meropenem and Gram-Positive-Bacterial-Infections

Lactococcus lactis cremoris (L. lactis cremoris) infections are very rare in humans. Only three case reports of brain abscess have been reported and the infectious routes and pathological features are still unknown. We experienced a subdural empyema due to L. lactis cremoris in an immunocompetent adult. A 33-year-old man was admitted with fever, right facial pain, left hemiparesis, and left hemianopsia. Computed tomography demonstrated low density fluid collection in the right falcotentorial subdural space. Magnetic resonance (MR) images revealed a high signal lesion on a diffusion-weighted image (DWI) and fluid attenuated inversion recovery (FLAIR) images in the right paratentorial and parafalcine subdural space, right maxillary sinus, and bilateral ethmoidal sinus. He underwent two sequential open surgeries for removal and drainage of empyema and was treated with antibiotics including meropenem and ampicillin. To our knowledge, this is the first report of subdural empyema caused by L. lactis cremoris infection. We report the case and discuss the pathological features with the previous literature.

Topics: Adult; Ampicillin; Combined Modality Therapy; Craniotomy; Decompression, Surgical; Dental Caries; Diagnostic Errors; Diffusion Magnetic Resonance Imaging; Empyema, Subdural; Ethmoid Sinusitis; Gram-Positive Bacterial Infections; Humans; Immunocompetence; Lactococcus lactis; Magnetic Resonance Imaging; Male; Maxillary Sinusitis; Meropenem; Thienamycins; Trigeminal Neuralgia

Bacillus cereus (B. cereus) is a Gram-positive rod that is widely distributed in the environment and can be a cause of food poisoning. We herein present a case of B. cereus necrotizing pneumonia in a patient with nephrotic syndrome under corticosteroid treatment after developing transient gastroenteritis symptoms. B. cereus was isolated from bronchial lavage fluid and transbronchial biopsy specimens. A multiplex polymerase chain reaction analysis of the toxin genes revealed a strain possessing enterotoxicity. The patient recovered after one week of intravenous meropenem followed by a combination of oral moxifloxacin and clindamycin. B. cereus is a pathogen that causes necrotizing pneumonia in immunocompromised hosts.

Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Aza Compounds; Bacillus cereus; Biopsy, Needle; Bronchoalveolar Lavage Fluid; Clindamycin; Drug Therapy, Combination; Fluoroquinolones; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Immunocompromised Host; Immunohistochemistry; Male; Meropenem; Moxifloxacin; Necrosis; Nephrotic Syndrome; Pneumonia, Bacterial; Quinolines; Radiography, Thoracic; Risk Assessment; Severity of Illness Index; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses gram-negative, gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum beta-lactamases. In patients with moderate to severe intra-abdominal infections, empirical monotherapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in <2.5% of patients each. Meropenem also has an improved CNS tolerability profile compared with imipenem/cilastatin.. Extensive comparative clinical data demonstrate that meropenem can be used effectively as empirical monotherapy in moderate to severe intra-abdominal infections. It also shows potential in the most severe forms of infection, although experience in this infection type remains limited. Compared with standard combination regimens, meropenem offers the benefits of ease of administration without the need for monitoring. It also offers improved CNS tolerability compared with imipenem/cilastatin with the option of a higher maximum dosage, which may be a particular advantage in patients with severe intra-abdominal infections.

Topics: Abdomen; Adult; Aged; Anti-Bacterial Agents; Drug Resistance, Microbial; Economics, Pharmaceutical; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Thienamycins

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

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

To describe and then compare an investigational carbapenem antibiotic, meropenem, with the only currently available antibiotic in this class, imipenem/cilastatin.. An English language search using MEDLINE (1988-1993); Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 1991; and Abstracts of the 32nd ICAAC, 1992.. All current scientific publications were reviewed for study design and quality. Emphasis was placed on susceptibility and pharmacokinetic analysis. Phase 3 clinical trials are now being completed and have only been published in abstract form. Hence, conclusions derived regarding efficacy were tempered.. Meropenem is active against a broad spectrum of gram-positive and -negative pathogens including beta-lactamase producers. Meropenem appears to be two- to fourfold less active than imipenem against gram-positive organisms. Meropenem is two- to fivefold more active against enterobacteriaceae. The two compounds appear to be equally active against Pseudomonas aeruginosa. Pharmacokinetic disposition is also similar for imipenem and meropenem. Meropenem may exhibit greater tissue penetration. Meropenem is not labile to renal hydrolysis and can be administered without a competitive antagonist of dihydropeptidase, such as cilastatin. In clinical trials, meropenem appears to be as safe and effective as imipenem/cilastatin or ceftazidime in the treatment of infections involving soft tissue, urinary tract, upper respiratory tract, abdominal processes, and febrile neutropenic episodes.. Meropenem is comparable to imipenem in terms of in vitro susceptibility pattern and pharmacokinetic disposition. Overall, meropenem seems to offer promise as the second of the carbapenem class of antibiotics. Clinical data are preliminary, and further data are needed.

