meropenem and Gram-Negative-Bacterial-Infections

Antimicrobial resistance is a growing threat to public health and an increasingly common problem for acute care physicians to confront. Several novel antibiotics have been approved in the past decade to combat these infections; however, physicians may be unfamiliar with how to appropriately utilize them. The purpose of this review is to evaluate novel antibiotics active against resistant gram-negative bacteria and highlight clinical information regarding their use in the acute care setting. This review focuses on novel antibiotics useful in the treatment of infections caused by resistant gram-negative organisms that may be seen in the acute care setting. These novel antibiotics include ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilistatin/relebactam, cefiderocol, plazomicin, eravacycline, and omadacycline. Acute care physicians should be familiar with these novel antibiotics so they can utilize them appropriately.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Boronic Acids; Cefiderocol; Ceftazidime; Cephalosporins; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Design; Drug Resistance, Multiple; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Heterocyclic Compounds, 1-Ring; Humans; Meropenem; Sisomicin; Tazobactam; Tetracyclines

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

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

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

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Boronic Acids; Cephalosporins; Clinical Trials as Topic; Drug Combinations; Gram-Negative Bacterial Infections; Heterocyclic Compounds, 1-Ring; Humans; Meropenem; Tazobactam

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Carbapenems; Cefiderocol; Ceftazidime; Cephalosporins; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Molecular Structure; Randomized Controlled Trials as Topic; Siderophores

Plazomicin is a novel semisynthetic parenteral aminoglycoside that inhibits bacterial protein synthesis. It was approved by the United States Food and Drug Administration for use in adults with complicated urinary tract infections (cUTI), including pyelonephritis. Plazomicin displays potent in vitro activity against Enterobacteriaceae, including both extended-spectrum β-lactamase-producing and carbapenem-resistant isolates. Plazomicin's enhanced Enterobacteriaceae activity is due to its stability to commonly encountered aminoglycoside-modifying enzymes that compromise the activity of traditional aminoglycosides. Plazomicin resistance in Enterobacteriaceae is via modification of the ribosomal binding site due to expression of 16S rRNA methyltransferases. Plazomicin does not display improved activity over traditional aminoglycosides against other problematic resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter baumannii. Plazomicin has been assessed in two phase III randomized controlled trials. The EPIC trial compared plazomicin and meropenem for the management of cUTI. In this trial, plazomicin demonstrated superiority in composite cure (81.7% vs 70.1%; difference 11.6%; 95% confidence interval [CI] 2.7-25.7) at the test-of-cure visit, which was driven by enhanced sustained microbiological eradication. The CARE trial compared plazomicin-based and colistin-based combinations in patients with serious infections due to carbapenem-resistant Enterobacteriaceae (CRE). In this analysis, plazomicin-based combinations were associated with numerically decreased mortality or serious disease-related complications when compared with colistin-based combinations (23.5% vs 50%, respectively; 90% CI -0.7 to 51.2). Furthermore, plazomicin was also associated with a lower incidence of nephrotoxicity than colistin. However, small sample sizes limit the interpretation of the findings in the CARE trial. Plazomicin is a novel aminoglycoside that offers clinicians an additional option for the management of CRE infections, with superior activity compared with traditional aminoglycosides and potentially improved efficacy and decreased toxicity compared with colistin.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Clinical Trials as Topic; Colistin; Dose-Response Relationship, Drug; Drug Approval; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Randomized Controlled Trials as Topic; Sisomicin; United States; United States Food and Drug Administration; Urinary Tract Infections

With the current carbapenem-resistant organism crisis, conventional approaches to optimizing pharmacokinetic-pharmacodynamic parameters are frequently inadequate, and traditional salvage agents (eg, colistin, tigecycline, etc) confer high toxicity and/or have low efficacy. However, several β-lactam agents with activity against carbapenem-resistant organisms were approved recently by the US Food and Drug Administration, and more are anticipated to be approved in the near future. The primary goal of this review is to assist infectious disease practitioners with preferentially selecting 1 agent over another when treating patients infected with a carbapenem-resistant organism. However, resistance to some of these antibiotics has already developed. Antibiotic stewardship programs can ensure that they are reserved for situations in which other options are lacking and are paramount for the survival of these agents.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Boronic Acids; Carbapenems; Cefiderocol; Ceftazidime; Cephalosporins; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Heterocyclic Compounds, 1-Ring; Meropenem; Tazobactam

The increasing incidence of infections caused by extended-spectrum beta-lactamase (ESBL)/AmpC-producing bacteria leads to increasing use of carbapenems and risk of carbapenem resistance. Treatment success of carbapenem-sparing beta-lactams (CSBs) for ESBL infections is unclear. The aim of this study was to appraise the clinical cure rate and estimate the cost-effectiveness of meropenem vs. CSBs (piperacillin-tazobactam, temocillin, ceftazidime-avibactam, and ceftolozane-tazobactam) for urinary tract infections (UTIs) or intra-abdominal infections (IAIs) due to ESBL/AmpC-producing bacteria. A systematic literature search of the Cochrane library, EMBASE, PubMed, and Web of Science was conducted to identify studies assessing the clinical cure rate of the antibiotics. To assess the cost-effectiveness of CSBs vs. meropenem, a combined decision analytic and Markov model was probabilistically analysed over a 5-year period. The main outcome was presented as the incremental cost-effectiveness ratio and evaluated with a threshold of €20 000 per life year gained (LYG). From 656 identified articles, 17 and 14 studies were included in the qualitative synthesis and quantitative synthesis, respectively. A clinical cure of ceftazidime-avibactam and ceftolozane-tazobactam was comparable to meropenem in patients with complicated IAIs (cIAIs) due to ESBL (Risk ratio [RR]=1·04, 95% confidence interval [CI]=0·95-1·13). Both temocillin and ceftolozane-tazobactam were deemed cost-effective compared to meropenem with €157·58 and €13 398·34 per LYG, respectively, in patients with UTIs due to ESBL. However, only ceftazidime-avibactam (plus metronidazole) was cost-effective for the treatment of IAIs, with €16 916·77 per LYG. These results show that several CSBs can be considered as viable candidates for the treatment of UTIs and IAIs caused by ESBL.

Topics: Anti-Bacterial Agents; beta-Lactams; Cost-Benefit Analysis; Gram-Negative Bacterial Infections; Humans; Meropenem

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

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

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

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

Increasing frequency of infections due to multi-drug resistant organisms is currently observed in the adult and pediatric population. Therapeutic options are unfortunately limited to treat such infections. It is the clinician's responsibility to use wide-spectrum antibiotics when appropriate, but also to limit the use of these drugs to the sole situations where such a potent treatment is required. Carbapenems are the most efficient beta-lactams, especially against gram-negative bacilli, and the most preserved from resistance so far. This review summarizes microbiological, pharmacokinetic and pharmacodynamic characteristics of currently available cabapenems. Their clinical use in different pediatric settings is then discussed, based on available published evidence. In order to maintain their microbiological efficiency and to limit the emergence of carbapem-resistant strains, carbapenems should be exclusively used for infections due to gram-negative bacilli showing resistance to other beta-lactams. In the next years meropenem should logically replace imipenem indications regarding its superior pharmacokinetic-pharmacodynamic properties, its higher tolerance and its easier use in the pediatric population.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Child; Drug Tolerance; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Thienamycins

Among the many different structurally distinct classes of beta-lactams, the carbapenem class is regarded as that which is most potent and which has the widest spectrum of antimicrobial activity. Rapidly bactericidal, and demonstrating time-dependent killing, carbapenemes have a spectrum of antimicrobial activity that includes Gram-positive and Gram-negative aerobic and anaerobic pathogens. Their in-vitro activity includes extended-spectrum beta-lactamase (ESBL)-producing pathogens and carbapenems are currently considered to be the treatment of choice for serious infections due to ESBL-producing organisms. However, isolates acquiring resistance under treatment have been reported. Imipenem, meropenem and ertapenem are licensed in the European Community and panipenem and biapenem are also available in Japan and South Korea. Other carbapenemes are under development.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Humans; Imipenem; Infusions, Parenteral; Meropenem; Thienamycins

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

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

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

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

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

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

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

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

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

Colistin-carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination therapy improves clinical outcomes for adults with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria.. A randomised controlled superiority trial was done in six hospitals in Israel, Greece, and Italy. We included adults with bacteraemia, ventilator-associated pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non-susceptible Gram-negative bacteria. Patients were randomly assigned (1:1) centrally, by computer-generated permuted blocks stratified by centre, to intravenous colistin (9-million unit loading dose, followed by 4·5 million units twice per day) or colistin with meropenem (2-g prolonged infusion three times per day). The trial was open-label, with blinded outcome assessment. Treatment success was defined as survival, haemodynamic stability, improved or stable Sequential Organ Failure Assessment score, stable or improved ratio of partial pressure of arterial oxygen to fraction of expired oxygen for patients with pneumonia, and microbiological cure for patients with bacteraemia. The primary outcome was clinical failure, defined as not meeting all success criteria by intention-to-treat analysis, at 14 days after randomisation. This trial is registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual.. Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406 patients to the two treatment groups. Most patients had pneumonia or bacteraemia (355/406, 87%), and most infections were caused by Acinetobacter baumannii (312/406, 77%). No significant difference between colistin monotherapy (156/198, 79%) and combination therapy (152/208, 73%) was observed for clinical failure at 14 days after randomisation (risk difference -5·7%, 95% CI -13·9 to 2·4; risk ratio [RR] 0·93, 95% CI 0·83-1·03). Results were similar among patients with A baumannii infections (RR 0·97, 95% CI 0·87-1·09). Combination therapy increased the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at risk of or with kidney injury).. Combination therapy was not superior to monotherapy. The addition of meropenem to colistin did not improve clinical failure in severe A baumannii infections. The trial was unpowered to specifically address other bacteria.. EU AIDA grant Health-F3-2011-278348.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Greece; Humans; Israel; Italy; Male; Meropenem; Middle Aged; Single-Blind Method; Treatment Outcome

