meropenem and Bacteremia

In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of 'susceptible' organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs. PubMed was searched to March 2019 with the terms 'carbapenem', 'meropenem', 'imipenem', 'doripenem', 'ertapenem', 'susceptibility' and 'outcomes'. Studies were included in the analysis if patients had Enterobacteriaceae bacteraemia treated with a carbapenem for ≥48 h and mortality was reported. Studies were excluded if all isolates were either susceptible or resistant to meropenem based on CLSI 2010 breakpoints or if only carbapenemase-producing isolates were included. Authors were contacted for patient-level data. The primary outcome was 30-day mortality, with planned subset analyses of patients treated with meropenem, receiving active combination therapy, treated in the ICU or infected with Klebsiella pneumoniae. Of 157 articles identified, 4 met the inclusion criteria (115 eligible patients). The odds of mortality increased with each increasing meropenem MIC dilution (OR = 1.51, 95% CI 1.06-2.15) as a continuous variable. A similar increase in odds was observed in patients treated with meropenem, treated in the ICU, infected with K. pneumoniae or receiving no other active antimicrobials. Increasing meropenem MICs in Enterobacteriaceae were associated with increased mortality; however, more work is needed to define optimal clinical decision rules for infections within the susceptible range.

Topics: Anti-Bacterial Agents; Bacteremia; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests

Capnocytophaga is a group of facultative anaerobic gram-negative bacteria present in the oral cavity of humans, dogs and cats, as part of their normal oral flora. Here, we described two cases of bloodstream infections (BSI) caused by Capnocytophaga in neutropenic autologous hematopoietic stem cell transplantation (auto-HSCT) patients with mucositis (Grade I and Grade III) identified by Maldi-Tof. They were successfully treated with β-lactam (meropenem and piperacillin-tazobactam). The species C. sputigena was confirmed by 16S rRNA gene sequencing in one patient. The review of literature showed that C. ochraceae was the most frequent species causing BSI in auto-HSCT patients and that the patients usually presented mucositis and were neutropenic at the onset of the infection.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Capnocytophaga; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Meropenem; Middle Aged; Mucositis; Neutrophils; Piperacillin; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Tazobactam; Transplantation, Autologous

Pantoea is a Gram-negative, non-encapsulated, non-spore-forming, ubiquitous straight rod which can be isolated from geographical and ecological sources such as plant surfaces, buckwheat seeds, human feces, and the environment. The genus Pantoea is a rare pathogen in a clinical setting, and is divided into 20 different species such as Pantoea agglomerans, Pantoea ananatis, Pantoea deleyi, Pantoea dispersa, Pantoea septica, Pantoea stewartii or Pantoea rwandensis. Pantoea dispersa has been reported to cause other infections, including respiratory infections, neonatal sepsis, and bloodstream infections. We report a case of Pantoea dispersa bacteremia caused by acute cholangitis. This is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis as far as we had searched.. A 38-year-old Japanese woman suffered from acute cholangitis; a blood culture showed that Gram-negative rod was positive. The treatment was successful with intravenously administered meropenem, and it was switched to orally administered levofloxacin according to microbiological susceptibility. The organism was identified as Pantoea dispersa by both genetic investigation by 16S ribosomal RNA and additional biochemical tests. To the best of our knowledge, this is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis.. The epidemiology and clinical features of Pantoea dispersa are still unknown. More cases of infections caused by Pantoea dispersa might be revealed with advancing technical methods, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16S ribosomal RNA analysis. Physicians must know that a variety of infections caused by Pantoea dispersa could occur in immunocompromised as well as immunocompetent patients.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Bacteremia; Bile Ducts; Cholangitis; Enterobacteriaceae Infections; Female; Humans; Immunocompetence; Immunocompromised Host; Levofloxacin; Meropenem; Pantoea

There is currently a paucity of published literature focused on the treatment of infections caused by NDM-producing organisms.. We describe a case of a bacteraemia caused by an extensively drug-resistant (XDR) New Delhi metallo-β-lactamase (NDM)-producing Serratia marcescens and review the treatment options for XDR NDM-producing Enterobacteriaceae.. Infections caused by New Delhi beta-lactamase (NDM)-producing Enterobacteriaceae are becoming increasingly prevalent worldwide. The presence of the enzyme results in multidrug-resistant and extensively drug-resistant phenotypes which often pose a treatment challenge. Despite this challenge, case reports and series have demonstrated good clinical outcomes with numerous treatment options in comparison to infections due to KPC-producing Enterobacteriaceae.. Further good-quality research focused on the treatment of NDM-producing Enterobacteriaceae is warranted.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Child; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Meropenem; Serratia Infections; Serratia marcescens; Thienamycins; Treatment Outcome

Herein we report two cases of infections caused by Tissierella praeacuta and a review of the literature. The first case was a septic pseudarthrosis of the left femur after multiple fractures. Two per-operative samples were positive with T. praeacuta. The patient was successfully treated by piperacillin - tazobactam and metronidazole. The second case was a bacteremia in a patient suffering from pyonephrosis and a hepatic abscess. The treatment was meropenem. No relapses were observed in both cases. Identification of the strains using MALDI-TOF coupled to mass spectrometry (MS) (Beckman coulter, France) was inconclusive in the two cases. Identification by 16S rRNA sequencing was then performed. This bacterium was susceptible to beta-lactams, chloramphenicol, rifampicine and metronidazole.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Femoral Neck Fractures; Femur; Firmicutes; Humans; Liver Abscess; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Polymerase Chain Reaction; Pseudarthrosis; Pyonephrosis; RNA, Ribosomal, 16S; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thienamycins; Treatment Outcome

We describe a 15-year-old patient with X-linked agammaglobulinemia who developed malabsorption and bacteremia due to infection of Helicobacter pylori and Campylobacter jejuni. The Campylobacter bacteremia was only recognized after subculturing of blood culture bottles that failed to signal in the automated system. After 2 weeks of treatment with meropenem and erythromycin for 4 weeks, the patient developed a relapse of bacteremia 10 months later with a high level erythromycin resistant C. jejuni. Sequencing revealed an A2058C mutation in the 23 S rRNA gene associated with this resistance. Treatment with doxycycline for 4 weeks finally resulted in complete eradication. This case report illustrates the importance for physicians to use adapted culture methods and adequate prolonged therapy in patients with an immunodeficiency. A summary of published case reports and series of patients with hypogammaglobulinemia or agammaglobulinemia with Campylobacter or Helicobacter bacteremia is given.

Topics: Adolescent; Agammaglobulinemia; Anti-Bacterial Agents; Bacteremia; Campylobacter Infections; Campylobacter jejuni; Doxycycline; Drug Resistance, Bacterial; Erythromycin; Genetic Diseases, X-Linked; Helicobacter Infections; Helicobacter pylori; Humans; Immunocompromised Host; Malabsorption Syndromes; Male; Meropenem; Mutation; Recurrence; Thienamycins

Infection with Campylobacter species is a predominant cause of food-borne gastroenteritis in the industrialized world. Bacteremia is detected in <1% of patients with diarrhea, mainly in immunocompromised hosts or those in the extremes of age. Reported here is the case of a 78-year-old, immunocompromised male patient with Campylobacter jejuni subsp. jejuni bacteremia complicated by cellulitis. The infection was characterized by a protracted course with several recurrences and refractoriness to multiple antibiotic regimens, responding only to a prolonged course of meropenem treatment. The frequency of cellulitis as reflected in previously reported series of Campylobacter bacteremia and the clinical characteristics of this difficult-to-treat infection are reviewed.

Topics: Aged; Bacteremia; Campylobacter Infections; Campylobacter jejuni; Cellulitis; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunocompromised Host; Male; Meropenem; Myelodysplastic Syndromes; Recurrence; Risk Assessment; Roxithromycin; Severity of Illness Index; Thienamycins; Treatment Outcome

Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant. Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7-10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population.. The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals.. NCT04478721.

Topics: Bacteremia; Cephalosporins; Clinical Trials, Phase III as Topic; Enterobacteriaceae; Humans; Meropenem; Multicenter Studies as Topic; Penicillins; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic

Although survival of children with hematological diseases and cancer has increased dramatically, febrile neutropenia (FN) is a frequently observed complication and is sometimes life-threatening in pediatric cancer patients. A prospective, randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) for pediatric patients with FN. Ninety-nine patients with 394 episodes were randomly assigned to receive MEPM or PIPC/TAZ. MEPM was administered at 120 mg/kg/day as a 1-h drip infusion 3 times a day. On the other hand, PIPC/TAZ was administered at 360 mg/kg/day as a 1-h drip infusion 4 times a day. MEPM was effective in 69.5% of the 200 episodes, and PIPC/TAZ was effective in 77.2% of the 193 episodes. Compared with our previous study of MEPM 120 mg/kg/day as a 1-h drip infusion 3 times a day versus PIPC/TAZ 337.5 mg/kg/day as a 1-h drip infusion 3 times a day, the success rate of the MEPM group was not different. However, the success rate of the PIPC/TAZ group was higher than in the previous study (p = 0.001). In particular, the success rate in patients ≥ 15 years of age was improved in the PIPC/TAZ group of the present study compared with the previous study (p = 0.005).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteremia; Body Weight; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Febrile Neutropenia; Historically Controlled Study; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Infusions, Intravenous; Maximum Tolerated Dose; Meropenem; Neoplasms; Piperacillin, Tazobactam Drug Combination; Stem Cell Transplantation; Young Adult

Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.. To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.. Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.. Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.. The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.. Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.. Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.. anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cause of Death; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification.. This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings.. The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.. NCT01732250 and 2012-004819-31; Pre-results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Greece; Humans; Israel; Italy; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Research Design; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.. The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.. The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Clinical Protocols; Drug Resistance, Microbial; Escherichia coli Infections; Humans; Klebsiella Infections; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sample Size; Thienamycins

An analysis of subjects with concurrent bacteraemia and either nosocomial pneumonia, complicated intra-abdominal infection or complicated urinary tract infection from six phase 3 clinical trials demonstrated similar cure rates and clearance of bacteraemia in patients treated with doripenem and comparator agents.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Female; Humans; Imipenem; Intraabdominal Infections; Male; Meropenem; Ofloxacin; Pneumonia; Thienamycins; Treatment Outcome; Urinary Tract Infections

Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance.. This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis.. In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods.. We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cefepime; Cephalosporins; Ciprofloxacin; Drug Administration Schedule; Female; Fever; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Meropenem; Middle Aged; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins

The bactericidal activity of β-lactams is determined by the time that concentrations in tissue and serum are above the minimum inhibitory concentration (T>MIC) for the pathogen. The aim of this study was to compare the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for meropenem between administration by bolus injection and a 3-h infusion. The study was a randomised, three-way, cross-over design in eight febrile neutropenic patients with bacteraemia. Each subject received meropenem in three regimens consecutively: (i) a bolus injection of 1g every 8 h (q8h) for 24 h; (ii) a 3-h infusion of 1 g q8h for 24 h; and (iii) a 3-h infusion of 2 g q8h for 24h. For pathogens with an MIC of 4 μg/mL, the PTA of achieving 40% T>MIC following administration of meropenem by a bolus injection of 1g q8h, a 3-h infusion of 1 g q8h and a 3-h infusion of 2g q8h was 75.7%, 99.24% and 99.96%, respectively. Only the 3-h infusion of 2 g q8h achieved a PTA >99% for 40% T>MIC for a MIC of 8μg/mL. By referral to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC distributions, the three regimens of meropenem were predicted to achieve a CFR≥90% against Escherichia coli and Klebsiella spp. In conclusion, a 3-h infusion of 2 g of meropenem q8h resulted in the highest PTA rates. The three regimens of meropenem had high probabilities of achieving optimal impact against E. coli and Klebsiella spp.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Critical Illness; Escherichia coli; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins; Treatment Outcome; Young Adult

It is important to take into consideration the duration for which the plasma concentration of the drug is higher than the Minimal Inhibitory Concentration during treatment with carbapenem antibiotics, because the antibiotics are time-dependent drugs. A preliminary study of the administration of carbapenem antibiotics on the basis of the pharmacokinetics/pharmacodynamics (PK/PD) was conducted.. Ten patients with intraabdominal infection.. The patients were divided into two groups: the first group was assigned to administration of a carbapenem antibiotic (meropenem) at a daily dose of 0.5 g in 3 divided doses, each dose by intravenous infusion over 3 hours (Group 3 H), and the other group was assigned to administration of each dose over 30 minutes (Group 30 M). The body temperature (BT), white blood cell count (WBC), serum C-reactive protein (CRP) level, and the systemic inflammatory reactive syndrome (SIRS) score before and 96 hours after the drug administration were compared between Group 3 H and Group 30 M.. There were 5 patients (mean age, 67.4+/-14.6 years) in Group 3H and 5 patients (mean age, 60.0+/-12.8 years) in Group 30 M. The evaluated parameters (BT, WBC, CRP, SIRS score) before the drug administration in Groups 3 H and 30M were not significant. Group 3 H showed significant decreases in the SIRS scores at 96 hours after the drug administration, however, there were no significant differences in the BT, WBC or CRP between the two groups.. Group 3 H showed early improvement in the SIRS scores. Administration of carbapenem antibiotics based on the PK/PD is important, and requires further studies.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Bacteremia; Carbapenems; Drug Administration Schedule; Female; Humans; Male; Meropenem; Middle Aged; Thienamycins

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Empiricism; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infant; Lymphoma, Non-Hodgkin; Male; Meropenem; Neoplasms; Neutropenia; Therapeutic Equivalency; Thienamycins; Treatment Outcome

Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia < 500/microliter, and fever > 38.5 degrees C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n = 34) and ceftazidime/amikacin (n = 37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p > 0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Ceftazidime; Cephalosporins; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Neutropenia; Thienamycins

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

To determine the antibacterial susceptibility pattern of bacteraemia isolates of Salmonella enterica serovar typhi and paratyphi.. The retrospective descriptive observational study was conducted at the Microbiology section of Dow Diagnostic Research and Reference Laboratory, and comprised blood culture reports from January 1, 2017, to Dec 30, 2020, which were screened for the presence of Salmonella typhi and paratyphi growth The frequency of the isolates and their antibiotic resistance patterns were analysed. Data was analysed using SPSS 20.. Of the 174,190 blood culture samples, 62,709(36%) were positive for bacterial growth. Salmonella were isolated in 8,689(13.8%) samples of which 8,041(92.5%) were Salmonella typhi, 529(6%) were Salmonella paratyphi A and 119(1.3%) were Salmonella paratyphi B. There was a drastic increase in resistance to third-generation cephalosporin in Salmonella typhi from 71(12.8%) in 2017 to 1,420(71%) in 2018, 2,850(74.6%) in 2019 and 1,251(77%) in 2020. All isolates were sensitive to meropenem and azithromycin.. A high number of extensively drug-resistant typhoid cases due to Salmonella typhi were found. All isolates were sensitive to meropenem and azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Resistance, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Pakistan; Retrospective Studies; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

