meropenem and Pneumonia--Bacterial

Topics: Achromobacter denitrificans; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Granulomatous Disease, Chronic; Humans; Infant; Male; Meropenem; Pneumonia, Bacterial

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

The prevalence of antibiotic-resistant bacteria continues to increase, particularly in patients in the intensive care unit with nosocomial pneumonia. The intention of this review is to provide an overview of severe nosocomial pneumonia, carbapenems and the problem of bacterial resistance to antimicrobial agents. Attention was focused on the efficacy, safety and pharmacodynamics of imipenem, meropenem, ertapenem and doripenem. Issues on the impact of appropriate empiric antibiotic therapy for nosocomial pneumonia patients considered at risk for resistant pathogens are discussed. Critical decision making regarding the use of carbapenems for treating severe nosocomial pneumonia requires careful consideration of the four Ds of optimal antimicrobial therapy: right Drug, right Dose, De-escalated to pathogen-directed therapy and right Duration of therapy.

Topics: Anti-Bacterial Agents; beta-Lactams; Carbapenems; Cross Infection; Doripenem; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Ertapenem; Humans; Imipenem; Meropenem; Patient Selection; Pneumonia, Bacterial; Respiratory Tract Infections; Severity of Illness Index; Thienamycins; Treatment Outcome

We report a case of a nosocomial Capnocytophaga spp. DF-1 pneumonia in an intubated 56-year-old man following coronary artery bypass grafting. We review Capnocytophaga spp., including the infections they produce and antibiotic susceptibilities.

Topics: Anti-Bacterial Agents; Capnocytophaga; Coronary Artery Bypass; Cross Infection; Gram-Negative Bacterial Infections; Humans; Immunocompetence; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Postoperative Complications; Respiration, Artificial; Thienamycins

The comparative effectiveness and safety of carbapenems with other beta-lactams and fluoroquinolones for the empirical treatment of patients with hospital-acquired pneumonia remains controversial. In the present study, a meta-analysis of 12 relevant randomised controlled trials was performed. Overall, carbapenems were associated with lower mortality than fluoroquinolones or beta-lactams, alone or in combination with aminoglycosides (odds ratio 0.72, 95% confidence interval 0.55-0.95). There was no difference between the compared antibiotics regarding treatment success (1.08, 0.91-1.29), microbiological success (1.04, 0.72-1.50) or development of adverse effects (0.81, 0.46-1.43). In the subset of patients with Pseudomonas aeruginosa pneumonia, carbapenems were associated with lower treatment success (0.42, 0.22-0.82) and lower eradication of P. strains (0.50, 0.24-0.89). Carbapenems are equivalent to fluoroquinolones or beta-lactams, alone or in combination with aminoglycosides, for the empirical treatment of immunocompetent adult patients with hospital-acquired pneumonia. However, there is limited evidence, based predominantly on unblinded randomised controlled trials, that carbapenems are associated with lower mortality than the comparators; this association was not observed in a subset analysis of randomised controlled trials with a high methodological quality score. In patients with Pseudomonas aeruginosa pneumonia, carbapenems are associated with worse outcomes than the comparators.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aminoglycosides; beta-Lactams; Carbapenems; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Fluoroquinolones; Humans; Immunocompetence; Intensive Care Units; Meropenem; Pneumonia, Bacterial; Pseudomonas Infections; Randomized Controlled Trials as Topic; Respiration, Artificial; Survival Rate; Thienamycins; Treatment Outcome

To review the laboratory diagnosis of extended-spectrum beta-lactamase (ESBL) and AmpC beta-lactamase-producing bacteria and evaluate potential treatment options.. A PubMed search, restricted to English-language articles, was conducted (1966-May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles.. All studies that evaluated laboratory methods for the detection of ESBLs and AmpC beta-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated.. Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC beta-lactamases are limited, particularly for plasmid-mediated AmpC beta-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC beta-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms.. Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute-recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC beta-lactamases. No established guidelines exist for the detection of AmpC beta-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC beta-lactamase-producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Thienamycins

The carbapenems are a group of broad-spectrum beta-lactam antibiotic agents of which there are three parenteral preparations currently available in South Africa, namely imimpenem/cilastatin, meropenem and ertapenem. Owing to the fact that imipenem/cilastatin and meropenem have a broad spectrum of activity that includes Pseudomonas and Acinetobacter species, they are ideal antibiotics for treatment of severe nosocomial infections. In contrast, ertapenem has limited in vitro activity against the latter non-fermentative gram-negative bacteria and is therefore more suitable for the treatment of certain severe community-acquired infections. This statement arises out of concerns about the general abuse of antibiotics such as the carbapenems, with the primary intention of highlighting the appropriate use of these agents.

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Carbapenems; Cilastatin; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Ertapenem; Humans; Imipenem; Lactams; Meropenem; Patient Selection; Pneumonia, Bacterial; Practice Patterns, Physicians'; Protease Inhibitors; South Africa; Surgical Wound Infection; Thienamycins; Urinary Tract Infections

Antimicrobial resistance is increasing among bacterial pathogens. In particular, organisms producing extended spectrum beta-lactamase enzymes (ESBLs) and AmpC chromosomal beta-lactamase enzymes are resistant to third generation cephalosporins and pose a formidable challenge in the management of seriously ill patients. Carbapenems are a class of broad-spectrum antibiotics with stability against ESBL and AmpC chromosomal beta-lactamases. They are well tolerated by patients. This review will examine the pharmacokinetic and pharmacodynamic properties of two carbapenems imipenem and meropenem and discuss their clinical use in children. References are limited to the English language and extend back to 1980. Sources include computerized databases such as MEDLINE searched using PubMed, and bibliographies of recent articles and books. Approximately 50% of the articles initially reviewed are included in the bibliography. Carbapenems are efficacious in the treatment of a variety of bacterial infections including meningitis, pneumonia, intraabdominal infections, bone, joint and urinary tract infections. The broad spectrum activity and comparatively low toxicity of carbapenems make them valuable therapeutic agents in the treatment of seriously ill patients with bacterial infections. These agents should be used judiciously in order to minimize the risk for development of carbapenem-resistant pathogens.

Topics: Child; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Neutropenia; Pneumonia, Bacterial; Thienamycins

Carbapenems are active beta-lactam antibiotics versus most of the gram positive and gram negative microorganisms and anaerobes although their activity is lacking in the case of Staphylococcus sp. resistant to methicillin, Enterococcus faecium and Streptococcus pneumoniae with high resistance to penicillin and some gram negative bacilli which naturally produce an methaloenzyme able to hydrolyze them such as Stenotrophomonas maltophilia. Imipenem, the first synthetized carbapenem requires administration with cilastatin to avoid inactivation by renal dehydropeptidase 1. Meropenem does not require being taken with the renal enzyme inhibitor, with its activity being similar to that of imipenem. In abdominal infection the carbapenems have shown to be the authentic monotherapy in this type of infections being as effective as the different schedules of antibiotic associations normally used. Treatment with carbapenems in bacterial meningitis should be currently limited to the cases produced by gram negative bacilli producers of wide spectrum beta-lactamases (WSBL), cases of meningitis by Pseudomonas aeruginosa or gram negative bacilli producers of inducible cephalosporinase. Meropenem is the carbapenem of choice probably in these cases because the carbapenems are often the only active antibiotics and meropenem, specifically, does not have the risk of convulsions observed with imipenem-cilastatin. The carbapenems have shown to be useful in skin and soft tissue infections as well as in obstetric and gynecologic infections as monotherapy similar to the schedules of the currently used antibiotic associations. In the case of nosocomial pneumonias, all the studies have evaluated the carbapenems in monotherapy as useful and effective, specially in the case of pneumonia by gram negative bacilli. Finally, in non filiated nosocomial sepsis and specially in the case of neutropenic patients, the use of carbapenems is particularly attractive in gram negative sepsis in intensive care units. The appearance in the last few years of strains of gram negative bacilli, producers of wide spectrum beta-lactamase or stable repressed hyperproducers of class I chromosomic cephalosporinase, as well as other multiresistant gram negative bacilli, such as Acinetobacter baumanii make the carbapenems, in many cases, the only effective antibiotic in this type of infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Cross Infection; Drug Therapy, Combination; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Skin Diseases, Infectious; Thienamycins

The survival of cystic fibrosis patients has improved through an aggressive, multidisciplinary approach to the therapy of pulmonary sepsis. Intravenous antibiotics play a major role in the care of cystic fibrosis patients, even though it is not possible to achieve persistent bacterial eradication due to the complex microbiology and pathology of these patients. The most important pathogen in older patients is Pseudomonas aeruginosa. The increasing incidence of Pseudomonas cepacia, strains of which can be highly resistant to many antibiotics, also represents an important challenge to the efficacy of antibiotic therapy. Choice of appropriate antimicrobial therapy is hampered by the fact that a single patient may harbour several different pseudomonas phenotypes with variable resistance patterns. Carbapenem antibiotics possess a wide range of activity against most Gram-negative and Gram-positive bacteria and are therefore a useful addition to the antimicrobial armamentarium available to the clinician. The new carbapenem meropenem is well tolerated at high doses by both children and adults. Results from a comparative trial against ceftazidime suggests that meropenem has a place in the management of cystic fibrosis.

Topics: Adult; Ceftazidime; Child; Child, Preschool; Clinical Trials as Topic; Cystic Fibrosis; Humans; Meropenem; Pneumonia, Bacterial; Pseudomonas Infections; Thienamycins

In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated.. Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7-14 days after the end of therapy) in the microbiological ITT (mITT) population.. The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: -4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: -18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: -4.51 to 19.38], respectively, were also comparable.. In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.