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

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

Meropenem is important for management of postneurosurgical meningitis, but the data about its penetration into cerebrospinal fluid (CSF) are inadequate. This prospective, open-label study investigated the pharmacokinetic profile of meropenem in patients with postneurosurgical meningitis, especially its CSF penetration.. A total of 82 patients with postneurosurgical meningitis were included to receive meropenem intravenously according to a regimen of 2 g every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4 doses, blood and CSF samples were collected simultaneously at predefined time points. The high-performance liquid chromatography ultraviolet method was used to determine the concentration of meropenem.. The peak meropenem concentration in blood and CSF was 43.2 ± 5.3 and 2.4 ± 0.3 mg/L in the group who received 2 g every 8 hours; 28.9 ± 2.7 and 1.2 ± 0.2 mg/L in the group who received 1g every 8 hours; and31.5 ± 3.4 and 1.6 ± 0.2 mg/L in the group who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6% ± 7.3%, 14.3% ± 1.7%, and 30.9% ± 24.2%, respectively.. Dosing regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of meropenem may be more useful for clearance of pathogens.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Prospective Studies; Thienamycins; Treatment Outcome

Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy.. To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS).. A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children's Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes.. A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group.. Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Infusions, Intravenous; Meropenem; Neonatal Sepsis; Prospective Studies; Thienamycins

Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli.. We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI.. In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG). The latter received meropenem according to a regimen decided by the attending physician. The SG received individualized meropenem therapy with a dosing strategy based on software developed from a meropenem population PK/PD model. The primary endpoint was clinical response to meropenem therapy. Secondary endpoints were the amount of antibiotics used and bacteriologic response.. Klebsiella pneumoniae was the most common pathogen (32.9%), followed by Pseudomonas aeruginosa (30.4%) and Escherichia coli (17.7%). A total of 63 (79.7%) patients achieved clinical success. Prevalence of clinical success was significantly higher in the SG than in the CG (89.7 vs. 70.0%; p = 0.029). The daily dose of meropenem was significantly lower in the SG than in the CG (1.5 vs. 2.0 g; p = 0.017). A total of 52 (65.8%) patients experienced bacteriologic success, the median duration of meropenem therapy was 9 days, and the median total dose of meropenem was 18.0 g. There were no significant differences between the groups in these parameters.. A strategy for meropenem dosing based on a population PK/PD model can improve clinical response and avoid overtreatment in elderly patients with an LRTI. ClinicalTrials.gov registration number NCT01944319.

Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Models, Biological; Prospective Studies; Respiratory System; Respiratory Tract Infections; Thienamycins; Treatment Outcome

Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB.. The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed.. Currently, there is no study being undertaken which analyzes empiric treatment of (VAP) with a suspicion of multi-resistance. Colistin, an off-patent antibiotic commercialized for more than 60 years, could widen the antibiotic alternatives for a high-mortality illness aggravated by antibiotic resistance.. This trial is registered with ClinicalTrials.gov (identifier: NCT01292031 ; registered on 29 June 2012) and EudraCT (identifier: 2010-023310-31; registered on 7 February 2011).

Topics: Anti-Bacterial Agents; Clinical Protocols; Colistin; Drug Resistance, Multiple, Bacterial; Europe; Gram-Negative Bacterial Infections; Humans; Incidence; Meropenem; Patents as Topic; Pneumonia, Ventilator-Associated; Research Design; Thienamycins; Time Factors; Treatment Outcome

ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results.. To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection.. We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011).. A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329).. Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Cohort Studies; Cross Infection; Drug Administration Schedule; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Teaching; Hospitals, Urban; Humans; Infusions, Intravenous; Intensive Care Units; Length of Stay; Male; Meropenem; Middle Aged; Missouri; Penicillanic Acid; Pilot Projects; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Delftia acidovorans (

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ceftazidime; Colistin; Delftia acidovorans; Female; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Stenotrophomonas maltophilia; Young Adult

To describe the first case of endophthalmitis caused by. An 83-year-old patient, affected by open-angle glaucoma and with a previous surgery of combined cataract extraction and Xen gel stent implantation, developed endophthalmitis 1 month after bleb needle revision with 5-fluorouracil injection. At presentation, best corrected visual acuity was hand movement, hypopyon was evident into the anterior chamber and a flat bleb with no sign of leakage was present over the Xen gel implant.. Immediate pars plana vitrectomy was performed, with intravitreal antibiotic administration and silicon oil tamponade.

Topics: Administration, Ophthalmic; Aged, 80 and over; Anti-Bacterial Agents; Cataract Extraction; Ceftazidime; Endophthalmitis; Eye Infections, Bacterial; Glaucoma Drainage Implants; Glaucoma, Open-Angle; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intraocular Pressure; Intravitreal Injections; Male; Meropenem; Postoperative Complications; Reoperation; Sphingobacterium; Stents; Tonometry, Ocular; Visual Acuity; Vitrectomy; Vitreous Body

We are writing this letter to provide an update of published information on antibiotics for cystic fibrosis (CF) pulmonary exacerbations to the State of the Art articles by Zobell et al. Information on meropenem-vaborbactam and cefiderocol were not available when the original articles were published. These new antibiotics, approved in 2017 and 2019, possess antipseudomonal properties like the other carbapenems and cephalosporins in the original articles however, existing literature refers to their use for other less common bacteria. As patients with CF age, the microorganisms in their bacterial cultures change and some can colonize multiple or uncommon bacterial species including, Burkholderia, Achromobacter, and Stenotrophomonas spp. In 2019, these nonlactose fermenting bacterial species made up for approximately 15% of respiratory microorganisms cultured in pediatric patients. Though infrequent, compared to Staphylococcus aureus or Pseudomonas aeruginosa, these bacteria are opportunistic pathogens and patients at the highest risk for these infections include those with CF. Like other Gram negative bacteria, Burkholderia, Achromobacter, and Stenotrophomonas spp., are frequently drug resistant and can make treatment extremely challenging, thus it is crucial that data for treatment of these less common pathogens be evaluated.

Topics: Anti-Bacterial Agents; Boronic Acids; Cefiderocol; Cephalosporins; Child; Cystic Fibrosis; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem

Colistimethate sodium (colistin) is used to treat multidrug-resistant gram negative infections. We describe the profile and outcomes of patients given colistin in a tertiary level government hospital in Manila, Philippines.. We performed a retrospective study of adult patients given intravenous colistin between January 2015 to June 2018 in the Philippine General Hospital. We defined clinical success as a composite of hemodynamic stability, quick Sequential Organ Failure Assessment (qSOFA) score, and microbiological cure.. 250 patients were included, half (49.2%) were admitted in the ICU. Median age was 55 years. There was an increase in qSOFA, APACHE II score, and septic shock from baseline to 24 h prior to colistin use. Most patients had pneumonia (90.8%) with extensively drug-resistant Acinetobacter baumannii as the most common isolate (78.8%). Colistin was given in combination with meropenem (96.4%) for a median of 12 days. Nephrotoxicity was seen in 30.8%, with renal replacement therapy needed in 6%. Clinical success was seen in 61.2% of patients and overall mortality was 41.6%.. Colistin was frequently used in combination with a carbapenem for treatment of XDR-related respiratory infections. Nephrotoxicity was a common adverse effect. Clinical success was modest and overall mortality was high.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Male; Meropenem; Middle Aged; Organ Dysfunction Scores; Philippines; Respiratory Tract Infections; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Young Adult

The escalating problem of the dissemination of carbapenemase-producing bacteria (CPB) has gained worldwide attention. The prompt diagnosis of CPB and precise identification of carbapenemases are imperative to enable specific antibiotic therapy and control the spread of these bacteria. The present study was designed to assess the performance of five important assays for the detection of carbapenemases. The modified carbapenem inactivation method (mCIM), CARBA-5, GeneXpert Carba-R, BD MAX Check-Points CPO, and GeneFields CPE assays were evaluated with an international collection of 159 bacterial isolates, including 93 CPB and 66 non-CPB isolates. The overall accuracy/sensitivity/specificity for carbapenemase detection were 100% (95% CI, 97.7%-100%)/100% (95% CI, 96.1%-100%)/100% (95% CI, 94.6%-100%) for mCIM, 98.7% (95% CI, 95.5%-99.9%)/97.9% (95% CI, 92.5%-99.7%)/100% (95% CI, 94.6%-100%) for CARBA-5, 96.9% (95% CI, 92.8%-99%)/95.7% (95% CI, 89.4%-98.8%)/98.5% (95% CI, 91.8%-99.9%) for GeneXpert Carba-R, 94.3% (95% CI, 89.5%-97.4%)/90.3% (95% CI, 82.4%-95.5%)/100% (95% CI, 94.6%-100%) for BD MAX Check-Points CPO, and 86.2% (95% CI, 79.8%-91.1%)/77.4% (95% CI, 67.6%-85.5%)/98.5% (95% CI, 91.8%-100%) for GeneFields CPE. Interestingly, mCIM and CARBA-5 assays showed 100% accuracy/sensitivity/specificity for detection of the target genes. Furthermore, all the other assays showed comparable high accuracy (96.9% to 100%), sensitivity (100%), and specificity (96.4% to 100%) for the detection of the target genes. On the basis of these results, a new scheme was proposed for their efficient application. These results confirmed the high sensitivity of the evaluated assays, and the proposed scheme is reliable and improves the overall sensitivity and specificity of the assays.