Topics: Clinical Trials as Topic; Drug Resistance, Microbial; Drugs, Investigational; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Renal Insufficiency; Thienamycins

In phase 3 clinical trials for ceftobiprole treatment of complicated skin and skin structure infections, 1,219 gram-positive and 276 gram-negative aerobic baseline pathogens were identified. Ceftobiprole inhibited all staphylococcal isolates, including methicillin-resistant strains, at MICs of

Topics: Anti-Bacterial Agents; Cephalosporins; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Skin Diseases, Bacterial; Staphylococcus

Complicated intra-abdominal infections (cIAIs) require surgical intervention and empiric antibacterial therapy. Doripenem, a broad-spectrum carbapenem, provides coverage of key gram-negative and -positive aerobes and anaerobes encountered in cIAI.. This study was designed to compare the efficacy and safety profile of doripenem and meropenem in hospitalized adult patients with cIAI.. In this prospective, multicenter, doubleblind, noninferiority study, hospitalized adults with cIAI were randomly assigned to receive doripenem 500 mg IV q8h or meropenem 1 g IV q8h. After a minimum of 9 doses and adequate clinical improvement (relative to before the start of IV study drug, decreased body temperature and white blood cell count, improved or absent signs and symptoms of cIAI, and return of normal bowel function), patients could be switched to oral amoxicillin/clavulanate. Antibacterial therapy (IV plus subsequent oral) was given for a total of 5 to 14 days. The coprimary efficacy end points were the clinical cure rate (complete resolution or significant improvement of signs or symptoms of the index infection) in patients microbiologically evaluable (>or=1 baseline pathogen isolated from an intra-abdominal culture that was susceptible to both IV study drug therapies) at the test-of-cure (TOC) visit (21-60 days after the completion of study drug therapy) and the clinical cure rate in the microbiological modified intent-to-treat (mMITT) population (a bacterial pathogen identified at baseline, regardless of its susceptibility to the study drug). Noninferiority was concluded if the lower limit of the 2-sided 95% CI for the difference (doripenem minus meropenem) in the proportion of patients classified as clinical cures was >or=-15%.. A total of 476 patients were enrolled. The microbiologically evaluable population (319 patients) was 62.7% male and 67.7% white, with a mean age and weight of 46.7 years and 77.2 kg, respectively. In this population, doripenem and meropenem were associated with clinical cure rates at the TOC visit of 85.9% and 85.3%, respectively. The corresponding treatment difference was 0.6% (95% CI, -7.7% to 9.0%); this difference was not statistically significant. Similarly, in the mMITT population (385 patients), the clinical cure rates were 77.9% and 78.9%, respectively, and the corresponding 1.0% treatment difference was not statistically significant (95% CI, -9.7% to 7.7%). Clinical cure rates were not significantly different between the 2 treatment arms in key subgroups (eg, age, sex, race, baseline Acute Physiology and Chronic Health Evaluation II score, primary infection site). Microbiological eradication rates for common pathogens isolated at study entry were not significantly different between the 2 treatment groups. Doripenem was well tolerated in the population studied. In the intent-to-treat population (471 patients), 83.0% and 78.0% of patients experienced >or=1 adverse event (AE) and 13.2% and 14.0% experienced >or=1 serious AE in the doripenem and meropenem treatment arms, respectively. In the doripenem and meropenem treatment arms, AEs resulted in study drug discontinuation in 5.1% and 2.1% of patients and death in 2.1% and 3.0% of patients, respectively.. The present study found that doripenem (500 mg q8h) was effective in the treatment of cIAI, was therapeutically noninferior to meropenem (1 g q8h), with a safety profile not significantly different from that of meropenem in this selected population of patients with cIAI.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Doripenem; Double-Blind Method; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins

The efficacy and tolerability of meropenem as empirical treatment in patients with hospital-acquired pneumonia was determined in a prospective, open-label, non-randomized trial. Patients from 28 centers in the USA received meropenem 1 g every 8 h intravenously. Of 255 patients enrolled, 111 were evaluable for efficacy, including 60 patients with ventilator-associated pneumonia. At end of treatment 74% of patients had a satisfactory clinical response and 64% had this response at follow-up, which could last up to 28 days after treatment. In patients with ventilator-associated pneumonia, a satisfactory clinical response was observed in 68% at the end of treatment and 63% at follow-up. The overall satisfactory response rate for individual pretreatment pathogens ranged from 65% to 100%. This study demonstrates that meropenem monotherapy is effective and well tolerated for patients with hospital-acquired pneumonia, including a subgroup of patients with ventilator-associated pneumonia.