The standard meropenem (MEPM) regimen allowed by insurance in Japan is 0.5 g two or three times a day. Differences in dosages and administration schedules in Japan were evaluated.. Patients with bacteremia for whom MEPM was used as the initial treatment at our institution between 2016 and 2021 were included. We retrospectively investigated patients classified into two groups: those treated according to severe infections (high-dose groupand others (low-dose group). After propensity score matching, we compared the probability of achieving free drug blood levels above the minimum inhibitory concentration (MIC) in 24 h (%fT > MIC) and outcomes.. The probability of 100% fT > MIC was significantly higher in the high-dose group (96.4% vs 74.5%, odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.2-0.4, P = < 0.001). Regarding outcomes, the 30-day mortality rate was significantly lower in the high-dose group (1.4% vs. 11.4%, OR = 8.0, 95% CI = 1.5-43.7, P = 0.019).. To improve outcomes in patients with bacteremia treated with MEPM, support for appropriate antimicrobial use is necessary for compliance with the dosage and administration schedule according to severe infections in initial treatment.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Humans; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Thienamycins

Infections caused by Robinsoniella peoriensis, particularly bacteremia, are rare, of which only six cases were reported R. peoriensis bloodstream infections. This case report describes an instance of R. peoriensis bacteremia arising while we treated the patient with piperacillin-tazobactam. We treated an 84-year-old female patient with peritoneal carcinoma and febrile neutropenia using piperacillin-tazobactam. The patient's fever subsided. However, she developed a fever again on the fourth day of treatment with piperacillin-tazobactam. Blood cultures taken at this time were positive for R. peoriensis. We substituted meropenem and vancomycin for piperacillin-tazobactam, after which the patient improved. We administered meropenem and vancomycin for 17 days. There is currently no appropriate established treatment for R. peoriensis. In this case, we isolated R. peoriensis from blood cultures using piperacillin-tazobactam, although it was susceptible to piperacillin-tazobactam in vitro. Therefore, monotherapy with penicillins, especially piperacillin-tazobactam, may not be sufficient for R. peoriensis infections, although it was susceptible in vitro. Carbapenem may be effective in the treatment of R. peoriensis bloodstream infections.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Female; Fever; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Vancomycin

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

Campylobacter bacteremia is an uncommon disease that mainly occurs in immunocompromised patients and is associated with antibiotic resistance, particularly in Campylobacter coli. We report a patient with persistent blood infection because of a multidrug-resistant (MDR) C. coli strain over a 3-month period. Through this period monotherapy with meropenem was associated with the development of resistance to it. Improving immunity status and a combined therapy for intestinal decolonization were useful to control persistent C. coli infection in this patient.

Topics: Anti-Bacterial Agents; Bacteremia; Campylobacter coli; Campylobacter Infections; Hematologic Neoplasms; Humans; Meropenem

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

Herein, we aimed to describe the outcomes of patients with blood stream infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) who received ertapenem plus meropenem combination treatment (EMCT). A total of 53 patients with culture proven CR-Kp bacteremia treated with ertapenem + meropenem were included. The patients with secondary bacteremia due to urinary tract infection exhibited a significantly lower 1-month mortality (OMM), particularly in those with microbiological eradication and those with end-of-treatment success. Salvage EMCT resulted in 49% 1-month survival.

Topics: Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ertapenem; Humans; Klebsiella pneumoniae; Meropenem; Salvage Therapy

The utility of weekly rectal swab surveillance cultures (RSSCs) as a resource to identify gut colonization with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and guide empirical antibiotic therapy in hematopoietic stem cell transplantation (HSCT) recipients continues to be a subject of interest. There is an urgent need to assess and justify modifications to empirical antibiotics based on regional epidemiology and patient groups. This study aimed to study the utility of weekly rectal swab surveillance cultures (RSSCs) to guide empirical antibiotic therapy and to examine the impact of gut colonization on transplantation outcomes. This retrospective analysis of 317 successive first HSCTs performed mainly for hemoglobinopathies was conducted in 3 pediatric bone marrow transplantation centers in the Indian subcontinent between April 2016 and April 2021. Transplantation, infection control, and febrile neutropenia management protocols were identical in the 3 centers. First-line antibiotics were chosen based on RCCS reports, with meropenem used for ESBL and high-dose meropenem with colistin used for carbapenemase-resistant colonization for first half of the study, with no adjustment made in the second half. Clinical response to antibiotics, long-term outcomes, antibiotic-resistant bacteremia, and acute graft-versus-host disease (GVHD) were analyzed. The log-rank test, chi-square, and Wilcoxon rank-sum tests were used to compare data using R Statistical software. Of the 871 weekly RSSCs done, 162 were positive for ESBL- or KPC-resistant organism. RCCSs were ESBL-positive in 106 patients (33%) and KPC-positive in 10 patients (3%). Among the 97 ESBL-positive patients for whom a antimicrobial susceptibility testing report was available, only 22 (25%) demonstrated clinical resistance to piperacillin-tazobactam (Pip-Taz). Among the 10 KPC-positive patients, only 4 (40%) demonstrated clinical resistance to Pip-Taz and 3 (30%) had clinical resistance to meropenem. Two-thirds of patients with ESBL-positive RSSC in whom first-line empirical antibiotics were used responded clinically. Even among the 15 patients who were resistant to first-line empirical antibiotics (Pip-Taz) on RSSC reports, 67% responded clinically to Pip-Taz. Twenty-seven of these patients (56%) never needed carbapenem therapy. Empirical Pip-Taz therapy in ESBL-positive patients did not prolong meropenem use within 100 d

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Child; Escherichia coli; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infection Control; Klebsiella pneumoniae; Meropenem; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; United States

Meropenem is a broad-spectrum carbapenem antibiotic with mostly renal excretion. Conflicting data are available regarding meropenem pharmacokinetics in critically ill neonates on concomitant continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Our objectives were to assess meropenem clearance in a neonate on CRRT and ECMO, compare it to previously published data and assess whether dose recommendations can be generalized in this population.. A 2.5 kg male infant with a large diaphragmatic hernia was delivered by cesarean section at week 35 and immediately mechanically ventilated due to shock and respiratory insufficiency. He underwent surgical correction of the hernia, but developed recurrent sepsis, multiorgan failure and pulmonary hypertension. He remained mechanically ventilated and required ECMO and continuous venovenous hemodiafiltration. He was started on meropenem 40 mg/kg/dose, every 8 hs for Enterobacter cloacae bacteremia and sepsis, but due to lack of clinical and microbiologic response despite in vitro susceptibility, he was started on a continuous meropenem infusion of 240 mg/kg/d, based on dose recommendations in a similar case. We measured steady state meropenem plasma concentrations on 2 occasions, during ECMO and continuous venovenous hemodiafiltration (CVVHDF) and then on CVVHDF only.. Meropenem serum concentrations were 90 and 64 mg/L on the first and second occasion (therapeutic target concentration, 10 mg/L) corresponding to a clearance of 1.9 and 2.6 mL/kg/min. This clearance estimate was substantially lower than that reported in toddlers on CRRT and ECMO in some studies.. In neonates and infants, meropenem clearance is difficult to predict because of dynamic ontogenetic changes in renal function. This problem is further aggravated in acutely ill infants with decreased renal function, renal replacement therapy and/or ECMO. Therefore, Target Concentration Intervention based on meropenem plasma concentrations is indispensable to ensure therapeutic exposure in this population.

Topics: Anti-Bacterial Agents; Bacteremia; Continuous Renal Replacement Therapy; Extracorporeal Membrane Oxygenation; Humans; Infant, Newborn; Male; Meropenem; Metabolic Clearance Rate

Hospital antibiograms guide initial empiric antibiotic treatment selections, but do not directly inform escalation of treatment among nonresponding patients.. Using gram-negative bacteremia as an exemplar condition, we sought to introduce the concept of an escalation antibiogram. Among episodes of gram-negative bacteremia between 2017 and 2020 from 6 hospitals in the Greater Toronto Area, we generated escalation antibiograms for each of 12 commonly used agents. Among organisms resistant to that antibiotic, we calculated the likelihood of susceptibility to each of the other 11 agents. In subgroup analyses, we examined escalation antibiograms across study years, individual hospitals, community versus hospital onset, and pathogen type.. Among 6577 gram-negative bacteremia episodes, the likelihood of coverage was ampicillin 31.8%, cefazolin 62.7%, ceftriaxone 67.1%, piperacillin-tazobactam 72.5%, ceftazidime 74.1%, trimethoprim-sulfamethoxazole 74.4%, ciprofloxacin 77.1%, tobramycin 88.3%, gentamicin 88.8%, ertapenem 91.0%, amikacin 97.5%, and meropenem 98.2%. The escalation antibiograms revealed marked shifts in likelihood of coverage by the remaining 11 agents. For example, among ceftriaxone-resistant isolates, piperacillin-tazobactam susceptibility (21.2%) was significantly lower than trimethoprim-sulfamethoxazole (54.2%, P < .0001), ciprofloxacin (63.0%, P < .0001), ertapenem (73.4%, P < .0001), tobramycin (80.1%, P < .0001), gentamicin (82.8%, P < .0001), meropenem (94.3%, P < .0001), and amikacin (97.1%, P < .0001). Trimethoprim-sulfamethoxazole was the second-ranked agent in the meropenem escalation antibiogram (49.6%) and first in the amikacin escalation antibiogram (86.0%). Escalation antibiograms were consistent across 4 study years and 6 hospitals.. Escalation antibiograms can be generated to inform empiric treatment changes in nonresponding patients. These tools can yield important insights such as avoiding the common maneuver of escalating from ceftriaxone to piperacillin-tazobactam in suspected gram-negative bacteremia.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Ceftriaxone; Ciprofloxacin; Ertapenem; Gentamicins; Gram-Negative Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Tobramycin; Trimethoprim, Sulfamethoxazole Drug Combination

Bloodstream infection poses a significant medical emergency that necessitates timely administration of appropriate antibiotics. Standard laboratory workup for antimicrobial susceptibility testing (AST) involves subculture of organisms from positive blood bottles followed by testing using broth microdilution; however, this process can take several days. The Accelerate Pheno Blood Culture panel (Pheno) provides rapid phenotypic testing of selected Gram-negative organisms directly from positive blood cultures. This has the potential to shorten the AST process to several hours and impact time to antimicrobial optimization and subsequent clinical outcomes; however, these metrics have not been assessed in pediatric populations. We retrospectively compared two patient cohorts with blood cultures positive for on-panel Gram-negative organisms: 82 cases tested by conventional AST methods, and 80 cases postintervention at our pediatric hospital. Susceptibility testing from the Pheno yielded 91.5% categorical agreement with a broth microdilution-based reference method with 7.4% minor error, 1.1% major error, and 0.1% very major error rates. The median time from blood culture positivity to AST decreased from 20.0 h to 9.7 h (

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Child; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Pediatric; Humans; Meropenem; Microbial Sensitivity Tests; Retrospective Studies

This case report describes a patient with post-neurosurgical infection and bacteremia caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae. There is limited evidence to guide antibiotic treatment decisions for such infections. The patient was treated with meropenem-vaborbactam (MEV). MEV monotherapy was associated with bacteremia clearance.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Boronic Acids; Drug Combinations; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests

Concerns regarding carbapenem-resistant Klebsiella pneumoniae (CR-Kp), especially in bloodstream infections (BSIs), are continuing to increase worldwide. Several novel agents with activity against BSI CR-Kp have been approved or are in late-stage clinical development. In this study, the antibacterial effects of ceftazidime/avibactam (CZA), aztreonam/avibactam (AZA), meropenem/vaborbactam (MEV), imipenem-cilastatin/relebactam (ICR) and eravacycline (ERV) against three colistin-resistant CR-Kp (COLR-Kp) and four CZA-resistant CR-Kp (CZAR-Kp) were tested by time-kill assay. Klebsiella pneumoniae ATCC® BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-β-lactamase genes. The results revealed that ERV resulted in re-growth of seven tested isolates. CZA and MEV showed a bactericidal effect against isolates harbouring blaKPC-2. ICR reduced the population of six isolates to >5 log10 CFU/mL compared with the initial count. AZA showed a bactericidal effect (>5 log10 CFU/mL) against seven isolates and a bacteriostatic effect (<3 log10 CFU/mL) against one CZAR-Kp isolate. Therefore, AZA and ICR are effective therapeutic candidates for COLR-Kp and CZAR-Kp isolates.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Bacteremia; beta-Lactamase Inhibitors; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Cilastatin; Colistin; Drug Combinations; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tetracyclines

We report a 1-day-old girl who was affected by peritonitis and bacteremia caused by Clostridium tertium following perforation of congenital intestinal atresia. Splenic infarction was also suspected during C. tertium bacteremia. C. tertium was identified by using mass spectrometry and 16S rRNA sequencing. This patient was successfully treated with emergency laparotomy and broad-spectrum antibiotics.

Topics: Anti-Bacterial Agents; Bacteremia; Clostridium Infections; Clostridium tertium; Female; Humans; Infant, Newborn; Meropenem; Peritonitis; Splenic Infarction; Vancomycin

The bacterium Campylobacter insulaenigrae was first isolated from marine mammals of Scotland in 2004. Only one case of C. insulaenigrae infection in humans has been previously reported.. An 89-year-old Japanese man without dementia was admitted to our hospital, because he presented with a fever of 38 °C and weakness in right leg since 5 days. He had organized chronic subdural hematoma (CSH), and no history of pre-infection. At the time of admission, he had paralysis of the extraocular muscle, ataxia, and low manual muscle test score of the right side. He was suspected to have Miller Fisher syndrome; however, these symptoms improved without any treatment. On day 22 in the hospital, the patient presented a fever of 38.8 °C, left cranial nerve disorder, and hemiplegia. On day 25, the patient presented with signs of meningeal irritation; cerebrospinal fluid examination indicated an increase in the number of apocytes and a low glucose level. A contrast magnetic resonance imaging (MRI) scan of the patient's head indicated a contrast enhancement effect in his right meninges. The blood culture showed presence of spirillums; 16S rRNA gene sequencing confirmed that the spirillums in the blood culture were Campylobacter insulaenigrae (C. insulaenigrae). We started treatment with meropenem for bacteremia and meningitis. When the symptoms improved, meropenem was replaced with ampicillin, based on the result of the drug sensitivity test. The treatment continued for 4 weeks.. We report the first case of meningitis caused by C. insulaenigrae bacteremia in humans, and the second clinical report of C. insulaenigrae infection in humans. The bacterial strains isolated from humans and marine mammals had different genotypes. This suggests that different genotypes could be responsible for differences in the hosts. Further case studies are needed to establish the reasons behind the difference in the manifestations of C. insulaenigrae infections reported so far.