Topics: Bacterial Proteins; beta-Lactamases; Chromatography; Data Accuracy; DNA, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Immunoassay; Meropenem; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

Cystic fibrosis is associated with significant morbidity and early mortality due to recurrent acute and chronic lung infections. The chronic use of multiple antibiotics without pathogen eradication increases the possibility of extensive drug resistance or even pan-drug resistance (PDR). It is imperative that new or alternative treatment options be explored. We present a clinical case of a 10-year-old female cystic fibrosis patient, infected with a PDR Achromobacter spp. She was treated with cefiderocol, meropenem/vaborbactam, and bacteriophage therapy (Ax2CJ45ϕ2) during two separate admissions in an attempt to clear her infection and restore baseline pulmonary function. The Centers for Disease Control and Prevention confirmed antibiotic susceptibilities, which showed resistance to both cefiderocol and meropenem/vaborbactam. However, after using all three agents concomitantly during the second treatment course, our patient's pulmonary function improved dramatically, and the Achromobacter spp. could not be isolated from sputum samples obtained 8 and 16 weeks after completion of therapy. Overall, the treatment regimen consisting of cefiderocol, meropenem/vaborbactam, and bacteriophage was safe and well-tolerated in our patient.

Topics: Achromobacter; Anti-Bacterial Agents; Bacteriophages; Boronic Acids; Cefiderocol; Cephalosporins; Child; Combined Modality Therapy; Cystic Fibrosis; Drug Combinations; Drug Resistance, Bacterial; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Heterocyclic Compounds, 1-Ring; Humans; Meropenem

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

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

The optimal method to screen for gastrointestinal colonization with carbapenem-resistant organisms (CRO) has yet to be established. The direct MacConkey (direct MAC) plate method demonstrates high sensitivity for CRO detection, but established zone diameter (ZD) criteria for ertapenem (≤27 mm) and meropenem (≤32 mm) result in high rates of false positives upon confirmatory testing. To increase specificity, we screened for CRO in two high-risk wards using the direct MAC plate method, recorded ZDs for each sample, and generated receiver operating characteristic (ROC) curves to evaluate the optimal ZD cutoff criteria. Of 6,868 swabs obtained over an 18-month period, 4,766 (69%) had growth on MAC plates, and 2,500 (36%) met criteria for further evaluation based on previously established ZDs around the carbapenem disks. A total of 812 (12%) swabs were confirmed positive for at least one CRO and included 213 (3%) carbapenemase-producing organisms (CPO), resulting in a specificity of 78% for the direct MAC plate method. Reducing the ertapenem and meropenem ZDs to ≤25 mm improved specificity to 83%, decreasing the confirmatory testing workload by 32%. The sensitivities with the lower ZD criteria were 89% for CRO and 94% for CPO, respectively. The direct MAC plate method criteria for CRO testing can be modified to balance the sensitivity and specificity of CRO while reducing the burden on clinical microbiology laboratories. These modifications can be particularly helpful in regions with a low CRO prevalence.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Disk Diffusion Antimicrobial Tests; Ertapenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Rectum; ROC Curve; Sensitivity and Specificity

The emergence, prevalence, and rapid spread of New Delhi metallo-β-lactamases (NDMs) in Gram-negative pathogens threaten our traditional regimen to treat bacterial infectious diseases. Discovery of novel NDMs inhibitors offers an alternative approach to restore the carbapenems activity. However, thus far, no clinical inhibitor of NDMs has been approved. In this study, the potential of peptides and analogues as carbapenems adjuvant in NDMs-positive pathogens was investigated. Herein, we successfully found that peptidomimetic 4 (PEP4) is a potential inhibitor of NDM enzymes. PEP4 displayed significant synergistic activity with Meropenem against NDM-expression Gram-negative bacteria

Topics: Animals; beta-Lactamase Inhibitors; beta-Lactamases; Disease Models, Animal; Drug Repositioning; Drug Synergism; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Mice; Molecular Structure; Peptidomimetics

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

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

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

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

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

New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens-including Gram-negative bacteria-to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.. To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.. The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time-kill assay and assays for the selection of resistant mutants.. We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time-kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.. These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Apoproteins; Ciprofloxacin; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Mutation; Transferrin

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Thienamycins

Antibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied and yet potentially widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen

Topics: Amdinocillin; Anti-Bacterial Agents; Drug Tolerance; Enterobacter aerogenes; Enterobacter cloacae; Escherichia coli; Gram-Negative Bacterial Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Spheroplasts

Intestinal colonization resistance is mainly exerted by commensal anaerobes.. To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients.. All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition.. Among the 352 included patients [median ICU stay 16 (9-30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition.. Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.

Topics: Aged; Anti-Bacterial Agents; Bacteria, Anaerobic; Carbapenems; Ceftriaxone; Cross Infection; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Intensive Care Units; Intestines; Male; Meropenem; Middle Aged; Propensity Score; Retrospective Studies

A series of novel pyridone conjugated monobactams with various substituents at the (4) position were synthesized and evaluated for their antibacterial activities against a panel of multidrug-resistant (MDR) Gram-negative bacteria in vitro. Compounds 46d, 54 and 75e displayed good to moderate activities against P. aeruginosa, among which the activity of 75e against P. aeruginosa was comparable to that of BAL30072 under iron limitation condition. Compounds 35, 46d, 54, 56a, 56c and 56d exhibited good to excellent antibacterial activities against E. coli and K. pneumoniae, which were comparable or superior to that of BAL30072. In vitro liver microsomal stability was further evaluated and the results manifested that Compounds 35, 46d and 54 were metabolically stable in human liver microsomes.

Topics: Anti-Bacterial Agents; Drug Design; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Monobactams; Pseudomonas aeruginosa; Pyridones

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

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

We herein describe a case of trauma-related wound infection with a subcutaneous abscess caused by both Enterobacter cancerogenus and Aeromonas hydrophila. An 89-year-old Japanese man was admitted to our hospital because of an injury that he had suffered in a car accident. The right dorsal region of the foot around the wound was reddish and swelling. The pus culture on his right foot grew E. cancerogenus and A. hydrophila. The patient was successfully treated with a 10-day course of meropenem and a 25-day course of levofloxacin. E. cancerogenus can therefore be a causative pathogen in skin and soft tissue infections among trauma patients.

Topics: Aeromonas hydrophila; Aged, 80 and over; Anti-Bacterial Agents; Asian People; Enterobacter; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Meropenem; Thienamycins; Treatment Outcome; Wound Infection

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

Empyema secondary to foreign body aspiration is rare in adults. We present a case of empyema in a 77-year-old male patient related to a remote aspiration event during a dental procedure. A CT of the chest and bronchoscopy confirmed that a metallic foreign body was located within the right lower lobe bronchus. His pleural fluid culture revealed

Topics: Aged; Anti-Bacterial Agents; Bronchoscopy; Empyema, Pleural; Foreign Bodies; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lung; Male; Meropenem; Respiratory Aspiration; Sphingomonas; Thienamycins; Tomography, X-Ray Computed

Meropenem-vaborbactam is a fixed-dose combination product of a carbapenem and a cyclic boronic acid β-lactamase inhibitor with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE). The efficacy of meropenem-vaborbactam for the treatment of complicated urinary tract infections and acute pyelonephritis was demonstrated in a Phase III trial (TANGO I). Preliminary data from TANGO II, a separate Phase III study, support the efficacy of meropenem-vaborbactam for the treatment of infections caused by CRE. Overall, meropenem-vaborbactam appears to be safe and well tolerated. It has favorable toxicity, pharmacokinetic and pharmacodynamic profiles compared with other antibiotics with activity against CRE. Meropenem-vaborbactam is an important addition to the current armamentarium of antimicrobial agents with activity against K. pneumoniae carbapenemase-producing CRE.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Boronic Acids; Clinical Trials, Phase III as Topic; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Gram-Negative Bacterial Infections; Humans; Meropenem; Treatment Outcome; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Child; Chromobacterium; Ciprofloxacin; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Intensive Care Units; Meropenem; Pneumonia, Necrotizing; Soil Microbiology; Tomography, X-Ray Computed

Lung abscess following flexible bronchoscopy is a rare and sometimes fatal iatrogenic complication. Here, we report the first case of a lung abscess caused by multidrug-resistant Capnocytophaga sputigena following bronchoscopy. A 67-year-old man underwent bronchoscopy to evaluate a lung mass. Seven days after transbronchial lung biopsy, he presented with an abscess formation in a lung mass. Empirical antibiotic therapy, including with garenoxacin, ampicillin/sulbactam, clindamycin and cefepime, was ineffective. Percutaneous needle aspiration of lung abscess yielded C. sputigena resistant to multiple antibiotics but remained susceptible to carbapenem. He was successfully treated by the combination therapy with surgery and with approximately 6 weeks of intravenous carbapenem. Finally he was diagnosed with a lung abscess with adenocarcinoma expressing high levels of programmed cell death ligand 1. The emergence of multidrug-resistant Capnocytophaga species is a serious concern for effective antimicrobial therapy. Clinicians should consider multidrug-resistant C. sputigena as a causative pathogen of lung abscess when it is refractory to antimicrobial treatment.

Topics: Aged; Anti-Bacterial Agents; B7-H1 Antigen; Biopsy, Fine-Needle; Bronchoscopy; Capnocytophaga; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Lung Abscess; Male; Meropenem; Sputum

Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF.. I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement.. This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity.