Topics: Adolescent; Adult; Aged; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Probability; Prospective Studies; Respiration, Artificial; Risk Assessment; Thienamycins; Treatment Outcome

To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia.. A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events.. The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ceftazidime; Cephalosporins; Double-Blind Method; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Thienamycins

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

Eggerthella lenta is a Gram-positive anaerobic bacillus that is an important cause of bloodstream infections. This study aims to test the susceptibility of Eggerthella lenta blood culture isolates to commonly used antibiotics for the empirical treatment of anaerobic infections.. In total, 49 positive blood cultures for Eggerthella lenta were retrospectively included from patients hospitalised at the Universitair Ziekenhuis Brussel, Belgium, between 2004 and 2018. Identification was done by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Antimicrobial susceptibility testing was performed using the reference agar dilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines with Brucella agar supplemented with 5 μg/mL hemin, 1 μg/mL vitamin K1 and 5% laked sheep blood. The minimal inhibitory concentrations were interpreted using the EUCAST breakpoints. Clinical characteristics were collected by reviewing the patient's medical records.. All isolates were susceptible to amoxicillin-clavulanate, metronidazole and meropenem. Eighty-eight % of them were susceptible to clindamycin and 94% (20% S, 74% I) were susceptible to piperacillin-tazobactam. The mean age of the patients was 64 (±20) and they showed a 30-day mortality of 27%. The source of infection was in 65.3% of the cases abdominal, 20.4% were sacral pressure ulcers and 14.3% were unknown causes. While all isolates were fully susceptible at standard dosing regimen to amoxicillin-clavulanate, most were only susceptible at increased exposure or resistant to piperacillin-tazobactam.. Our results suggest to be careful with the use of piperacillin-tazobactam and clindamycin in the empirical treatment of Eggerthella lenta infections.

Topics: Actinobacteria; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria, Anaerobic; Belgium; Blood; Clindamycin; Female; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitals, University; Humans; Male; Meropenem; Metronidazole; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Coinfection; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecalis; Enterococcus faecium; Eye Neoplasms; Febrile Neutropenia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Leukemia, Myeloid, Acute; Male; Melanoma; Meropenem; Middle Aged; Neoplasms, Second Primary; Pseudomonas Infections; Tigecycline

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

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

Objective This study aimed to investigate the epidemiology and changes in antibacterial susceptibility of children in Shenmu City, northern Shaanxi, and provide a basis for rational drug use. Methods The distribution and drug resistance pattern of pathogenic bacteria isolated from children were retrospectively analysed. Results A total of 573 strains of pathogens were cultivated. A total of 201 (35.07%) strains of Gram-positive cocci and 183 (31.93%) strains of Gram-negative cocci were detected. A total of 189 (32.98%) strains of fungi were detected. The resistance rate of Staphylococcus to penicillin was 100% and that to erythromycin was 90.69%. There were varying degrees of resistance to other drugs, but no single strain had vancomycin resistance. Gram-negative bacilli were generally resistant to ampicillin, but had low resistance to the combined preparation of enzyme inhibitors, quinolones, and aminoglycosides, and were highly sensitive to imipenem and meropenem. Conclusion Gram-negative bacilli are the main pathogens of bacterial infection in the paediatric ward. Strengthening clinical monitoring of bacterial distribution in paediatric clinical isolates and understanding changes in drug resistance are important for guiding the rational use of antibiotics. These measures could also prevent emergence and spreading of resistant strains.