Topics: Anti-Bacterial Agents; Cephalosporins; Hospitals; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Prospective Studies; Pseudomonas aeruginosa; Tazobactam; Ventilators, Mechanical

After the MERINO trial with piperacillin/tazobactam, the efficacy of β-lactam/tazobactam combinations in serious infections involving extended-spectrum β-lactamase (ESBL)-producing pathogens merits special evaluation.. To further confirm the efficacy of ceftolozane/tazobactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) involving ESBL-positive and/or AmpC-producing Enterobacterales.. Retrospective subgroup analysis of the ASPECT-NP trial comparing ceftolozane/tazobactam with meropenem for treating HABP/VABP in mechanically ventilated adults (ClinicalTrials.gov NCT02070757). ESBLs were identified using whole genome sequencing. Chromosomal AmpC production was quantified employing a high-sensitivity mRNA transcription assay.. Overall, 61/726 (8.4%) participants had all baseline lower respiratory tract (LRT) isolates susceptible to both study treatments and ≥1 baseline ESBL-positive/AmpC-overproducing Enterobacterales isolate. In this subgroup (ceftolozane/tazobactam n = 30, meropenem n = 31), baseline characteristics were generally comparable between treatment arms. The most frequent ESBL-positive and/or AmpC-overproducing Enterobacterales isolates (ceftolozane/tazobactam n = 31, meropenem n = 35) overall were Klebsiella pneumoniae (50.0%), Escherichia coli (22.7%), and Proteus mirabilis (7.6%). The most prevalent ESBLs were CTX-M-15 (75.8%), other CTX-M (19.7%), and SHV (4.5%); 10.6% of isolates overproduced chromosomal AmpC. Overall, 28 day all-cause mortality was 6.7% (2/30) with ceftolozane/tazobactam and 32.3% (10/31) with meropenem (25.6% difference, 95% CI: 5.54 to 43.84). Clinical cure rate at test-of-cure, 7-14 days after end of therapy, was 73.3% (22/30) with ceftolozane/tazobactam and 61.3% (19/31) with meropenem (12.0% difference, 95% CI: -11.21 to +33.51). Per-isolate microbiological response at test-of-cure was 64.5% (20/31) with ceftolozane/tazobactam and 74.3% (26/35) with meropenem (-9.8% difference, 95% CI: -30.80 to +12.00).. These data confirm ceftolozane/tazobactam as an effective treatment option for HABP/VABP involving ceftolozane/tazobactam-susceptible ESBL-positive and/or AmpC-producing Enterobacterales.

Topics: Adult; Anti-Bacterial Agents; Cephalosporins; Escherichia coli; Hospitals; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Retrospective Studies; Tazobactam; Ventilators, Mechanical

Ceftolozane/tazobactam, a combination antibacterial agent comprising an anti-pseudomonal cephalosporin and β-lactamase inhibitor, is approved for the treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Participants in the ASPECT-NP trial received ceftolozane/tazobactam (3 g [2 g ceftolozane/1 g tazobactam] every 8 h) or meropenem (1 g every 8 h). Participants failing prior antibacterial therapy for the current HABP/VABP episode at study entry had lower 28-day all-cause mortality (ACM) rates with ceftolozane/tazobactam versus meropenem treatment. Here, we report a post hoc analysis examining this result.. The phase 3, randomized, controlled, double-blind, multicenter, noninferiority trial compared ceftolozane/tazobactam versus meropenem for treatment of adults with ventilated HABP/VABP; eligibility included those failing prior antibacterial therapy for the current HABP/VABP episode at study entry. The primary and key secondary endpoints were 28-day ACM and clinical response at test of cure (TOC), respectively. Participants who were failing prior therapy were a prospectively defined subgroup; however, subgroup analyses were not designed for noninferiority testing. The 95% CIs for treatment differences were calculated as unstratified Newcombe CIs. Post hoc analyses were performed using multivariable logistic regression analysis to determine the impact of baseline characteristics and treatment on clinical outcomes in the subgroup who were failing prior antibacterial therapy.. In the ASPECT-NP trial, 12.8% of participants (93/726; ceftolozane/tazobactam, n = 53; meropenem, n = 40) were failing prior antibacterial therapy at study entry. In this subgroup, 28-day ACM was higher in participants who received meropenem versus ceftolozane/tazobactam (18/40 [45.0%] vs 12/53 [22.6%]; percentage difference [95% CI]: 22.4% [3.1 to 40.1]). Rates of clinical response at TOC were 26/53 [49.1%] for ceftolozane/tazobactam versus 15/40 [37.5%] for meropenem (percentage difference [95% CI]: 11.6% [- 8.6 to 30.2]). Multivariable regression analysis determined concomitant vasopressor use and treatment with meropenem were significant factors associated with risk of 28-day ACM. Adjusting for vasopressor use, the risk of dying after treatment with ceftolozane/tazobactam was approximately one-fourth the risk of dying after treatment with meropenem.. This post hoc analysis further supports the previously demonstrated lower ACM rate for ceftolozane/tazobactam versus meropenem among participants who were failing prior therapy, despite the lack of significant differences in clinical cure rates.. gov registration NCT02070757 . Registered February 25, 2014, clinicaltrials.gov/ct2/show/NCT02070757 .

Topics: Adult; Anti-Bacterial Agents; Cephalosporins; Hospitals; Humans; Meropenem; Monobactams; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Tazobactam; Vasoconstrictor Agents; Ventilators, Mechanical

Nosocomial pneumonia due to multidrug-resistant Gram-negative pathogens poses an increasing challenge. We compared the efficacy and safety of cefiderocol versus high-dose, extended-infusion meropenem for adults with nosocomial pneumonia.. We did a randomised, double-blind, parallel-group, phase 3, non-inferiority trial in 76 centres in 17 countries in Asia, Europe, and the USA (APEKS-NP). We enrolled adults aged 18 years and older with hospital-acquired, ventilator-associated, or health-care-associated Gram-negative pneumonia, and randomly assigned them (1:1 by interactive response technology) to 3-h intravenous infusions of either cefiderocol 2 g or meropenem 2 g every 8 h for 7-14 days. All patients also received open-label intravenous linezolid (600 mg every 12 h) for at least 5 days. An unmasked pharmacist prepared the assigned treatments; investigators and patients were masked to treatment assignment. Only the unmasked pharmacist was aware of the study drug assignment for the infusion bags, which were administered in generic infusion bags labelled with patient and study site identification numbers. Participants were stratified at randomisation by infection type and Acute Physiology and Chronic Health Evaluation II (APACHE II) score (≤15 and ≥16). The primary endpoint was all-cause mortality at day 14 in the modified intention-to-treat (ITT) population (ie, all patients receiving at least one dose of study drug, excluding patients with Gram-positive monomicrobial infections). The analysis was done for all patients with known vital status. Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference between cefiderocol and meropenem groups was less than 12·5%. Safety was investigated to the end of the study in the safety population, which included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03032380, and EudraCT, 2016-003020-23.. Between Oct 23, 2017, and April 14, 2019, we randomly assigned 148 participants to cefiderocol and 152 to meropenem. Of 292 patients in the modified ITT population, 251 (86%) had a qualifying baseline Gram-negative pathogen, including Klebsiella pneumoniae (92 [32%]), Pseudomonas aeruginosa (48 [16%]), Acinetobacter baumannii (47 [16%]), and Escherichia coli (41 [14%]). 142 (49%) patients had an APACHE II score of 16 or more, 175 (60%) were mechanically ventilated, and 199 (68%) were in intensive care units at the time of randomisation. All-cause mortality at day 14 was 12·4% with cefiderocol (18 patients of 145) and 11·6% with meropenem (17 patients of 146; adjusted treatment difference 0·8%, 95% CI -6·6 to 8·2; p=0·002 for non-inferiority hypothesis). Treatment-emergent adverse events were reported in 130 (88%) of 148 participants in the cefiderocol group and 129 (86%) of 150 in the meropenem group. The most common treatment-emergent adverse event was urinary tract infection in the cefiderocol group (23 patients [16%] of 148) and hypokalaemia in the meropenem group (23 patients [15%] of 150). Two participants (1%) of 148 in the cefiderocol group and two (1%) of 150 in the meropenem group discontinued the study because of drug-related adverse events.. Cefiderocol was non-inferior to high-dose, extended-infusion meropenem in terms of all-cause mortality on day 14 in patients with Gram-negative nosocomial pneumonia, with similar tolerability. The results suggest that cefiderocol is a potential option for the treatment of patients with nosocomial pneumonia, including those caused by multidrug-resistant Gram-negative bacteria.. Shionogi.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefiderocol; Cephalosporins; Double-Blind Method; Female; Gram-Negative Bacterial Infections; Healthcare-Associated Pneumonia; Humans; Male; Meropenem; Pneumonia, Bacterial

Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding.. ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors.. Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam.. There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam.. clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.