Topics: Amikacin; Anti-Bacterial Agents; Child; Ciprofloxacin; Clindamycin; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Methicillin-Resistant Staphylococcus aureus; Rhodospirillaceae; Stenotrophomonas maltophilia; Virulence

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

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

To use a pre-clinical infection model to assess the antibacterial effect of human simulations of dosing with ceftolozane/tazobactam (with or without amikacin) or meropenem against Enterobacteriaceae and Pseudomonas aeruginosa.. An in vitro pharmacokinetic model was used to assess changes in bacterial load and profiles after exposure to mean human serum concentrations over 168 h. Changes in area under the bacterial kill curve (AUBKC; log cfu/mL·h) and growth on 4 × MIC recovery plates were the co-primary outcome measures.. Simulations of ceftolozane/tazobactam at 1 g/0.5 g or 2 g/1 g q8h or meropenem 2 g q8h all produced a >4 log reduction in bacterial load of Escherichia coli. Meropenem had smaller AUBKC values, indicating greater reduction in bacterial load than ceftolozane/tazobactam. Meropenem was also more effective than ceftolozane/tazobactam against Klebsiella pneumoniae strains. All regimens were equally effective in reducing P. aeruginosa bacterial load measured by AUBKC but growth on 4 × MIC recovery plates and changes in population profiles were only seen with meropenem. Addition of amikacin at 15 mg/kg q24h or 7.5 mg/kg q12h to 2 g/1 g of ceftolozane/tazobactam produced greater reductions in bacterial load but generated changes in amikacin population profiles with the 7.5 mg/kg q12h amikacin simulation.. The doses of ceftolozane/tazobactam simulated were highly effective in reducing the bacterial load of E. coli (MIC ≤0.25 mg/L), but less so for K. pneumoniae (MIC 4 mg/L). For both species, meropenem produced an overall greater reduction in pathogen load. Ceftolozane/tazobactam and meropenem were equally effective as monotherapy against P. aeruginosa but emergence of resistance occurred with meropenem. Addition of amikacin to ceftolozane/tazobactam reduced the bacterial load of P. aeruginosa at the expense of emergence of resistance to amikacin.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Load; beta-Lactamase Inhibitors; Cephalosporins; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Models, Theoretical; Tazobactam

Topics: Animals; Anti-Bacterial Agents; Drug Discovery; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Microbial Sensitivity Tests; Monobactams; Pyridones; Rats, Sprague-Dawley; Structure-Activity Relationship; Thiazoles

Cefiderocol (S-649266), a siderophore cephalosporin, utilizes a novel mechanism of entry into the periplasmic space of Gram-negative bacteria and is broadly stable to ESBLs and carbapenemases.. A collection of carbapenem-resistant Gram-negative bacteria isolated from clinical specimens in 18 Greek hospitals was tested for susceptibility to cefiderocol, meropenem, ceftazidime, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam, amikacin, ciprofloxacin, colistin and tigecycline. Broth microdilution plates were used to determine MICs.. In total 189 non-fermentative Gram-negative bacteria (107 Acinetobacter baumannii and 82 Pseudomonas aeruginosa ) and 282 Enterobacteriaceae (including 244 Klebsiella pneumoniae , 14 Enterobacter cloacae and 11 Providencia stuartii ) were studied. For both A. baumannii and P. aeruginosa the MIC 90 of cefiderocol was 0.5 mg/L. For K. pneumoniae , E. cloacae and P. stuartii the MIC 90 of cefiderocol was 1, 1 and 0.5 mg/L, respectively. Tigecycline was the second most active antibiotic, followed by colistin.. Cefiderocol exhibited greater antimicrobial activity in vitro against carbapenem-resistant Gram-negative bacteria than comparator antibiotics.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cefepime; Cefiderocol; Ceftazidime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Greece; Humans; Inpatients; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Thienamycins; Tigecycline

The occurrence of carbapenem- and colistin-resistance among Gram-negative bacteria is increasing worldwide. The aim of this study was to understand the distribution of carbapenem- and colistin-resistance in two areas in Tamil Nadu, India.. The clinical isolates (n=89) used in this study were collected from two diagnostic centres in Tamil Nadu, India. The bacterial isolates were screened for meropenem- and colistin-resistance. Further, resistance genes blaNDM-1, blaOXA-48-like, blaIMP, blaVIM, blaKPC, mcr-1 and mcr-2 and integrons were studied. The synergistic effect of meropenem in combination with colistin was assessed.. A total of 89 bacterial isolates were studied which included Escherichia coli (n=43), Klebsiella pneumoniae (n=18), Pseudomonas aeruginosa (n=10), Enterobacter cloacae (n=6), Acinetobacter baumannii (n=5), Klebsiella oxytoca (n=4), Proteus mirabilis (n=2) and Salmonella paratyphi (n=1). MIC testing showed that 58/89 (65 %) and 29/89 (32 %) isolates were resistant to meropenem and colistin, respectively, whereas 27/89 (30 %) isolates were resistant to both antibiotics. Escherichia coli, K. pneumoniae, K. oxytoca, Pseudomonas aeruginosa, and Enterobacter cloacae isolates were blaNDM-1-positive (n=20). Some strains of Escherichia coli, K. pneumoniae and K. oxytoca were blaOXA-181-positive (n=4). Class 1, 2 and 3 integrons were found in 24, 20 and 3 isolates, respectively. Nine NDM-1-positive Escherichia coli strains could transfer carbapenem resistance via plasmids to susceptible Escherichia coli AB1157. Meropenem and colistin showed synergy in 10/20 (50 %) isolates by 24 h time-kill studies.. Our results highlight the distribution of carbapenem- and colistin-resistance in Gram-negative bacteria isolated from the Tamil Nadu region in South India.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Synergism; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; India; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Thienamycins

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

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

Inappropriate use of broad-spectrum antimicrobials affects adversely both the individual patient and the general public. The aim of the study was to identify patients at risk for excessively prolonged carbapenem treatment in the ICU as a target for antimicrobial stewardship interventions.. Case-control study in a network of 11 ICUs of a university hospital. Patients with uninterrupted meropenem therapy (MT) > 4 weeks were compared to controls. Controls were defined as patients who stayed on the ICU > 4 weeks and received meropenem for ≤ 2 weeks. Associations between case-control status and potential risk factors were determined in a multivariate logistic regression model.. Between 1. Surgical patients with peritonitis and patients with known colonization with MDR Gram-negative bacteria are at risk for excessively prolonged carbapenem therapy and represent an important target population for antimicrobial stewardship interventions.

Topics: Aged; Anti-Bacterial Agents; Case-Control Studies; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Length of Stay; Male; Mediastinitis; Meropenem; Middle Aged; Odds Ratio; Peritonitis; Pneumonia; Risk Factors; Thienamycins; Time Factors

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

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

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

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

The Middle East is regarded as a secondary reservoir for OXA-48 and New Delhi metallo-β-lactamase (NDM) carbapenemases. One of the main challenges in clinical microbiology diagnostics is the detection of carbapenemases. For this reason simple screening methods have been sought to detect carbapenemase producers to determine appropriate therapeutic measures and implement infection control interventions. The present study aimed to evaluate the efficacy of the modified Hodge test (MHT) and a boronic acid-based combined disk test using carbapenems as substrates for the phenotypic determination of OXA-48 and NDM type carbapenemases in 45 epidemiologically unrelated carbapenem-resistant clinical isolates of Klebsiella pneumoniae (13 isolates), Acinetobacter baumanii (20 isolates), and Pseudomonas aeruginosa (12 isolates).. Boronic acid disk test using meropenem as substrate and 600 µg of 3- aminophenylboronic acid (APB) was the most sensitive method (83.33 %) for detection of OXA-48, while the most specific method was MHT (100 %). As regards NDM carbapenemase, boronic acid disk tests using imipenem and 600 µg of APB per disk, and meropenem with 300 or 600 µg of APB were the most  sensitive methods (87.50 %), while the most specific method was the MHT (100 %).. The results of the present study indicate that phenotypic screening with the MHT and the boronic acid disk test may be used to detect OXA-48 and NDM carbapenemases in Gram-negative bacilli clinical isolates, and that these tests can be easily applied in tertiary care settings with minimal infrastructure.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Boronic Acids; Carbapenems; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meropenem; Phenotype; Polymerase Chain Reaction; Thienamycins

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

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

Caulobacter spp. are Gram-negative bacteria that have rarely been found to be pathogenic in humans.. This report describes the first case, to our knowledge, of meningitis in an adult patient caused by Caulobacter spp. A 75-year-old man was operated for a glioblastoma with no evident signs of primary infection in the wound site. Eight days after surgery, the patient developed signs and symptoms of meningitis. Caulobacter was then isolated on 3 separate occasions in the patient's cerebrospinal fluid. Thereafter, specific antibiotic therapy began. After 2 weeks of therapy, the patient was discharged with complete resolution of any related symptoms.. Caulobacter spp. can cause adult meningitis even where there is no evidence of surgical site infection.