Topics: Aged, 80 and over; Ampicillin; Bacteremia; Campylobacter; Campylobacter Infections; Humans; Japan; Magnetic Resonance Imaging; Male; Meningitis; Meropenem; Microbial Sensitivity Tests; RNA, Ribosomal, 16S; Sequence Analysis, RNA

Polymicrobial. We conducted a single-center retrospective cohort study of patients with KP-BSI from 1 January 2013 to 31 December 2018 and collected the clinical data by reviewing electronic medical records.. Of the 818 patients with KP-BSI recruited, 13.9% (114/818) were polymicrobial KP-BSI. The severity of illness in polymicrobial and monomicrobial KP-BSI was similar, while the rate of resistance to carbapenems was obviously higher in polymicrobial KP-BSI (78.1% vs. 65.6%,. It was observed that polymicrobial KP-BSI accounted for a significant proportion among all KP-BSI in the current study. Hospitalization in burn ward and intensive care unit was an independent risk factor for the development of polymicrobial KP-BSI. The patients with polymicrobial KP-BSI had a higher rate of carbapenem-resistant

Topics: Adult; Aged; Bacteremia; Carbapenems; Ertapenem; Female; Hospitalization; Humans; Imipenem; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Odds Ratio; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Topics: Bacteremia; beta-Lactamases; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem

Topics: Anti-Bacterial Agents; Bacteremia; Cefotaxime; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Autologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006-2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empirical antibiotics), and those in the 2013-2017 period are group 2 (levofloxacin prophylaxis and meropenem as empirical antibiotics). The incidence of febrile neutropenia was 72% in group 1 and 86.2% in group 2 (p = 0.004). The majority of infectious episodes were associated with fever of unknown origin: 55% in group 1 and 59% in group 2. Febrile of unknown origin episodes were 82.6% in group 1 and 80% in group 2. Significant differences between both groups were found in age, hypogammaglobulinemia, and advanced disease at ASCT. No differences were found between groups regarding the most common agent documented in positive blood cultures (Gram+ were 66.6% in group 1 and 69% in group 2 (p = 0.68)). Mortality within 100 days of transplant was low, 1.87%. Regardless of the prophylactic regimen used, most patients experience febrile episodes in the ASCT setting, fever of unknown origin is the most common infection complication, and Gram+ agents are prevalent in both groups. Mortality rates were low. According to our results, ASCT is a safe procedure and there is no clear benefit in favor of levofloxacin versus ciprofloxacin prophylaxis. Both anti-infectious approaches are acceptable, yielding similar outcomes.

Topics: Adolescent; Adult; Aged; Amikacin; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftazidime; Ciprofloxacin; Febrile Neutropenia; Female; Fever of Unknown Origin; Hematologic Neoplasms; Humans; Incidence; Levofloxacin; Male; Meropenem; Middle Aged; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Transplantation, Autologous; Uruguay; Young Adult

Topics: Amniocentesis; Amniotic Fluid; Bacteremia; Burkholderia cepacia; Burkholderia Infections; Cesarean Section; Female; Fetal Diseases; Gestational Age; Humans; Male; Meropenem; Middle Aged; Pregnancy

Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients' clinical care.. We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes.. Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to Alcaligenes faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%.. The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.

Topics: Adult; Aged; Aged, 80 and over; Alcaligenes faecalis; Anti-Bacterial Agents; Bacteremia; Ceftazidime; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome

Topics: Acinetobacter baumannii; Aged; Bacteremia; Colistin; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Risk Factors; Survival Analysis

There are few prospective studies with sufficient duration in time to evaluate clinical and antibiotic resistance impact of antibiotic stewardship programs (ASP). This is a descriptive study between January 2012 and December 2017, pre-post intervention. A meropenem ASP was initiated in January 2015; in patients who started treatment with meropenem, an infectious disease physician performed treatment recommendations to prescribers. Prospective information was collected to evaluate adequacy of meropenem prescription to local guidelines and to compare results between cases with accepted or rejected intervention. Analysis was performed to verify variables associated with intervention acceptance and with any significant change in meropenem consumption, hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs), and 30-day all-cause crude death in MDR BSIs. Adequacy of meropenem prescription and de-escalation from meropenem treatment to narrower-spectrum antibiotic improved progressively over time, after ASP implementation (p < 0.001). Interventions on prescription were performed in 330 (38.7%) patients without meropenem justified treatment; in 269, intervention was accepted and in 61 not. Intervention acceptance was associated with shorter duration of treatment, cost, and inpatient days (p < 0.05); intervention rejection was not associated with severity of patient. During the period 2015-2017, meropenem consumption decreased compared with 2012-2014 (rate ratio [RR] 0.67; 95% CI 0.58-0.77, p < 0.001). Also decreased were hospital-acquired MDR BSI rate (RR 0.63; 95% CI 0.38-1.02, p = 0,048) and 30-day all-cause crude death in MDR BSIs (RR 0.45; 95% CI 0.14-1.24, p = 0.096), coinciding in time with ASP start-up. The decrease and better use of meropenem achieved had a sustained clinical, economic, and ecological impact, reducing costs and mortality of hospital-acquired MDR BSIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Child; Cross Infection; Female; Humans; Length of Stay; Male; Meropenem; Middle Aged; Prospective Studies; Young Adult

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Drug Combinations; Drug Resistance, Multiple, Bacterial; Hepatic Artery; Heterocyclic Compounds, 1-Ring; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Male; Meropenem; Microbial Sensitivity Tests; Salvage Therapy; Thrombosis; Young Adult

Topics: Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Escherichia coli; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tazobactam

Topics: Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Escherichia coli; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tazobactam

A 13-year old neutropenic boy succumbed to bacteremia and sepsis with a Pseudomonas aeruginosa strain that rapidly developed resistance to carbapenems during meropenem monotherapy. Whole genome sequencing of the susceptible and resistant blood culture isolates revealed the meropenem-resistant phenotype to be caused by truncation of the OprD gene, which added to a preexisting inactivated mexR gene.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Blood Culture; Fatal Outcome; Humans; Male; Meropenem; Mutation; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Deletion; Whole Genome Sequencing

We assessed the antimicrobial-inactivation capability of BacT/Alert (FA Plus and FN Plus) or Bactec (Plus Aerobic/F and Plus Anaerobic/F) media for 40 antibiotic-bacterium combinations in simulated adult blood cultures. Aside from high recovery rates (93.2% and 88.4%, respectively), we showed that at the lowest but clinically relevant antibiotic concentrations, both BacT/Alert and Bactec media recovered all the organisms tested with drugs except for

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacteria; Blood Culture; Culture Media; Escherichia coli; Humans; Meropenem; Pseudomonas aeruginosa; Time Factors

Although open chest management optimizes hemodynamics after cardiac surgery, it increases postoperative infections and leads to increased mortality. Despite the importance of antibiotic prophylaxis during open chest management, no specific recommendations exist. We aimed to compare the occurrence rates of bloodstream infection and surgical site infection between the different prophylactic antibiotic regimens for open chest management after pediatric cardiac surgery.. Retrospective, single-center, observational study.. PICU at a tertiary children's hospital.. Consecutive patients younger than or equal to 18 years old with open chest management after cardiac surgery followed by delayed sternal closure, between January 2012 and June 2018.. None.. We compared the composite occurrence rate of postoperative bloodstream infection and surgical site infection within 30 days after cardiac surgery between three prophylactic antibiotic regimens: 1) cefazolin, 2) cefazolin + vancomycin, and 3) vancomycin + meropenem. In 63 pediatric cardiac surgeries with open chest management, 17 bloodstream infections, and 12 surgical site infections were identified postoperatively. The composite occurrence rates of bloodstream infection and surgical site infection were 10 of 15 (67%), 10 of 19 (53%), and nine of 29 (31%) in the cefazolin, cefazolin + vancomycin, and vancomycin + meropenem regimens, respectively (p = 0.07). After adjusting for age, open chest management duration, extracorporeal membrane oxygenation use, and nasal methicillin-resistant Staphylococcus aureus colonization in multivariable analysis, there was no significant difference between the cefazolin and the cefazolin + vancomycin regimens (p = 0.19), while the vancomycin + meropenem regimen had a lower occurrence rate of bloodstream infection and surgical site infection than the cefazolin regimen (odds ratio, 0.0885; 95% CI, 0.0176-0.446; p = 0.003).. In this study, a lower occurrence rate of postoperative bloodstream infection and surgical site infection was observed among patients with broad-spectrum antibiotic regimen after pediatric cardiac surgery with open chest management. Further studies, ideally randomized controlled studies investigating the efficacy of broad-spectrum antibiotics and their complications, are warranted before routine implementation of broad-spectrum prophylactic antibiotic regimen.

Topics: Age Factors; Antibiotic Prophylaxis; Bacteremia; Cardiac Surgical Procedures; Cefazolin; Drug Therapy, Combination; Extracorporeal Membrane Oxygenation; Female; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Male; Meropenem; Postoperative Complications; Retrospective Studies; Surgical Wound Infection; Vancomycin

We describe a ceftriaxone-resistant

Topics: Abdominal Pain; Adult; Agglutination Tests; Anti-Bacterial Agents; Azithromycin; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ceftriaxone; Denmark; Drug Resistance; Escherichia coli; Female; Fever; Humans; Meropenem; Microbial Sensitivity Tests; Pakistan; Plasmids; Polymerase Chain Reaction; Pregnancy; Salmonella typhi; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Travel; Typhoid Fever; Whole Genome Sequencing

Topics: Animals; Antibodies, Bispecific; Bacteremia; Immunotherapy; Meropenem; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Treatment Outcome

We investigated variations in the rate of persister cell formation against meropenem in 68 Klebsiella pneumoniae isolates from blood. The persister cell formation rates varied markedly but were not significantly different between the patient survival group and death group at 30 days. In addition, they were not associated with the patients' underlying diseases. However, the isolates of CC15 and CC23 showed higher survival rates against 10× MIC of meropenem than CC11. The survival rate of persister cells was less for amikacin and colistin than that for ciprofloxacin. When combinations of meropenem and other antibiotics were administered, persister formation rates decreased compared with those against only meropenem. However, no synergistic effect to remove persister cells was observed. Further investigation is needed to understand persister cell formation in K. pneumoniae with respect to the mechanism involved and clinical implications and that diverse strategies should be explored to remove persister cells.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Tolerance; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Phenotype

We present a case of a 55-year-old Filipino man who was transferred from another institution where he was recently diagnosed with Crohn's disease but not started on any immunosuppressants. He underwent laparoscopic cholecystectomy with T-tube placement a few weeks prior to admission. On workup, abdominal CT scan was unremarkable, but blood cultures on the third hospital day grew

Topics: Anti-Bacterial Agents; Bacteremia; Burkholderia cepacia; Burkholderia Infections; Drug Therapy, Combination; Humans; Male; Meropenem; Middle Aged; Nebulizers and Vaporizers; Pneumonia; Treatment Outcome

Early detection of resistance in sepsis due to Gram-negative organisms may lead to improved outcomes by reducing the time to effective antibiotic therapy. Traditional methods of resistance detection require incubation times of 18 to 48 h to detect resistance. We have utilised automated specimen processing, digital imaging and zone size measurements in conjunction with direct disc susceptibility testing to develop a method for the rapid screening of Gram-negative blood culture isolates for resistance. Positive clinical blood cultures with Gram-negative organisms were prospectively identified and additional resistant mock specimens were prepared. Broth was plated and antibiotic-impregnated discs (ampicillin, ceftriaxone, piperacillin-tazobactam, meropenem, ciprofloxacin, gentamicin) were added. Plates were incubated, digitally imaged and zone sizes were measured using the BD Kiestra WorkCell laboratory automation system. Minimum, clinically useful, incubation times and optimised zone size cut-offs for resistance detection were determined. We included 187 blood cultures in the study. At 5 h of incubation, > 90% of plates yielded interpretable results. Using optimised zone size cut-offs, the sensitivity for resistance detection ranged from 87 to 100%, while the specificity ranged from 84.7 to 100%. The sensitivity and specificity for piperacillin-tazobactam resistance detection was consistently worse than for the other agents. Automated direct disc susceptibility screening is a rapid and sensitive tool for resistance detection in Gram-negative isolates from blood cultures for most of the agents tested.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Blood Culture; Ceftriaxone; Ciprofloxacin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Gentamicins; Gram-Negative Bacteria; Humans; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

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

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Tertiary Care Centers; Thienamycins; Treatment Outcome

A 65-year-old Japanese man with bilateral carotid atherosclerosis presented with right neck pain and fever. Contrast-enhanced computed tomography suggested carotid arteritis, and carotid ultrasonography showed an unstable plaque. The patient developed a cerebral embolism, causing a transient ischemic attack. Helicobacter cinaedi was detected in blood culture, and H. cinaedi-associated carotid arteritis was diagnosed. Empirical antibiotic therapy was administered for 6 weeks. After readmission for recurrent fever, he was treated another 8 weeks. Although the relationship between H. cinaedi infection and atherosclerosis development remains unclear, the atherosclerotic changes in our patient's carotid artery might have been attributable to H. cinaedi infection.

Topics: Aged; Anti-Bacterial Agents; Arteritis; Bacteremia; Carotid Artery Diseases; Ceftriaxone; Helicobacter; Helicobacter Infections; Humans; Male; Meropenem; Thienamycins

The treatment of Achromobacter xylosoxidans bacteremia is challenged by antimicrobial resistance and the paucity of data. We aimed at offering a contemporary description of this uncommon entity.. Retrospective case series of 13 episodes of A. xylosoxidans bacteremia diagnosed over a 10-year period (November 2007 to May 2017) in our tertiary care center.. Solid organ cancer and heart failure were the most common comorbidities (4/13 [30.7%]). All but one episodes were hospital-acquired. Most patients had received previous antibiotic therapy (7/13 [53.8%]) and had a central venous catheter in place (6/13 [46.1%]). Primary and intravascular catheter were the most common sources (4/13 [30.7%] each). Meropenem was the agent with best in vitro activity (92.3% [12/13] of susceptible isolates). All-cause 30-day mortality (overall 23.1%) was higher in patients with primary bacteremia (50.0% vs. 11.1%; P-value=0.203) and prior chemotherapy (66.7% vs. 10.0%; P-value=0.108).. Bacteremia due to A. xylosoxidans constitutes a serious infection among immunocompromised hosts. Carbapenem-based therapy may be appropriate in most cases.

Topics: Achromobacter denitrificans; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Child; Comorbidity; Female; Gram-Negative Bacterial Infections; Heart Failure; Humans; Immunocompromised Host; Incidence; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Retrospective Studies; Thienamycins; Young Adult

Topics: Adult; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Drug Combinations; Enterobacter aerogenes; Enterobacteriaceae Infections; Heterocyclic Compounds, 1-Ring; Humans; Male; Meropenem; Microbial Sensitivity Tests; Renal Dialysis; Serratia marcescens; Treatment Outcome

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP-6 CPE infections. We describe two patients who developed bacteremia caused by IMP-6 CPE after surgery for cancer who were successfully treated with amikacin plus high-dose prolonged-infusion meropenem. Both patients were treated over a 2-week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic-related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP-6 CPE.