Topics: Aged; Anti-Bacterial Agents; Cephalosporins; Double-Blind Method; Equivalence Trials as Topic; Female; Healthcare-Associated Pneumonia; Humans; Logistic Models; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Retrospective Studies; Tazobactam

In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.. This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin-meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin-meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure.. The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31-1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22-2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26-1.04) or 14-day mortality (aOR1.09, 95% CI 0.60-1.96).. In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

Topics: Aged; Aged, 80 and over; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Treatment Outcome

Nosocomial pneumonia due to antimicrobial-resistant pathogens is associated with high mortality. We assessed the efficacy and safety of the combination antibacterial drug ceftolozane-tazobactam versus meropenem for treatment of Gram-negative nosocomial pneumonia.. We conducted a randomised, controlled, double-blind, non-inferiority trial at 263 hospitals in 34 countries. Eligible patients were aged 18 years or older, were undergoing mechanical ventilation, and had nosocomial pneumonia (either ventilator-associated pneumonia or ventilated hospital-acquired pneumonia). Patients were randomly assigned (1:1) with block randomisation (block size four), stratified by type of nosocomial pneumonia and age (<65 years vs ≥65 years), to receive either 3 g ceftolozane-tazobactam or 1 g meropenem intravenously every 8 h for 8-14 days. The primary endpoint was 28-day all-cause mortality (at a 10% non-inferiority margin). The key secondary endpoint was clinical response at the test-of-cure visit (7-14 days after the end of therapy; 12·5% non-inferiority margin). Both endpoints were assessed in the intention-to-treat population. Investigators, study staff, patients, and patients' representatives were masked to treatment assignment. Safety was assessed in all randomly assigned patients who received study treatment. This trial was registered with ClinicalTrials.gov, NCT02070757.. Between Jan 16, 2015, and April 27, 2018, 726 patients were enrolled and randomly assigned, 362 to the ceftolozane-tazobactam group and 364 to the meropenem group. Overall, 519 (71%) patients had ventilator-associated pneumonia, 239 (33%) had Acute Physiology and Chronic Health Evaluation II scores of at least 20, and 668 (92%) were in the intensive care unit. At 28 days, 87 (24·0%) patients in the ceftolozane-tazobactam group and 92 (25·3%) in the meropenem group had died (weighted treatment difference 1·1% [95% CI -5·1 to 7·4]). At the test-of-cure visit 197 (54%) patients in the ceftolozane-tazobactam group and 194 (53%) in the meropenem group were clinically cured (weighted treatment difference 1·1% [95% CI -6·2 to 8·3]). Ceftolozane-tazobactam was thus non-inferior to meropenem in terms of both 28-day all-cause mortality and clinical cure at test of cure. Treatment-related adverse events occurred in 38 (11%) of 361 patients in the ceftolozane-tazobactam group and 27 (8%) of 359 in the meropenem group. Eight (2%) patients in the ceftolozane-tazobactam group and two (1%) in the meropenem group had serious treatment-related adverse events. There were no treatment-related deaths.. High-dose ceftolozane-tazobactam is an efficacious and well tolerated treatment for Gram-negative nosocomial pneumonia in mechanically ventilated patients, a high-risk, critically ill population.. Merck & Co.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cephalosporins; Cross Infection; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Tazobactam; Treatment Outcome

Efficacy of colistin and ampicillin-sulbactam have not been compared in treatment of ventilator-associated pneumonia due to A. baumannii. Efficacy of colistin and ampicillin-sulbactam in combination with meropenem were compared in treatment of ventilator-associated pneumonia due to carbapenem-resistant A. baumannii.. 47 patients with ventilator-associated pneumonia due to carbapenem-resistant A. baumannii were randomized to receive meropenem/colistin or meropenem/ampicillin-sulbactam for 14 days. Clinical and microbiological responses and 28-day mortality were considered as outcomes.. Clinical response (75 vs 69.6%; p = 0.75) and microbial eradication (87.50 vs 91.3%; p = 0.59) were comparable between meropenem/colistin and meropenem/ampicillin-sulbactam groups, respectively.. In this study, clinical and microbiological response were comparable between the meropenem/colistin and meropenem/ampicillin-sulbactam groups.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Ampicillin; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sulbactam

Healthcare-associated pneumonia (HCAP) may have a more severe course than community-acquired pneumonia (CAP); hence, it is more likely to be caused by drug-resistant bacterial pathogens and anaerobes involved in aspiration pneumonia. We compared the efficacy and safety of initial empiric therapy with piperacillin/tazobactam (PIPC/TAZ, 13.5 g/day) with that of meropenem (MEPM, 1.5 g/day) as single broad-spectrum regimens with gram-negative and anaerobic coverage in patients with HCAP in Japan. The clinical cure rate was 75.9 % (22/29 cases) in the PIPC/TAZ group and 64.3 % (18/28 cases) in the MEPM group. The clinical efficacy rate was 87.9 % (29/33 cases) in the PIPC/TAZ group and 74.2 % (23/31 cases) in the MEPM group. The bacteriological eradication rate was 94.4 % (17/18) in the PIPC/TAZ group and 87.5 % (14/16) in the MEPM group. Adverse drug reactions were seen in 22.4 % (11/49 cases) of patients in the PIPC/TAZ group and 17.4 % (8/46 cases) of patients in the MEPM group. Although not statistically different, the PIPC/TAZ group had a slightly higher efficacy rate than the MEPM group. Both treatment regimens are tolerable and might be appropriate to use as initial empiric therapy for HCAP in Japan. To investigate the differences in efficacy profiles of those two regimens, a further confirmatory study with a larger cohort as determined by a power analysis is recommended.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Female; Humans; Japan; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Prospective Studies; Statistics, Nonparametric; Thienamycins; Treatment Outcome

It is known that beta-lactam antibiotics exhibit time-dependent bactericidal activity. Several studies have found continuous infusion of meropenem more effective than intermittent infusion in maintaining constant serum concentrations in excess of the minimum inhibitory concentration. However, limited data exist on the clinical efficacy of meropenem administered by continuous infusion.. To evaluate the clinical efficacy of continuous versus intermittent infusion of meropenem for the treatment of ventilator-associated pneumonia (VAP) due to gram-negative bacilli.. A retrospective cohort study was conducted of patients with VAP caused by gram-negative bacilli who received initial empiric antibiotic therapy with meropenem. We analyzed 2 contemporary cohorts: one group received meropenem by continuous infusion (1 g over 360 min every 6 h), the other by intermittent infusion (1 g over 30 min every 6 h). The administration method was prescribed according to the physician's discretion. Patients received meropenem plus tobramycin for 14 days.. There were no significant differences between patient groups with regard to gender, age, APACHE-II at intensive care unit admission, diagnosis, microorganism responsible for VAP, or organ dysfunction severity at the time VAP was suspected. The group receiving medication by continuous infusion showed a greater clinical cure rate than the group treated with intermittent infusion (38 of 42, 90.47%, vs 28 of 47, 59.57%, respectively, with OR 6.44 [95% CI 1.97 to 21.05; p < 0.001]).. Meropenem administered by continuous infusion may have more clinical efficacy than intermittent infusion.

Topics: Anti-Bacterial Agents; Cohort Studies; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Respiration, Artificial; Retrospective Studies; Thienamycins; Treatment Outcome

The objectives of this study were to develop a meropenem population pharmacokinetic model using patient data and use it to explore alternative dosage regimens that could optimize the currently used dosing regimen to achieve higher likelihood of pharmacodynamic exposure against pathogenic bacteria. We gathered concentration data from 79 patients (ages 18-93 years) who received meropenem 0.5, 1, or 2 g over 0.5- or 3-hour infusion every 8 hours. Meropenem population pharmacokinetic analysis was performed using the NONMEM program. A 2-compartment model fit the data best. Creatinine clearance, age, and body weight were the most significant covariates to affect meropenem pharmacokinetics. Monte Carlo simulation was applied to mimic the concentration-time profiles while 1 g meropenem was administrated via infusion over 0.5, 1, 2, and 3 hours. The 3-hour prolonged infusion improved the likelihood of obtaining both bacteriostatic and bactericidal exposures most notably at the current susceptibility breakpoints.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Community-Acquired Infections; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Meropenem; Metabolic Clearance Rate; Middle Aged; Models, Biological; Monte Carlo Method; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Thienamycins; Time Factors

Adequacy and effectiveness of empirical antibacterial therapy of severe nosocomial infections with meropenem vs. combined regimens of antibacterial therapy were investigated and the ratio of the cost and effectiveness of the compared regimens was evaluated. A prospective, randomized, open, comparative study of two initiative regimens of empirical antibacterial therapy of severe nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the standard regimen with the use of betalactams and fluoroquinolones in combination with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of nosocomial pneumonia (including the ventilator-associated one) or abdominal infection with the signs of severe sepsis and severity of APACHE II > 14 were enrolled. The patients were stratified into 2 groups subject to the disease severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out of 166 patients with recorded nosocomial infection were included into the final estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62 patients were treated with meropenem and in the treatment of 73 patients the standard antibacterial therapy was used. In the group of the patients treated with meropenem there were stated significantly higher clinical effectiveness (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in the clinical and bacteriological effectiveness of meropenem and the standard therapy was more evident in the subgroups of more severe patients (APACHE > 20). With the use of meropenem the probability of recovery from nosocomial infection was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem provided significantly higher eradication of the pathogens: P. aeruginosa (88 and 40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3 times as frequent as with the use of the standard antibacterial therapy (33.9%). The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower vs. the control. Therefore, the empirical therapy of severe nosocomial infections with meropenem proved to be more adequate and from the economic viewpoint more advantageous vs. the standard combined regimens of antibacterial thera

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactams; Costs and Cost Analysis; Cross Infection; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Meropenem; Metronidazole; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Russia; Thienamycins; Treatment Outcome

The time that concentrations in serum are above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic parameter correlating with the therapeutic efficacy of beta-lactam antibiotics. The aim of this study was to demonstrate the T>MIC of meropenem when administered by a 3-h infusion compared with that when administered by bolus injection. The study was conducted with nine patients with ventilator-associated pneumonia. Each subject received meropenem in three regimens consecutively: (i) bolus injection of 1 g every 8 h for 24 h; (ii) 3-h infusion of 1 g every 8 h for 24 h; and (iii) 3-h infusion of 2 g every 8 h for 24 h. Following bolus injection, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 28.33% +/- 11.67%, 45.89% +/- 22.90%, 57.00% +/- 24.82%, and 74.67% +/- 17.94% of an 8-h interval, respectively. For the 3-h infusion of 1 g of meropenem, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 37.78% +/- 20.57%, 58.11% +/- 24.38%, 72.67% +/- 21.97%, and 93.56% +/- 6.84% of an 8-h interval, respectively. For the 3-h infusion of 2 g of meropenem, the percentages of the T>MICs of 16, 8, 4, and 1 microg/ml were 57.89% +/- 24.26%, 72.89% +/- 22.40%, 85.56% +/- 16.42%, and 98.56% +/- 3.28% of an 8-h interval, respectively. In conclusion, a 3-h infusion resulted in greater T>MICs than those after a bolus injection. For the treatment of infections caused by pathogens with intermediate resistance, a 3-h infusion of 2 g of meropenem every 8 h can provide concentrations in serum above the MIC of 16 microg/ml for almost 60% of an 8-h interval.