Topics: Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fungi; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Imipenem; Infant; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Mycoses; Penicillins; Retrospective Studies; Thienamycins; Vancomycin

Infections are major causes of morbidity and mortality in the early postoperative period after liver transplant. We observed a high rate of enterococcal infections at our center. Therefore, we added an intraoperative single shot of vancomycin to the standard regimen of meropenem given over 5 days. The aim of this study was to determine the prevalence of both Enterococcus faecium and Enterococcus faecalis infections during the first 28 days after surgery depending on the type of antibiotic prophylaxis and their implications on mortality and morbidity.. Our retrospective cohort analysis included 179 patients: 93 patients received meropenem only and 86 patients were treated with meropenem plus vancomycin.. During the first 28 days after transplant, microbiological tests showed that 51 patients (28.5%) were positive for Enterococcus faecium and 25 patients (14.0%) were positive for Enterococcus faecalis. Enterococcus faecium infections appeared significantly more often in patients without vancomycin (P = .013). In the second week after transplant, there was a significant reduction in Enterococcus faecium infections in the meropenem plus vancomycin group (P = .015). Enterococcus faecalis infections occurred more often in the patients receiving meropenem alone, but results were not statistically significant (P = .194). There was a trend toward more frequent renal replacement therapy in the meropenem plus vancomycin group. We found no differences between the groups regarding survival after 1 and 2 years, length of hospital stay, or duration in the intensive care unit. Overall 1-year survival was 78.8% (141/179 patients).. Although postoperative Enterococcus species infections can be reduced after liver transplant by adding vancomycin to the intraoperative antibiotic regimen, it does not improve the long-term outcomes.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Enterococcus faecalis; Enterococcus faecium; Female; Germany; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Intraoperative Care; Liver Transplantation; Male; Meropenem; Middle Aged; Prevalence; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vancomycin

Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP.. We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively.. Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare-related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin-tazobactam; P > 0·05), but comparable concerning third-generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; P = 0·002).. Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Liver Cirrhosis; Male; Meropenem; Middle Aged; Peritonitis; Prospective Studies; Streptococcal Infections; Thienamycins

Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants. We synthesized 5-alkyloxytryptamine analogs and found that an alkyl chain length of 6-12 carbons and a primary ammonium group are necessary for the antibacterial activity of the compounds, and an alkyl chain length of 6-10 carbons increased the membrane permeability of Gram-positive and Gram-negative bacteria. Although several of the most potent analogs also have activity against the membranes of human embryonic kidney cells, we demonstrate that below the minimum inhibitory concentration (MIC)-where mammalian cell toxicity is low-these compounds may be successfully used as adjuvants for chloramphenicol, tetracycline, ciprofloxacin, and rifampicin against clinical strains of Salmonella typhimurium, Acinetobacter baumannii and Staphylococcus aureus, reducing MIC values by as much as several logs.

Topics: Acinetobacter baumannii; Alkylation; Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; HEK293 Cells; Humans; Salmonella typhimurium; Staphylococcus aureus; Tryptamines

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

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

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

We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.. Burada mantle hücreli lenfoma tanısı ile R-CHOP (rituksimab, siklofosfamid, doksorubisin, vinkristin, prednizolon) kemoimmünoterapisi ile tedavi edilen ve muhtemelen Leuconostoc cinsi etkene bağlı pürülan menenjit gelişen 64 yaşında bir erkek hastayı sunuyoruz. Hastanın rituksimab tedavisinin olası komplikasyonlarından biri olan ağır hipogammaglobulinemisi bulunmakta olup, bildiğimiz kadarı ile ve mevcut tıbbi literatürün taranması sonrasında, olgumuz R-CHOP protokolü ile tedavi sonrası Leuconostoc cinsi etkene bağlı pürülan menejit gelişen mantle hücreli lenfoma tanılı ilk hastadır. Pürülan menenjit tanısı klinik bulgular, laboratuvar ve beyin-omurilik sıvısının sitolojik bulguları ve Leuconostoc izole ettiğimiz kan kültürünü temel alıyordu. Hasta meropenem tedavisi ile tamamen iyileşti.

Topics: Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Multiple, Bacterial; Gram-Positive Bacterial Infections; Humans; Leuconostoc; Lymphoma, Mantle-Cell; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Opportunistic Infections; Rituximab; Thienamycins

Bacillus cereus is an aerobic, spore-forming, gram-positive rod. It has historically been associated with "fried rice syndrome," a foodborne diarrheal and emetic illness resulting from eating fried rice dishes that have been sitting at room temperature for hours. We report the case of a 9-year-old boy who developed culture-positive B cereus fasciitis of the right lower extremity after being impaled on a tree branch. This case report further elucidates and emphasizes the importance of recognizing B cereus as a possible cause of severe soft-tissue infection. It must be included in the differential diagnosis of gas gangrene and necrotizing fasciitis.