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins; Treatment Outcome

In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring.. A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality.. Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis.. Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Cross Infection; Drug Monitoring; Female; Humans; Imipenem; Infant; Intensive Care Units; Male; Meropenem; Middle Aged; Piperacillin; Pneumonia; Prognosis; Tertiary Care Centers; Thienamycins; Urinary Tract Infections; Vancomycin; Young Adult

Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients.. Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and β-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined.. Thirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal β-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%.. Mortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

Topics: Adolescent; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Fever; Fluoroquinolones; Humans; Male; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins

Topics: Bacteremia; Cephalosporins; Drug Resistance, Bacterial; Humans; Immunocompromised Host; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Carbapenem-resistant Pseudomonas aeruginosa infections have been a challenge and issue in hospital settings. However, the clinical impact of P. aeruginosa blood isolates resistant only to carbapenems has never been discussed previously.. To assess the risk factors and clinical significance of bacteremia caused by carbapenem resistance only P. aeruginosa (CROPA), a 6-year retrospective case-control study was conducted. The CROPA strains were defined as isolates susceptible to ciprofloxacin, antipseudomonal penicillins and cephalosporins, and aminoglycosides but resistant to one antipseudomonal carbapenem (imipenem or meropenem) or both. The controls were selected among patients with bacteremia due to P. aeruginosa susceptible to all above classes of antipseudomonal antibiotics, which was defined as all-susceptible P. aeruginosa.. Twenty-five patients had at least one blood culture positive for CROPA, and 50 controls had all-susceptible P. aeruginosa bacteremia. CROPA bacteremia had a high 30-day mortality rate (72.0%), as compared to 26.0% for the controls (p < 0.001). Through multivariate analysis, carbapenem exposure was the only risk factor for developing CROPA bacteremia (p = 0.002). A comparison between the surviving and deceased patients with CROPA bacteremia showed that nine (50%) of those who died, but none of the survivors, received carbapenems as the initial empirical therapy (p = 0.027).. Carbapenem exposure was associated with emergence of CROPA infections. Repeated carbapenem use in such patients might increase rates of inappropriate initial empirical treatment and mortality. Prudent carbapenem use is important to reduce the emergence of CROPA.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Case-Control Studies; Cephalosporins; Ciprofloxacin; Cross Infection; Female; Hospitals; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Mortality; Multivariate Analysis; Odds Ratio; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Risk Factors; Severity of Illness Index; Taiwan; Thienamycins

European centers (n = 226) involved in the Tigecycline Evaluation and Surveillance Trial (TEST, 2004-2014) submitted data and bacterial isolates.. Minimal inhibitory concentrations and susceptibility were determined using Clinical and Laboratory Standards Institute methods and European Committee on Antimicrobial Susceptibility Testing breakpoints.. The rates of the following resistant pathogens increased from 2004 to 2014: extended-spectrum β-lactamase (ESBL)-positive Escherichia coli (from 8.9 to 16.9%), multidrug-resistant Acinetobacter baumannii complex (from 15.4 to 48.5%), and ESBL-positive Klebsiella pneumoniae (from 17.2 to 23.7%). The rate of methicillin-resistant Staphylococcus aureus was 27.5% in 2004 and 28.9% in 2014. Resistance to the carbapenems (imipenem and meropenem) was 37.4 and 14.5% for A. baumannii complex and Pseudomonas aeruginosa, respectively. Carbapenem resistance was ≤4.3% among the Enterobacteriaceae and 0.2% against Streptococcus pneumoniae. The resistance to tigecycline ranged between 7.4% against ESBL-producing K. pneumoniae and 0.0% against S. aureus.. The carbapenems and tigecycline were active against Enterobacteriaceae. Agents with activity against A. baumannii complex and P. aeruginosa are limited. The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Thienamycins; Tigecycline

The objective of this study was to assess the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem (MEM) in critically-ill patients with bloodstream infections (BSI) due to Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) with MEM minimum inhibitory concentrations (MICs) ≥16 mg/L. Nineteen critically-ill patients with KPC-Kp BSI were given combination therapy including MEM, tigecycline, plus colistin or gentamicin (according to susceptibility testing). MEM was administered as an extended 3-hour infusion of 2 g every 8 hours, or adjusted according to renal function. MEM plasma concentrations were determined by high-performance liquid chromatography. PK/PD targets for MEM were defined as T > 40% 1×MIC and T > 40% 4×MIC. Possible synergisms between MEM and coadministered agents were assessed by time-kill assays based on plasma levels for MEM and on fixed plasma concentrations for the other agents. In none of 19 patients MEM reached any PK/PD target. The actual MEM MICs were 256, 512, and 1024 mg/L in 1, 3, and 15 isolates, respectively. However, theoretically, the PK/PD target of T > 40% 1×MIC could have been achieved in 95%, 68%, 32% and 0% of the isolates for MIC equal to 8, 16, 32, and 64 mg/L, respectively. No synergisms were observed between MEM and coadministered agents. In conclusion, high-dose MEM failed to reach PK/PD targets in 19 patients with BSI due to KPC-Kp with very high MEM MICs. On a theoretical basis, our results suggest a possible usefulness of MEM against resistant blood isolates with MICs up to 32 mg/L.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Synergism; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline

Topics: Actinomycetales Infections; Aged; Anti-Bacterial Agents; Bacteremia; Diagnosis, Differential; Drug Therapy, Combination; Erythema Multiforme; Glucocorticoids; Humans; Male; Meropenem; Prednisolone

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative.. We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes.. Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cohort Studies; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Treatment Outcome

There have been various reports concerning Helicobacter cinaedi infections. However, few reports have examined central nervous system infections.. A 52-year-old man was transferred from the local hospital because of a persistent headache and suspected intracranial subdural empyema. Neurosurgical drainage was performed via burr holes. Gram staining and results from abscess cultures were negative. The blood culture yielded H. cinaedi. He was given an antibiotic regimen consisting of 2 g of ceftriaxone twice a day, but the size of the abscess was not reduced in size at all after 3 weeks of treatment. Neurosurgical drainage was performed again, and the antimicrobial regimen was switched to 2 g of meropenem 3 times a day. The size of the abscess was reduced after 2 weeks of the second drainage and antimicrobial drug change to meropenem. After 4 weeks treatment with meropenem, the patient was discharged, and his symptoms had completely resolved.. H. cinaedi infection should be considered in the differential diagnosis of subdural empyema cases for which Gram staining and abscess culture results are negative. Meropenem can be a first-line drug of choice or an effective alternative treatment for H. cinaedi central nervous system infections.

Topics: Abscess; Anti-Bacterial Agents; Anti-Infective Agents; Bacteremia; Ceftriaxone; Drainage; Empyema, Subdural; Helicobacter; Helicobacter Infections; Humans; Male; Meropenem; Middle Aged; Thienamycins; Treatment Outcome

We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40.7%) had severe sepsis (five) or septic shock (six). The clinical and microbiological success was 77.8 and 74.1% respectively. Crude mortality was 29.6% with attributable mortality of 11.1%. Adverse events, none of them severe, were reported in four patients (14.8%). The double-carbapenem combination as an exclusive regimen represents a safe and valid salvage therapy for untreatable infections by extensively- or pandrug-resistant KPC-producing K.pneumoniae.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Catheter-Related Infections; Female; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Prospective Studies; Salvage Therapy; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

We report a community-acquired bloodstream infection with Acinteobacter ursingii in an HIV-negative woman who injected drugs. The infection was successfully treated with meropenem. Species identification was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Improved identification of Acinetobacter spp. by using this method will help identify clinical effects of this underdiagnosed pathogen.

Topics: Acinetobacter; Acinetobacter Infections; Bacteremia; Community-Acquired Infections; Female; Humans; Meropenem; Middle Aged; Thienamycins

This study investigated the mechanisms underlying the carbapenem resistance of bloodstream isolates of Pseudomonas aeruginosa obtained from two Korean hospitals. Of the 79 P. aeruginosa isolates, 22 and 21 were resistant to imipenem and meropenem, respectively. The 22 imipenem-resistant P. aeruginosa isolates were classified into 7 sequence types (STs) and 13 pulsotypes. Twelve imipenem-resistant isolates from one hospital were found to belong to the international clone ST111. Two imipenem-resistant P. aeruginosa ST235 isolates carried the bla IMP-6 gene, but the remaining 20 isolates did not produce carbapenemases. Mutations in the oprD gene and a related decrease in gene expression were found in 21 and 5 isolates, respectively. However, all imipenemresistant P. aeruginosa isolates showed no significant expression of OprD in the outer membrane as compared with that of carbapenem-susceptible PAO1 strain. Overexpression of genes associated with efflux pumps, including mexB, mexD, mexF, and mexY, was not found in any imipenem-resistant isolate. One imipenem-resistant P. aeruginosa isolate overexpressed the ampC gene. Our results show that the low permeability of drugs due to the mutational inactivation of OprD is primarily responsible for carbapenem resistance in bloodstream isolates of P. aeruginosa from Korean hospitals.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Meropenem; Multidrug Resistance-Associated Proteins; Mutation; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Republic of Korea; Thienamycins

Meropenem-susceptible and -resistant Aeromonas dhakensis isolates from blood cultures of a fatal case of septicemia were analyzed. The two isolates were homologous and gene expression of metallo-β-lactamase in the resistant strain was upregulated. Physicians should be aware of the possibility of the induction of carbapenem-resistance, following the use of carbapenems in the treatment of Aeromonas infection.

Topics: Adolescent; Aeromonas; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Blood; Female; Gene Expression Profiling; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Thienamycins; Time Factors; Up-Regulation

Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited therapeutic options, innovative antimicrobial combinations against carbapenem-resistant Enterobacteriaceae causing severe infections are necessary.A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was complicated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Klebisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of meropenem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock.The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Kidney Transplantation; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Surgical Wound Infection; Thienamycins

Previous studies reported decreased mortality in patients with carbapenemase-producing Klebsiella pneumoniae bloodstream infections (BSIs) treated with combination therapy but included carbapenem-susceptible and -intermediate isolates, as per revised CLSI breakpoints. Here, we assessed outcomes in patients with BSIs caused by phenotypically carbapenem-resistant K. pneumoniae (CRKP) according to the number of in vitro active agents received and whether an extended-spectrum beta-lactam (BL) antibiotic, including meropenem, or an extended-spectrum cephalosporin was administered. We retrospectively reviewed CRKP BSIs at two New York City hospitals from 2006 to 2013, where all isolates had meropenem or imipenem MICs of ≥4 μg/ml. Univariate and multivariable models were created to identify factors associated with mortality. Of 141 CRKP BSI episodes, 23% were treated with a single active agent (SAA), 26% were treated with an SAA plus BL, 28% were treated with multiple active agents (MAA), and 23% were treated with MAA plus BL. Ninety percent of isolates had meropenem MICs of ≥16 μg/ml. Thirty-day mortality was 33% overall and did not significantly differ across the four treatment groups in a multivariable model (P = 0.4); mortality was significantly associated with a Pitt bacteremia score of ≥4 (odds ratio [OR], 7.7; 95% confidence interval [CI], 3.2 to 18.1; P = 0.1), and immunosuppression was protective (OR, 0.4; 95% CI, 0.2 to 1.0; P = 0.04). Individual treatment characteristics were also not significantly associated with outcome, including use of SAAs versus MAA (26% versus 38%, P = 0.1) or BL versus no BL (26% versus 39%, P = 0.1). In summary, in patients with CRKP BSIs caused by isolates with high carbapenem MICs, the role of combination therapy remains unclear, highlighting the need for prospective studies to identify optimal treatment regimens.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cephalosporins; Drug Therapy, Combination; Female; Humans; Imipenem; Immunosuppressive Agents; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Retrospective Studies; Survival Analysis; Thienamycins; Treatment Outcome

Infection is a major determinant of clinical outcome among patients in the intensive care unit. However, these data are lacking in most developing countries; hence, we set out to describe the profile of nosocomial infection in one of the major tertiary hospitals in northern Nigeria.. Case records of patients who were admitted into the intensive care unit over a 4-year period were retrospectively reviewed. A preformed questionnaire was administered, and data on clinical and microbiological profile of patients with documented infection were obtained.. Eighty-our episodes of nosocomial infections were identified in 76 patients. Road traffic accident (29/76, 38.2%) was the leading cause of admission. The most common infections were skin and soft tissue infections (30/84, 35.7%) followed by urinary tract infection (23/84, 27.4%). The most frequent isolates were Staphylococcus aureus (35/84, 41.7%), Klebsiella pneumoniae (18/84, 21.4%), and Escherichia coli (13/84, 15.5%). High rate of resistance to cloxacillin (19/35, 54.3%) and cotrimoxazole (17/26, 65.4%) was noted among the S aureus isolates. All the Enterobacteriaceae isolates were susceptible to meropenem, whereas resistance rate to ceftriaxone was high (E coli, 55.6%; K pneumoniae, 71.4%; Proteus spp, 50%).. Infection control practice and measures to curtail the emergence of antimicrobial resistance need to be improved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Ceftriaxone; Cloxacillin; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nigeria; Pneumonia, Bacterial; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tertiary Care Centers; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Bloodstream infections (BSI) are life-threatening emergencies. Identification of the common pathogens and their susceptibility patterns is necessary for timely empirical intervention.. We conducted a 4-year retrospective analysis of blood cultures from all patients excluding neonates at the Korle-Bu Teaching hospital, Ghana, from January 2010 through December 2013. Laboratory report data were used to determine BSI, blood culture contamination, pathogen profile, and antimicrobial resistance patterns.. Overall, 3633 (23.16 %) out of 15,683 blood cultures were positive for various organisms. Pathogen-positive cultures accounted for 1451 (9.3 %, 95 % CI 8.5-9.8 %). Infants recorded the highest true blood culture positivity (20.9 %, n = 226/1083), followed by the elderly (13.3 %, n = 80/601), children (8.9 %, n = 708/8000) and adults (7.2 %, n = 437/6000) (p = 0.001 for Marascuilo's post hoc). Overall occurrence of BSI declined with increasing age-group (p = 0.001) but the type of isolates did not vary with age except for Citrobacter, Escherichia coli, Klebsiella, Salmonella, and Enterococcus species. Gram negative bacteria predominated in our study (59.8 %, n = 867/1451), but the commonest bacterial isolate was Staphylococcus aureus (21.9 %, n = 318/1451)-and this trend run through the various age-groups. From 2010 to 2013, we observed a significant trend of yearly increase in the frequency of BSI caused by cephalosporin-resistant enterobacteria (Chi square for trend, p = 0.001). Meropenem maintained high susceptibility among all Gram-negative organisms ranging from 96 to 100 %. Among Staphylococcus aureus, susceptibility to cloxacillin was 76.6 %.. Our study shows a significantly high blood culture positivity in infants as compared to children, adults and the elderly. There was a preponderance of S. aureus and Gram-negative bacteria across all age-groups. Meropenem was the most active antibiotic for Gram-negative bacteria. Cloxacillin remains a very useful anti-staphylococcal agent.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Blood Culture; Cephalosporins; Child; Child, Preschool; Cloxacillin; Drug Resistance, Bacterial; Female; Ghana; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals, Teaching; Humans; Infant; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Thienamycins

Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Aztreonam; Bacteremia; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Retrospective Studies; Rifampin; Teicoplanin; Thienamycins; Vancomycin

Bacteremia due to Pseudomonas aeruginosa resistant to carbapenems is a public health problem due to the limitations it places on therapeutic options, as well as the increased time patients must spend in hospital, costs and the risk of mortality. . To evaluate the risk factors for presentation of bacteremia due to carbapenem-resistant P. aeruginosa acquired in the Hospital Universitario San Ignacio between January 2008 and June 2014. . This was a case control study in which the case patients presented bacteremia due to P. aeruginosa resistant to carbapenems and the control group included patients with P. aeruginosa susceptible to this group of antibiotics. Variables such as the previous use of meropenem and ertapenem, immunosuppression and neoplasia were measured. Mortality and duration of hospital were also described. . In all, 168 patients were evaluated, of which 42 were cases and 126 controls. Using a multivariate model, the risk factors related to bacteremia due to carbapenem-resistant P. aeruginosa acquired in hospital were the following: use of parenteral nutrition (OR=8.28; 95% CI: 2.56-26.79; p=0); use of meropenem (OR=1.15; 95% CI: 1.03-1.28; p=0.01); and use of ciprofloxacin (OR=81.99; 95% CI: 1.14-5884; p=0.043). . In order to prevent the emergence of carbapenem-resistant P. aeruginosa, antimicrobial control programs should be strengthened by promoting the prudent administration of carbapenems and quinolones. The correct use of parenteral nutrition should also be monitored.