Topics: Acinetobacter; Adolescent; Adult; Aged; Anti-Bacterial Agents; Cross-Over Studies; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Thienamycins; Treatment Outcome; Ventilators, Mechanical

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

In this open, prospective, study were enrolled 204 hospitalized elderly patients with severe (88 males, 116 females, age range 70-94). Patients were randomized to receive one of the following antibiotic treatment regimens: meropenem 500 mg i.v. t.i.d. (52); imipenem/cilastatin 500 mg i.v. t.i.d. (51), clarithromycin 500 mg + ceftriaxone 1 g i.v. b.i.d. (52), clarithromycin 500 mg + amikacin 250 mg i.v. b.i.d. (49). In 99 cases causative germs were isolated (24 meropenem, 26 imipenem, 23 clarithromycin + ceftriaxone, 26 ceftriaxone + amikacin). A satisfactory clinical, bacteriological response was achieved respectively in 86.5% 77% in meropenem; 86.3% 71% in imipenem/cilastatin; 69% 61% in ceftriaxone + clarithromycin and in 85.7% 77% in clarithromycin + amikacin. The mean total cost for each patient was $1,560; $1,620; $1,760 and $1,792 in meropenem, imipenem/cilastatin, clarithromycin + ceftriaxone and clarithromycin + amikacin respectively. This study shows that treatment with either meropenem or imipenem is as efficacious as conventional therapy in the treatment of community acquired pneumonia (CAP), and that meropenem is the most cost-effective.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Clarithromycin; Community-Acquired Infections; Costs and Cost Analysis; Drug Combinations; Drug Costs; Drug Therapy, Combination; Female; Hospitalization; Humans; Imipenem; Male; Meropenem; Pneumonia, Bacterial; Prospective Studies; Thienamycins; Treatment Outcome

We performed a prospective, open label, randomized study in intensive care unit patients with ventilator-associated pneumonia (VAP) to determine the efficacy and safety of empiric intravenous (i.v.) meropenem monotherapy compared with the combination of ceftazidime plus amikacin. A total of 140 patients receiving mechanical ventilation and diagnosed with pneumonia were included in the study. Patients were randomized to receive either 1 g meropenem i.v. every 8 hours or 2 g ceftazidime i.v. every 8 hours plus 15 mg/kg amikacin daily, administered to patients with normal renal function as two daily doses. Satisfactory clinical responses (cure or improvement) were achieved at the end of treatment in 68.1% of meropenem-treated patients and 54.9% in the ceftazidime/amikacin-treated group (relative risk 1.25; 95% confidence interval >1.00, 1.55). When non-evaluable patients were excluded from the analysis, the satisfactory clinical response was 82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively (p = 0.044). Logistic regression demonstrated that treatment with meropenem and both the basic traumatic and medical pathologies were significantly associated with a satisfactory response. Adverse events judged to be possibly or probably related to treatment were reported by seven (10.1%) patients in the meropenem group and by eight patients (11.3%) in the ceftazidime/amikacin group. The results of this study confirm that monotherapy with meropenem is well tolerated and provides superior efficacy to the conventional combination of ceftazidime and amikacin in combating VAP.

Topics: Aged; Amikacin; Analysis of Variance; Ceftazidime; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Odds Ratio; Pneumonia, Bacterial; Prospective Studies; Respiration, Artificial; Thienamycins; Treatment Outcome

This study aimed at evaluating the efficacy and safety of meropenem as first choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in Hospital das Clínicas (HC) - University of São Paulo; a hospital with high incidence of antimicrobial resistance. Prospective, open, and non-comparative trial with meropenem were done in patients with ventilator-associated or aspiration NP in 2 ICUs at HC - University of São Paulo. Etiologic investigation was done through bronchoalveolar lavage and blood cultures prior to study entry. Twenty-five (25) critically ill patients with NP were enrolled (mean age 40 years). Ventilator-acquired pneumonia was responsible for 76% of cases and aspiration NP for 24%. Specific etiologic agents were identified and considered to be clinically and temporally responsible for NP in 11 (44%) patients. A. baumanii was responsible for 6 cases (55%), P. aeruginosa for 3 (27%), and S. aureus for 2 (18%). At completion of treatment, 19 patients (76%) showed either cure (48%) or improvement (28%) after use of meropenem therapy. Mortality was 12% at the end of therapy (8% after excluding 1 non-evaluable patient). After 4 to 6 weeks of follow-up, 12 (48%) patients had improved or been totally cured, and overall mortality was 24%. Clinical complications were observed in 11 patients (44%), with none of them definitely related to the study drug. Meropenem as monotherapy was effective and well-tolerated in most NP patients in our ICU. The low mortality rate in this study might have been due to first choice use of this drug. Controlled, drug comparative clinical trials are needed to support this preliminary observation.

Topics: Adult; Aged; Cross Infection; Female; Humans; Intensive Care Units; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Thienamycins; Ventilators, Mechanical

We performed a prospective, open label, randomized study in intensive care unit patients with ventilator-associated pneumonia (VAP) to determine the efficacy and safety of empiric intravenous (i.v.) meropenem monotherapy compared with the combination of ceftazidime plus amikacin. A total of 140 patients receiving mechanical ventilation and diagnosed with pneumonia were included in the study. Patients were randomized to receive either 1 g meropenem i.v. every 8 hours or 2 g ceftazidime i.v. every 8 hours plus 15 mg/kg amikacin daily, administered to patients with normal renal function as two daily doses. Satisfactory clinical responses (cure or improvement) were achieved at the end of treatment in 68.1% of meropenem-treated patients and 54.9% in the ceftazidime/amikacin treated group (relative risk 1.25; 95% confidence interval > 1.00, 1.55). When non-evaluable patients were excluded from the analysis, the satisfactory clinical response was 82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively (p = 0.044). Logistic regression demonstrated that treatment with meropenem and both the basic traumatic and medical pathologies were significantly associated with a satisfactory response. Adverse events judged to be possible or probably related to treatment were reported by seven (10.1%) patients in the meropenem group and by eight patients (11.3%) in the ceftazidime/amikacin group. The results of this study confirm that monotherapy with meropenem is well tolerated and provides superior efficacy to the conventional combination of ceftazidime and amikacin in combating VAP.

Topics: Amikacin; Ceftazidime; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Respiration, Artificial; Superinfection; Thienamycins

An open, multicenter study with 144 patients, aged between 18 and 94 years, was performed to compare the efficacy and safety of meropenem with imipenem/cilastatin in the hospital treatment of community-acquired pneumonia. Patients were randomized to receive either intravenous meropenem (500 mg every 8 h) or intravenous imipenem/cilastatin (1,000 mg every 12 h). The primary end point was considered to be clinical efficacy and the secondary end points were bacteriological response and safety assessment. At the end of therapy, cure or improvement in signs and symptoms as a satisfactory clinical response was observed in 57 of 64 (89.1%) meropenem-treated patients and in 60 of 66 (90.9%) imipenem/cilastatin patients. The mean duration of treatment was 10 days for meropenem and 9.7 days for imipenem/cilastatin. In patients who were followed up for weeks 2-4, the response was satisfactory (100%) for both treatments. A satisfactory bacteriological response, defined as either presumed or confirmed eradication of all pathogens, was found in eight patients who had received meropenem and in 14 patients who had received imipenem/cilastatin. Response was considered satisfactory in 100% of the meropenem group and in 92.9% of the imipenem/cilastatin group and at follow-up, it was 100% for both treatments. Drug-related adverse events were reported in three (4.2%) meropenem-treated patients and in eight (11.0%) imipenem/cilastatin-treated patients. None of these events was classified as serious. The results of this study show that the clinical and bacteriological efficacy and tolerability of meropenem (500 mg every 8 h) are similar to that of imipenem/cilastatin (1,000 mg every 12 h) in the hospital treatment of community-acquired pneumonia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cilastatin; Community-Acquired Infections; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Safety; Thienamycins

This analysis comprises data pooled from two clinical trials of meropenem (0.5 g 8-hourly) versus ceftazidime (1 g 8-hourly) in hospitalized patients with community-acquired pneumonia. The clinical and bacteriological responses to treatment were assessed in relation to a range of risk factors previously linked to a poor clinical outcome. 393 patients (198 meropenem, 195 ceftazidime) were clinically evaluable while 230 (113 meropenem, 117 ceftazidime) were bacteriologically evaluable. Meropenem was highly effective, independent of associated risk factors, producing overall satisfactory clinical and bacteriological response rates at the end of therapy of 91.4% and 94.7%, respectively, similar to those produced by ceftazidime (90.3% and 92.3%, respectively). Clinical and bacteriological treatment outcome were similar in patients with up to three of the following key risk factors: age > or =65 years, male gender, serum urea >7 mmol/L, serum albumin <35 g/L and difficult-to-treat pathogens. Meropenem also achieved high clinical (85.7%) and bacteriological (89.3%) success rates in patients requiring ventilation, as did ceftazidime (81.6% and 87.1%, respectively). Both agents were highly effective against both Gram-negative and Gram-positive causative pathogens, including those organisms normally considered difficult to treat and typical of nosocomial pneumonia (e.g. Enterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa). Thus, meropenem and ceftazidime were highly effective in patients hospitalized with community-acquired pneumonia, irrespective of a number of concurrent risk factors (including those regarded as key risk factors). Furthermore, the analysis points to a role for meropenem 0.5 g 8-hourly in the treatment of nosocomial pneumonias that do not require intensive care unit admission and/or mechanical ventilation. Overall, this novel analysis of trial data suggests that incorporation of key risk factor endpoints into the initial design of pneumonia studies may prove to be a useful approach in defining appropriate antibiotic treatment for specific patient groups.