Topics: Aged; Brain Neoplasms; Caulobacter; Cerebrospinal Fluid; Glioblastoma; Gram-Negative Bacterial Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Postoperative Complications; Thienamycins; Virulence

Ventriculoperitoneal shunt (VPS) infections are a major cause of morbidity and mortality in patients with hydrocephalus. Most data about these infections come from the Western literature. Few data about infecting organisms in Africa are available, yet knowledge of these organisms is important for the prevention and treatment of infectious complications. The purpose of this study was to determine the organisms cultured from infected shunts in a rural Kenyan hospital.. The authors conducted a retrospective study of patients with VPS infections recorded in the neurosurgical database of BethanyKids at Kijabe Hospital between September 2010 and July 2012.. Among 53 VPS infections confirmed by culture, 68% occurred in patients who were younger than 6 months. Seventy-nine percent of the infections occurred within 2 months after shunt insertion. Only 51% of infections were caused by Staphylococcus species (Staphylococcus aureus 25%, other Staphylococcus species 26%), whereas 40% were caused by gram-negative bacteria. All S. aureus infections and 79% of other Staphylococcus infections were sensitive to cefazolin, but only 1 of 21 gram-negative bacteria was sensitive to it. The majority of gram-negative bacterial infections were multidrug resistant, but 17 of the 20 gram-negative bacteria were sensitive to meropenem. Gram-negative bacterial infections were associated with worse outcomes.. The high proportion of gram-negative infections differs from data in the Western literature, in which Staphylococcus epidermidis is by far the most common organism. Once a patient is diagnosed with a VPS infection in Kenya, immediate treatment is recommended to cover both gram-positive and gram-negative bacterial infections. Data from other Sub-Saharan countries are needed to determine if those countries have the same increased frequency of gram-negative infections.

Topics: Adolescent; Ampicillin; Anti-Bacterial Agents; Child; Child, Preschool; Chloramphenicol; Ciprofloxacin; Drug Resistance, Bacterial; Female; Gentamicins; Gram-Negative Bacterial Infections; Humans; Hydrocephalus; Infant; Kenya; Male; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Thienamycins; Treatment Outcome; Ventriculoperitoneal Shunt

A total of 368 nonreplicate gram-negative bacteria with resistance to imipenem or meropenem were collected to search for carbapenemase genes, class 1 integrons, and insertion sequence with common region 1 (ISCR1). The carbapenemase genes blaIMP-4, blaKPC-2, and blaNDM-1 were found in two Enterobacteriaceae and seven Pseudomonas aeruginosa isolates, nine Klebsiella pneumoniae isolates, and seven Enterobacteriaceae and two Acinetobacter spp. isolates. The class D OXA-type carbapenemase genes blaOXA-23-like, blaOXA-24-like, blaOXA-58, and blaOXA-51-like were detected in 59 (34.9%), 2 (1.2%), 16 (9.5%), and 126 (74.6%) Acinetobacter strains. This is the first description of blaNDM-1 in Enterobacter hormaechei and Acinetobacter genomic species 13TU. Of the integrase-positive strains, 135 (90.0%) Acinetobacter spp., 22 (61.1%) P. aeruginosa, and 14 (100%) Enterobacteriaceae isolates were identified by five, ten, and four different gene cassette arrays, respectively. Three novel gene cassette arrays aadB-aadA1, dfrA25, and dfrA16-aadA2 were reported for the first time in some species. Of the ISCR1-positive strains, the nonfermentative strains (102 Acinetobacter spp. and 13 P. aeruginosa. isolates) contained the same arrangement blaPER-1-putative glutathione-S-transferase-novel type ABC transporter, and three Enterobacteriaceae isolates harbored three different arrangements. Four distinct complex class 1 integron structures were observed. The complex class 1 integron detected in New Delhi, metallo-β-lactamase (NDM-1)-producing E. hormaechei, was found to coexist in the NDM-1-carrying plasmid. Our results suggested that we should pay more attention to the strict implementation of infection control measures and active antibiotic resistance surveillance to avoid the rapid spread or outbreak of carbapenemase-producing gram-negative bacteria.

Topics: Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Drug Resistance, Bacterial; Genes, Bacterial; Glutathione Transferase; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Integrons; Meropenem; Mutagenesis, Insertional; Thienamycins

Meropenem is an anti-Gram-negative antimicrobial, the time-dependent activity of which may be maximized through administration by continuous infusion.. The objectives of this study were to characterize the pharmacokinetics of continuous infusion meropenem in relation to body size and Cockcroft-Gault estimated creatinine clearance (CLCR) in overweight and obese patients with stable and unstable kidney function with the intent of creating a nomogram for optimal dosing.. Patients from a single institution with a body mass index ≥25 kg/m(2) receiving meropenem by continuous infusion with measurement of meropenem steady-state concentrations (C ss) were identified. Individual Bayesian estimates of meropenem volume of distribution of the central compartment (V c) and clearance (CL) were calculated and relationships to body size descriptors and CLCR estimated using these body size descriptors were defined by regression. Kidney function stability was defined based on median absolute deviation, stratification by the ratio of maximum to minimum serum creatinine (SCr) and individual patient-level regression of SCr over time. The influence of kidney function stability on meropenem CL estimation by CLCR was tested.. A total of 375 patients (77.9 % male) with 846 C ss values (62.4 % of patients with ≥2 measurements) were identified. The median daily dose of meropenem and frequency of infusion bag changes were 2000 mg/day and four times per day, respectively. The meropenem C ss values were ≥16, ≥8, ≥4, and ≥2 mg/L for 41.1, 76.1, 97.4, and 99.9 % of observations, respectively. The median (range) age, weight, and BMI were 66 (24-90) years, 90 (70-250) kg, and 30.8 (25.1-81.6) kg/m(2), respectively. The mean [standard deviation (SD)] serum creatinine at baseline was 1.57 (1.37) mg/dL. The mean (SD) V c was 28.1 (1.36) L and not related to body size, while CL was 8.85 (6.40) L/h and best related to CLCR estimated using adjusted body weight (ABW). The meropenem CL to CLCR relationship was not significantly impacted by the presence or absence of kidney function stability. The user-friendly dosing nomogram based on CLCR estimated using ABW showed that optimal drug exposure [Css ≥ minimum inhibitory concentration (MIC)] may be obtained even against multi-drug resistant (MDR) pathogens when considering dosages up to 1250 mg every 6 h by continuous infusion.. Meropenem CL is best estimated using CLCR with ABW in patients with a BMI ≥25 kg/m(2) and this relationship is not altered by unstable kidney function. Application of our dosing nomogram may improve the care of overweight and obese patients with severe MDR Gram-negative infections treated with meropenem by continuous infusion.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bayes Theorem; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Kidney; Kidney Function Tests; Male; Meropenem; Middle Aged; Obesity; Obesity, Morbid; Overweight; Thienamycins

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

Multidrug-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are endemic to hospitals in New York City and other regions. RPX7009 is a novel β-lactamase inhibitor with activity against serine carbapenemases. We tested the activity of meropenem plus RPX7009 against 4,500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem-RPX7009 combination was found to have excellent in vitro activity against Escherichia coli, K. pneumoniae, and Enterobacter spp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producing Enterobacteriaceae strains were inhibited by meropenem (≤1 μg/ml) plus RPX7009 (8 μg/ml). In a limited number of strains, the combination appeared to have reduced activity against KPC-producing K. pneumoniae isolates with diminished ompK35 and ompK36 expression. The addition of RPX7009 did not affect the activity of meropenem against Acinetobacter baumannii and Pseudomonas aeruginosa. The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producing Enterobacteriaceae and deserves further study. Other approaches will be needed to address multidrug-resistant A. baumannii and P. aeruginosa, which typically possess different mechanisms of carbapenem resistance.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Boronic Acids; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Heterocyclic Compounds, 1-Ring; Hospitals; Humans; Meropenem; Microbial Sensitivity Tests; New York City; Thienamycins

A 13-year-old female experienced a recurrence of baclofen pump-related central nervous system (CNS) infection caused by Achromobacter, despite absence of retained foreign material. Due to the failure of meropenem (120 mg/kg/d in divided doses every 8 hours and infused over 30 minutes) in the initial infection, the dose was infused over 4 hours during the recurrence. Meropenem is an antibiotic for which efficacy is time dependent, and 4-hour versus 30-minute infusions have been shown to prolong the time the concentration of the antibiotic exceeds the minimum inhibitory concentration (MIC) of the organism at the site of infection (T>MIC). Meropenem serum concentrations were obtained and indicated that T>MIC was at least 75% of the dosing interval. Our patient improved with no noted recurrences or adverse effects on the extended-infusion meropenem regimen. Utilization of extended-infusion beta-lactam dosing whenever possible in the treatment of serious infections caused by gram-negative organisms should be considered, as this dosing appears to be safe and improves the probability of achieving pharmacokinetic/pharmacodynamic goals.

Topics: Achromobacter denitrificans; Adolescent; Anti-Bacterial Agents; Baclofen; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Humans; Infusion Pumps, Implantable; Injections, Spinal; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Muscle Relaxants, Central; Recurrence; Thienamycins

Ceftazidime is the only anti-pseudomonal beta-lactam that has been reported to be administered by extended infusion in pediatric cystic fibrosis (CF) patients. A small pediatric pharmacokinetic/pharmacodynamic study has been published regarding the use of intermittent extended infusion doripenem in the treatment of an acute pulmonary exacerbation (APE) in pediatric CF patients; however, clinical use of intermittent extended infusion doripenem in pediatric CF patients has not been previously reported. We present three cases administering intermittent extended infusion doripenem in pediatric CF patients for the treatment of an APE in the case of replacing meropenem due to shortage. The delivery of beta-lactam antibiotics via intermittent extended infusion should be considered in order to optimize the pharmacodynamics of beta-lactams in the treatment of an APE.