Topics: Bacteremia; beta-Lactams; Carbapenems; Case-Control Studies; Ciprofloxacin; Drug Resistance, Bacterial; Ertapenem; Hospitals; Humans; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Thienamycins

We report a case of Campylobacter volucris bacteremia in an immunocompromised patient with polycythemia vera and alcoholic liver cirrhosis. To our knowledge, this is the first case report in which this organism has been isolated from a human clinical specimen.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Campylobacter; Campylobacter Infections; Drug Resistance, Bacterial; Humans; Immunocompromised Host; Male; Meropenem; Thienamycins

Topics: Anti-Bacterial Agents; Bacteremia; Female; Gastroenteritis; Humans; Infant, Newborn; Male; Meropenem; Rotavirus Infections; Thienamycins; Vancomycin

Topics: Anti-Bacterial Agents; Bacteremia; Bacteriological Techniques; Caulobacteraceae; Female; Gram-Negative Bacterial Infections; Humans; Meropenem; Thienamycins; Treatment Outcome

The absence of meningeal signs and symptoms is rare in patients with bacterial meningitis and may lead to a delay in diagnosis and treatment. Furthermore, the onset of bacterial meningitis associated with pneumocephalus is a rare complication of ear infections. We herein report a rare case of otogenic meningitis complicated by pneumocephalus that was initially missed due to the absence of typical meningeal signs and symptoms and later diagnosed correctly based on a thorough review of the patient's systems.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Dexamethasone; Humans; Male; Meningitis, Bacterial; Meningitis, Pneumococcal; Meropenem; Pneumocephalus; Thienamycins; Treatment Outcome; Vancomycin

Streptobacillus moniliformis is the etiological agent of rat-bite fever, a rare disease in Asia that is difficult to diagnose. We describe an elderly patient living in rat-infested conditions who presented with severe sepsis. He was successfully treated with meropenem, and blood culture revealed infection with S. moniliformis.

Topics: Aged; Animals; Asian People; Bacteremia; Fusobacterium Infections; Humans; Male; Meropenem; Rat-Bite Fever; Rats; Streptobacillus; Thienamycins

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

Topics: Anti-Bacterial Agents; Antiviral Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Ceftazidime; Colectomy; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Ganciclovir; Humans; Immunosuppressive Agents; Intestine, Small; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Ciprofloxacin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin; Treatment Failure

IMP-type metallo-β-lactamase enzymes have been reported in different geographical areas and in various Gram-negative bacteria. However, the risk factors and epidemiology pertaining to IMP-type metallo-β-lactamase-producing Enterobacter cloacae (IMP-producing E. cloacae) have not been systematically evaluated. We conducted a retrospective, matched case-control study of patients from whom IMP-producing E. cloacae isolates were obtained, in addition to performing thorough molecular analyses of the clinically obtained IMP-producing E. cloacae isolates. Unique cases with IMP-producing E. cloacae isolation were included. Patients with IMP-producing E. cloacae were matched to uninfected controls at a ratio of 1 to 3. Fifteen IMP-producing E. cloacae cases were identified, with five of the isolates being obtained from blood, and they were matched to 45 uninfected controls. All (100%) patients from whom IMP-producing E. cloacae isolates were obtained had indwelling devices at the time of isolation, compared with one (2.2%) uninfected control. Independent predictors for isolation of IMP-producing E. cloacae were identified as cephalosporin exposure and invasive procedures within 3 months. Although in-hospital mortality rates were similar between cases and controls (14.3% versus 13.3%), the in-hospital mortality of patients with IMP-producing E. cloacae-caused bacteremia was significantly higher (40%) than the rate in controls. IMP-producing E. cloacae isolates were frequently positive for other resistance determinants. The MICs of meropenem and imipenem were not elevated; 10 (67%) and 12 (80%) of the 15 IMP-producing E. cloacae isolates had a MIC of ≤ 1 μg/ml. A phylogenetic tree showed a close relationship among the IMP-producing E. cloacae samples. Indwelling devices, exposure to cephalosporin, and a history of invasive procedures were associated with isolation of IMP-producing E. cloacae. Screening for carbapenemase production is important in order to apply appropriate clinical management and infection control measures.

Topics: Aged; Aged, 80 and over; Bacteremia; Bacterial Proteins; beta-Lactamases; Cephalosporins; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Hospital Mortality; Humans; Imipenem; Infection Control; Inosine Monophosphate; Japan; Male; Meropenem; Middle Aged; Phylogeny; R Factors; Retrospective Studies; Risk Factors; Tertiary Healthcare; Thienamycins

A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.

Topics: Agammaglobulinemia; Bacteremia; Campylobacter fetus; Campylobacter Infections; Empyema, Pleural; Humans; Immunization, Passive; Immunocompromised Host; Lung; Male; Meropenem; Pleural Effusion; Pleurisy; Radiography; Thienamycins; Young Adult

Ertapenem plus doripenem or meropenem were given in three patients suffering from pandrug-resistant, KPC-2-positive Klebsiella pneumoniae bacteremia (2 patients) and urinary tract infection (1 patient), respectively. All responded successfully, without relapse at follow-up. The results obtained should probably be attributed to ertapenem's increased affinity for the carbapenemases hindering doripenem/meropenem degradation in the environment of the microorganism.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenems; Doripenem; Drug Combinations; Drug Resistance, Bacterial; Ertapenem; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Thienamycins; Treatment Outcome; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Bacteremia; Bacteriuria; Brazil; Drug Resistance, Bacterial; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Linear Models; Meropenem; Microbial Sensitivity Tests; Rectum; Thienamycins

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactams; Case-Control Studies; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Risk Factors; Thienamycins; Treatment Outcome

Enterococcus is an important cause of bacteraemia. Previous epidemiological studies examining risk factors for enterococcal bacteraemia have used traditional case-control study designs, which can be potentially biased. This case-case-control study examining risk factors for enterococcal bacteraemia was conducted over 10 years (January 2000 to December 2009) in a tertiary, university-affiliated hospital. There were 440 episodes of enterococcal bacteraemia, 80 of which were caused by vancomycin-resistant Enterococcus (VRE). Two multivariable models were generated, comparing VRE and vancomycin-susceptible Enterococcus (VSE) with the same control group. VRE bacteraemia was associated with central venous catheter use (OR 11.6, 95% CI 2.6-51.5), neutropenia (OR 16.9, 95% CI 2.4-120.2), and allogenic bone marrow transplantation (OR 18.0, 95% CI 2.4-133.4). In contrast, VSE bacteraemia risk factors included: age (OR 1.0, 95% CI 1.0-1.1), exposure to metronidazole (OR 8.7, 95% CI 1.7-43.5), and gastrointestinal disease (OR 6.4, 95% CI 1.2-34.5). Meropenem use decreased the risk of VSE bacteraemia (OR 0.3, 95% CI 0.1-0.9). Hypoalbuminaemia was the only factor identified in both models (VRE, OR 6.0, 95% CI 1.7-21.1; VSE, OR 3.3, 95% CI 1.4-7.7). The absence of substantial overlap of risk factors for VRE and VSE argues in favour of differences in pathogenesis. These data suggest that environmental sources are more important in VRE bacteraemia. Endogenous sources, particularly the gastrointestinal tract, play a pivotal role in VSE bacteraemia. This study highlights the importance of infection control protocols to reduce the risk of VRE bacteraemia.

Topics: Adult; Age Factors; Aged; Bacteremia; Bone Marrow Transplantation; Case-Control Studies; Catheterization, Central Venous; Enterococcus; Female; Gastrointestinal Diseases; Hospitals; Humans; Hypoalbuminemia; Male; Meropenem; Metronidazole; Middle Aged; Multivariate Analysis; Neutropenia; Odds Ratio; Phenotype; Risk Factors; Thienamycins; Transplantation, Homologous; Vancomycin; Vancomycin Resistance

Acinetobacter species have emerged as opportunistic nosocomial pathogens in intensive care units. Epidemic spread and outbreaks of multidrug-resistant or carbapenem-resistant Acinetobacter baumannii infections have been described worldwide. Species distribution, antimicrobial resistance and genotypes were investigated for Acinetobacter species isolates collected from a single institution in Korea over 7 years. Two hundred and eighty-seven Acinetobacter species isolates were collected from patients with bloodstream infections in one Korean hospital from 2003 to 2010. Most of them belonged to the Acinetobacter calcoaceticus-baumannii complex (94.4 %). The most frequently isolated species was A. baumannii (44.2 %), followed by Acinetobacter nosocomialis (formerly Acinetobacter genomic species 13TU) (34.1 %). The proportion of A. baumannii increased significantly from 2008 to 2010 (40.4 to 50.0 %). From 2008, imipenem and meropenem resistance rates increased significantly compared with 2003-2007 (12.9 % and 20.5 %, respectively, to 41.4 % and 41.5 %, respectively). An increased carbapenem resistance rate between the two periods was identified more clearly amongst A. baumannii isolates. Polymyxin-resistant A. baumannii isolates emerged in 2008-2010, despite the availability of few isolates. The increase of carbapenem resistance in A. baumannii might be due to the substitution of main clones. Although ST92 and ST69 were the most prevalent clones amongst A. baumannii in 2003-2007 (47.8 % and 15.9 %, respectively), ST75 and ST138 had increased in 2008-2010 (39.7 % and 25.9 %, respectively). Although ST92 showed moderate resistance to carbapenems, most ST75 and ST138 isolates were resistant to carbapenems. All ST75 and ST138 isolates, but only one ST92 isolate, contained the bla(OXA-23-like) gene. Increased carbapenem resistance in Acinetobacter species and A. baumannii isolates might be due to the expansion of specific carbapenem-resistant clones.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Genotype; Hospitals; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Republic of Korea; Species Specificity; Thienamycins

This study assessed the impact of ertapenem and other carbapenems on mortality in patients with monomicrobial extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteremia.. This non-concurrent prospective study included adult patients with ESBL-EC bacteremia during a 2.5-year period at a 2200-bed teaching hospital. We used a multivariate logistic regression model and Cox's proportional hazards model including propensity score analysis to assess variables associated with 30-day mortality.. Of 71 patients who met the study criteria, nine died within 3 days. Among the 62 remaining patients who received definitive antimicrobial therapy, 13 died within 30 days. Male gender, ICU stay, solid tumor, and primary bacteremia were independent predictors of 30-day mortality, whereas definitive antimicrobial therapy using either ertapenem or imipenem/meropenem was protective (p<0.001 and p=0.002, respectively). Adjustment by propensity score found that ertapenem appeared to exhibit more favorable outcomes, but the difference fell short of statistical significance (hazard ratio 0.02, p=0.06). Inappropriate initial therapy was not a significant predictor of mortality.. ICU stay, but not initial choice of empirical antimicrobial therapy, was a major predictor of mortality. Using a carbapenem as definitive therapy was a protective factor for 30-day mortality. The choice of ertapenem is reasonable for less severely-ill patients who are at risk of ESBL-EC bacteremia and unlikely to have infection due to Pseudomonas aeruginosa.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Escherichia coli; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Propensity Score; Thienamycins

Biapenem (BIPM) has high bactericidal activity against Pseudomonas aeruginosa and similar activity in vitro as meropenem (MEPM). We used a murine model to examine the efficacy of biapenem against ventilator-associated pneumonia (VAP) caused by P. aeruginosa. Mice were treated by intraperitoneal injection with 100 mg/kg BIPM or MEPM every 12 h beginning 12 h after inoculation with P. aeruginosa. Survival was evaluated for 7 days, and 24 h after infection, lung histopathology was analyzed and the number of viable bacteria in the lungs and blood was counted. In addition, the pharmacokinetics of BIPM and MEPM were analyzed after the initial treatment. BIPM and MEPM significantly prolonged survival compared to control (P < 0.05). The lungs of mice treated with BIPM or MEPM had significantly fewer viable bacteria (3.54 ± 0.28 vs. 3.77 ± 0.14 log(10) CFU/ml) than in the lungs of control mice (6.65 ± 0.57 log(10) CFU/ml) (P < 0.05). Furthermore, viable bacteria were not detected in the blood of mice treated with BIPM or MEPM (control 2.85 ± 0.85 log(10) CFU/ml) (P < 0.05). Histopathological examination of lung specimens indicated that BIPM and MEPM prevent the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. The % time above MIC for BIPM and MEPM was 15.4% and 18.3% in plasma and 19.8% and 19.8% in lungs, respectively. These results show that BIPM and MEPM significantly prolongs survival and reduces the number of viable bacteria in a murine model of VAP caused by P. aeruginosa. Therefore, BIPM might be a potent and effective treatment for VAP caused by this bacterium.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Colony Count, Microbial; Disease Models, Animal; Histocytochemistry; Lung; Male; Meropenem; Mice; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Specific Pathogen-Free Organisms; Statistics, Nonparametric; Thienamycins

The aim of this study was to determine the current susceptibility of hospital isolates of contemporary Gram-negative pathogens to the carbapenems doripenem, imipenem and meropenem. Between May and October 2008, seven centres in Germany were invited to collect and submit Pseudomonas aeruginosa, Enterobacteriaceae and other Gram-negative bacterial Intensive Care Unit (ICU)/non-ICU isolates from patients with complicated intra-abdominal infections (cIAIs), bloodstream infections (BSIs) or nosocomial pneumonia (NP). Susceptibility was determined at each centre by Etest. A central laboratory performed species confirmation as well as limited susceptibility and quality control testing. In total, 363 isolates were collected, comprising 46.0% Enterobacteriaceae, 45.2% P. aeruginosa, 4.7% Acinetobacter spp. and 4.1% other Gram-negatives. Most isolates (47.9%) were collected from NP, 32.8% were from cIAIs and 19.3% from BSIs; 57.3% were obtained from ICU patients. The MIC(90) values (minimum inhibitory concentration for 90% of the isolates) for doripenem, meropenem and imipenem were, respectively, 4, 16 and 32 mg/L against P. aeruginosa, 0.06, 0.06 and 0.5mg/L against Enterobacteriaceae and ≥ 64 mg/L for each carbapenem against other Gram-negative isolates. Using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 81.1%, 75.6% and 79.3% of P. aeruginosa were susceptible to doripenem, imipenem and meropenem, respectively. Against all pathogens combined, MIC(90) values for ICU versus non-ICU isolates, respectively, were 4 mg/L vs. 1mg/L for doripenem, 8 mg/L vs. 1mg/L for meropenem and ≥ 64 mg/L vs. 8 mg/L for imipenem. Doripenem showed comparable activity against P. aeruginosa from patients with BSIs, cIAIs or NP. Similar findings were observed for Enterobacteriaceae and other Gram-negatives, including Acinetobacter spp. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against Gram-negative pathogens collected in Germany.