Topics: Adolescent; Adult; Age Factors; Aged; Ceftazidime; Cephalosporins; Community-Acquired Infections; Female; Humans; Intensive Care Units; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Respiration, Artificial; Risk Factors; Sex Factors; Thienamycins; Treatment Outcome

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

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

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Antineoplastic Agents; Cell Line; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Structure; Pneumonia, Bacterial; Pore Forming Cytotoxic Proteins; Structure-Activity Relationship; Wasp Venoms

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

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

A 60-year-old woman received meropenem/colistin treatment for bilateral pneumonia caused by a ST15 carbapenemase producing Klebsiella pneumoniae. The patient recovered but re-infection with the same (ST15), but now colistin-resistant K. pneumoniae, occurred. The molecular mechanism of the emerged colistin resistance was identified as mgrB gene modification by insertion element (IS) IS903B.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Recurrence

Topics: Aged; Anti-Bacterial Agents; Ceftazidime; Cohort Studies; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Klebsiella Infections; Male; Melioidosis; Meropenem; Middle Aged; Mortality; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Proportional Hazards Models; Retrospective Studies; Severity of Illness Index; Streptococcal Infections

The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Expression; Hospitalization; Humans; Isoenzymes; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; Plasmids; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory System; Retrospective Studies; Tazobactam; United States

Topics: Aged; Anti-Bacterial Agents; Burkholderia cepacia complex; Burkholderia Infections; Causality; Fatal Outcome; Humans; Liver Cirrhosis; Male; Meropenem; Middle Aged; Pneumonia, Bacterial; Thienamycins

In the present study 60 samples were collected from lower respiratory tract of patients suffering from Ventilator Associated Pneumonia (VAP) admitted in surgical and medical Intensive Care Units (ICUs) of Khyber Teaching Hospital, Peshawar, Pakistan. Recovered pathogens were characterized and their susceptibility pattern against commonly used antibacterial agents investigated. Most frequent bacterial pathogen found was methicillin- resistant Staphylococcus aureus (MRSA) (40%) followed by members of Enterobacteriaceae (22%; of which Escherichia coli (50%), Klebsiella pneumonia (30%), Enterobacter cloacae (10%) and Citrobacter freundii (10%), Pseudomonas aeruginosa 20% and Acinetobacter baumannii 18%. Majority of the specimens yielded polymicrobial growth (85.75% polymicrobial growth compared to 14.25% specimens yielding monomicrobial growth). The susceptibility pattern showed that A. baumannii was the most resistant bacterial pathogen. Based on the results of susceptibility pattern obtained in the present study, combination of linezolid with meropenem and colistin has been found to be the best combination option for empirical therapy for VAP pathogens in this region.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Case-Control Studies; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Linezolid; Male; Meropenem; Microbial Sensitivity Tests; Pakistan; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sputum; Trachea

High-dose meropenem (MEPM; 6 g/day) has been approved as a treatment for purulent meningitis; however, little is known regarding its in vivo efficacy in refractory lower respiratory tract infections. The purpose of this study was to evaluate the efficacy of MEPM at 6 g/day in a murine model of severe pneumonia caused by MEPM-resistant Pseudomonas aeruginosa Experimental pneumonia induced by MEPM-resistant P. aeruginosa was treated with normal-dose MEPM (150 mg/kg of body weight, simulating a 3-g/day regimen in humans) or high-dose MEPM (500 mg/kg, simulating a 6-g/day regimen in humans). Mice treated with high-dose MEPM showed significantly restored survival relative to that of untreated mice and tended to show a survival rate higher than that of mice treated with normal-dose MEPM. The viable bacterial counts (of two clinical isolates) in the lungs decreased significantly in mice treated with high-dose MEPM from those for untreated mice (P < 0.001) or mice treated with normal-dose MEPM (P, <0.01 and <0.05). The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was also significantly lower in mice treated with high-dose MEPM than in untreated mice. The free MEPM concentration in the epithelial lining fluid (ELF) exceeded 16 μg/ml for 85 min in mice treated with high-dose MEPM, but not for mice treated with normal-dose MEPM. Our results demonstrate that high-dose MEPM (6 g/day) might provide better protection against pneumonia caused by MEPM-resistant strains of P. aeruginosa than the dose normally administered (less than 3 g/day).

Topics: Animals; Anti-Bacterial Agents; Biological Availability; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Drug Administration Schedule; Female; Humans; Lung; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Mucosa; Survival Analysis; Thienamycins; Treatment Outcome

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

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

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

Nocardia, a branching, filamentous bacteria, is widely distributed in the environment and can cause human infection in immune-compromised hosts. Inhalation of Nocardia leads to pulmonary disease. Microbiology laboratory processed the clinical samples from patients with respiratory infections. Smears were prepared from the samples and were stained and cultured. Five cases were positive for Nocardia. They were treated with the trimethoprim-sulfamethoxazole combination. The disease was cured in three patients, and two died due to other comorbid conditions leading to complications. Nocardiosis is encountered in parts of the world even where it is not endemic due to increased world travel. So physicians and laboratory staff should be aware of this and try to diagnose it. Early detection can lead to the prompt initiation of treatment and reduced mortality in these patients. Patients with disseminated or severe nocardiosis should be treated with combination therapy with two or more active agents.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Cough; Diabetes Mellitus; Dyspnea; Female; Humans; Imipenem; Immunocompromised Host; India; Male; Meropenem; Middle Aged; Nocardia Infections; Pneumonia, Bacterial; Pulmonary Disease, Chronic Obstructive; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

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

High-level carbapenem resistance is worryingly increasing in clinical isolates and is often attributed to carbapenemase expression. This study aimed to determine the mechanisms leading to high-level meropenem resistance in six carbapenemase-negative Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients and seven carbapenemase-positive isolates from patients suffering from hospital-acquired pneumonia (HAP). MICs were determined in the absence or presence of l-arginine or glycine-glutamate as competitive substrates for OprD (OccD1) or OpdP (OccD3), respectively, or the efflux pump inhibitor Phe-Arg β-naphthylamide (PAβN). β-Lactamases were screened by phenotypic tests and/or PCR. The oprD gene and its promoter were sequenced; protein expression was evidenced by SDS-PAGE. mexA, mexX, mexC and mexE transcripts were evaluated by real-time and semiquantitative PCR. Meropenem/imipenem MICs were 64-128/16-32 mg/L and 128/128-256 mg/L in CF and HAP isolates, respectively; PAβN reduced meropenem MICs to 4-16 mg/L only and specifically in CF isolates; porin competitors had no effect on MICs. All isolates showed an increase in transcription levels of mexA, mexX and/or mexC and mutations in oprD leading to production of truncated proteins. AmpC-type cephalosporinases were overexpressed in CF isolates and VIM-2 was expressed in HAP isolates. Antibiotic exclusion from bacteria by concomitant efflux and reduced uptake is sufficient to confer high-level resistance to meropenem in isolates overexpressing AmpC-type cephalosporinases. As efflux is preponderant in these isolates, it confers a paradoxical phenotype where meropenem is less active than imipenem. Concomitant susceptibility testing of both carbapenems and rapid elucidation of the most probable resistance mechanisms is thus warranted.

Topics: Anti-Bacterial Agents; beta-Lactamases; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors; Gene Expression Profiling; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Polymerase Chain Reaction; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA; Thienamycins

The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia.. Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method.. Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma.. The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Cross Infection; Female; Humans; Infusions, Intravenous; Male; Meropenem; Middle Aged; Plasma; Pneumonia, Bacterial; Prospective Studies; Respiratory Mucosa; Thienamycins; Young Adult

Meropenem (MEPM) and doripenem (DRPM), whose antipseudomonal activity is more potent than that of other carbapenem antimicrobials, were used in the study. Monte Carlo simulation of drug concentrations was performed to develop an administration plan for MEPM and DRPM that takes into account the pharmacokinetics (PK)-pharmacodynamics (PD) of MEPM and DRPM and the renal function of each patient. Drug administration plans were proactively applied to patients with pneumonia to determine the usefulness of the method by assessing treatment efficacy and safety.. Patients with healthcareassociated pneumonia and an indication for MEPM or DRPM chemotherapy underwent drug administration in accordance with the MEPM and DRPM treatment plan developed by the PK-PD software applications. The primary efficacy endpoints were the clinical and bacteriological efficacy of the drugs agains pneumonia. The safety of the antimicrobials was assessed based on abnormal laboratory findings and the seizure disorders in accordance with the criteria for safety evaluation of antimicrobial agents.. This study examined 12 and 11 patients in the MEPM and DRPM group, respectively; however, 3 DRPM patients were excluded due to the administration of anti-methicillin-resistant Staphylococcus aureus drugs after the initiation of DRPM treatment. MEPM and DRPM drug administration was determined to be safe and effective in all patients.. The present results suggest that the Monte Carlo simulation-based PK-PD software is an effective tool for planning individualized antimicrobial chemotherapy with carbapenem in accordance with the PK-PD theory of antimicrobials. It is also possible to propose safe and effective drug administration plans for patients with healthcare-associated pneumonia.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Computer Simulation; Doripenem; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Computer-Assisted; Female; Humans; Kidney; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Pneumonia, Bacterial; Prospective Studies; Software; Thienamycins; Treatment Outcome

Pseudomonas aeruginosa is an opportunistic bacterial pathogen capable of causing a wide range of disease manifestations, including severe bacterial pneumonia. Recently, clinics have reported a rise in nosocomial infections with multidrug resistant (MDR) species, including MDR strains of P. aeruginosa. In order to quickly evaluate the efficacy of new therapeutics for MDR infections, highly reproducible and validated animal models need to be developed for pre-clinical testing. Here, we describe the characterization of two murine models to study MDR P. aeruginosa respiratory disease. We evaluated and compared these models using a non-invasive intratracheal instillation method and established the 50% lethal dose, course of infection, biometric parameters of disease and degree of pneumonia development for each model. Further, we tested meropenem as a proof-of-concept therapeutic and report efficacy data that suggests that the leukopenic model could serve a robust pre-clinical model to test novel therapeutics.