Topics: Adolescent; Anti-Bacterial Agents; Burkholderia cenocepacia; Burkholderia Infections; Carbapenems; Child; Cystic Fibrosis; Disease Progression; Doripenem; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Pseudomonas stutzeri; Rhodospirillaceae; Thienamycins; Tobramycin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

Topics: Anti-Bacterial Agents; Critical Illness; Drug Dosage Calculations; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Medication Errors; Meropenem; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Thienamycins

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

VIM and KPC are two major families of carbapenemases involved in nosocomial outbreaks of multidrug-resistant Gram-negative bacilli. To rapidly detect bla(VIM)- and bla(KPC)-encoding strains, three multiplex PCR-based methods were designed and validated: (i) a real-time PCR to detect all reported VIM alleles, namely bla(VIM-1-19, 23-37); (ii) a real-time PCR to identify bla(VIM)-type and bla(KPC) carbapenemases in an ultrarapid single reaction; and (iii) a standard PCR to amplify and sequence all VIM alleles. All three methods detected 33 VIM-positive samples among 107 Gram-negative isolates with imipenem and meropenem minimum inhibitory concentrations ≥1 mg/L. The three methods displayed 100% sensitivity, specificity and concordance. Sequencing of the bla(VIM) amplicons revealed that 30 samples encoded bla(VIM-1) and 3 samples encoded bla(VIM-2). The real-time assay, optimised for the simultaneous detection of bla(VIM) and bla(KPC), identified 3 and 12 isolates positive for both bla(VIM)/bla(KPC) and for bla(KPC), respectively. The analytical sensitivity of the real-time assays was linear over 6 log dilutions, with a reproducible detection limit of 1 CFU. No cross-reactivity was detected. The developed assays provide powerful tools for rapid identification of VIM and KPC carbapenemase producers, therefore contributing to the prevention and containment of resistance dissemination.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Molecular Diagnostic Techniques; Multiplex Polymerase Chain Reaction; Sensitivity and Specificity; Thienamycins

The problem of antimicrobial resistance is exemplified by multidrug-resistant (MDR) isolates of Gram-negative species. Of particular concern are expanded-spectrum cephalosporin-resistant isolates of Enterobacteriaceae, epidemic lineages of Acinetobacter baumannii producing OXA-type carbapenemases, and MDR Pseudomonas aeruginosa. In this study, the in vitro activity of the novel monosulfactam BAL30072 was investigated both alone and in combination with meropenem against a diverse collection of commonly encountered Gram-negative pathogens. Thirty-one isolates were studied, including type strains and clinical isolates with defined mechanisms conferring resistance to various antimicrobial agents including to carbapenems, colistin and tigecycline. BAL30072 minimum inhibitory concentrations (MICs) were determined in the presence and absence of meropenem (1:1, w/w) by agar dilution. Potential synergy or antagonism between BAL30072 and meropenem was investigated using standard chequerboard assays. Versus MDR A. baumannii strains producing class D oxacillinases, BAL30072 MICs were all ≤4 mg/L with the exception of the isolate belonging to the UK 'Burn' lineage. BAL30072 exhibited MIC values of 0.5 mg/L to >64 mg/L towards the five P. aeruginosa strains. Against three meropenem-susceptible Escherichia coli, including the CTX-M-15 extended-spectrum β-lactamase-producer, BAL30072 exhibited MICs of 0.25-2 mg/L; higher MICs were recorded against some of the Enterobacteriaceae isolates tested. The in vitro data suggest that BAL30072 has a potential role in the treatment of infections due to Gram-negative pathogens, including those with important resistances to other agents. In addition, BAL30072 shows powerful synergistic activity in combination with meropenem, potentially expanding its coverage for the treatment of infections caused by problematic species.

Topics: Anti-Bacterial Agents; Drug Synergism; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Monobactams; Thiazoles; Thienamycins

Ertapenem (preferred choice for ESBL-producing organisms) use exhibited an increasing trend from 2006 to 2008. As extensive use of ertapenem might induce the mutation of resistant bacteria strains to ertapenem, we aimed to assess the appropriateness and impact of ertapenem-use, on ESBL production, the trends of gram-negative bacterial resistance and on the utilization of other antibiotics in our institution.. Inpatients who received a dose of ertapenem during 1 January 2006 to 31 December 2008, were reviewed. Pertinent patient clinical data was extracted from the pharmacy databases and assessed for appropriateness based on dose and indication. Relevant data from Network for Antimicrobial Resistance Surveillance (Singapore) (NARSS) was extracted, to cross-correlate with ertapenem via time series to assess its impact on hospital epidemiology, trends of gram-negative resistance and consumption of other antibiotics from 2006 to mid-2010.. 906 cases were reviewed. Ertapenem therapy was appropriate in 72.4% (93.7% success rate). CNS adverse events were noted in 3.2%. Readmission rate (30-day) due to re-infection (same pathogen) was 5.5%. Fifty cases had cultures growing Pseudomonas aeruginosa within 30 days of ertapenem initiation, with 25 cases growing carbapenem-resistant Pseudomonas aeruginosa.Ertapenem use increased from 0.45 DDD/100 patient days in 2006 to 1.2 DDD/100 patient days in mid-2010. Overall, the increasing trend of ertapenem consumption correlated with 1) increasing incidence-densities of ciprofloxacin-resistant/cephalosporin-resistant E. coli at zero time lag; 2) increasing incidence-densities of ertapenem-resistant Escherichia. coli and Klebsiella spp. at zero time lag; 3) increasing incidence-density of carbapenem-resistant Pseudomonas aeruginosa, at zero time lag.Increasing ertapenem consumption was significantly correlated with decreasing consumption of cefepime (R2 = 0.37344) 3 months later. It was significantly correlated with a decrease in imipenem consumption (R2 = 0.31081), with no time lag but was correlated with subsequent increasing consumption of meropenem (R2 = 0.4092) 6 months later.. Ertapenem use was appropriate. Increasing Ertapenem consumption did not result in a decreasing trend of ESBL producing enterobacteriaceae and could result in the selection for multi-drug resistant bacteria.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Ertapenem; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, General; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Singapore; Thienamycins; Young Adult

Topics: Bacteria; Bacterial Proteins; beta-Lactamases; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; Meropenem; Thienamycins

Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated from hospitalised patients. MICs for carbapenems were determined for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii obtained from the COMPACT II programme conducted in the Asia-Pacific region. Monte Carlo simulations were undertaken to assess the pharmacodynamic profile of carbapenems against each of the pathogens. All carbapenem regimens achieved optimal exposures [cumulative fraction of response (CFR) ≥90%] against E. coli and K. pneumoniae. Against P. aeruginosa, doripenem achieved 81.3-95.3% CFR, imipenem achieved 55.2-77.9% CFR and meropenem achieved 71.9-91.3% CFR; only doripenem regimens of 4-h infusion of 1000 mg every 8h (q8h) and 1-h and 4-h infusion of 2000 mg q8h and a meropenem regimen of 3-h infusion of 2000 mg q8h obtained optimal exposures; all carbapenem regimens showed slight (1-7%) improvement in CFRs in favour of isolates collected from ICU sources. Against A. baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens achieved optimal exposure in or outside the ICU. Owing to the high potency of carbapenems against these Enterobacteriaceae populations, standard regimens are likely to perform well in the Asia-Pacific region. However, larger doses combined with prolonged infusions will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa and A. baumannii that are prevalent in these countries.

Topics: Anti-Bacterial Agents; Carbapenems; Doripenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pacific Islands; Thienamycins; Time Factors

Novel siderophore-linked monobactams with in vitro and in vivo anti-microbial activity against MDR Gram-negative pathogens are described.

Topics: Animals; Binding Sites; Blood Proteins; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Monobactams; Rats; Structure-Activity Relationship

The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing Enterobacteriaceae has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL(Cr)) estimates for use in daily clinical practice to target the steady-state concentrations (C(ss)s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL(m)) and CL(Cr) was retrospectively assessed in a cohort of critically ill patients (group 1, n = 67) to create a formula for dosage calculation to target C(ss). The performance of this formula was validated in a similar cohort (group 2, n = 56) by comparison of the observed and the predicted C(ss)s. A significant relationship between CL(m) and CL(Cr) was observed in group 1 (r = 0.72, P < 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CL(Cr) (ml/min) + 2.85] × target C(ss) × (24/1,000), led to a significant correlation between the observed and the predicted C(ss)s (r = 0.92, P < 0.001). Dosing nomograms based on CL(Cr) were created to target the meropenem C(ss) at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance.

Topics: Aged; Algorithms; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Chromatography, High Pressure Liquid; Cohort Studies; Creatinine; Critical Illness; Enterobacteriaceae; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nomograms; Spectrophotometry, Ultraviolet; Thienamycins

Animal bites are typically harmless, but in rare cases infections introduced by such bites can be fatal. Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis. The tendency of C. canimorsus infections to present with varied symptoms, the organism's fastidious nature, and difficulty of culturing make this a challenging diagnosis. Rarely, bacterial cytotoxins such as those produced by C. canimorsus may act as causative agents of TTP, further complicating the diagnosis. Early recognition is crucial for survival, and the variability of presentation must be appreciated. We present the first known case of C. canimorsus infection resulting in TTP that initially presented as splenic infarction.. 72-year-old Caucasian male presented with a four-day history of abdominal pain, nausea, vomiting, diarrhea, and intermittent confusion. On presentation, vital signs were stable and the patient was afebrile. Physical examination was unremarkable apart from petechiae on the inner left thigh, and extreme diffuse abdominal pain to palpation and percussion along with positive rebound tenderness. Initial investigations revealed leukocytosis with left shift and thrombocytopenia, but normal liver enzymes, cardiac enzymes, lipase, INR and PTT. Abdominal CT demonstrated a non-enhancing spleen and hemoperitoneum, suggesting complete splenic infarction. Although the patient remained afebrile, he continued deteriorating over the next two days with worsening thrombocytopenia. After becoming febrile, he developed microangiopathic hemolytic anemia and hemodynamic instability, and soon after was intubated due to hypoxic respiratory failure and decreased consciousness. Plasma exchange was initiated but subsequently stopped when positive blood cultures grew a gram-negative organism. The patient progressively improved following therapy with piperacillin-tazobactam, which was switched to imipenem, then meropenem when Capnocytophaga was identified.. There is a common misconception amongst practitioners that the presence of systemic infection excludes the possibility of TTP and vice versa. This case emphasizes that TTP may occur secondary to a systemic infection, thereby allowing the two processes to coexist. It is important to maintain a wide differential when considering the diagnosis of either TTP or C. canimorsus infection since delays in treatment may have fatal consequences.