Topics: Bacteremia; Carbapenems; Cross Infection; Doripenem; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Germany; Humans; Imipenem; Intensive Care Units; Intraabdominal Infections; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quality Control; Thienamycins

A retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P = 0.1) or sepsis-related mortality rate (P = 0.2) for patients with bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34; P < 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24; P = 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88; P = 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P = 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤ 0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P = 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems for Enterobacteriaceae.

Topics: Adult; Bacteremia; beta-Lactams; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Thienamycins; Young Adult

Among 213 Pseudomonas aeruginosa isolates collected from 10 South Korean hospitals, 57 isolates (26.8%) were carbapenem-resistant. All but three of the isolates had a relevant decrease of oprD expression. However, decreased oprD expression was also detected in five of ten carbapenem-susceptible isolates. Outer membrane protein analysis confirmed porin loss in carbapenem-resistant P. aeruginosa isolates. Based on the mutations of oprD gene sequences, carbapenem-resistant P. aeruginosa isolates could be classified into five oprD mutational groups. However, there was no difference of OprD expression or carbapenem minimum inhibitory concentrations among the five mutational groups. Among the 57 carbapenem-resistant P. aeruginosa isolates, 41 (71.9%) overexpressed efflux systems or ampC. MexAB-OprM and AmpC overexpression (56.1% and 47.4%, respectively) was prevalent and was significantly associated with carbapenem resistance. However, no synergistic effect of efflux systems and AmpC on carbapenem resistance was evident. In conclusion, combination of several mutation-driven mechanisms leading to OprD inactivation and overexpression of efflux systems was the main carbapenem resistance mechanism, but acquisition of a transferable resistance determinant such as metallo-β-lactamase could be problematic in clinical settings in South Korea.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Gene Silencing; Genes, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Mutation; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Republic of Korea; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins; Urinary Tract Infections

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Infections; Ceftazidime; Drug Resistance, Bacterial; Escherichia coli; Fever; Gram-Positive Bacteria; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hospitalization; Humans; Israel; Meropenem; Middle Aged; Odds Ratio; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Treatment Outcome; Young Adult

The majority of nosocomial infections in Taiwan hospitals are caused by drug-resistant Gram-negative bacteria (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, and various species of Enterobacteriaceae. Carbapenems are important agents for treating infections caused by these GNB. Recently, doripenem was approved for use in Taiwan in August 2009. However, data on its in vitro activity against nosocomial GNB isolated from Taiwan remain limited. The study was designed to look into this clinical issue.. A total of 400 nonduplicated nosocomial blood isolates isolated in 2009, inclusive of P. aeruginosa (n = 100), A. baumannii (n = 100), and Enterobacteriaceae (n = 200), were randomly selected from the bacterial bank preserved at National Taiwan University Hospital. Susceptibilities of these 400 isolates to various antibiotics, including doripenem, imipenem, meropenem, ceftazidime, amikacin, ciprofloxacin, colistin, and tigecycline were determined by using Etest.. Doripenem demonstrated similar in vitro activity to imipenem and meropenem against P. aeruginosa (87%, vs. 85% and 89%), A. baumannii (56%, vs. 60% and 60%), and Enterobacteriaceae (100%, vs. 98.5% and 99.5%). The prevalence of carbapenem-resistant (any one of three tested carbapenems) P. aeruginosa, A. baumannii, and Enterobacteriaceae isolates was 15%, 44%, and 0.5%, respectively.. Doripenem was as effective as imipenem and meropenem in our study. However, there was a significant proportion of carbapenem resistance among the tested isolates. Hence, longitudinal surveillance is necessary to monitor the resistance trend.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Drug Resistance, Bacterial; Enterobacteriaceae; Gram-Negative Bacteria; Hospitals, University; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Taiwan; Thienamycins

A total of 950 gram-negative bacterial isolates from patients with bacteremia and urinary tract infections were collected from tertiary-care hospitals in Korea. In vitro antimicrobial susceptibility testing was performed using broth microdilution test according to Clinical and Laboratory Standards Institute protocol. In general, carbapenems such as doripenem, imipenem, and meropenem were very active against Enterobacteriaceae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Acinetobacter sp. isolates. Doripenem was more potent than imipenem against most Enterobacteriaceae species except Proteus spp. based on minimum inhibitory concentration (MIC)(50) and MIC(90). In addition, doripenem displayed similar activity to meropenem but was superior to imipenem against ceftazidime-resistant Enterobacteriaceae isolates. For P. aeruginosa and Acinetobacter spp. isolates, MIC(50)s of doripenem were 1 and 0.5 mg/L, respectively, which were the same with those of meropenem but two- to fourfold lower than those of imipenem (both 2 mg/L). On the basis of the in vitro data, we conclude that doripenem has equivalent or more activity than other carbapenems such as imipenem and meropenem against most gram-negative pathogens from Korea. Thus, doripenem may be a promising new antimicrobial agent for the treatment of infections caused by gram-negative pathogens in Korea.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Doripenem; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Korea; Meropenem; Microbial Sensitivity Tests; Republic of Korea; Thienamycins; Urinary Tract Infections

Nontypeable Haemophilus influenzae (NTHi) commonly colonizes the upper respiratory tract of children and causes otitis media, sinusitis, and bronchitis. Invasive NTHi diseases such as meningitis and septicemia have rarely been reported, especially in children with underlying predisposing conditions such as head trauma and immune compromise. However, we report a previously healthy 2-year-old girl who developed meningitis and septicemia caused by NTHi biotype ΙΙΙ. She was treated with dexamethasone, meropenem, and ceftriaxone, and recovered uneventfully. We wish to emphasize that NTHi should be borne in mind as a potential pathogen that can cause meningitis and septicemia, even in previously healthy children.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacteremia; Ceftriaxone; Child, Preschool; Dexamethasone; Female; Haemophilus influenzae; Humans; Japan; Meningitis, Haemophilus; Meropenem; Thienamycins

For 244 patients with bacteremia due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae treated by ertapenem (73, 29.9%) or either imipenem or meropenem (171, 70.1%), the therapeutic efficacy was evaluated. Ertapenem therapy was effective for patients with ESBL-producing E. coli or K. pneumoniae bacteremia in terms of mortality and microbiological responses, as compared with imipenem or meropenem.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Thienamycins; Treatment Outcome

The aim of this study was to determine the in vitro activities of doripenem, imipenem, and meropenem against clinical gram-negative isolates. A total of 596 clinical isolates were obtained from intensive care unit (ICU) and non-ICU patients in 10 centers over Turkey between September-December 2008. The origin of the isolates was patients with nosocomial pneumonia (42.4%), bloodstream infections (%40.4), and complicated intraabdominal infections (17.1%). Of the isolates, 51.8% were obtained from ICU patients. The study isolates consisted of Pseudomonas spp. in 49.8%, Enterobacteriaceae in 40.3%, and other gram-negative agents in 9.9%. The minimum inhibitory concentrations (MIC) for doripenem, imipenem and meropenem were determined for all isolates in each center using Etest® strips (AB Biodisk, Solna, Sweden). Of the isolates, 188 (31.5%) were resistant to at least one of the carbapenems. MIC50 of doripenem against Pseudomonas spp. Was 1 mg/L which was similar to that of meropenem and two-fold lower than imipenem. Susceptibility to carbapenems in P.aeruginosa was 64% for doripenem at an MIC level of 2 mg/L, 53.9% and 63% for imipenem and meropenem at an MIC level of 4 mg/L, respectively. Doripenem and meropenem showed similar activity with the MIC90 of 0.12 mg/L whereas imipenem was four-fold less active at 0.5 mg/L. Against other gramnegative pathogens, mostly Acinetobacter spp., MIC50 was 8 mg/L for doripenem and 32 mg/L for other two carbapenems. P.aeruginosa isolates were inhibited 84.2% with doripenem and 72.1% with meropenem at the MIC level of 8 mg/L. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against pathogens collected in this study. Against Pseudomonas spp., doripenem was the most active of the three carbapenems. Doripenem and meropenem were equally active against Enterobacteriaceae and at least four-fold more active than imipenem. It was concluded that doripenem seemed to be a promising agent in the treatment of nosocomial pneumonia, blood stream infections and intraabdominal infections particularly in patients who were under risk of developing antimicrobial resistance.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenems; Cross Infection; Doripenem; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Thienamycins; Turkey

Gram-negative bacterial resistance to antibiotics is of increasing concern. Carbapenem resistance among strains of Klebsiella pneumoniae is a relatively new phenomenon. Resistance attributable to production of carbapenemases is notoriously difficult to combat.. Case report and review of the pertinent English-language literature.. A patient, hospitalized for aortic dissection complicated by intra-abdominal catastrophe and acute kidney injury, developed bacteremia exhibiting meropenem non-susceptibility secondary to expression of bla(KPC-2). High-dose, continuous-infusion meropenem achieved serum drug concentrations above the minimum inhibitory concentration and eradicated the infection.. This is the first report of a meropenem-non-susceptible carbapenamase-positive Klebsiella pneumoniae blood stream infection treated successfully with high-dose, continuous-infusion meropenem. Application of this regimen in certain patients, such as those with mild-to-moderate renal insufficiency, may be a reasonable option for multi-drug-resistant nosocomial infections.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Serum; Thienamycins; Treatment Outcome

Bacteremias caused by Klebsiella pneumoniae producing extended-spectrum beta-lactamase (ESBL-KP; n = 52) and producing both ESBL and AmpC-type DHA-1 beta-lactamase (ESBL-PMABL-KP; n = 20) were analyzed. Higher MIC(50)s and MIC(90)s for carbapenems, ciprofloxacin, and piperacillin-tazobactam were observed with ESBL-PMABL-KP than with ESBL-KP. Patients with oxyimino-β-lactam exposure and high modified Pitt bacteremia scores (HMPBSs) were at higher risk, while those with piperacillin-tazobactam and aminoglycoside exposure were at lower risk for ESBL-KP bacteremia. Patients with fluoroquinolone exposure, diabetes mellitus, and HMPBS were at higher risk, while those with aminoglycoside exposure were at lower risk, for ESBL-PMABL-KP bacteremia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Case-Control Studies; Ciprofloxacin; Female; Humans; Klebsiella pneumoniae; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmids; Young Adult

Persistent bacteraemia arising from a case of post-operative mediastinitis as a result of a Proteus mirabilis isolate, possessing two class 1 integrons carrying bla(VIM-1) and aadA2 gene cassettes located on chromosomal and plasmidic DNA, respectively, is reported. Despite the in vitro susceptibility to carbapenems, meropenem therapy failed, whereas the patient responded to treatment with cefepime plus amikacin. To our knowledge, this is the first report of metallo-beta-lactamase production in a clinical isolate of P. mirabilis in Italy.

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Chromosomes, Bacterial; DNA, Bacterial; Humans; Integrons; Italy; Male; Meropenem; Plasmids; Proteus Infections; Proteus mirabilis; Surgical Wound Infection; Thienamycins; Treatment Failure; Treatment Outcome

Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the in vitro activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory.. Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam.. Cumulative susceptibility rates against Escherichia coli were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other Enterobacteriaceae, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All Staphylococci, Streptococci and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains.. Compared to imipenem, meropenem displays lower MICs against Enterobacteriaceae, Escherichia coli and Pseudomonas aeruginosa. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against Enterobacteriaceae and Acinetobacter but not P. aeruginosa. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.

Topics: Anti-Bacterial Agents; Bacteremia; France; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Thienamycins; Wound Infection

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Bacterial; Humans; Male; Meropenem; Nocardia; Nocardia Infections; RNA, Bacterial; RNA, Ribosomal, 16S; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

A significant increase in the rate of vancomycin-resistant Enterococcus faecium (VREfm) bacteremia at our health service, despite improved infection control, prompted us to investigate the cause.. E. faecium bacteremia (including VREfm) over a 12-year period (1998-2009) was investigated using multilocus sequence typing, antibiotic and antiseptic susceptibility profiles, optical mapping, and whole genome sequencing of historical and recent isolates.. For 10 years, the rate of bacteremia due to vanB VREfm remained stable and sequence type (ST) 17 was predominant. In 2005, ST203 vancomycin-susceptible E. faecium first appeared at our institution, and from March 2007, coinciding with the appearance of a vanB VREfm ST203, the rate of VRE bacteremia has increased exponentially. Although we found no difference in antiseptic susceptibility or presence of genes encoding putative virulence determinants (esp(Efm), hyl(Efm), and fms genes), comparative genomics revealed almost 500 kb of unique sequence when an ST17 and an ST203 VREfm isolate were compared, suggesting that other genomic factors are responsible for the apparent success of E. faecium.. The application of multilocus sequence typing has uncovered the emergence of an epidemic clone of E. faecium ST203 that appears to have acquired the vanB locus and has caused a sustained outbreak of VRE bacteremia.