Topics: Anti-Bacterial Agents; Bacillus cereus; Child; Clindamycin; Debridement; Fasciitis; Fasciotomy; Gram-Positive Bacterial Infections; Humans; Lower Extremity; Male; Meropenem; Reoperation; Soft Tissue Infections; Therapeutic Irrigation; Thienamycins; Vancomycin; Wounds, Penetrating

Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark.. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study.. One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin-tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test).. Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin-tazobactam could be a favorable choice.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Cephalosporins; Denmark; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Kaplan-Meier Estimate; Liver Cirrhosis; Male; Meropenem; Middle Aged; Mycoses; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Thienamycins

Lactobacilli are Gram-positive rod-shaped bacteria that inhabit the oral cavity, gastrointestinal tract, vagina and nasal cavity. In this report, a rare case of Lactobacillus jensenii endocarditis in a 47-year-old immunocompetent patient is described. Blood cultures and a replaced mitral valve were positive for L. jensenii as assessed by 16S rRNA gene sequencing. Based on susceptibility tests the patient was successfully treated with a mixture of teicoplanin and meropenem antimicrobial therapy.

Topics: Anti-Bacterial Agents; Blood; DNA, Bacterial; DNA, Ribosomal; Endocarditis, Bacterial; Female; Gram-Positive Bacterial Infections; Humans; Lactobacillus; Meropenem; Microbial Sensitivity Tests; Middle Aged; Mitral Valve; Molecular Sequence Data; Sequence Analysis, DNA; Teicoplanin; Thienamycins

The case of a patient who previously had permanent acupuncture needles placed in the knee joint and had been doing well, with no evidence of infection, but who eventually underwent a revision total knee arthroplasty due to acupuncture needle-associated prosthetic infection is presented. The microorganism responsible for the infection was Enterococcus faecalis, a bacterium which rarely causes infection following arthroplasty. This case should be highlighted to increase the awareness of healthcare providers to acupuncture-associated subclinical infection that may be exacerbated by surgical manipulation.

Topics: Acupuncture Therapy; Ampicillin; Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Drug Therapy, Combination; Enterococcus faecalis; Female; Gram-Positive Bacterial Infections; Humans; Knee Joint; Knee Prosthesis; Meropenem; Middle Aged; Prosthesis-Related Infections; Reoperation; Sulbactam; 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

Topics: Antibiotic Prophylaxis; Child; Child, Preschool; Critical Illness; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Incidence; Infant; Intensive Care Units, Pediatric; Male; Meropenem; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Thienamycins

Between 1 September 2005 and 30 June 2006, 19 medical centers collected 4,180 isolates recovered from clinical specimens from patients in intensive care units (ICUs) in Canada. The 4,180 isolates were collected from 2,292 respiratory specimens (54.8%), 738 blood specimens (17.7%), 581 wound/tissue specimens (13.9%), and 569 urinary specimens (13.6%). The 10 most common organisms isolated from 79.5% of all clinical specimens were methicillin-susceptible Staphylococcus aureus (MSSA) (16.4%), Escherichia coli (12.8%), Pseudomonas aeruginosa (10.0%), Haemophilus influenzae (7.9%), coagulase-negative staphylococci/Staphylococcus epidermidis (6.5%), Enterococcus spp. (6.1%), Streptococcus pneumoniae (5.8%), Klebsiella pneumoniae (5.8%), methicillin-resistant Staphylococcus aureus (MRSA) (4.7%), and Enterobacter cloacae (3.9%). MRSA made up 22.3% (197/884) of all S. aureus isolates (90.9% of MRSA were health care-associated MRSA, and 9.1% were community-associated MRSA), while vancomycin-resistant enterococci (VRE) made up 6.7% (11/255) of all enterococcal isolates (88.2% of VRE had the vanA genotype). Extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae occurred in 3.5% (19/536) and 1.8% (4/224) of isolates, respectively. All 19 ESBL-producing E. coli isolates were PCR positive for CTX-M, with bla CTX-M-15 occurring in 74% (14/19) of isolates. For MRSA, no resistance against daptomycin, linezolid, tigecycline, and vancomycin was observed, while the resistance rates to other agents were as follows: clarithromycin, 89.9%; clindamycin, 76.1%; fluoroquinolones, 90.1 to 91.8%; and trimethoprim-sulfamethoxazole, 11.7%. For E. coli, no resistance to amikacin, meropenem, and tigecycline was observed, while resistance rates to other agents were as follows: cefazolin, 20.1%; cefepime, 0.7%; ceftriaxone, 3.7%; gentamicin, 3.0%; fluoroquinolones, 21.1%; piperacillin-tazobactam, 1.9%; and trimethoprim-sulfamethoxazole, 24.8%. Resistance rates for P. aeruginosa were as follows: amikacin, 2.6%; cefepime, 10.2%; gentamicin, 15.2%; fluoroquinolones, 23.8 to 25.5%; meropenem, 13.6%; and piperacillin-tazobactam, 9.3%. A multidrug-resistant (MDR) phenotype (resistance to three or more of the following drugs: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) occurred frequently in P. aeruginosa (12.6%) but uncommonly in E. coli (0.2%), E. cloacae (0.6%), or K. pneumoniae (0%). In conclusion, S. aureus (MSSA and MRSA), E.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Canada; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Population Surveillance