Topics: Aged; Animals; Anti-Bacterial Agents; Bites and Stings; Capnocytophaga; Dogs; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Purpura, Thrombotic Thrombocytopenic; Splenic Infarction; Thienamycins

Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Glomerular Filtration Rate; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Kidney; Kidney Function Tests; Male; Meropenem; Microbial Sensitivity Tests; Thienamycins

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

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

Due to escalating antimicrobial resistance amongst Gram-negative organisms, the choice of effective empirical antimicrobial regimens has become challenging. Monte Carlo simulations were conducted for conventional and prolonged infusion regimens of doripenem, imipenem and meropenem using pharmacokinetic data from adult patients with conserved renal function. Minimum inhibitory concentration data against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were incorporated from the COMPACT surveillance programme in the Asia-Pacific region of the world. The cumulative fraction of response (CFR) was determined for each regimen against each bacterial population. All simulated carbapenem regimens achieved an optimal CFR against E. coli and K. pneumoniae (94.5-100% CFR). Against P. aeruginosa, doripenem achieved 78.7-92.6% CFR, imipenem achieved 60.4-79.0% CFR and meropenem achieved 73.0-85.1% CFR. The only dosing regimen to achieve ≥ 90% CFR against P. aeruginosa was doripenem 1000 mg and 2000 mg every 8 h (4-h infusion). Carbapenem CFRs against A. baumannii were much lower (29.2-54.4% CFR). CFRs for non-fermenting isolates were ca. 10% lower for isolates collected in the Intensive Care Unit. Carbapenem resistance amongst Enterobacteriaceae remains low in the Asia-Pacific region and thus standard carbapenem dosing regimens had a high likelihood of achieving pharmacodynamic exposures. However, larger doses combined with prolonged infusion will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives that are common in these countries. The safety and efficacy of these high dosing regimens will need to be confirmed in the clinical setting.

Topics: Anti-Bacterial Agents; Asia; Australia; Carbapenems; Doripenem; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Injections, Intravenous; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Thienamycins

First identified in 1977, Sphingomonous Paucimobilis has emerged as an opportunistic human pathogen. It is primarily known to cause a range of mostly nosocomial, non-life-threatening infections that typically are easily treated by antibiotic therapy. Sources of its isolation linked to clinical disease include blood, spinal fluid and leg ulcers. It has also been reported as a rare cause of peritonitis in patients on continuous ambulatory peritoneal dialysis. We present a case of a child with peritonitis due to this organism. Clinical features, bacteriology and treatment option and response have been discussed.

Topics: Anti-Bacterial Agents; Child; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Sphingomonas; Thienamycins; Treatment Outcome

Doripenem is a new carbapenem recently introduced into Europe. The COMParative Activity of Carbapenem Testing (COMPACT) study compared the susceptibility of common Gram-negative bacilli causing serious infections in hospitalized patients with doripenem, imipenem and meropenem.. Gram-negative isolates (4498 total: 2171 Pseudomonas species; 1910 Enterobacteriaceae; and 417 other Gram-negative bacilli) were collected from 80 centres in 16 countries in Europe, the Middle East and Africa during 2008-09. The MICs of doripenem, imipenem and meropenem were determined using Etest methodology and broth microdilution. Susceptibility was interpreted according to CLSI, EUCAST and FDA breakpoints.. The MIC(90)s of doripenem, imipenem and meropenem for all isolates were 8, ≥64 and 32 mg/L, respectively. Doripenem had the lowest MIC(90) for Pseudomonas species at 16 mg/L, with imipenem and meropenem values of ≥64 mg/L. Enterobacteriaceae were highly susceptible to all three carbapenems, with MIC(90)s of doripenem, imipenem and meropenem of 0.06, 0.5 and 0.12 mg/L, respectively. Other Gram-negative isolates, predominantly Acinetobacter baumannii, were resistant to all three carbapenems (MIC(90) ≥64 mg/L). Susceptibility to doripenem was observed in 14.9% of isolates resistant to imipenem and/or meropenem.. Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

Topics: Africa; Anti-Bacterial Agents; Carbapenems; Cross Infection; Doripenem; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Middle East; Thienamycins

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Doripenem; Drug Resistance, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Random Allocation; Rectum; Stenotrophomonas maltophilia; Thienamycins

Gram-negative bacillary (GNB) ventriculitis and meningitis are rare but serious complications after neurosurgery. Prospective studies on antibiotic treatment for these infections are lacking, and retrospective reports are sparse. At our hospital in Uppsala, Sweden, meropenem has been recommended as empirical therapy since 1996, with the addition of intraventricular gentamicin in cases that do not respond satisfactorily to treatment. In this study, we retrospectively compare the efficacy of combination treatment with intraventricular gentamicin to that of systemic antibiotics alone. In addition, we report our experience of meropenem for the treatment of GNB ventriculomeningitis.. Adult consecutive patients with gram-negative bacteria isolated from cerebrospinal fluid during a 10-year period and with postneurosurgical GNB ventriculitis or meningitis were included retrospectively. Data were abstracted from the medical records.. Thirty-one patients with neurosurgical GNB ventriculitis or meningitis and follow-up for 3 months were identified. The main intravenous therapies were meropenem (n = 24), cefotaxime (n = 3), ceftazidime (n = 2), imipenem (n = 1), and trimethoprim-sulfamethoxazole (n = 1). Thirteen patients were given combination treatment with appropriate intraventricular gentamicin. These patients had a higher cure rate and a lower relapse rate than did those treated with intravenous antibiotics alone (P = .03). Relapse occurred in 0 of 13 patients treated intraventricularly and in 6 of 18 patients treated with systemic antibiotics alone. The mortality rate was 19%; 3 patients in each group died, but in no case was death considered to be attributable to meningitis.. Our results support combination treatment with intraventricular gentamicin for postneurosurgical GNB ventriculomeningitis. Meropenem seems to be an effective and safe alternative for the systemic antibiotic treatment of these neurointensive care infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cerebral Ventriculitis; Cerebrospinal Fluid; Drug Therapy, Combination; Gentamicins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infusions, Intraventricular; Meningitis, Bacterial; Meropenem; Middle Aged; Retrospective Studies; Surgical Wound Infection; Sweden; Thienamycins; Treatment Outcome; Young Adult

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

We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Carbapenems; Doripenem; Drug Resistance, Bacterial; Ertapenem; Escherichia coli; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; In Vitro Techniques; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Mutation; Phenotype; Pseudomonas aeruginosa; Thienamycins

Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 microg/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 microg/ml but increased in the presence of meningitis (approximately 0.5 microg/ml or 34 to 67% of serum levels).

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Female; Gram-Negative Bacterial Infections; Humans; Infant; Male; Treatment Outcome

The Chinese Meropenem Surveillance Study (CMSS) programme was initiated in 2003 with the aim of monitoring the antimicrobial activity of broad-spectrum agents against nosocomial Gram-negative bacilli in China. From 2003 to 2008, a total of 3892 isolates were collected from 10 teaching hospitals. The minimum inhibitory concentrations (MICs) of 11 antimicrobial agents were determined by the agar dilution method. During the study period, a marked decrease in the susceptibility of Acinetobacter spp. to meropenem and imipenem was noticed, from 94.6% to 60.7% and from 92.5% to 62.1%, respectively. However, for Pseudomonas aeruginosa the susceptibility was relatively stable, with susceptibility rates of 86.2% to 76.0% for meropenem and 74.8% to 70.5% for imipenem. Meropenem and imipenem exhibited the highest activities against enterobacterial organisms, with ranges of MIC(90) values (MIC for 90% of the organisms) from 0.064mg/L to 0.25mg/L and 0.25 to 4mg/L, respectively. Except for Acinetobacter spp., the next most active agent against the majority of isolates was amikacin, with susceptibility ranging from 78.8% to 93.3%, followed by piperacillin/tazobactam (73.7% to 98.2%), cefoperazone/sulbactam (63.9% to 99.1%), cefepime (67.0% to 95.4%) and ceftazidime (54.5% to 93.3%). The percentage of isolates positive for extended-spectrum beta-lactamases among Escherichia coli, Klebsiella spp. and Proteus mirabilis ranged from 50.9% to 66.7%, 25.4% to 42.4% and 8.9% to 24.2%, respectively. These CMSS results have demonstrated increasing resistance of Acinetobacter spp. to carbapenems, resulting from the spread of highly resistant clones. Continued surveillance studies, including CMSS, as well as potent measures for controlling the spread of resistant clones are required.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; China; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

We present the first reported case of severe intravascular haemolysis associated with the use of meropenem in a 64 year old man. The report highlights a further possible drug related cause of intravascular haemolysis. The patient, who had a background of dialysis dependent renal failure, epilepsy and learning difficulties, was admitted to the intensive care unit following laparotomy and large bowel resection. His background also included a reported childhood allergy to penicillin. Along with initial haemodynamic and ventilatory support he was treated with cefuroxime, metronidazole and gentamicin without incident. He went on to develop an abdominal collection, for which treatment included meropenem. Associated with the administration of meropenem was the development of severe intravascular haemolysis confirmed by laboratory analysis and microscopy, which resolved on cessation of meropenem therapy. We discuss the possible mechanisms involved in the development of drug induced haemolysis and suggest the most likely cause in this case.