Topics: Anti-Bacterial Agents; Australia; Bacteremia; Bacterial Proteins; Bacterial Typing Techniques; Communicable Diseases, Emerging; Cross Infection; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecium; Genomics; Gram-Positive Bacterial Infections; Humans; Incidence; Meropenem; Microbial Sensitivity Tests; Phylogeny; Thienamycins; Vancomycin; Vancomycin Resistance

The aim of our study was to determine the prevalence of Pseudomonas aeruginosa bacteremia, risk factors, and outcome of patients treated at the Hospital of Kaunas University of Medicine.. All hospitalized patients with blood culture positive for Pseudomonas aeruginosa during the 5-year period were included. A retrospective data analysis was performed to evaluate patients' risk factors and mortality caused by P. aeruginosa bacteremia.. A total of 47 (58.8%) bacteremia episodes occurred in an intensive care unit (ICU). A primary source of bacteremia was identified in 50 (62.5%) episodes. Overall mortality rate was 58.8%. Univariate risk factors analysis showed the factors, which significantly increased the risk of death: mechanical ventilation (13.67 times, P<0.001), patient hospitalization in the ICU (8.51 times, P<0.001), acute respiratory failure (8.44 times, P<0.001), infection site in the respiratory tract (4.93 times, P=0.003), and central vein catheter (4.44 times, P=0.002). Timely and appropriate treatment and surgery were significant protective factors for 30-day mortality (11.1 and 5.26 times, respectively; P=0.001). Meropenem-resistant Pseudomonas aeruginosa strains caused bacteremia more frequently in patients older than 65 years than meropenem-sensitive strains (57.9%, n=11). All 19 patients with meropenem-resistant Pseudomonas aeruginosa bacteremia received inappropriate empirical antibiotic therapy.. Treatment at the intensive care unit, mechanical ventilation, acute respiratory failure, source of infection in respiratory tract, and central vein catheter are the major risk factors associated with an increased mortality rate in patients with Pseudomonas aeruginosa bacteremia. The patients older than 65 years are at increased risk for bacteremia caused by carbapenem-resistant Pseudomonas aeruginosa strains. Carbapenems are not antibiotics of the choice of treatment for Pseudomonas aeruginosa bacteremia at the Hospital of Kaunas University of Medicine.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Data Interpretation, Statistical; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Intensive Care Units; Lithuania; Male; Meropenem; Middle Aged; Odds Ratio; Pseudomonas aeruginosa; Pseudomonas Infections; Respiration, Artificial; Retrospective Studies; Risk Factors; Thienamycins; Time Factors

Clostridium difficile (CD) infection is almost always confined to the colon causing a spectrum of illness ranging from diarrhoea to fulminant colitis. CD infection of the small intestine has been described but the identification of CD toxin in the stoma effluent of a patient with an end ileostomy is rare. We describe a 91-year-old woman, with a history of proctocolectomy for ulcerative colitis, presenting with profuse ileostomy diarrhoea after a course of antibiotics. Ileostomy effluent was positive for CD toxin but the patient died despite appropriate treatment. This suggests that the small intestine is susceptible to CD infection in antibiotic-treated patients many years after a colectomy. CD enteritis should be considered in all patients with increased ileostomy diarrhoea despite the absence of a colon.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colectomy; Colitis, Ulcerative; Enterocolitis, Pseudomembranous; Fatal Outcome; Female; Humans; Ileostomy; Infusions, Intravenous; Intestine, Small; Meropenem; Postoperative Complications; Staphylococcal Infections; Thienamycins

A 79-year-old woman presented with fever, lethargy and weight loss. Clinically, the patient was confused, frail and had a systolic murmur. Her temperature was 38 °C and she remained persistently febrile. Initial investigations revealed neutrophilia with an elevated C reactive protein level. Multiple peripheral blood cultures grew Achromobacter xylosoxidans, a Gram-negative rod, which is a very rare cause of infection in patients who are immunocompetent. Subsequent transoesophageal echocardiography confirmed endocarditis with obvious vegetations on the mitral valve. The patient was treated with intravenous meropenem and cotrimoxazole in line with microbiology guidance. Surgical intervention in the form of mitral valve replacement was considered, but the patient was felt to be at prohibitive risk. After 6 weeks of intravenous antibiotics, a repeat transoesophageal echocardiogram showed no improvement in the mitral valve vegetation, which had increased in size. At this stage, her clinical course was complicated by major upper gastrointestinal bleeding requiring transfusion, multiorgan failure and ultimately death.

Topics: Achromobacter denitrificans; Aged; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Echocardiography, Transesophageal; Endocarditis, Bacterial; Fatal Outcome; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Meropenem; Mitral Valve; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination

A novel Klebsiella pneumoniae carbapenemase (KPC) variant, designated bla(KPC-5), was discovered in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate from Puerto Rico. Characterization of the upstream region of bla(KPC-5) showed significant differences from the flanking regions of other bla(KPC) variants. Comparison of amino acid sequences with those of other KPC enzymes revealed that KPC-5 was an intermediate between KPC-2 and KPC-4, differing from KPC-2 by a single amino acid substitution (Pro(103)-->Arg), while KPC-4 contained Pro(103)-->Arg plus an additional amino acid change (Val(239)-->Gly). Transformation studies with an Escherichia coli recipient strain showed differences in the properties of the KPC variants. KPC-4 and KPC-5 both had pIs of 7.65, in contrast with the pI of 6.7 for KPC-2. KPC-2 transformants were less susceptible to the carbapenems than KPC-4 and KPC-5 transformants. These data correlated with higher rates of imipenem hydrolysis for KPC-2 than for KPC-4 and KPC-5. However, KPC-4 and KPC-5 transformants had higher ceftazidime MICs, and the enzymes from these transformants had slightly better hydrolysis of this drug than KPC-2. KPC-4 and KPC-5 were more sensitive than KPC-2 to inhibition by clavulanic acid in both susceptibility testing and hydrolysis assays. Thus, KPC enzymes may be evolving through stepwise mutations to alter their spectra of activity.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; beta-Lactamases; Clavulanic Acid; Drug Resistance, Bacterial; Enzyme Inhibitors; Genetic Variation; Hydrolysis; Isoelectric Focusing; Klebsiella pneumoniae; Microbial Sensitivity Tests; Phenotype; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction

Pyomyositis is an infection of skeletal muscle that involves the formation of intramuscular abscesses. It occurs most commonly in immunocompromised patients. Pyomyositis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has never been reported in the literature. A 48-year-old female patient developed ESBL-producing E. coli bacteremia and pyomyositis on the twelfth day of cefpirome therapy for neutropenic fever after chemotherapy due to acute myeloid leukemia. She recovered completely after a three-week course of meropenem and surgical excision. Pyomyositis should be included in the differential diagnosis when fever and muscular swelling develop in a patient with neutropenic status after chemotherapy. Early recognition of symptoms and proper diagnostic procedures are key to diagnosing pyomyositis. Both adequate antibiotics and surgical intervention are important for the successful treatment of pyomyositis caused by ESBL-producing E. coli.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Leukemia, Myeloid, Acute; Meropenem; Middle Aged; Pyomyositis; Thienamycins

To determine the associations between the source of infection and antibiotic resistance in patients with Pseudomonas aeruginosa bacteremia.. A retrospective analysis of 50 patients with Pseudomonas aeruginosa bacteremia was carried out. If sepsis was suspected, blood culture was incubated in an automatic system BACTEC 9240. Then bacteria were identified, and their antibiotic resistance was estimated by disc diffusion method. If Pseudomonas aeruginosa strains were resistant to three or more antibiotics, they were considered as multidrug-resistant.. The origin of bacteremia was confirmed in 33 (66%) patients. Lower respiratory tract was the predominant source of Pseudomonas aeruginosa bacteremia (81.8%, n=27) as compared with infection of wound (39.4%, n=13), urinary tract (15.2%, n=5), and drain or cerebrospinal fluid (9.1%, n=3) (P<0.05). Eighteen percent (n=9) of strains, which caused bacteremia, were resistant to ceftazidime; 38% (n=19), to piperacillin; 22% (n=11), to imipenem; 26% (n=13), to meropenem; 24% (n=12), to ciprofloxacin; 40% (n=20), to gentamicin; and only 8% (n=4), to amikacin. Multidrug-resistant Pseudomonas aeruginosa strains were more frequently isolated if a source of infection was wound comparing to a source of other localization (61.5%, n=8 and 20.0%, n=4, respectively; P<0.05). Resistance of Pseudomonas aeruginosa strains to imipenem was associated with resistance to ciprofloxacin (13.2%, n=5 and 50.0%, n=6, retrospectively; P<0.05), but resistance to meropenem--both to ciprofloxacin and amikacin.. The predominant source of Pseudomonas aeruginosa bacteremia was lower respiratory tract, and multidrug-resistant strains caused bacteremia more frequently if a source infection was wound. Pseudomonas aeruginosa resistance to carbapenems was associated with resistance to ciprofloxacin and resistance to meropenem--also to amikacin. Resistance of strains to ceftazidime and piperacillin was associated with resistance to gentamicin.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; Bacteriological Techniques; Ceftazidime; Ciprofloxacin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Gentamicins; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Retrospective Studies; Thienamycins; Wound Infection

Topics: Anti-Bacterial Agents; Bacteremia; Burkholderia pseudomallei; Carbapenems; Debridement; Developing Countries; Humans; Leg; Male; Melioidosis; Meropenem; Middle Aged; Thailand; Thienamycins; Treatment Outcome

We report a relapsed case of a 25 year-old man with multi-drug resistant Salmonella serovar Typhi (MDRST) bacteremia who had recently returned from travel in India. Due to unresponsiveness to ciprofloxacin and ceftriaxone, we examined the strain's resistance to quinolones and extended-spectrum beta-lactamases (ESBLs). The strain had a single gyrA mutation at codon 83 (Ser83Phe), which explains its decreased susceptibility to fluoroquinolone and resistance to nalidixic acid. In the screening tests of ESBLs, TEM-1 was positive, which is beta-lactamase but not ESBL. The patient was finally successfully treated with meropenem and aztreonam. In the presence of clinical unresponsiveness despite favorable sensitivity tests, further laboratory evaluations are needed, which should include studies of genes related to antibiotic resistance and ESBLs. In addition, further prospective trials should be done about the possible inclusion of antibiotics not yet mentioned in the current guidelines. With MDRST on the rise worldwide, the most optimal and effective line of antibiotic defense needs to be devised.

Topics: Adult; Anti-Bacterial Agents; Aztreonam; Bacteremia; Drug Resistance, Bacterial; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Male; Meropenem; Salmonella typhi; Thienamycins; Typhoid Fever

Extended-spectrum-beta-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. Of the 129 patients considered, 56 (43.4%) received IIAT for 48 to 120 h (mean, 72 h). Independent risk factors for IIAT include an unknown BSI source (odds ratios [OR], 4.86; 95% confidence interval [CI], 1.98 to 11.91; P = 0.001), isolate coresistance to >or=3 antimicrobials (OR, 3.73; 95% CI, 1.58 to 8.83; P = 0.003), hospitalization during the 12 months preceding BSI onset (OR, 3.33; 95% CI, 1.42 to 7.79; P = 0.005), and antimicrobial therapy during the 3 months preceding BSI onset (OR, 2.65; 95% CI, 1.11 to 6.29; P = 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient's history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Risk Factors; Treatment Failure

Meropenem (MEM; 2 g/8 hr; minimum inhibitory concentration [MIC] = 256 mg/L) plus sulbactam (SUL; 1 g/8 hr; MIC = 128 mg/L) (two-drug-therapy period), and subsequent additional intravenous colistin (COL; 2.5 mg/kg/12 hr) and intraventricular (COL, 5 mg/day; MIC = 1 mg/L) (three-drug-therapy period) were sequentially used in a patient with postneurosurgery bacteremic meningitis due to a multidrug-resistant Acinetobacter baumannii (MDRAB) isolate (AB(1)). We detected 4- to 32-fold increases in peak or trough cerebrospinal fluid bactericidal titer and serum bactericidal titer in three-drug-therapy period when comparing to those in two-drug-therapy period. The time-kill study with MEM, SUL, and COL alone or varied combinations (all at 1 x MIC) against AB(1) and another genetically nonrelated MDRAB isolate (AB(134) [MICs of MEM = 64 mg/L, SUL = 16 mg/L, and COL = 1 mg/L]) was performed. The two-drug combinations (MEM + SUL, MEM + COL, and SUL + COL) each elicited different inhibitory effect on AB(1) and AB(134) at 6 hr. Bacterial regrowth at 24 hr was observed in the experiments in which the MDRAB isolate was inhibited earlier by COL alone (AB(1) and AB(134)), by MEM plus SUL (AB(1)), and by MEM plus COL (AB(134)), but not in SUL plus COL, and MEM + SUL + COL. Combined use of COL with MEM and/or SUL may provide good therapeutic options, even though MEM and SUL are in vitro resistance to the MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Neurosurgical Procedures; Postoperative Complications; Sulbactam; Thienamycins; Time Factors

Topics: Anti-Bacterial Agents; Bacteremia; Chromobacterium; Fatal Outcome; Gentamicins; Gram-Negative Bacterial Infections; Hospitals, Public; Humans; Infant; Male; Meropenem; Protein Synthesis Inhibitors; Sri Lanka; Thienamycins

Bloodstream infections (BSI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Predictive Value of Tests; Proteus mirabilis; Risk Factors; Survival Analysis; Treatment Outcome

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

Topics: Bacteremia; Community-Acquired Infections; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae Infections; Gene Transfer, Horizontal; Humans; Infectious Disease Transmission, Professional-to-Patient; Integrons; Microbial Sensitivity Tests; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Sequence Analysis, DNA; Treatment Outcome

A patient genetically diagnosed with X-linked agammaglobulinemia repeatedly developed bacteremia due to Campylobacter coli (C. coli) for one year and seven months in spite of immunoglobulin replacement therapy. Throughout the clinical course, C. coli with identical genetic patterns was repeatedly isolated from both blood and stool cultures, thus indicating that the patient had latent intestinal infection. The bacteremia was always accompanied by reactive arthritis. Since the immunoglobulin level was extremely low with severe B cell deficiency, the reactive arthritis must have been induced in a humoral immunity-independent manner. Adding oral minocycline following intravenous meropenem was very effective; the stool cultures became negative and the patient has been well for more than one year without relapse of bacteremia.