Topics: Animals; Anti-Bacterial Agents; Biometry; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Resistance, Multiple, Bacterial; Female; Lethal Dose 50; Meropenem; Mice, Inbred BALB C; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Treatment Outcome

Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been previously reported to be administered by continuous infusion (CI) in pediatric CF patients. We present two cases administering intravenous (IV) meropenem and ticarcillin-clavulanate by CI in pediatric CF patients. The delivery of beta-lactam antibiotics via CI should be considered in order to optimize the pharmacodynamics (PD) of beta-lactams in the treatment of acute pulmonary exacerbations (APE).

Topics: Adolescent; Anti-Bacterial Agents; Clavulanic Acids; Cystic Fibrosis; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Meropenem; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rhodospirillaceae; Thienamycins; Ticarcillin

Chromobacterium violaceum is sensitive to temperature and the infection is usually confined to tropical or subtropical regions. Since Japan has a warm climate, C. violaceum has been scarcely isolated from clinical specimens. With global warming, however, the geographical distribution of C. violaceum infection is likely to change. We report two cases of C. violaceum nosocomial pneumonia that occurred at an intensive care center in Japan. C. violaceum was first detected from a patient in the same center as a pathogenic organism of pneumonia. Later, the organism was isolated from sputum and a ventilator circuit tube of another patient in the center. The two patients were admitted to the center in nearby beds for several days. All of the pathogens were confirmed to be C. violaceum by the nucleic acid sequence of the 16S rRNA gene and were proven to be genetically identical organisms by pulsed field gel electrophoresis. Both patients were managed with well-humidified and heated oxygen using a venturi mask and ventilator to promote excretion of sputum. It was thought that the medical respiratory care devices that provide a humid and warm environment, an optimal condition for proliferation of C. violaceum, can contribute to C. violaceum infection in a hospital environment.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Chromobacterium; Cross Infection; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Pneumonia, Bacterial; Sputum; Thienamycins

Acinetobacter baumannii has been reported increasingly as a significant causative organism of various nosocomial infections, including hospital-acquired pneumonia (HAP). The aim of this study was to investigate the clinical characteristics of HAP induced by carbapenem-resistant A. baumannii (CRAB) in elderly patients and the in vitro antimicrobial effects of cefoperazone/sulbactam combination therapy.. Seventy-one elderly patients in the geriatric ward of the General Hospital of the People's Liberation Army (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard method was used to determine the in vitro drug sensitivity of 60 CRAB strains to antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline, or levofloxacin). The occurrence of carbapenemase genes was detected by PCR.. CRAB-induced HAP occurred mostly in patients with underlying diseases. Prior to onset, most patients had received antimicrobial therapies including broad-spectrum β-lactams, invasive mechanical ventilation, and catheterization. The 30-day survival rate was 95.1% in patients using cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and 73.3% in patients not using cefoperazone/sulbactam (p<0.05). When cefoperazone/sulbactam was used in combination with minocycline, levofloxacin, and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains, but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified.. CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of serum albumin, but with elevated levels of C-reactive protein and creatinine. Cefoperazone/sulbactam in combination with minocycline, meropenem, and levofloxacin had a synergistic and additive in vitro bacteriostatic action on CRAB.

Topics: Acinetobacter baumannii; Aged; Aged, 80 and over; Anti-Bacterial Agents; C-Reactive Protein; Carbapenems; Cefoperazone; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Female; Humans; Levofloxacin; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Sulbactam; Thienamycins

The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on β-lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on β-lactams was evaluated at standard (10(5) CFU/mL) and high (10(7) CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000 mg/kg four times daily, %T>MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T>MIC; 28.65%) at low/standard (10(4) CFU/mouse) and high (10(6) CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Disease Models, Animal; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Meropenem; Mice, Inbred BALB C; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Survival Analysis; Thienamycins

Pseudomonas aeruginosa pneumonia remains a difficult therapeutic problem. Optimal doses and modes of administration of single agents often do not result in acceptable outcomes. Further, emergence of resistance occurs frequently in this setting with single-agent chemotherapy. The purpose of these experiments was to evaluate combination chemotherapy with meropenem plus tobramycin for P. aeruginosa in a murine pneumonia model. Neutropenia was induced by cyclophosphamide. Pharmacokinetics of meropenem and tobramycin were determined using a population pharmacokinetic approach. Both drugs were given at 4-h intervals. Meropenem was administered as total daily doses of 30 to 600 mg/kg of body weight, while tobramycin doses ranged from 50 to 400 mg/kg. Combination therapy evaluated all combinations of 50, 100, and 150 mg/kg/day of tobramycin doses with 60 or 300 mg/kg/day of meropenem. Total and drug-resistant organisms were enumerated. Meropenem alone had a near-maximal effect at 60 mg/kg/day (3.18 log10 [CFU/g] kill from stasis). The time > MIC in epithelial lining fluid (ELF) at this dose was 35.25% of 24 h. For tobramycin alone, the near-maximal effect was at 150 mg/kg/day and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) in ELF was 240.3. Resistance suppression occurred at an ELF AUC/MIC ratio of 110.6. For combination therapy, the near-maximal effect was reached at 60 mg/kg/day and 50 mg/kg/day of meropenem and tobramycin, which produced a 35.25% time > MIC in ELF and an ELF AUC/MIC ratio of 80.1. The interaction was additive. All combination regimens suppressed resistance. Combination therapy produced additive drug interaction and suppressed all resistance amplification. It is likely that optimal therapy for Pseudomonas aeruginosa pneumonia will involve a combination of agents.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lung; Meropenem; Mice; Microbial Sensitivity Tests; Models, Theoretical; Pneumonia, Bacterial; Pseudomonas aeruginosa; Thienamycins; Tobramycin; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colombia; Cross Infection; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pneumonia, Bacterial; Stroke; Thienamycins

The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB).. A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 10⁷ colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25μl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined.. A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs.. Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Disease; Animals; Anti-Bacterial Agents; Carbapenems; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Cytokines; Disease Models, Animal; Drug Combinations; Drug Resistance, Bacterial; Female; Imipenem; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia, Bacterial; Stem Cells; Thienamycins

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactam Resistance; Carbapenems; Colony Count, Microbial; Disease Models, Animal; Doripenem; Humans; Imipenem; Lung; Meropenem; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Thienamycins; Treatment Outcome

We describe the first report of simultaneous blood infection with KPC-2 producing Klebsiella pneumoniae and Escherichia coli in a Brazilian patient. We highlight the importance of implementing efficient infection control measures to limit the spread of these phenotypes in a hospital setting.

Topics: Aged, 80 and over; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Catheter-Related Infections; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pneumonia, Bacterial; Thienamycins

Doripenem is a carbapenem with potent broad-spectrum activity against Gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae. As the incidence of extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacilli is increasing, it was of interest to examine the in vivo comparative efficacy of doripenem, imipenem, and meropenem against a Klebsiella pneumoniae isolate expressing the TEM-26 ESBL enzyme. In a murine lethal lower respiratory infection model, doripenem reduced the Klebsiella lung burden by 2 log(10) CFU/g lung tissue over the first 48 h of the infection. Treatment of mice with meropenem or imipenem yielded reductions of approximately 1.5 log(10) CFU/g during this time period. Seven days postinfection, Klebsiella titers in the lungs of treated mice decreased an additional 2 log(10) CFU/g relative to those in the lungs of untreated control animals. Lipopolysaccharide (LPS) endotoxin release assays indicated that 6 h postinfection, meropenem- and imipenem-treated animals had 10-fold more endotoxin in lung homogenates and sera than doripenem-treated mice. Following doripenem treatment, the maximum endotoxin release postinfection (6 h) was 53,000 endotoxin units (EU)/ml, which was 2.7- and 6-fold lower than imipenem or meropenem-treated animals, respectively. While the levels of several proinflammatory cytokines increased in both the lungs and sera following intranasal K. pneumoniae inoculation, doripenem treatment, but not meropenem or imipenem treatment, resulted in significantly increased interleukin 6 levels in lung homogenates relative to those in lung homogenates of untreated controls, which may contribute to enhanced neutrophil killing of bacteria in the lung. Histological examination of tissue sections indicated less overall inflammation and tissue damage in doripenem-treated mice, consistent with improved antibacterial efficacy, reduced LPS endotoxin release, and the observed cytokine induction profile.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactamases; Carbapenems; Cytokines; Disease Models, Animal; Doripenem; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lung; Meropenem; Mice; Mice, Inbred C3H; Microbial Sensitivity Tests; Pneumonia, Bacterial; 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

Topics: Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Enterobacteriaceae Infections; Epilepsy, Tonic-Clonic; Female; Humans; Liver Cirrhosis; Meropenem; Middle Aged; Pneumonia, Bacterial; Thienamycins; Valproic Acid

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

To analyse the bacterial pathogens and drug sensitivities for neonatal community-acquired pneumonia.. Seven hundred sixty sputum samples from newborns with community-acquired pneumonia were cultured to determine microbial organisms present and their drug sensitivities.. Of the 760 specimens, 425 grew pathogens for a 55.9% positive rate. Among the 425 positive cultures, 278 grew gram-negative organisms (65.4%), 142 grew gram-positive organisms (33.3%), while 5 grew fungus (1.3%). The most common gram-negative organisms were Escherichia coli, Klebsiella pneumoniae and Hemophilus influenzae, while the most common gram-positive organisms were Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus. To the gram-negative organisms, the most sensitive drugs were meropenem, imipenem and amikacin, while to the gram-positive ones were vancomycin, teicoplanin and quinupristin/dalfopristin.. The most common causative bacteria were gram-negative organisms, which were highly sensitive to Meropenem, Imipenem and Amikacin, yet often treatable with more focused antibiotic coverage, which depended on the bacterium identified.