Doripenem, a 1beta-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (microg/ml) were established by broth microdilution. By MIC(90), doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, < or =0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC(90) of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum beta-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC(90)/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC(90) = 2, 89.1%S) was twice as active by MIC(90) as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including beta-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of beta-lactam resistance.

Topics: Anti-Bacterial Agents; Carbapenems; Doripenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; United States

Doripenem was evaluated against 527 recent clinical isolates, i.e., 404 Bacteroides fragilis isolates and 123 gram-positive anaerobe isolates. Against B. fragilis, doripenem was as active as imipenem, meropenem, and piperacillin-tazobactam and more active than ertapenem or ampicillin-sulbactam. Doripenem was active against isolates resistant to ertapenem, ampicillin-sulbactam, cefoxitin, clindamycin, and moxifloxacin. All of the gram-positive isolates tested were susceptible to doripenem.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Bacteroides fragilis; Carbapenems; Doripenem; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests

Since 1997, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum agents against pathogens from hospitalized patients. In the United States, 2894 isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae, 643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All isolates were tested by broth microdilution methods. Meropenem (MIC(90) range, 0.12-2 microg/mL) exhibited the lowest resistance rates (1.9-2.4%) against Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance (17.3-18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli. Confirmed extended-spectrum beta-lactamase-producing isolate rates for E. coli, Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%, respectively. Meropenem remained active against Gram-positive pathogens such as staphylococci (methicillin-susceptible; MIC(90), 0.12-0.25 microg/mL), Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel beta-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.

Topics: Academic Medical Centers; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins; United States

The meropenem susceptibility surveillance study was performed between 2002 and 2006 in Japan. Meropenem resistance against Pseudomonas aeruginosa was nearly constant at about 10% during the period. For all species of the bacteria tested, the MIC(90) of meropenem in 2006 was not more than 4-fold higher than that in 2002 and 2004.

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Japan; Meropenem; Microbial Sensitivity Tests; Sentinel Surveillance; Thienamycins

The activities of several tricyclic heteroaryl isothiazolones (HITZs) against an assortment of gram-positive and gram-negative clinical isolates were assessed. These compounds target bacterial DNA replication and were found to possess broad-spectrum activities especially against gram-positive strains, including antibiotic-resistant staphylococci and streptococci. These included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-nonsusceptible staphylococci, and quinolone-resistant strains. The HITZs were more active than the comparator antimicrobials in most cases. For gram-negative bacteria, the tested compounds were less active against members of the family Enterobacteriaceae but showed exceptional potencies against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. Good activity against several anaerobes, as well as Legionella pneumophila and Mycoplasma pneumoniae, was also observed. Excellent bactericidal activity against staphylococci was observed in time-kill assays, with an approximately 3-log drop in the numbers of CFU/ml occurring after 4 h of exposure to compound. Postantibiotic effects (PAEs) of 2.0 and 1.7 h for methicillin-susceptible S. aureus and MRSA strains, respectively, were observed, and these were similar to those seen with moxifloxacin at 10x MIC. In vivo efficacy was demonstrated in murine infections by using sepsis and thigh infection models. The 50% protective doses were

Topics: Animals; Anti-Infective Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Mice; Microbial Sensitivity Tests; Quinolones; Thiazoles