Topics: Administration, Oral; Adult; Agammaglobulinemia; Anti-Bacterial Agents; Arthritis, Reactive; Bacteremia; Campylobacter coli; Campylobacter Infections; Chromosomes, Human, X; Feces; Genetic Linkage; Humans; Injections, Intravenous; Intestinal Diseases; Male; Meropenem; Minocycline; Recurrence; Thienamycins; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Blood; Culture Media; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Prevalence; Thienamycins

Ochrobactrum anthropi (formerly Achromobacter spp.) is an aerobic, motile, oxidase positive and lactose negative gram negative bacillus which is widely distributed in the environment and water sources. In recent publications, O. anthropi has an increasing importance as a nosocomial infection agent. The aim of this report was to present a case of O. anthropi bacteremia developed after endoscopic retrograde cholangiopancreatography (ERCP). A 89-year old female patient presented with high fever one day after ERCP performed due to klatskin tumour. O. anthropi had been grown in blood culture (BacT/ALERT 3D, bioMérieux, Durham, USA), and the isolate was identified by automatized system (VITEK, bioMerieux, Marcy l'Etoile, France). Since there was no clinical response to empirical ceftriaxone therapy, it was switched to meropenem, which was found effective by VITEK antibiotic susceptibility detection system. The patient was treated successfully with meropenem therapy (3 x 1 gr/day, 10 days). As a result, in case of suspected post-ERCP bacteremia, unconventional microorganisms such as O. anthropi should be taken into consideration.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cholangiopancreatography, Endoscopic Retrograde; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Ochrobactrum anthropi; Thienamycins

Infections caused by multidrug-resistant Acinetobacter baumannii have become a therapeutic challenge for clinicians worldwide. Although colistin and tigecycline have been successful in treating patients with these infections, these agents are not available on a worldwide basis. We describe four critically ill patients in Taiwan who were diagnosed with multidrug-resistant Acinetobacter baumannii bacteremia. All bacterial isolates from these patients were resistant to commonly available antibiotics, including carbapenems and sulbactam; however, combination therapy with a carbapenem and sulbactam led to favorable clinical outcomes in all four patients. We also conducted an in vitro study using isolates from these patients that showed that this drug combination had a synergistic effect with enhanced antibacterial activity against the isolates. Thus, a carbapenem-sulbactam combination may be a therapeutic alternative for multidrug-resistant Acinetobacter baumannii bacteremia in countries where colistin and tigecycline are not available for clinical use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Illness; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Sulbactam; Taiwan; Thienamycins

The coagulase-negative bacterial species Staphylococcus sciuri is widely distributed in the natural environment. Although principally found in animals, S. sciuri is occasionally isolated from human samples. In this paper, S. sciuri bacteremia which was associated with an indwelling catheter of a patient with acute myeloid leukemia (AML) and neutropenia was presented. An empirical intravenous antibiotic therapy (meropenem, vancomycin) was initiated with the preliminary diagnosis of febrile neutropenia and catheter infection. The catalase and oxidase positive, tube coagulase negative strain isolated from three of the concurrent blood cultures and intravenous catheter culture has been identified as S. sciuri. The isolate was found resistant to penicilin and oxacilline. This case has emphasized the importance of identification of coagulase-negative staphylococci isolated from the cultures of patients with haematological malignancy.

Topics: Anti-Bacterial Agents; Bacteremia; Catheters, Indwelling; Drug Resistance, Bacterial; Female; Humans; Leukemia, Myeloid, Acute; Meropenem; Middle Aged; Neutropenia; Oxacillin; Penicillin Resistance; Staphylococcal Infections; Staphylococcus; Thienamycins; Vancomycin

Pharmacodynamic investigations with antimicrobials define the relationship between the infecting organism and achievable drug concentrations with clinical outcome.. To examine this relationship for meropenem in a population of patients who are at high risk of infection-related morbidity and mortality.. The study was a retrospective analysis of a multicenter, randomized, blinded clinical trial. A population-based predictive model was created using data from adults with febrile neutropenia and the nonparametric modeling program, NPEM. Patient age, body weight, and serum creatinine level were covariates in the model used to predict unbound concentrations for each patient. Pathogen susceptibility was estimated using product literature minimum inhibitory concentrations for effectiveness against 50% of microorganisms (MIC50) for specific organisms. The pharmacodynamic index of percent time above MIC (% T>MIC) was analyzed for its association with clinical outcome.. A 2-compartment pharmacokinetic model using patient covariates of body weight and renal function best described the pharmacokinetics of meropenem in febrile neutropenic patients. Sixty patients with confirmed gram-positive or -negative bacteremia were studied. An average of 83% T>MIC was identified for the 42 clinical responders compared with 59% T>MIC for the 18 nonresponders (p = 0.04). An 80% clinical response rate was evident when the % T>MIC for meropenem exceeded 75% of the dosing interval (p = 0.01).. To our knowledge, this is the first published report of a relationship between a pharmacodynamic index and clinical outcome in a febrile neutropenic population. Based on this relationship, dosing with intravenous meropenem 500 mg every 6 hours is predicted to be comparable to the currently recommended 1 g every 8 hours for serious infections. Our model provides further justification for a prospective clinical trial to evaluate a pharmacodynamically targeted meropenem dosing schedule as to its ability to improve clinical outcome in these patients.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Drug Administration Schedule; Female; Fever; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Neutropenia; Retrospective Studies; Thienamycins; Treatment Outcome

Extended spectrum beta-lactamases (ESBLs) usually associated with multiple drug resistance, including beta-lactam and non-beta-lactam antibiotics. This resistance can cause Limitation in the choice of drugs appropriate for using in clinical practice, especially in life-threatening infections. In this study we aimed to investigate in vitro activity of meropenem, ciprofloxacine and amikacin against ESBL-producing and non-producing blood isolates of Escherichia coli and Klebsiella pneumoniae strains. Fifty-eight E. coli (21 ESBL-producing, 37 non-ESBL producing) and 99 K. pneumoniae (54 ESBL-producing, 45 non-ESBL producing) strains were included in the study. The presence of ESBL was investigated by double disk synergy test and E-test methods. Antibiotic susceptibility test was done by microdilution method according to NCCLS guideline. In vitro susceptibilities of ESBL producing E. coli and K. pneumoniae strains were found as 100% for meropenem, 33.3% and 25.9% for ciprofloxacine, 94.5% and 83.3% for amikacin. It was observed that; meropenem was equally active agent in both ESBL-producing and non-producing strains, and its activity was not affected by ESBL production. Whereas amikacin activity was minimally affected and ciprofloxacine activity was markedly decreased by ESBL production. In conclusion, meropenem seems to be better choice of antibiotic should be used for ESBL positive life-threatening infections, because of remaining highest activity.

Topics: Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Blood; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins

Antimicrobial resistance of isolates and risk factors for mortality were retrospectively investigated in 71 adult patients with Serratia marcescens bacteremia. During the 4-year study period, 78 clinically significant episodes of S. marcescens bacteremia occurred in 71 patients. The mean age of the patients was 65 years (range, 25-86 years) with a male predominance (45 patients, 63%). Most of the bacteremic episodes were nosocomial (78%), and 34% were polymicrobial. The overall mortality rate within 2 weeks after the onset of bacteremia was 41%. The presence of malignancy and critical illness at initial presentation were independent risk factors for mortality. By disk susceptibility test, 72 isolates were resistant to cefotaxime (92%) but susceptible to ceftazidime (99%). All isolates were susceptible to meropenem. Among the 47 patients with monomicrobial S. marcescens bacteremia, the mortality rate within 5 days of onset in patients receiving appropriate empirical antimicrobial therapy was lower than that in patients receiving inappropriate therapy although this difference was not significant (14% vs 28%, p = 0.27). Among the patients with cefotaxime-resistant but ceftazidime-susceptible S. marcescens bacteremia treated with ceftazidime, 6 of 7 patients (86%) survived for more than 2 weeks, suggesting the potential effectiveness of ceftazidime in the treatment of cefotaxime-resistant Serratia infections. Further clinical studies are required to delineate the clinical role of ceftazidime therapy for infections caused by S. marcescens with this resistant phenotype.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Ceftazidime; Critical Illness; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Serratia Infections; Serratia marcescens; Taiwan; Thienamycins

In patients with iron overload, opportunistic infections are an underestimated risk. Yersinia enterocolitica is a rare organism to be isolated in this setting. The authors report a case of disseminated Y. enterocolitica sepsis in a 5-year-old boy with sideroblastic anemia. Ultrasound examination revealed massive ascites, a pseudo-appendicitis, and hypoechogenic lesions corresponding to abscess formations in the liver and spleen. The initial antibiotic therapy consisted of cefotaxime, gentamicin, and metronidazole, but only treatment with ciprofloxacin and meropenem led to defervescence and clinical stabilization. The risk of developing uncommon infections in patients with iron overload should be acknowledged by all physicians, and the relevance of ultrasound examination is emphasized. In this case, only a detailed history revealed that several days before the onset of diarrhea, the child was feeding a deer; this is how infection was probably acquired.

Topics: Anemia, Sideroblastic; Anti-Bacterial Agents; Bacteremia; Child, Preschool; Ciprofloxacin; Humans; Iron Overload; Liver Abscess; Male; Meropenem; Splenic Diseases; Thienamycins; Transfusion Reaction; Ultrasonography; Yersinia enterocolitica; Yersinia Infections

The in vitro antimicrobial susceptibility of organisms isolated from bacteraemic versus non-bacteraemic patients was evaluated using data (1997-2001) from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme. Minimum inhibitory concentration values and susceptibility breakpoints of meropenem and other broad-spectrum antimicrobials were determined using standard methodology. Three thousand one hundred and thirty-six blood culture (BC) isolates and 17261 non-BC isolates were obtained from 51 European MYSTIC centres. Gram-positive bacteria appeared to be more prevalent in BC isolates compared with other sources. Escherichia coli, methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa were isolated most frequently. Antimicrobial susceptibility of isolates from bacteraemic versus non-bacteraemic patients was similar. Meropenem and imipenem were the most active agents against the majority of the Gram-positive and Gram-negative organisms. Ceftazidime, gentamicin and ciprofloxacin generally exhibited the lowest activities against the most commonly isolated organisms. Meropenem was most active against P. aeruginosa and showed the highest potency and activity against all extended-spectrum and AmpC beta-lactamase producers. These results are relevant to the choice of initial, empirical therapy for patients with suspected bacteraemia.

Topics: Anti-Bacterial Agents; Bacteremia; Blood; Culture Media; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

A case of acute generalized exanthematous pustulosis (AGEP) is presented. The case is notable for the recurrent episodes of AGEP, caused by three beta-lactam antibiotics (piperacillin, ceftazidime, and meropenem) in septicemic patient. The case represents the first report of the reaction developing in response to these three antibiotics. The report is also notable for the spontaneous resolution of the rash in all the three episodes.

Topics: Acute Disease; Anti-Bacterial Agents; Bacteremia; Ceftazidime; Diabetes Mellitus; Diagnosis, Differential; Exanthema; Hepatitis, Alcoholic; Humans; Male; Meropenem; Middle Aged; Piperacillin; Pseudomonas aeruginosa; Pseudomonas Infections; Recurrence; Thienamycins

Infectious complications are the major causes of morbidity and mortality in children receiving chemotherapy for malignant diseases. Granulocytopenia carries the risk of bacterial infection, and also, if prolonged, of fungal infection. The aim of this study was to evaluate the clinical effectiveness of meropenem in immunocompromised children in association with isolated bacteria from blood cultures and clinical background.. Retrospective study of all febrile episodes when meropenem was used in neutropenic children between January 1998 and December 2002 in the haemato-oncological units of the authors hospital. During the study period meropenem was used in 87 febrile events diagnosed in 55 patients (mean age 10 years 5 months), and 328 bacterial cultures were performed. Blood samples were taken from each patient with granulocytopenia (< 0.5 G/l) and fever (> or = 38 degrees C), prior to the start of any antibiotic therapy. For the microbiological process Bactec 9050 (Becton Dickinson) blood culture systems were used.. Microorganisms were detected and identified in 64 (19.5%) from the 328 hemocultures. There was a predominance of Gram-positive strains, 67% (43/64)--the most common bacteria being coagulase negative Staphylococcus (cnS). From the 87 periods in 43 cases (49.4%) the infection was documented microbiologically. In 16 additional cases the infection was proven clinically (based on the clinical course, laboratory and radiologic results) and 32.2% (28/87) of the febrile neutropenic episodes were considered to be fever of unknown origin. Meropenem was used in a mean dose of 60.8 (30-120) mg/kg/die, for 9.3 (2-24) days. The success rate of the meropenem therapy -excluding the proven fungal (n = 13) or cnS (n = 15) infections-was 72.9%. No severe side effects occurred in any regimens.. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of feverish neutropenic cancer children.

Topics: Adolescent; Adult; Anti-Infective Agents; Antineoplastic Agents; Bacteremia; Bacterial Infections; Child; Child, Preschool; Female; Fever; Humans; Infant; Male; Meropenem; Mycoses; Neoplasms; Neutropenia; Retrospective Studies; Thienamycins; Treatment Outcome

Septicemic melioidosis is often fatal despite treatment with antibiotics such as ceftazidime to which Burkholderia pseudomallei, the causal pathogen, is sensitive in vitro. We report a near-fatal case of septicemic melioidosis with persistent B. pseudomallei bacteremia despite intravenous ceftazidime in which combination therapy with meropenem and ciprofloxacin, splenectomy and correction of metabolic acidosis allowed for hospital discharge. The choice of antibiotic agents was supported by intracellular minimum inhibitory concentration analysis using B. pseudomallei co-culture in Acanthamoeba trophozoites. The patient's B. pseudomallei isolates were indistinguishable by pulsed-field gel electrophoresis from clinical and environmental isolates previously analyzed during investigation of a Western Australian melioidosis outbreak. A combination of antibiotics known to possess intracellular activity against B. pseudomallei, surgery and supportive critical care may provide a means of improving the probability of survival in persistent septicemic melioidosis.

Topics: Adult; Bacteremia; Burkholderia pseudomallei; Ceftazidime; Cephalosporins; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Melioidosis; Meropenem; Spleen; Thienamycins; Western Australia

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

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

In an in vitro dynamic model we compared the antimicrobial effects of two carbapenems, imipenem (MIC, 1 microg/ml) and meropenem (MIC, 0.25 microg/ml) on Pseudomonas aeruginosa. The antibiotics were administered either as short-time infusions once or three times a day or as continuous infusions with steady-state levels ranging from 0.5 to 20 microg/ml. From the resulting kill curves the period of time until the onset of bacterial death (dt), the rate constant of bacterial death (ka), the maximal reduction of CFU (mr), and the period of time until bacterial regrowth occurred (tr) were determined. Additionally, the occurrence of bacterial resistance during the simulations (rq) and the postantibiotic effect (PAE) were recorded. For both investigated carbapenems no significant difference in dt, ka, mr, and PAE values between the short-time infusions and continuous infusions with steady-state levels above 2 microg/ml could be detected. The tr was longest with continuous infusions of over approximately 24 h, corresponding to steady-state levels of 3 microg/ml for imipenem and 2.5 microg/ml for meropenem. An increase in MIC was observed only during continuous infusions with steady-state levels below 2 microg/ml. Independent of the chosen method of application and despite the lower MIC of meropenem, imipenem was slightly more effective than meropenem.

Topics: Bacteremia; Carbapenems; Drug Administration Schedule; Imipenem; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Thienamycins

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacteremia; Cerebrospinal Fluid; Clarithromycin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Infant; Infusions, Intravenous; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Otitis Media; Streptococcus pneumoniae; Thienamycins

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.

Topics: Anti-Bacterial Agents; Bacteremia; Bacteria; Ceftazidime; Drug Resistance, Microbial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins