache; Heart Valve Prosthesis Implantation; Humans; Meropenem; Middle Aged; Nocardia; Nocardia Infections; Platelet Aggregation Inhibitors; Radiography, Thoracic; Sepsis; Treatment Outcome; Warfarin

The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane.. To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA.. A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC).. The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required.. We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Continuous Renal Replacement Therapy; Critical Illness; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Prospective Studies; Pseudomonas aeruginosa; Sepsis

The progressive increase of infections produced by extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae (XDR-CPKP) represents an important threat to public health. Unfortunately, optimal therapeutic options are scarce. Retrospective studies have recommended combined therapy with more than one antibiotic and, more recently, a double-carbapenem regimen has been reported to be an effective alternative therapy. Here, we describe an episode of sepsis in an immunocompromised patient after allogeneic hematopoietic stem cell transplantation, caused by an XDR-CPKP. Several in vitro synergy tests revealed a synergistic effect combining ertapenem and meropenem, which were used as combination therapy achieving clinical and microbiological success.

Topics: Adult; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; beta-Lactams; Drug Combinations; Ertapenem; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Sarcoma, Myeloid; Sepsis; Thienamycins; Transplantation, Homologous; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Gram-Negative Bacteria; Humans; Meropenem; Probability; Sepsis; Tazobactam

Topics: Bacteremia; Cefepime; Gram-Negative Bacteria; Humans; Meropenem; Piperacillin; Sepsis; Tazobactam

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131), respectively. When a target range of non-species-related breakpoint - 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of β-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Bacterial Infections; beta-Lactams; Cefotaxime; Drug Monitoring; Female; Humans; Length of Stay; Male; Meropenem; Patient Readmission; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Sepsis; Sweden; Thienamycins

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on β-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland-Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 μg/mL, 10.91 μg/mL, and 4.41 μg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130-250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Creatinine; Female; Hospitals, University; Humans; Intensive Care Units; Kidney; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Monte Carlo Method; Sepsis; Treatment Outcome

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Cross Infection; Female; Hospitals; Humans; Incidence; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Prospective Studies; Recurrence; Risk Factors; Sepsis; Thienamycins; Tigecycline; Time Factors

Topics: Adult; Anemia, Hemolytic; Anti-Bacterial Agents; Diagnosis, Differential; Escherichia coli Infections; Female; Hemolytic-Uremic Syndrome; Humans; Meropenem; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Sepsis

Antimicrobial resistance is one of the most significant health challenges worldwide. Meropenem is a broad spectrum beta-lactam antibiotic that possesses high activity against Gram-positive and Gram-negative bacteria. However, it has a short plasma half-life, and thus requiring frequent administration of high doses. For the first time, meropenem-loaded chitosan nanoparticles were prepared and evaluated as a potential tool to overcome antimicrobial resistance and to improve pharmacokinetics of the drug. Spherical nanosized particles were prepared and demonstrated ultrahigh encapsulation efficiency of meropenem (i.e. 76.3%). The nanoparticles could be stored in a freeze-dried powdered form while maintaining their physicochemical characteristics. In vitro, higher antibacterial activities of the drug-loaded nanoparticles were observed against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, as compared to the free drug. The nanoparticles were then tested in a septic rat model of Klebsiella pneumoniae and showed exceptional improvement of survival and bacterial clearance, as compared to the animals treated with the free drug. Hence, meropenem-loaded chitosan nanoparticles might have great potential for overcoming antimicrobial resistance.

Topics: Animals; Anti-Bacterial Agents; Chitosan; Escherichia coli; Klebsiella pneumoniae; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Models, Animal; Nanoparticles; Rats; Sepsis; Thienamycins

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Humans; Iatrogenic Disease; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Tazobactam; Thienamycins; Tobramycin

A 43-year-old farmer presented with acute onset pneumonia, septicaemia and peripheral facial nerve palsy (left side).

Topics: Adult; Anti-Bacterial Agents; Burkholderia pseudomallei; Diagnosis, Differential; Drug Administration Schedule; Facial Paralysis; Farmers; Humans; Male; Melioidosis; Meropenem; Sepsis; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Bacteriological Techniques; Female; Granulomatosis with Polyangiitis; Humans; Immunocompromised Host; Immunosuppressive Agents; Magnetic Resonance Imaging; Meropenem; Nocardia Infections; Opportunistic Infections; Pseudomonas Infections; Sepsis; Treatment Outcome

The objective of this study was to test the efficacy of an inhibitor of the New Delhi metallo-β- lactamase (NDM-1). Inhibiting expression of this type of antibiotic-resistance gene has the potential to restore antibiotic susceptibility in all bacteria carrying the gene.. We have constructed a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) that selectively inhibits the expression of NDM-1 and examined its ability to restore susceptibility to meropenem in vitro and in vivo .. In vitro , the PPMO reduced the MIC of meropenem for three different genera of pathogens that express NDM-1. In a murine model of lethal E. coli sepsis, the PPMO improved survival (92%) and reduced systemic bacterial burden when given concomitantly with meropenem.. These data show that a PPMO can restore antibiotic susceptibility in vitro and in vivo and that the combination of PPMO and meropenem may have therapeutic potential against certain class B carbapenem-resistant infections in multiple genera of Gram-negative pathogens.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Meropenem; Mice; Microbial Sensitivity Tests; Morpholinos; Sepsis; Thienamycins

A patient with well-controlled HIV-1 infection presented with fever and rigors, a widespread maculopapular rash, and severe generalised arthralgia. Sepsis of unknown aetiology was diagnosed, and treatment with broad-spectrum antimicrobials commenced. Following initial clinical improvement, a right knee septic arthritis developed. Microscopy and culture of the joint aspirate were negative for organisms but 16S rDNA PCR identified Neisseria meningitidis DNA, subsequently verified as capsular genogroup C, thus confirming a diagnosis of disseminated meningococcal sepsis with secondary septic arthritis.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Arthritis, Infectious; Exanthema; Fever; HIV Infections; Humans; Male; Meningococcal Infections; Meropenem; Middle Aged; Neisseria meningitidis, Serogroup C; Polymerase Chain Reaction; Sepsis; Thienamycins; Treatment Outcome

Distributive shock is a hyperdynamic process resulting from excessive vasodilatation. Impaired blood flow causes inadequate tissue perfusion, which can lead to end-organ damage. Although the most common etiology is septic shock, anaphylactic and other etiologies should be considered.. We report the case of a 30-year-old female who presented to the emergency department with nonspecific symptoms and hypotension after a viral upper respiratory infection. Her physical examination revealed mild edema and rebound tenderness in the right upper and bilateral lower quadrants. She also presented with hypotension concomitant with hypoperfusion symptoms, which were manifested by the loss of consciousness in the hour after her presentation. Neither etiologic agent nor drug use history was provided at the presentation; these may have caused anaphylaxis; however, she later reported that she took a propolis extract 1 day earlier. The hypotensive state was refractory to large amount of crystalloid infusion and a series of examinations were performed to determine the shock etiology. Computed tomography images showed pneumonic infiltrates in the lower zone of the right lung, an enlarged liver, a thickened gallbladder wall, and an extensive amount of free fluid in the perihepatic and retroperitoneal areas. All radiologic changes were thought to be due to a secondary condition that triggers them, none were considered as septic focus. Capillary leak syndrome was considered in differential diagnosis and 3 days after her presentation, her hypotension improved and she was discharged in a healthy state. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Capillary leak syndrome is a variant of distributive shock. After assessing other etiologies for this condition, emergency physicians should focus on a triggering event that may have caused hypoalbuminemia and a fluid shift.