The beta-lactam antibiotics mimic the D-alanyl(4)-D-alanine(5) extremity of peptidoglycan precursors and act as "suicide" substrates of the DD-transpeptidases that catalyze the last cross-linking step of peptidoglycan synthesis. We have previously shown that bypass of the dd-transpeptidases by the LD-transpeptidase of Enterococcus faecium (Ldt(fm)) leads to high level resistance to ampicillin. Ldt(fm) is specific for the L-lysyl(3)-D-alanine(4) bond of peptidoglycan precursors containing a tetrapeptide stem lacking D-alanine(5). This specificity was proposed to account for resistance, because the substrate of Ldt(fm) does not mimic beta-lactams in contrast to the D-alanyl(4)-D-alanine(5) extremity of pentapeptide stems used by the DD-transpeptidases. Here, we unexpectedly show that imipenem, a beta-lactam of the carbapenem class, totally inhibited Ldt(fm) at a low drug concentration that was sufficient to inhibit growth of the bacteria. Peptidoglycan cross-linking was also inhibited, indicating that Ldt(fm) is the in vivo target of imipenem. Stoichiometric and covalent modification of Ldt(fm) by imipenem was detected by mass spectrometry. The modification was mapped into the trypsin fragment of Ldt(fm) containing the catalytic Cys residue, and the Cys to Ala substitution prevented imipenem binding. The mass increment matched the mass of imipenem, indicating that inactivation of Ldt(fm) is likely to involve rupture of the beta-lactam ring and acylation of the catalytic Cys residue. Thus, the spectrum of activity of beta-lactams is not restricted to transpeptidases of the DD-specificity, as previously thought. Combination therapy with imipenem and ampicillin could therefore be active against E. faecium strains having the dual capacity to manufacture peptidoglycan with transpeptidases of the LD- and DD-specificities.

Topics: Acylation; Aminoacyltransferases; Ampicillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactams; Dipeptides; Dose-Response Relationship, Drug; Enterococcus faecium; Enzyme Precursors; Gram-Positive Bacterial Infections; Imipenem; Mass Spectrometry; Substrate Specificity; Trypsin

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global study that provides antimicrobial susceptibility data in centers prescribing meropenem. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 5208 bacterial isolates from 9 Turkish centers between 2000 and 2003. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.3%), imipenem (97.6%), cefepime (80.0%), piperacillin-tazobactam (73.6%), ceftazidime (70.3%), ciprofloxacin (70.1%), cefotaxime (66.9%), and tobramycin (67.2%). The production of extended-spectrum beta-lactamases (ESBLs) was detected in 48.7% of Klebsiella pneumoniae and in 19.5% of Escherichia coli isolates. Of ESBL producing K. pneumoniae isolates, 75.7% were resistant to tobramycin, 40.3% to ciprofloxacin, and 48.3% to piperacillin-tazobactam. Only piperacillin/tazobactam and carbapenems were active against more than 50% of Pseudomonas aeruginosa at the National Committee for Clinical Laboratory Standards-susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. These data confirm the continued potency of meropenem against Enterobacteriaceae in units where it is actively being prescribed.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins; Turkey

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 876 strains of Gram-positive bacteria, 1764 strains of Gram-negative bacteria, and 198 strains of anaerobic bacteria obtained from 30 medical institutions during 2006 was measured. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, all of the MEPM-resistant strains were resistant to imipenem (IPM). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (41.8%) and ciprofloxacin-resistant P. aeruginosa (33.3%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 4.3% (6 strains) in Escherichia coli, 1.1% (1 strain) in Citrobacter freundii, 21.7% (5 strains) in Citrobacter koseri, 3.1% (4 strains) in Klebsiella pneumoniae, 3.3% (3 strains) in Enterobacter cloacae, 0.8% (1 strain) in Serratia marcescens, and 4.9% (2 strains) in Providencia spp. The proportion of metallo-beta-lactamase strains was 3.1% (10 strains) in P. aeruginosa. 4. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 11 years after available for commercial use.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Japan; Meropenem; Thienamycins; Time Factors

A 26-year-old man was admitted with fever and abdominal pain. Abdominal ultrasonography and Doppler ultrasound eventually revealed portal vein thrombosis and a pyogenic liver abscess (17x11x11 cm). Lactococcus lactis was isolated from a culture of the abscess material. This organism is not a common pathogen in humans. This is the first published description of portal vein thrombosis and pyogenic liver abscess due to L. lactis.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Catheterization; Drainage; Gram-Positive Bacterial Infections; Heparin; Humans; Lactococcus lactis; Liver Abscess; Male; Meropenem; Microbial Sensitivity Tests; Portal Vein; Thienamycins; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Enterococcal meningitis is an uncommon disease usually caused by Enterococcus faecalis and Enterococcus faecium and is associated with a high mortality rate. Enterococcus casseliflavus has been implicated in a wide variety of infections in humans, but never in meningitis.. A 77-year-old Italian female presented for evaluation of fever, stupor, diarrhea and vomiting of 3 days duration. There was no history of head injury nor of previous surgical procedures. She had been suffering from rheumatoid arthritis for 30 years, for which she was being treated with steroids and methotrexate. On admission, she was febrile, alert but not oriented to time and place. Her neck was stiff, and she had a positive Kernig's sign. The patient's cerebrospinal fluid was opalescent with a glucose concentration of 14 mg/dl, a protein level of 472 mg/dl, and a white cell count of 200/muL with 95% polymorphonuclear leukocytes and 5% lymphocytes. Gram staining of CSF revealed no organisms, culture yielded E. casseliflavus. The patient was successfully treated with meropenem and ampicillin-sulbactam.. E. casseliflavus can be inserted among the etiologic agents of meningitis. Awareness of infection of central nervous system with Enterococcus species that possess an intrinsic vancomycin resistance should be increased.