Topics: Anti-Bacterial Agents; China; Community-Acquired Infections; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Infant, Newborn; Male; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Retrospective Studies; Sputum; Thienamycins; Vancomycin

The aim of this study was to compare doripenem with imipenem and meropenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia and then to compare different doripenem doses and methods of intravenous administration.. Using a rabbit experimental model of pneumonia, efficacy was assessed following 2 days of treatment by colony counts of different tissues (lung, spleen and blood culture).. Mean pulmonary bacterial loads were 3.17 ± 0.53, 3.42 ± 0.61 and 2.75 ± 0.59 log(10) cfu/g for imipenem, doripenem (0.5 g three times daily) and meropenem, respectively, compared with 7.57 ± 0.99 cfu/g for control animals. At a higher dose (1 g three times daily), doripenem showed significantly better efficacy (2.70 ± 0.65 log(10) cfu/g) than the standard regimen of doripenem. Sterilization of spleen cultures was achieved with standard regimens of imipenem (1 g three times daily) and a higher dose of doripenem.. In this model of P. aeruginosa pneumonia, doripenem had an efficacy equivalent to that of meropenem and imipenem at a high dose of 1 g three times a day and lower efficacy at a standard dose (0.5 g three times daily) than the other two agents in terms of bacteria cultivated from spleens. Doripenem is a new drug that offers new therapeutic options, especially for difficult-to-treat infections such as pneumonia due to non-fermenting Gram-negative bacteria.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Blood; Carbapenems; Disease Models, Animal; Doripenem; Female; Imipenem; Infusions, Intravenous; Lung; Meropenem; Plasma; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Spleen; Thienamycins; Treatment Outcome

In Japan, an increase in the elderly population is associated with an increased incidence of aspiration pneumonia. Treatment guidelines for aspiration pneumonia recommend the use of antibiotics effective against anaerobic bacteria, such as carbapenems. However, the role of anaerobic bacteria in aspiration pneumonia and the clinical efficacy of meropenem in elderly aspiration pneumonia patients have only begun to be investigated.. A prospective study of 62 elderly hospitalized patients with aspiration pneumonia (34 males, 28 females; mean age 86.6 years) was conducted. The causative organisms of aspiration pneumonia, including anaerobic bacteria, were investigated using fiberoptic bronchoscopy. In addition, the efficacy and safety of intravenous meropenem for this treatment of this condition were evaluated.. When disease severity was classified according to the Japanese Respiratory Society (JRS) guidelines, 80.7% of the cases in this study were graded as "most severe". The overall detection rate of bacteria was 87.1% (monomicrobial, 32.3%; polymicrobial, 54.8%). Of the 111 pathogens detected (14 anaerobic pathogens remained unidentified), anaerobic bacteria accounted for 19.8% and gram-negative enteric bacilli made up 19.8%. The overall clinical efficacy rate of meropenem therapy (1.0 g/day) was 61.3%. The mortality rate was 9.7%, and anaerobic bacteria coexisted with aerobic bacteria in 66.7% of the patients who died.. The use of antibiotics effective against anaerobic bacteria may be necessary for patients with potentially fatal aspiration pneumonia. Meropenem therapy for aspiration pneumonia is clinically effective and tolerable in elderly patients.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Female; Humans; Male; Meropenem; Pneumonia, Aspiration; Pneumonia, Bacterial; Prospective Studies; Sputum; Thienamycins

We compared the clinical effects of continuous infusion and intermittent infusion of meropenem (MEPM) on bacterial pneumonia in the elderly. The subjects were elderly patients (over 65) with moderate community-acquired bacterial pneumonia whose performance status was 3 or 4. They were randomly divided into an intermittent group (0.5 g MEPM was infused morning and evening) and a continuous infusion group (1.0 g/day over 24 hours was infused continuously), and the clinical effects were reviewed prospectively. Clinical efficacy on the third day was 64.0% in the intermittent infusion group and 72.0% in the continuous infusion group, and the overall clinical efficacy was 76.0% in the intermittent infusion group and 80.0% in the continuous infusion group. Administration periods were 13.2 +/- 5.7 days in the intermittent infusion group and 12.1 +/- 4.5 days in the continuous infusion group. These results show no statistically significant difference, and suggest that continuous infusion of MEPM did not have better clinical effect than intermittent administration twice a day in the treatment of elderly patients with moderate community-acquired bacterial pneumonia.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Female; Humans; Infusions, Intravenous; Male; Meropenem; Pneumonia, Bacterial; Random Allocation; Thienamycins

Botulism is the acute, flaccid paralysis caused by a neurotoxin produced by Clostridium botulinum. In the infant, clinical symptoms are usually unspecific such as poor feeding, weak suck, feeble cry, drooling, followed by a symmetric, descending, flaccid paralysis beginning with the cranial nerve musculature. The initial symptoms of the disease are often similar to several diseases and therefore differential diagnosis is very difficult and rarely suspected by the physician. Since 2004 only 22 cases of infant botulism have been reported in Italy. Since most paediatricians are unfamiliar with the clinical manifestations of infant botulism, the diagnosis can be easily missed. Hence the disease may well be underestimated and underreported. We report a clinical case of botulism presenting initially with abdominal distention, thereby mimicking acute abdomen.

Topics: Abdomen, Acute; Anti-Bacterial Agents; Botulism; Clostridium botulinum; Diagnosis, Differential; Electroencephalography; Follow-Up Studies; Humans; Incidence; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Pneumonia, Bacterial; Thienamycins; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

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

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

Strong data are lacking on the cross-reactivity between individual carbapenems. We describe a 48-year-old woman with ventilator-associated Pseudomonas aeruginosa pneumonia who received an 8-day course of imipenem-cilastatin and experienced a delayed (i.e., nonimmediate) hypersensitivity reaction, evidenced by an extensive erythematous macular morbilliform rash and an increased eosinophil count. Eight days after completion of therapy, the pneumonia returned, and it was decided to avoid using imipenem-cilastatin; she was administered a 14-day course of meropenem. To our knowledge, this is the first report of a nonimmediate hypersensitivity reaction to imipenem-cilastatin without cross-reactivity to meropenem. This suggests that if carbapenem therapy is unavoidable, meropenem may be cautiously administered in patients with a known allergy to imipenem-cilastatin.

Topics: Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Cross Reactions; Drug Combinations; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Imipenem; Meropenem; Middle Aged; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

To examine the clinical efficacy of antibacterial chemotherapy for life-threatening pneumonia, we investigated the clinical outcome after a prolonged infusion regimen of meropenem based on a pharmacokinetics/pharmacodynamics (PK/PD) theory. In 42 patients with severe pneumonia, the clinical efficacy of a prolonged (4 h) drip infusion regimen of meropenem (4 h-group; 0.5 g, b.i.d.; 18 patients) was compared with that of a standard (0.5-1 hour) infusion regimen of meropenem (1 h-group; 0.5 g, b.i.d.; 24 patients). Although there was no significant difference in the duration of meropenem-administration and the rate of decrease in CRP between the 4 h-group and 1 h-group, the mortality rate in the 4 h-group (5.6%) was significantly lower (p < 0.05) than that in the 1 h-group (37.5%). In this study, the meropenem-concentration in the blood of each patient and the MIC of meropenem against the causative bacteria in each patient were not determined; however, it was thought that the superior life-saving effect of meropenem in the 4h-group was mainly due to prolongation of the time above MIC realized by the prolonged infusion regimen. These results suggested that prolongation of infusion time of meropenem was usefu for improvement of the clinical efficacy against life-threatening pneumonia.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Infusions, Intravenous; Male; Meropenem; Pneumonia, Bacterial; Thienamycins

The epidemiological impact of Acinetobacter baumannii nosocomial infections in a Sicilian intensive care unit (ICU) was investigated to determine the Acinetobacter-specific infection rates, to estimate the preventable proportion of Acinetobacter infections, i.e., those resulting from cross-transmission, and to investigate the molecular epidemiology of antimicrobial resistance in Acinetobacter. The impact of Acinetobacter nosocomial infection in the ICU was determined to be 3.0 new cases per 100 admissions. Site-specific rates confirmed that ICU-acquired pneumonia was the most important infection type. The incidence rate, adjusted by the number of patient-days, was 3.3 infections/1000 patient-days. The estimated preventable proportion of A. baumannii nosocomial infections in the ICU was 66.7%. A class 1 integron, characterised by its gene cassette content, was present in all A. baumannii isolates of four different pulsed-field gel electrophoresis types, and was associated significantly with clones implicated in cross-transmission episodes. Furthermore, the same integron was detected in two genetically distinct isolates responsible for recurrent infection in the same patient, suggesting the occurrence of horizontal gene transfer in vivo. Even in an endemic setting with low infection rates, spread of A. baumannii was caused mainly by infection control shortcomings that require appropriate surveillance and control policies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Microbial; Electrophoresis, Gel, Pulsed-Field; Gene Transfer, Horizontal; Humans; Imipenem; Integrons; Intensive Care Units; Italy; Meropenem; Morbidity; Pneumonia, Bacterial; Thienamycins

The in vivo activities of imipenem, meropenem, and cefepime were studied in a model of rat pneumonia caused by a plasmid-mediated AmpC beta-lactamase ACT-1-producing Klebsiella pneumoniae strain (K. pneumoniae strain 12) and a derivative porin-deficient mutant (K. pneumoniae strain 12dp). No differences between these activities were seen with K. pneumoniae 12. Only meropenem showed an activity slightly better than that of imipenem with K. pneumoniae 12dp.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Colony Count, Microbial; Imipenem; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Plasmids; Pneumonia, Bacterial; Porins; Rats; Rats, Wistar; Thienamycins; Treatment Outcome

We studied the clinical effect of continuous infusion over 24 hours of meropenem (MEPM) on bacterial pneumonia in the elderly (over 65). The subjects were 26 patients (community-acquired pneumonia: moderate, n = 9; severe, n= 4; hospital-acquired pneumonia: group III, n = 13) whose performance status was 3 or 4. MEPM 1.0g/day was infused continuously for 7-14 days, and its clinical efficacy, bacteriological efficacy, and side effects were examined prospectively. It was effective in 23 of the 26 patients (community-acquired pneumonia: moderate, 8/9; severe, 3/4; hospital-acquired pneumonia: group III, 12/13; efficacy rate: 88.5%). Bactericidal effects were obtained in 3 strains of Klebsiella pneumoniae, 2 strains of Streptococcus pneumoniae, 2 strains of methicillin-sensitive Staphlococcus aureus, 1 strain of Streptococcus agalactiae and 1 strain of Proteus mirabilis, but not in 2 strains of methicillin-resistant S. aureus, 1 strain of Pseudomonas aeruginosa and 1 strain of Serratia marcescens. Mild abnormal laboratory findings were observed in 2 patients: elevation of GPT, gamma-GTP, BUN and elevation of ALP. Based on the above, continuous infusion of MEPM on bacterial pneumonia in the elderly obtained excellent clinical effects. Further study is needed to compare the efficacy of continuous versus intermittent administration of MEPM.

Topics: Aged; Aged, 80 and over; Community-Acquired Infections; Cross Infection; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Meropenem; Pneumonia, Bacterial; Prospective Studies; Thienamycins

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Colony Count, Microbial; Guinea Pigs; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Lung; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Porins; Thienamycins; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Fatal Outcome; Humans; Imipenem; Male; Meropenem; Pneumonia, Bacterial; Thienamycins

To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease.. Ten thousand-subject Monte Carlo simulation.. Research center.. None.. Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin. Prevalence of causative pathogens was based on the 2000 SENTRY Antimicrobial Surveillance Study, and minimum inhibitory concentration (MIC) values were obtained using the 2003 US MYSTIC database. The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated. Bactericidal targets were defined as 40% T>MIC for the carbapenems, 50% T>MIC for other beta-lactams, and an area under the curve (AUC)/MIC ratio of 125 for ciprofloxacin. A sensitivity analysis was performed using two alternate models to determine the impact of varying pathogen prevalence on target attainment.. Meropenem and imipenem provided high probabilities of achieving their bactericidal target of 40% T>MIC, with target attainments of 98% for all regimens. At the bactericidal end point of 50% T>MIC, cefepime 2 g every 8 hrs displayed the highest target attainment at 99.9%, followed by cefepime 2 g every 12 hrs, ceftazidime 2 g every 8 hrs, piperacillin/tazobactam 4.5 g every 6 hrs and 3.375 g every 6 hrs, cefepime 1 g every 12 hrs, and ceftazidime 1 g every 8 hrs with target attainments of 95.0%, 92.5%, 92.3%, 91.3%, 90.3%, and 67.9%, respectively. Ciprofloxacin presented the lowest probability of achieving its bactericidal target of an AUC/MIC ratio of 125, with target attainments of 54.7% and 12.0% when given as 400 mg every 8 hrs and 400 mg every 12 hrs, respectively.. Meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin/tazobactam have high probabilities of achieving adequate pharmacodynamic exposures when given for the empirical treatment of nosocomial pneumonia in the absence of methicillin-resistant S. aureus. Ceftazidime 1g every 8 hrs and ciprofloxacin produce low target attainment rates and will not likely result in high clinical success rates when given as monotherapy.

Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Thienamycins

A 31-year-old man with cystic fibrosis was diagnosed with multidrug-resistant Burkholderia cepacia pneumonia. Meropenem 2000 mg every 8 hours was administered as a 3-hour infusion to maximize pharmacodynamic exposure; oral minocycline 100 mg twice/day was also given. Blood samples were collected to confirm meropenem concentrations. Concentrations above the mimimum inhibitory concentration (MIC) of 8 microg/ml were achieved for 52% of the dosing interval, which is greater than what is required for a bactericidal effect. The patient's condition improved, he was discharged, and completed a 3-week course of the antibiotic regimen. After 6 months, he had remained at his baseline level of health. This case demonstrates that pharmacodynamic principles can be used to design an antibiotic dosing regimen that can achieve optimal exposures when the MIC is above that considered susceptible to conventional dosing strategies.

Topics: Adult; Burkholderia cepacia; Burkholderia Infections; Cystic Fibrosis; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Humans; Infusions, Intravenous; Male; Meropenem; Pneumonia, Bacterial; Thienamycins

This study reviews the case of a 67-year-old man who initially presented with high fever and dyspnea. He was subsequently admitted for treatment of pneumonia. On admission, severe leucopenia and thrombopenia were observed in the peripheral blood, with significant phagocytosis of hematopoietic cells including erythroblasts and leukocytes by macrophages in the bone marrow. Following the administration of antibiotic therapy, an improvement in pneumonia and cytopenia symptoms was noted. Clinically, we diagnosed this case as bacteria-associated hemophagocytic syndrome (BAHS) with community-acquired pneumonia. In general BAHS is seen following severe hematologic disease or pneumonia, and so the treatment of BAHS is quite difficult. This particular case had no additional hematologic disorder, and all presenting symptoms of BAHS were resolved immediately following the improvement in pneumonia with post-antibiotic therapy.

Topics: Aged; Community-Acquired Infections; Cytokines; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Histiocytosis, Non-Langerhans-Cell; Humans; Inflammation Mediators; Male; Meropenem; Pneumonia, Bacterial; Thienamycins; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Bronchitis, Chronic; Carbapenems; Gram-Negative Bacteria; Gram-Positive Cocci; Humans; Imipenem; Injections, Intramuscular; Injections, Intravenous; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Thienamycins

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

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Therapy, Combination; Humans; Meropenem; Pneumonia, Bacterial; Respiration, Artificial; Thienamycins

The antibacterial activities of imipenem-cilastatin, meropenem-cilastatin, cefepime and ceftazidime against Enterobacter cloacae NOR-1, which produces the carbapenem-hydrolyzing beta-lactamase NmcA and a cephalosporinase, and against one of its in vitro-obtained ceftazidime-resistant mutant were compared by using an experimental model of pneumonia with immunocompetent rats. The MICs of the beta-lactams with an inoculum of 5 log(10) CFU/ml were as follows for E. cloacae NOR-1 and its ceftazidime-resistant mutant, respectively: imipenem, 16 and 128 microg/ml, meropenem, 4 and 32 microg/ml, cefepime, <0.03 and 1 microg/ml, and ceftazidime, 1 and 512 microg/ml. The chromosomally located cephalosporinase and carbapenem-hydrolyzing beta-lactamase NmcA were inducible by cefoxitin and meropenem in E. cloacae NOR-1, and both were stably overproduced in the ceftazidime-resistant mutant. Renal impairment was induced (uranyl nitrate, 1 mg/kg of body weight) in rats to simulate the human pharmacokinetic parameters for the beta-lactams studied. Animals were intratracheally inoculated with 8.5 log(10) CFU of E. cloacae, and therapy was initiated 3 h later. At that time, animal lungs showed bilateral pneumonia containing more than 6 log(10) CFU of E. cloacae per g of tissue. Despite the relative low MIC of meropenem for E. cloacae NOR-1, the carbapenem-treated rats had no decrease in bacterial counts in their lungs 60 h after therapy onset compared to the counts for the controls, regardless of whether E. cloacae NOR-1 or its ceftazidime-resistant mutant was inoculated. A significant decrease in bacterial titers was observed for the ceftazidime-treated rats infected with E. cloacae NOR-1 only. Cefepime was the only beta-lactam tested effective as treatment against infections due to E. cloacae NOR-1 or its ceftazidime-resistant mutant.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; beta-Lactamases; Carbapenems; Cefepime; Ceftazidime; Cephalosporins; Creatinine; Drug Resistance, Microbial; Enterobacter cloacae; Enterobacteriaceae Infections; Half-Life; Imipenem; Kidney Diseases; Male; Meropenem; Penicillinase; Pneumonia, Bacterial; Protein Binding; Rats; Rats, Wistar; Thienamycins; Uranyl Nitrate

Topics: Anti-Bacterial Agents; Ceftazidime; Cephalosporins; Critical Illness; Cross Infection; Drug Therapy, Combination; Humans; Meropenem; Pneumonia, Bacterial; Severity of Illness Index; Thienamycins; Tobramycin; Treatment Outcome

Pneumonia in critical ill patients, most of them associated with insaturation of an artificial a way and the use of mechanical ventilation, involves important morbi/mortality in the Intensive Care Units. Knowledge of pathogenesis, risk factors, and implicated microorganisms in developing of this major infectious complication, in the context of infections which rise in the critically ill patients, allow us to apply prophylaxis measures which could decrease its incidence, and establish antimicrobial therapy, which permit us to cover all the etiologic possibilities. Availability in the arsenal of the powerful antimicrobial, of a new carbapenemic, meropenem, and based on the different studies and clinic assays, allow to recommend its use with warranties and efficacy, in the empirical or's in concretely those due to Pseudomonas aeruginosa, enterobacteriaceae, (in general or producers of ample spectrum beta-lactamases), and Acinetobacter spp., in monotherapy or combined therapy, with aminoglycosides.

Topics: Clinical Protocols; Critical Illness; Humans; Meropenem; Pneumonia, Bacterial; Thienamycins