Topics: Adult; Anaphylaxis; Anti-Bacterial Agents; Capillary Leak Syndrome; Diagnosis, Differential; Emergency Service, Hospital; Female; Headache; Humans; Hypotension; Meropenem; Myalgia; Norepinephrine; Sepsis; Shock; Thienamycins; Tomography, X-Ray Computed; Vasodilation; Vasodilator Agents; Vomiting

Ecthyma gangrenosum (EG) is an aggressive cutaneous disease caused by local or systemic infection with Pseudomonas aeruginosa. EG is characterized by cutaneous manifestations ranging from nodule and papule, to necrotic ulceration with surrounding erythema, especially with black eschar or central crust. EG presents with characteristic skin lesions which is important to establish diagnosis of sepsis caused by P aeruginosa, a serious condition that can be treated efficiently if diagnosed early.. A 3-month-old female infant was presented with characteristic skin lesions of EG and developed sepsis 3 days later.. Ecthyma gangrenosum and sepsis caused by Pseudomonas aeruginosa.. Meropenem was used in combination with ceftazidime at first and excision of necrotic skin lesions was performed later.. Cure.. Early recognition of EG plays an important role in providing appropriate empiric antibiotic treatment at early stage of sepsis, and improves the prognosis. Surgical excision may be helpful if no improvement was achieved via antibiotic treatment.

Topics: Anti-Bacterial Agents; Ceftazidime; Female; Gangrene; Humans; Infant; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Pyoderma Gangrenosum; Sepsis; Thienamycins

Nocardia is a Gram-positive aerobic pathogen that usually affects immunocompromised patients. We report a case of pulmonary infection caused by a rare Nocardia species, Nocardia beijingensis, in a 50-year-old woman who had received alemtuzumab for the treatment of her multiple sclerosis. The invasive pulmonary infection was successfully treated with meropenem.

Topics: Alemtuzumab; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Female; Humans; Immunocompromised Host; Immunologic Factors; Meropenem; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Nocardia Infections; Pneumonia, Bacterial; Sepsis; Thienamycins

Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Ertapenem; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sepsis; Thienamycins

The pharmacokinetics of β-lactam antibiotics have not been well defined in critically ill patients with cirrhosis.. We reviewed data from critically ill patients with cirrhosis and matched controls in whom routine therapeutic drug monitoring of two broad-spectrum β-lactam antibiotics (piperacillin/tazobactam and meropenem) had been performed. Serum drug concentrations were measured twice by high-performance liquid chromatography. Antibiotic pharmacokinetics were calculated using a one-compartment model. We considered that therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration of Pseudomonas aeruginosa during optimal periods of time for each drug (≥ 50% for piperacillin/tazobactam; ≥ 40% for meropenem).. We studied 38 patients with cirrhosis (16 for piperacillin/tazobactam and 22 for meropenem) and 38 matched controls. Drug dosing was similar in the two groups. The pharmacokinetics analysis showed a lower volume of distribution of meropenem (P = 0.05) and a lower antibiotic clearance of piperacillin/tazobactam (P = 0.009) in patients with cirrhosis than in the matched controls. Patients with cirrhosis were more likely than those without cirrhosis to have excessive serum β-lactam concentrations (P = 0.015), in particular for piperacillin/tazobactam.. Standard β-lactam antibiotics regimens resulted in excessive serum concentrations in two thirds of the patients with cirrhosis. This was particularly true for piperacillin/tazobactam, probably because of reduced drug clearance.

Topics: Aged; Anti-Bacterial Agents; Belgium; Case-Control Studies; Chromatography, High Pressure Liquid; Critical Illness; Databases, Factual; Drug Monitoring; Female; Humans; Liver Cirrhosis; Logistic Models; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

Aerococcus urinae is an uncommon pathogen that was first identified in 1992. Herein, we report a case of bloodstream infection caused by A. urinae, which occurred in a 92-year-old Korean female patient with an underlying urologic infection who had altered consciousness. The blood culture yielded positive results for A. urinae; however, identifying A. urinae was challenging. Ultimately, we used 16S ribosomal RNA (rRNA) gene sequencing to identify the organism. The patient recovered after being treated with ertapenem and meropenem. To our knowledge, this is the first report of a case of A. urinae sepsis in South Korea.

Topics: Aerococcus; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Ertapenem; Female; Gram-Positive Bacterial Infections; Humans; Meropenem; Remission Induction; RNA, Ribosomal, 16S; Sepsis; Sequence Analysis, RNA; Thienamycins; Urinary Tract Infections

Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day.

Topics: Amikacin; Anti-Bacterial Agents; Conjunctivitis; Escherichia coli; Escherichia coli Infections; Humans; Infant, Newborn; Male; Meropenem; Sepsis; Thienamycins; Treatment Outcome

Thyroid abscess is a very rare clinical condition. It usually occurs in immunocompromised individuals or those with underlying malignancy. We report a case of multiple thyroid abscesses in the patient with Pre B acute lymphoblastic leukaemia which developed secondary to hematogenous spread from pyomyositis of right calf muscle. The patient developed sepsis-associated disseminated intravascular coagulation, which got resolved after thyroidectomy. He became afebrile after surgical intervention. Unfortunately, all the cultures were negative. Since there are few case series and reports, there are no clear guidelines for management of thyroid abscess. We conclude that though rare, thyroid abscess may be the cause of persistent fever in immunocompromised patients.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Clindamycin; Drainage; Fever; Humans; Male; Meropenem; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Pyomyositis; Sepsis; Teicoplanin; Thienamycins; Thyroid Diseases; Thyroid Gland; Thyroidectomy; Treatment Outcome

Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of β-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age. Drug concentrations were considered adequate if they remained 4-8× the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval. A total of 41 TDM results (27 MEM; 14 TZP) were obtained in 26 ECMO patients, with 41 matched controls. There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0.38 (0.27-0.68) vs. 0.46 (0.33-0.79)L/kg; P=0.37], half-life [2.6 (1.8-4.4) vs. 2.9 (1.7-3.7)h; P=0.96] and clearance [132 (66-200) vs. 141 (93-197)mL/min; P=0.52]. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these β-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.

Topics: Adult; Anti-Bacterial Agents; beta-Lactams; Case-Control Studies; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Sepsis; Serum; Thienamycins; Treatment Outcome

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

A 35-year-old patient in intensive care with severe burn injury developed episodes of sepsis. Blood culture yielded a multidrug-resistant Pseudomonas aeruginosa and treatment was commenced with amikacin (minimum inhibitory concentration (MIC) 2-4 mg/L, dose 20 mg/kg adjusted body weight 24-hourly) and meropenem (MIC 8 mg/L, dose 2 g IV 8-hourly and later 6-hourly). Despite the use of extended infusions with β-lactam therapeutic drug monitoring and doses that were more than 2.5 times higher than standard meropenem doses, resistance emerged. This case report describes the application of therapeutic drug monitoring to optimize β-lactam therapy in a difficult-to-treat critically ill patient.

Topics: Adult; Amikacin; Anti-Bacterial Agents; beta-Lactams; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance, Bacterial; Female; Humans; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Thienamycins

Listeria monocytogenes is a facultative intracellular parasitic bacterium that is Gram positive, catalase positive, oxidase negative, and a facultative anaerobe. It is known to infect humans through food. It is a bacillus with low virulence, but can cause meningitis and sepsis in infants and immunocompromised patients.. A case of 75-year-old Japanese female with small cell carcinoma of the thymus and pleural dissemination is described. She was treated with carboplatin and etoposide and showed a partial response. However, the tumor recurred 6 months later. Therefore, we again administered carboplatin and etoposide. Though peritoneal dissemination was suspected based on abdominal computed tomography findings after two courses, the assessment was stable disease. She was occasionally treated for constipation. She developed chills, rigor, and diarrhea, necessitating admission on the 7th day of the third course of chemotherapy. We suspected intestinal infection, and cefepime was thus administered. However, her blood pressure dropped and neutropenia manifested on the 4th day of admission. We therefore switched the antibiotic from cefepime to meropenem and also administered granulocyte-colony stimulating factor. Listeria monocytogenes was detected by two blood cultures, and the antimicrobial medication was thus switched to ampicillin, in consideration of sensitivity. Her general condition improved and she was able to leave the hospital on the 19th day after admission.. During chemotherapy, factors such as impaired bowel movements, malnutrition, and myeloablation can contribute to the development of severe infections. It is necessary to comprehensively assess a patient's state and treat all aspects of illness.

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Antineoplastic Agents; Carboplatin; Carcinoma, Small Cell; Cefepime; Cephalosporins; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Listeria monocytogenes; Listeriosis; Meropenem; Neoplasm Recurrence, Local; Sepsis; Thienamycins; Thymus Gland; Thymus Neoplasms; Treatment Outcome

A 69-year-old man developed motor aphasia and right hemiparesis with severe headache, during the treatment of cellulitis and sepsis due to cat bites. Brain CT showed a low density, crescent-shaped lesion in the left subdural space, which was hypointense on brain diffusion-weighted imaging (DWI). One week later, when his neurological symptoms had worsened, the signal of the subdural lesion had changed to hyperintense on DWI. The lesion was capsule-shaped when enhanced by Gadolinium. The signal changes on DWI of the lesion indicated the existing hematoma had changed to an empyema, or so-called infected subdural hematoma, due to a hematogenous bacterial infection. Pasteurella multocida, a resident microbe in the oral cavity of cats, could be the responsible pathogen in this case. The patient recovered completely after treatment with intravenous high dose antibiotics. This is an important case report describing the transformation from a chronic subdural hematoma into a subdural empyema by DWI.

Topics: Aged; Animals; Anti-Bacterial Agents; Bites and Stings; Cats; Ceftriaxone; Cellulitis; Diffusion Magnetic Resonance Imaging; Disease Progression; Drug Therapy, Combination; Empyema, Subdural; Headache; Hematoma, Subdural, Chronic; Humans; Male; Meropenem; Paresis; Pasteurella Infections; Pasteurella multocida; Sepsis; Thienamycins; Treatment Outcome

An increasingly reported entity, Lemierre's syndrome classically presents with a recent oropharyngeal infection, internal jugular vein thrombosis and the presence of anaerobic organisms such as Fusobacterium necrophorum. The authors report a normally fit and well 17-year-old boy who presented with severe sepsis following a 5-day history of a sore throat, myalgia and neck stiffness requiring intensive care admission. Blood cultures grew F. necrophorum and radiological investigations demonstrated left internal jugular vein, cavernous sinus and sigmoid sinus thrombus, left vertebral artery dissection and thrombus within the left internal carotid artery. Imaging also revealed two areas of acute ischaemia in the brain, consistent with septic emboli, skull base (clival) osteomyelitis and an extensive epidural abscess. The patient improved on meropenem and metronidazole and was warfarinised for his cavernous sinus thrombosis. He has an on-going left-sided hypoglossal (XIIth) nerve palsy.

Topics: Adolescent; Anti-Infective Agents; Anticoagulants; Cranial Fossa, Posterior; Fever; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Hypoglossal Nerve Diseases; Jugular Veins; Lemierre Syndrome; Male; Meropenem; Metronidazole; Osteomyelitis; Pharyngitis; Sepsis; Thienamycins; Treatment Outcome; Warfarin

Pantoea agglomerans is a plant pathogen which very rarely causes an opportunistic infection. Human beings are usually infected by thorn prick injuries or by contaminated parenteral fluids. Pantoea agglomerans has been reported as a cause of neonatal sepsis very rarely and to the best of our knowledge this is the first reported case from India.. A 4-day-old Asian baby boy from the rural area of Odisha, India, was admitted to our neonatal intensive care unit when he presented with fever, tachypnea and chest retraction. Pantoea species were isolated from his blood culture.. He was treated successfully with meropenem administered intravenously and other supportive measures. Early detection and proper management may cause a favorable outcome.

Topics: Anti-Bacterial Agents; Diagnosis, Differential; Enterobacteriaceae Infections; Humans; India; Infant, Newborn; Male; Meropenem; Pantoea; Sepsis; Thienamycins

Topics: Animals; Anti-Bacterial Agents; Bone Marrow Transplantation; Capnocytophaga; Disease Progression; Dog Diseases; Dogs; Female; Graft vs Host Disease; Gram-Negative Bacterial Infections; Humans; Leukemia, Myeloid, Acute; Meropenem; Middle Aged; Postoperative Complications; Saliva; Sepsis; Spleen; Thienamycins; Thrombocytosis; Treatment Outcome; Vancomycin

Multidrug-resistant Acinetobacter baumannii becomes an increasing challenge due to the overuse of antibiotics. Combination therapies are considered as effective options to overcome this matter. The present study was to investigate the synergistic activity of meropenem combined with other antibiotics in vitro and in vivo. Checkerboard assay and time-kill assay were performed to study the combination effects in vitro. For the animal model, a murine sepsis model injected with inoculums intraperitoneally was used. Susceptibility test showed that all the twelve strains in this study were resistant to most of the antibiotics except rifampicin. In combination, meropenem plus rifampicin exhibited synergistic activity against six of twelve strains. In the sepsis model, meropenem monotherapy had no therapeutic effect in this model while it can enhance the activity of rifampicin in both survival rate and bacterial clearance from blood. Moreover, combination therapy significantly reduced plasma IL-6 levels compared with rifampicin monotherapy. Pharmacokinetic analysis of rifampicin was also performed in this study. These data above showed that there was synergistic activity between meropenem and rifampicin against multidrug-resistant Acinetobacter baumannii both in vitro and for experimental model of sepsis. It suggested that combining meropenem with rifampicin may be appropriate in treating multidrug-resistant Acinetobacter baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Male; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Rifampin; Sepsis; Thienamycins; Treatment Outcome

Meropenem is a broad-spectrum antibiotic, often used for the empirical treatment of infections in critically ill patients with acute kidney injury. Meropenem has clinically insignificant protein binding and, as a carbapenem antibiotic, shows time-dependent bacterial killing, meaning that the unbound or free antibiotic concentration in blood should be maintained above the minimal inhibitory concentration of the pathogen for at least 40 % of the dosing interval. We developed and validated simple chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure plasma, filtrate-dialysate, and urine concentrations of meropenem. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH(TM) (2.1 × 100 mm id, 1.7 μm) reverse-phase C(18) column, with a water/acetonitrile linear gradient containing 0.1 % formic acid at a 0.4-mL/min flow rate. Meropenem and its internal standard (ertapenem) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode. The limits of quantification were 0.27, 0.24, and 1.22 mg/L, and linearity was observed between 0.27-150, 0.24-150, and 1.22-2,000 mg/L for plasma, filtrate-dialysate, and urine samples, respectively. Coefficients of variation and relative biases were less than 13.5 and 8.0 % for all biological fluids. Recovery values were greater than 68.3 %. Evaluation of the matrix effect showed ion suppression for meropenem and ertapenem. No carry-over was observed. The validated methods are useful for both therapeutic drug monitoring and pharmacokinetic studies. It could be applied to daily clinical laboratory practice to measure the concentration of meropenem in plasma, filtrate-dialysate, and urine.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Body Fluids; Chromatography, Liquid; Critical Illness; Drug Monitoring; Humans; Meropenem; Renal Replacement Therapy; Sepsis; Spectrometry, Mass, Electrospray Ionization; Thienamycins

To evaluate the treatment outcome of severe peritonitis in rats with increasing age.. Thirty Wistar rats stratified in three groups: group I - six month-old; group II - 12 month-old; and group III - 18 month-old, underwent autogenously fecal peritonitis (6 ml/kg rat), and were treated with intravenous meropenem. The survival animals were followed-up for 45 days. The variables were expressed by their mean and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee.. There was a significant increase in the mortality and morbidity in elderly rats. Of interest, even among young survival rats presenting with severe residual abscesses both in the abdomen and thorax cavities, they present an almost normal life.. The treatment of severe autogenously fecal peritonitis with intravenous meropenem reached reasonable results in rats with six and twelve months of age, even considering residual abscesses on abdomen and thorax cavities. However, the great majority (80%) of elderly rats could not overcome the initial severe infectious challenge, proving that ageing is a very important risk factor for impairing immune response. Thus, sepsis remains a challenging situation, especially in elderly.

Topics: Administration, Intravenous; Age Factors; Animals; Anti-Bacterial Agents; Feces; Meropenem; Peritonitis; Rats, Wistar; Reproducibility of Results; Risk Factors; Sepsis; Severity of Illness Index; Thienamycins; Time Factors; Treatment Outcome

The scope of extracorporeal membrane oxygenation (ECMO) is expanding; however, optimal drug prescription during ECMO remains a developing science. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This open-label, descriptive, matched-cohort pharmacokinetics (PK) study aimed to compare the PK of meropenem in ECMO patients to critically ill patients with sepsis not receiving ECMO (controls).. Eleven adult patients on ECMO (venovenous (VV) ECMO, n = 6; venoarterial (VA) ECMO, n = 5) receiving intravenous (IV) meropenem were included. Meropenem plasma concentrations were determined using validated chromatography. Population PK analysis was performed using non-linear mixed effects modelling. This data was compared with previously published meropenem PK data from 10 critically ill adult patients not on ECMO (preserved renal function (n = 5) or receiving renal replacement therapy (RRT) (n = 5). Using these data, we then performed Monte Carlo simulations (n = 1,000) to describe the effect of creatinine clearance on meropenem plasma concentrations.. In total, five (two VV, three VA) out of eleven ECMO patients received RRT. The other six patients (four VV, two VA) had no significant impairment in renal function. A two-compartment model adequately described the data. ECMO patients had numerically higher volume of distribution (0.45 ± 0.17 versus 0.41 ± 0.13 L/kg, P = 0.21) and lower clearance compared to controls (7.9 ± 5.9 versus 11.7 ± 6.5 L/h, P = 0.18). Variability in meropenem clearance was correlated with creatinine clearance or the presence of RRT. The observed median trough concentrations in the controls were 4.2 (0.0 to 5.7) mg/L. In ECMO patients, while trough meropenem concentrations >2 mg/L were achieved in all patients, a more aggressive target of >8 mg/L for less susceptible microorganisms was observed in only eight out of eleven patients, with five of them being on RRT.. ECMO patients exhibit high PK variability. Decreased meropenem CL on ECMO appears to compensate for ECMO and critical illness-related increases in volume of distribution. Routine target concentrations >2 mg/L are maintained with standard dosing (1 g IV 8-hourly). However, an increase in dose may be necessary when targeting higher concentrations or in patients with elevated creatinine clearance.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Critical Illness; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Meropenem; Middle Aged; Monte Carlo Method; Renal Replacement Therapy; Sepsis; Thienamycins; Young Adult

Salmonella enterica serovar Minnesota is a rarely isolated organism in clinical samples mainly grown from stool cultures. Sepsis due to Salmonella is known in severely immunocompromised patients, but so far urosepsis due to S. enterica serovar Minnesota has not been described. We report a case of a 31-year-old patient suffering from Crohn's disease treated with infliximab and azathioprine, in whom was implanted a double-J ureteric catheter for urolithiasis. The patient presented with urinary tract infection and severe sepsis. S. enterica serovar Minnesota was grown from urine and blood cultures. After empiric antimicrobial treatment with meropenem and vancomycin, treatment was changed to ceftriaxone. Antimicrobial treatment was continued for a total of 3 weeks without evidence of Salmonella recurrence on follow-up visits. Salmonella spp. rarely cause urinary tract infection and sepsis. However, in immunocompromised patients, non-typhoidal salmonellosis merits a thorough clinical and microbiological evaluation.

Topics: Adult; Antibodies, Monoclonal; Ceftriaxone; Crohn Disease; Humans; Infliximab; Male; Meropenem; Recurrence; Salmonella enterica; Salmonella Infections; Sepsis; Thienamycins; Urinary Catheters; Urinary Tract Infections; Urolithiasis; Vancomycin

Topics: Aged; Drug Resistance, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Phenotype; Sepsis; Thienamycins

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

Resistance to carbapenems is a significant therapeutic threat. The increasing frequency of car bapenemase enzymes among Gram-negative bacilli makes their early detection and differentiation urgent. Carbapenemases belonging to Class A are most commonly produced by members of family Enterobacteriaceae and are inhibited to various degrees by clavulanic acid. The present study is aimed to determine the occurrence and phenotypic detection of Class A carbapenemases in Escherichia coli and Klebsiella pneumoniae blood isolates from septicemic patients.. A total of 75 isolates of K. pneumoniae and 25 E. coli were screened for resistance to carbapenems by using meropenem and imipenem discs and meropenem E-test. Positive strains were then subjected to a modified Hodge test combined with carbapenemase inhibition tests to phenotypically detect and differentiate Class A serine carbapenemases from other classes of carbapenem hydrolyzing enzymes.. The screening test showing the number of isolates resistant to meropenem and imipenem were 41 and 35 for K. pneumoniae and nine and four for E. coli, respectively. A total of 25 (33.3%) K. pneumoniae isolates and two (8.0%) E. coli isolates were classified as Class A carbapenemase producers. Multidrug resistance with coexistence of extended spectrum-beta-lactamases occurred in 44.4% isolates. However, all of the isolates were susceptible to colistin, polymyxin B, and tigecycline by disc diffusion test.. We conclude from the present study that Class A carbapenemases appear to be the predominant cause of resistance to carbapenems in Enterobacteriaceae at our center and, thus, phenotypic detection based on simple methods should be employed routinely in clinical microbiology laboratories.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Prevalence; Sepsis; Tertiary Care Centers; Thienamycins

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

Acute renal failure caused by interstitial nephritis as part of a drug hypersensitivity syndrome constitutes a rare, but potentially life-threatening adverse drug reaction. We describe a patient with a mild maculo-papular rash accompanied by eosinophilia after prolonged treatment with meropenem, vancomycin, and moxifloxacin. Subsequently, a rapidly progressing renal failure developed which dominated the clinical picture. Upon cessation of all suspected drugs and therapy with high-dose steroids for 6 weeks, the renal function slowly returned to normal.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Aortic Valve; Aza Compounds; Biopsy; Diagnosis, Differential; Drug Eruptions; Drug Therapy, Combination; Endocarditis, Bacterial; Eosinophilia; Fluoroquinolones; Glucocorticoids; Humans; Kidney; Legionnaires' Disease; Male; Meropenem; Moxifloxacin; Nephritis, Interstitial; Quinolines; Sepsis; Skin; Thienamycins; Vancomycin

A woman aged 56 years of age had a community-acquired left neck abscess and internal jugular vein thrombosis with septicemia due to extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae. Even though she was treated with intravenous meropenem, the bacteremia persisted. She was complicated with multiple brain abscesses, seizure, and leucopenia. After a combination of intravenous fosfomycin and meropenem, her clinical condition became stable. Combination treatment was continued for 2 months and she recovered. In individual cases of Lemierre syndrome with brain abscess caused by ESBL-producing Enterobacteriaceae, fosfomycin combination therapy may be the alternative choice.

Topics: Anti-Bacterial Agents; beta-Lactamases; Brain; Brain Abscess; Community-Acquired Infections; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Lemierre Syndrome; Meropenem; Middle Aged; Sepsis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

To demonstrate the pharmacokinetic profile of meropenem when administered by 3-hour infusion in patients undergoing continuous veno-venous hemofiltration (CVVH).. The study was conducted in 10 patients, who were treated with CVVH. Each subject received meropenem in 3-hour infusion of 500 mg every 6 hours. Blood samples were collected before infusion (0 hour) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6 hours (just before the infusion of the next dose) after the beginning of the fourth infusion. The concentrations of meropenem in plasma were measured by high-performance liquid chromatography method, and mean serum meropenem concentration-time curve was plotted.. Peak plasma drug concentrations measured 3 hours post-infusion were (25.05 ± 5.64) mg/L, and trough levels after 6 hours of infusion were (13.03 ± 3.01) mg/L. The area under the plasma concentration-time curve (AUC) was (118.42 ± 26.78) mg x h⁻¹ x L⁻². The elimination half-life (T1/2) was (3.74 ± 0.55) hours. The mean residence time (MRT) was (4.99 ± 0.84) hours. The volume of distribution (Vb) was (22.85 ± 9.85) L and clearance of meropenem (CL) was (4.49 ± 1.32) L/h. The percentage of time that the serum drug concentration was above the minimum inhibitory concentration (MIC) accounting for the interval time of infusion (%T>MIC) was 100% (MIC 8 mg/L) in all the 10 patients.. Based on these data, we concluded that satisfactory pharmacodynamic parameters could be attained in CVVH patients treated with meropenem by a prolonged infusion time of 3 hours with a dosage of 500 mg for every 6 hours.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Area Under Curve; Female; Hemofiltration; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Sepsis; Thienamycins

We aimed to compare infection rates for two 3-day antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy (TRUSgbp) and demonstrate local microbiological trends. In 2008, 558 men and, in 2009, 625 men had TRUSgpb. Regimen 1 (2008) comprised 400 mg Ofloxacin immediately before biopsy and 200 mg 12-hourly for 3 days. Regimen 2 (2009) comprised Ofloxacin 200 mg 12-hourly for 3 days commencing 24 hours before biopsy. 20/558 (3.6%) men had febrile episodes with regimen 1 and 10/625 (1.6%) men with regimen 2 (P = 0.03). E. coli was the most frequently isolated organism. Overall, 7/13 (54%) of positive urine cultures were quinolone resistant and (5/13) 40% were multidrug resistant. Overall, 5/9 (56%) patients with septicaemia were quinolone resistant. All patients were sensitive to Meropenem. There was 1 (0.2%) death with regimen 1. Commencing Ofloxacin 24 hours before TRUSgpb reduced the incidence of febrile episodes significantly. We observed the emergence of quinolone and multidrug-resistant E. coli. Meropenem should be considered for unresolving sepsis.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Biopsy; Cephalosporins; Drug Resistance, Bacterial; Drug Resistance, Multiple; Fever; Humans; Male; Meropenem; Middle Aged; Ofloxacin; Prospective Studies; Prostate; Prostatic Neoplasms; Quinolones; Sepsis; Thienamycins; Treatment Outcome

Topics: Amikacin; Facial Dermatoses; Fatal Outcome; Female; Gangrene; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Meropenem; Necrosis; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Skin Diseases, Bacterial; Skin Ulcer; Thienamycins

One of the first-line drugs for empirical antibiotic therapy in patients with hospital-acquired infections is meropenem. An often neglected problem in sepsis is that patients with a normal serum creatinine concentration (SCr) might display augmented renal clearance (ARC). Here we describe two cases of sepsis with subtherapeutic exposures with standard meropenem dosing in whom therapy could be optimised by therapeutic drug monitoring (TDM). A 37-year-old man with acute lymphatic leukaemia and sepsis had a normal SCr at the beginning of his Intensive Care Unit (ICU) stay but showed decreased SCr of between 30 μmol/L and 40 μmol/L during his stay. He failed to achieve effective plasma concentrations with the meropenem standard dose of 3 g/day. Estimated glomerular filtration rate revealed values between 120 mL/min and 160 mL/min. He required a high meropenem daily dosage of 12 g that was far above the approved maximum dose. A 66-year-old patient undergoing surgery of a pulmonary aspergilloma presented SCr persistently <50 μmol/L, indicating ARC between 120 mL/min and 150 mL/min. This patient required 8 g of meropenem to achieve effective plasma concentrations. TDM may represent an invaluable approach to optimising drug exposure of β-lactam antibiotics in patients with ARC in the ICU. Further trials are clearly needed to become better informed about empirical dosing regimens usable in the ICU setting with regard to the relevance of ARC. In the meantime, daily measurement of creatinine clearance as well as TDM can be used to identify patients who manifest ARC, thereby allowing drug therapy to achieve the therapeutic range.

Topics: Adult; Aged; Anti-Bacterial Agents; Drug Monitoring; Humans; Intensive Care Units; Male; Meropenem; Metabolic Clearance Rate; Plasma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sepsis; Thienamycins

We evaluated the efficacy of NXL104, a novel β-lactamase inhibitor, in combination with ceftazidime (CAZ) in two murine infection models (septicemia and thigh infection). We chose two KPC-producing Klebsiella pneumoniae strains (VA-361 and VA-406) showing MICs of CAZ of ≥256 μg/ml. Septicemia was induced by the intraperitoneal injection of KPC-producing K. pneumoniae followed 30 min later by a single subcutaneous treatment with CAZ alone or CAZ-NXL104 in ratios of 2:1, 4:1, 8:1, and 16:1. In this model, the median effective doses for 50% (ED(50)) of the animals for CAZ alone versus VA-361 and VA-406 were 1,578 and 709 mg/kg of body weight, respectively. When combined with NXL104 at 2:1, 4:1, 8:1, and 16:1 ratios, the CAZ ED(50)s for VA-361 and VA-406 were reduced to 8.1 and 3.5 mg/kg, 15.1 and 3.8 mg/kg, 16.9 and 7.2 mg/kg, and 29.5 and 12.1 mg/kg, respectively. For thigh infection, neutropenia was induced by the intraperitoneal injection of cyclophosphamide at days -4 and -1 preinfection. Infection was established by the intramuscular injection of KPC-producing K. pneumoniae into the right thigh. Mice were treated 1.5 h postinfection with either CAZ alone or CAZ-NXL104 at constant ratios of 4:1. When thighs were removed at 24 h postinfection, a >2-log CFU reduction was observed for mice treated with CAZ-NXL104 at doses of ≥128:32 mg/kg. In contrast, CAZ doses of ≥1,024 mg/kg were unable to reduce the numbers of CFU. Despite resistance to CAZ and possessing a complex β-lactamase background, NXL104 combined with CAZ proved to be very effective in murine models of infection due to contemporary highly resistant KPC-producing K. pneumoniae isolates.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Disease Models, Animal; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Sepsis

An infected cephalhematoma is a rare condition in neonates. We report a case of an 18-day-old neonate who was diagnosed with an infected cephalhematoma caused by an extended spectrum beta-lactamase (ESBL)-producing Escherichia coli complicated with septicemia, meningitis, and skull osteomyelitis. He was successfully treated with meropenem and surgical incision and drainage. ESBL-producing E. coli may cause infection of a cephalhematoma in neonates.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drainage; Escherichia coli; Hematoma; Humans; Infant, Newborn; Male; Meningitis, Escherichia coli; Meropenem; Osteomyelitis; Sepsis; Skull; Thienamycins

The microbiological tests of 769 blood samples from 220 patients, treated in 4 intensive care units of the N.V. Sklifosovsky Research Institute for Emergency Medical Service within a period from January 2009 to June 2010, were analysed. Etiologically significant microorganisms were detected in 323 samples (42%). 253 isolates were used in the analysis. Grampositive and gramnegative pathogens were detected in 47 and 42% of the cases respectively. Candida and anaerobic organisms were isolated in 8 and 3% of the cases respectively. Staphylococcus aureus and enterococci were isolated in 24 and 15% of the cases respectively. Nonfermenting gramnegative bacteria and enterobacteria were revealed in 25 and 17% of the cases respectively. Differences in the spectrum of the sepsis pathogens depending on the patients contingent were shown. The maximum summary susceptibility of the grampositive cocci was observed with respect to vancomycin and linezolid and that of the gramnegative bacteria was stated with respect to imipenem and meropenem.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Candida; Cross Infection; Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Infection Control; Intensive Care Units; Linezolid; Meropenem; Moscow; Oxazolidinones; Sepsis; Thienamycins; Vancomycin

Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. The objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume CVVHF with high-volume exchanges (> or = 4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] every 8 h) are sufficient for treatment of less susceptible organisms such as Burkholderia pseudomallei (MIC, 4 mg/liter); and, finally, to compare the clearances observed in this study with data from previous studies using lower-volume exchanges (1 to 2 liters/h). We recruited 10 eligible patients and collected serial pre- and postfilter blood samples and ultrafiltrate and urine samples. A noncompartmental method was used to determine meropenem pharmacokinetics. The cohort had a median age of 56.6 years, a median weight of 70 kg, and a median APACHE II (acute physiology and chronic health evaluation) score of 25. The median (interquartile range) values for meropenem were as follows: terminal elimination half-life, 4.3 h (2.9 to 6.0); terminal volume of distribution, 0.2 liters/kg (0.2 to 0.3); trough concentration, 7.7 mg/liter (6.2 to 12.9); total clearance, 6.0 liters/h (5.2 to 6.2); hemofiltration clearance, 3.5 liters/h (3.4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (R(2) = 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as B. pseudomallei.

Topics: Anti-Bacterial Agents; Critical Illness; Hemofiltration; Humans; Meropenem; Prospective Studies; Sepsis; 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

In performed study the effectiveness of meropenem administration was estimated after therapeutic using in infections treatment after coronary artery bypass graft surgery on the base of antibiotic concentrations determined by HPLC method in the plasma samples of patients. The aim of the present study was to determine pharmacokinetic parameters of meropenem in patients' plasma samples after multiple intravenous antibiotic administration and the estimation of meropenem concentrations to MIC of bacterial pathogens. The biological material to our study was taken in 2; 4; 5 and 6 day of the antibiotic therapy. The solid phase extraction was used to the isolation of meropenem from the plasma samples. Applied chromatographic conditions of antibiotic included the column LiChrisopher 100 RP-18 (5 microm, 250 mm x 4 mm); the mobile phase comprised phosphate buffer pH 7,0/acetonitrile (92:8); DAD with detection at 296 nm. The maximal meropenem concentration in the steady state (Css(max)) in 2 day of treatment 0.25 h after administration of the next dose of antibiotic was 17.58 microg/ml. In the plasma samples which were taken in the end of the dosage regimen (8 h) in subsequent days the antibiotic was not fund. Only in one patient the minimal concentration in the steady state (Css(min)) was 0.87-0.89 microg/ml and exceeded MIC for Staphylococcus aureus, Enterobacter Escherichia coli i Serratia. The shorter frequency of drug administration has to be consider to assure the therapeutic range of antibiotic concentrations.

Topics: Aged; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Coronary Artery Bypass; Drug Administration Schedule; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Poland; Sepsis; Thienamycins

Osteomyelitis in newborn infants is a rare infection. Lower extremity joints are commonly affected. Most of the cases have a haematogenous spread. Aerobes are the common group of organism involved, of which Staphylococcus aureus is the commonest. Klebsiella osteomyelitis has been reported as a cause of Osteomyelitis. However, to the best of our knowledge, this is the first case report of Klebsiella pneumoniae associated osteomyelitis in an infant from Pakistan.

Topics: Anti-Bacterial Agents; Follow-Up Studies; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Osteomyelitis; Radiography; Sepsis; Shoulder Joint; Thienamycins; Treatment Outcome

Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis. One case of granulocytopenia, four of pancytopenia and fifteen of leucopenia worldwide have been reported. With the use of ciprofloxacin becoming more and more widespread, these two rare but fatal complications of ciprofloxacin should be borne in mind.

Topics: Administration, Oral; Adult; Agranulocytosis; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukopenia; Meropenem; Neutropenia; Risk Factors; Sepsis; Stevens-Johnson Syndrome; Thienamycins

We describe what we believe to be the first case of neonatal sepsis caused by CTX-M-producing Escherichia coli, in a low-weight preterm infant, born to a colonized mother who had received antibiotic treatment antepartum. Increased dissemination of extended-spectrum beta-lactamase-producing E. coli in the community should be borne in mind for empirical therapy of sepsis in high-risk newborns.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Infectious Disease Transmission, Vertical; Male; Meropenem; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Thienamycins

Topics: Animals; Anti-Bacterial Agents; Biomarkers; Cytokines; Drug Therapy, Combination; Fibrinolytic Agents; Meropenem; Protein C; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Sepsis; Survival Analysis; Thienamycins

Opportunistic infections contribute to morbidity and mortality of patients undergoing hematopoietic stem cell transplantation and treatment for malignancies. Rothia mucilaginosa, a gram-positive bacterium, is responsible for rare, but often fatal meningitis in severely immunocompromised patients. We describe two cases of meningitis from discrete strains of R. mucilaginosa on our pediatric bone marrow transplant unit, summarize the published cases of R. mucilaginosa meningitis in oncology and stem cell transplant patients, and provide updated recommendations regarding the use of antibiotic therapy in this patient population.

Topics: Actinomycetales Infections; Adolescent; Anti-Bacterial Agents; Ceftazidime; Cerebrospinal Fluid Shunts; Child; Cord Blood Stem Cell Transplantation; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Immunocompromised Host; Leukemia, Megakaryoblastic, Acute; Male; Meningitis, Bacterial; Meropenem; Micrococcaceae; Opportunistic Infections; Postoperative Complications; Rifampin; Sepsis; Thienamycins; Vancomycin

Initial antibiotic treatment of severe infections can lead to clinical deterioration due to sudden endotoxin release and concomitant exaggerated inflammatory response. Antibiotic-induced morphological changes may contribute to this phenomenon. High-dose ceftazidime, which inhibits penicillin-binding protein (PBP)-1 in Gram-negative bacteria, causes quick bacteriolysis and low endotoxin release. Low-dose ceftazidime leads to PBP-3 inhibition, which causes bacterial filament formation, associated with high endotoxin releases. PBP-2-specific antibiotics induce spheroplasts, again associated with low endotoxin release. We hypothesized that antibiotic type, concentration and regimen influence bacterial morphology, endotoxin levels and inflammatory response.. Neutropenic mice with Escherichia coli or Pseudomonas aeruginosa sepsis were treated with ceftazidime or meropenem 10-320 mg/kg as an intravenous bolus or as continuous tail vein infusions of 0.1 mL/h. Four hours later, bacterial counts, morphology, plasma endotoxin, pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] and antibiotic concentrations were measured.. Continuous infusion of 80 mg/kg ceftazidime was the lowest dose preventing filaments in E. coli infections. Bolus treatment resulted in filament formation, irrespective of the dose. During continuous treatment, IL-6 and TNF-alpha concentrations were higher compared with bolus treatment and controls for both antibiotics and both strains. A clear relationship between cfu counts in muscle and circulating IL-6 was shown (r=- 0.579, P=0.007), suggesting that plasma IL-6 is a valuable indicator of bacterial killing at the infection site.. Our findings show that not PBP affinity but the method of antibiotic administration is crucial during initial treatment of severe infections.

Topics: Animals; Anti-Bacterial Agents; Ceftazidime; Colony Count, Microbial; Cytokines; Endotoxins; Escherichia coli; Escherichia coli Infections; Female; Meropenem; Mice; Penicillin-Binding Proteins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals, Urban; Humans; India; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose.. Retrospective cohort study with a cost-minimization analysis.. A 417-bed, privately owned community hospital.. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005.. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001).. An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Costs and Cost Analysis; Drug Administration Schedule; Drug Costs; Hospitals, Community; Humans; Logistic Models; Meropenem; Middle Aged; Retrospective Studies; Sepsis; Thienamycins; Treatment Outcome

A 15-year-old girl developed a persistent bacteraemia with Klebsiella pneumoniae accompanied by systemic symptoms including high fever and rigors after appendectomy. Extensive laboratory and imaging work-up, including tests for an intra-vascular source of infection, did not reveal the origin of the persistent bacteraemia. The Klebsiella pneumoniae isolates were susceptible to gentamicin and colistin and intermediately susceptible to meropenem. The septicaemia persisted despite the intravenous administration of meropenem 1 g and later 2 g every 8 h in combination with intravenous gentamicin and later colistin. The patient was cured only after the continuous intravenous administration of meropenem of 6 g/d.

Topics: Adolescent; Anti-Bacterial Agents; Appendectomy; Appendicitis; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Postoperative Complications; Sepsis; Thienamycins

Topics: Adult; Aged; Anticonvulsants; Drug Interactions; Humans; Male; Meropenem; Seizures; Sepsis; Thienamycins; Valproic Acid

Topics: Brain Abscess; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Infant, Newborn; Klebsiella Infections; Meningitis, Bacterial; Meropenem; Sepsis; Thienamycins; Treatment Outcome

Topics: Candida; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant, Newborn; Meropenem; Pneumonia, Bacterial; Sepsis; Thienamycins; Treatment Outcome

To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy.. A prospective, clinical study.. General intensive care unit of a university hospital.. Ten critically ill adult patients being treated with meropenem and receiving continuous veno-venous hemofiltration (hemofiltration rates, 1-2 L/hr) (n = 5) or continuous venovenous hemodiafiltration (hemofiltration rates, 1-1.5 L/hr; dialysis rates, 1-1.5 L/hr) (n = 5) via a polyacrylonitrile hollow fiber 0.9-m2 filter.. Patients received a meropenem dose of 1 g iv every 12 hrs as a 5-min bolus.. Meropenem concentrations were measured by high-performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration-time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficients and filter clearances. The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations (MICs) for pathogens that may be encountered in intensive care patients. Serum concentrations exceeded 4 mg/L (MIC90 for Pseudomonas aeruginosa) during 67% of the dosage period in all patients. Sub-MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follows: elimination half-life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving coefficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important.. A meropenem dose of 1g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno-venous hemofiltration or continuous venovenous hemofiltration with a 0.9-m2 polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr. A lower dose would not be sufficient for the empirical treatment of potentially life-threatening infections in all patients.

Topics: Acute Kidney Injury; Adult; Aged; Critical Care; Female; Half-Life; Hemodiafiltration; Hemofiltration; Humans; Injections, Intravenous; Linear Models; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Prospective Studies; Sepsis; Thienamycins

Emphysematous pyelonephritis most often presents as an acute medical emergency, typically in a septic diabetic patient with acute renal failure. The management of this condition has traditionally been surgical, with nephrectomy. However, some recent reports have described successful medical interventions. We describe a case of acute bilateral emphysematous pyelonephritis in a frail patient not suitable for bilateral nephrectomy and long-term dialysis. This condition was managed medically, not surgically, with intensive antibiotic and circulatory support. The outcome was complete recovery after months of hospital-based treatment. We discuss the management of this rare but important condition in detail.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Combined Modality Therapy; Diabetes Mellitus, Type 2; Emphysema; Hemofiltration; Humans; Male; Meropenem; Middle Aged; Pyelonephritis; Sepsis; Thienamycins; Treatment Outcome; Vancomycin

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

In order to evaluate the antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates from blood and cerebrospinal fluid that were obtained from January, 1993 to December, 1994. The results are summarized as follows; 1. The MIC-range, 50% MIC (MIC50) and 90% MIC (MIC90) of MEPM were equal to those of imipenem (IPM) and panipenem (PAPM) against Streptococcus pneumoniae including benzylpenicillin (PCG)-insensitive or -resistant S. pneumoniae, Streptococcus agalactiae and Listeria monocytogenes which are Gram-positive strains, and were stronger than those of ampicillin (ABPC) and cefotaxime (CTX). 2. The MIC-range, MIC50 and MIC90 of these 3 drugs of carbapenems (MEPM, IPM and PAPM) were different against Escherichia coli and Haemophilus influenzae which are Gram-negative strains. The MIC90 of MEPM was < or = 0.025 microgram/ml and those of IPM and PAPM were 0.2 microgram/ml against E. coli. The MIC90 of MEPM was 0.1 microgram/ml, that of IPM was 25 micrograms/ml and that of PAPM was 6.25 micrograms/ml against H. influenzae. Thus, the antimicrobial activity of MEPM was stronger than those of IPM and PAPM. The MIC90's of IPM and PAPM against H. influenzae were high with the MIC of IPM at 12.5 approximately 25 micrograms/ml and the MIC of PAPM at 3.13 approximately 12.5 micrograms/ml against 3 IPM-resistant strains among 17 isolates. 3. The MIC90 of ABPC was 0.39 microgram/ml and that of CTX was 0.1 microgram/ml against 20 strains of S. pneumoniae including 6 strains of PCG-insensitive or resistant S. pneumoniae. The MIC90 of ABPC and CTX were higher than those of 3 carbapenem drugs. There were E. coli of 8 strains with ABPC-high resistance (the MIC of ABPC was > 100 micrograms/ml) and 2 strains for which MIC of CTX were 0.39 microgram/ml and 3.13 micrograms/ml. It was found that 29.4% of H. influenzae were beta-lactamase producing strains. 4. It appeared that antimicrobial activities of carbapenems, particularly MEPM were strong against clinical isolates from blood and cerebrospinal fluid. MEPM will be first choice drug by empiric therapy in infections including sepsis and purulent meningitis.

Topics: Ampicillin; Blood; Cefotaxime; Cephalosporins; Cerebrospinal Fluid; Escherichia coli; Humans; Imipenem; Listeria monocytogenes; Meningitis, Bacterial; Meropenem; Penicillins; Sepsis; Streptococcus agalactiae; Streptococcus pneumoniae; Thienamycins