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Cerebrospinal Fluid; Enterococcus; Female; Gram-Positive Bacterial Infections; Humans; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Sigmoid Diseases; Sulbactam; Thienamycins

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program provides antimicrobial susceptibility data. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 12645 bacterial isolates from 14 European centers between 1997 and 2002. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.9%) > imipenem (97.7%) > ciprofloxacin (86.0%) > piperacillin-tazobactam (85.6%) > ceftazidime (85.4%) > gentamicin (85.4%) > tobramycin (85.0%) > cefotaxime (83.8%). The carbapenems were also found to be the most active of the classes tested against nonfermentative Gram-negative bacilli. Against methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, all beta-lactams tested (except ceftazidime) had susceptibility rates of > or = 99.0% and > or = 94.3%, respectively. Over the 6-year period, there was no loss of activity or increase in resistance rate for either carbapenem against any of the species tested. These data confirm the continued potency and broad-spectrum activity of meropenem in units where it is actively being prescribed.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospitalization; Humans; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

To compare the in-vitro sensitivity of meropenem with imipenem and other antibiotics against clinically significant bacteria.. A longitudinal survey.. Department of Medical Microbiology, in a tertiary care university hospital.. Specimens obtained from patients attending various clinics at tertiary care and teaching hospital in Harare. Those submitted to the Public Health Bacteriology Laboratory were analysed.. Rates of resistance or susceptibility of the various bacteria to the antibiotics employed in the study.. There was excellent in-vitro bacterial activity of meropenem against virtually all clinically significant Gram positive and Gram negative isolates when compared with other antibiotics such as imipenem, ciprofloxacin, gentamicin, penicillin, ampicillin, fusidic acid, tetracyclines, erythromycin and clindamycin (p < 0.5). All isolates of Streptococcus pyogenes, Pseudomonas aeruginosa, Enterobacteriaceae, Neisseria meningitidis were susceptible to meropenem. Meropenem showed 99% overall in-vitro sensitivity against Gram positive and Gram negative bacteria. About 80% of staphylococci were resistant to penicillin whereas at least 20-25% of S. aureus, coagulase negative staphylococci, S. pyogenes showed resistance to ampicillin, erythromycin, gentamicin, tetracycline and clindamycin.. Meropenem is not included in the list of routinely tested antibiotics in our laboratory, a major tertiary laboratory in the country. As a result of the ultra-broad spectrum of activity, we recommend its inclusion in our routine antibiotic sensitivity testing and observe that there is a great potential for meropenem in the treatment of infections caused by several genera of bacteria in our environment.

Topics: Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Longitudinal Studies; Meropenem; Microbial Sensitivity Tests; Thienamycins; Zimbabwe

The in vitro antibacterial activity of meropenem and up to 26 other antibiotics was compared under routine conditions at 92 German centers from March to June 1995 with use of the agar diffusion method against 18632 recent isolates from ICU--hemato-oncology--and pediatric patients. Overall, meropenem was the most active drug exhibiting a higher activity against gram-negative aerobes than imipenem, but somewhat less active against staphylococci and enterocooci. The overall resistance rates of most antibiotics tested was higher compared to the recently published surveillance data of the Paul-Ehrlich-Society in Germany. The main reason for this discrepancy is the higher percentage of test strains which were recovered from intensive care unit patients in the present study. These data confirm similar results from the USA and underscore the pressing need for the implementation of a nationwide antimicrobial surveillance system which is risk-stratified by hospital size, ICU- versus non-ICU-patients, and body site from which the isolates are recovered.

Topics: Anti-Bacterial Agents; Bacteria, Aerobic; Bacterial Infections; beta-Lactam Resistance; Drug Resistance, Microbial; Germany; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Lactams; Meropenem; Thienamycins

Topics: Enterococcus faecalis; Gram-Positive Bacterial Infections; Meropenem; Microbial Sensitivity Tests; Thienamycins