Topics: Acute Disease; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Hemolysis; Humans; Male; Meropenem; Middle Aged; Severity of Illness Index; Thienamycins

The meropenem yearly Susceptibility Test Information Collection (MYSTIC) programme is a global, longitudinal resistance surveillance network that monitors the activity of meropenem and compares its activity with other broadspectrum antimicrobial agents. We now report the antimicrobial efficacy of meropenem compared to other broad-spectrum agents within the selective Gram-negative pathogen groups from two Croatian Hospitals investigated between 2002-2007. A total of 1510 Gram-negative pathogens were tested and the minimum-inhibitory concentrations (MICs) were determined by broth microdilution method according to CLSI.There was no resistance to either imipenem or meropenem observed for Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis in both medical centers. High resistance rates of K. pneumoniae to ceftazidime (18%), cefepime (17%) and gentamicin (39%) are raising concern. Acinetobacter baumannii turned out to be the most resistant Gram-negative bacteria with 81% resistant to ceftazidime, 73% to cefepime, 69% to gentamicin and 71% to ciprofloxacin. Almost 20% of Pseudomonas aeruginosa strains were resistant to imipenem, 13% to meropenem, 69% to gentamicin and 38% to ciprofloxacin.The prevalence of extended-spectrum beta-lactamases (ESBLs) in E. coli was 10% and in K. pneumoniae 49%. PCR and sequencing of the amplicons revealed the presence of SHV-5 in nine E. coli strains and additional tem-1 beta-lactamase five strains. Five K. pneumoniae strains were positive for bla(SHV-5 )gene. Eight ESBL positive Enterobacter spp. strains were found to produce tem and CtX-m beta-lactamases. Plasmid-mediated AmpC beta-lactamases were not found among K. pneumoniae, E. coli and Enterobacter spp. Three A. baumannii strains from Zagreb University Center were identified by multiplex PCR as OXA-58 like producers. Six A. baumannii strains from Split University Center were found to possess an ISAba1 insertion sequence upstream of bla(OXA-51 )gene. According to our results meropenem remains an appropriate antibiotic for the treatment of severe infections caused by Gram-negative bacteria. These data indicate that despite continued use of meropenem, carbapenem resistance is not increasing among species tested, except for A. Baumannii, in the two study hospitals and suggest that clinicians can still administer carbapenems as a reliable and effective choice in managing serious nosocomial infections.

Topics: Anti-Infective Agents; beta-Lactamases; Croatia; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Thienamycins

The Comparative Activity of Carbapenems Testing (COMPACT) Study was designed to determine the in vitro potency of doripenem compared with imipenem and meropenem against a large number of contemporary Gram-negative pathogens from more than 100 centres across Europe and the Asia-Pacific region and to assess the reliability of Etest methodology for doripenem minimum inhibitory concentration (MIC) determination against these pathogens. Data from eight countries within the Asia-Pacific region, which collected 1612 bacterial isolates, are presented here. Etest methodology was found to be a reliable method for MIC determination. Doripenem showed in vitro activity similar to or better than meropenem and at least four-fold better than imipenem against Enterobacteriaceae. Against Pseudomonas aeruginosa, doripenem was also the most active of the three carbapenems in vitro. However, in vitro results do not necessarily correlate with clinical outcome.

Topics: Anti-Bacterial Agents; Asia; Carbapenems; Doripenem; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Pacific Islands; Thienamycins

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

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

The carbapenems are broad-spectrum beta-lactam antibiotics with activity against most organisms encountered in the pediatric intensive care unit (PICU). In anticipation of their increased use in critically ill children, we measured the effect of sustained meropenem use on the pattern of Gram-negative bacillus colonization in patients admitted to a tertiary care PICU.. : Prospective preintervention/postintervention comparison.. Medical/surgical PICU.. Consecutive PICU admissions over 2.5 yrs.. After a 6-mo baseline period, all children with serious infections admitted to the PICU during the subsequent 2 yrs were administered meropenem. The incidence of colonization by Gram-negative bacilli resistant to one of a battery of broad-spectrum parenteral agents, and by organisms resistant specifically to meropenem, during the baseline period was compared with the period of preferred meropenem use.. During the period of preferred meropenem use, the amount of meropenem used increased >seven-fold, whereas the use of other advanced generation beta-lactams was reduced by nearly 80%. The mean prevalence of colonization by antibiotic-resistant bacilli in general was not statistically altered during the period of meropenem preference (7.3 organisms/100 patient-days, vs. 9.4 organisms/100 patient-days at baseline, p < 0.09). The prevalence of colonization by Gram-negative organisms resistant specifically to meropenem was 0.61 organisms/100 patient-days during the baseline period vs. 1.04 organisms/100 patient-days during the period of meropenem preference (p < 0.30). The incidence of nosocomial infections did not change, and the prevalence of nosocomial infections caused by meropenem-resistant organisms was always <1% of all admissions during the period of meropenem preference.. There was no statistically detectable effect on the prevalence of colonization by Gram-negative organisms resistant to one or more classes of broad-spectrum parenteral antibiotics, or to colonization by organisms resistant specifically to meropenem, when meropenem was the preferred antibiotic in a PICU.

Topics: Antibiotic Prophylaxis; Child; Child, Preschool; Colony Count, Microbial; Cross Infection; Drug Resistance, Microbial; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Incidence; Infant; Intensive Care Units, Pediatric; Male; Meropenem; Microbial Sensitivity Tests; Probability; Prospective Studies; Risk Assessment; Thienamycins; Treatment Outcome

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

Chromobacterium violaceum infection is uncommon but potentially fatal, with a clinical picture similar to melioidosis but with different antibiotic sensitivities and treatment. This infection can involve any organ, but we believe this is the first reported case of C. violaceum endocarditis.

Topics: Adult; Aortic Valve; Chromobacterium; Ciprofloxacin; Drug Therapy, Combination; Echocardiography, Transesophageal; Endocarditis, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Liver Abscess, Pyogenic; Meropenem; Thienamycins; Tomography, X-Ray Computed

Topics: Anti-Bacterial Agents; Chromobacterium; Ciprofloxacin; Drug Therapy, Combination; Endocarditis, Bacterial; Gram-Negative Bacterial Infections; Humans; Liver Abscess, Pyogenic; Meropenem; Thienamycins

Brachyspira pilosicoli BM4442, isolated from the feces of a patient with diarrhea at the Hospital Saint-Michel in Paris, was resistant to oxacillin (MIC > 256 microg/ml) but remained susceptible to cephalosporins and to the combination of amoxicillin and clavulanic acid. Cloning and sequencing of the corresponding resistance determinant revealed a coding sequence of 807 bp encoding a new class D beta-lactamase named OXA-63. The bla OXA-63 gene was chromosomally located and not part of a transposon or of an integron. OXA-63 shared 54% identity with FUS-1 (OXA-85), an oxacillinase from Fusobacterium nucleatum subsp. polymorphum, and 25 to 44% identity with other class D beta-lactamases (DBLs) and contained all the conserved structural motifs of DBLs. Escherichia coli carrying the bla OXA-63 gene exhibited resistance to benzylpenicillin and amoxicillin but remained susceptible to amoxicillin in combination with clavulanic acid. Mature OXA-63 consisted of a 31.5-kDa polypeptide and appeared to be dimeric. Kinetic analysis revealed that OXA-63 exhibited a narrow substrate profile, hydrolyzing oxacillin, benzylpenicillin, and ampicillin with catalytic efficiencies of 980, 250, and 150 mM(-1) s(-1), respectively. The enzyme did not apparently interact with oxyimino-cephalosporins, imipenem, or aztreonam. Unlike FUS-1 and other DBLs, OXA-63 was strongly inhibited by clavulanic acid (50% inhibitory concentration [IC50] of 2 microM) and tazobactam (IC50 of 0.16 microM) and exhibited low susceptibility to NaCl (IC50 of >2 M). OXA-63 is the first DBL described for the anaerobic spirochete B. pilosicoli.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Brachyspira; Cloning, Molecular; Diarrhea; Feces; Gram-Negative Bacterial Infections; Humans; Kinetics; Molecular Sequence Data; Oxacillin; Penicillin Resistance; Sequence Analysis, DNA

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

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

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

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

Metallo-beta-lactamases (MBLs) can confer resistance to most beta-lactams, including carbapenems. Their emergence in gram-negative pathogens is a matter of major concern. Italy was the first European country to report the presence of acquired MBLs in gram-negative pathogens and is one of the countries where MBL producers have been detected repeatedly. Here, we present the results of the first Italian nationwide survey of acquired MBLs in gram-negative pathogens. Of 14,812 consecutive nonreplicate clinical isolates (12,245 Enterobacteriaceae isolates and 2,567 gram-negative nonfermenters) screened for reduced carbapenem susceptibility during a 4-month period (September to December 2004), 30 isolates (28 Pseudomonas aeruginosa isolates, 1 Pseudomonas putida isolate, and 1 Enterobacter cloacae isolate) carried acquired MBL determinants. MBL producers were detected in 10 of 12 cities, with a predominance of VIM-type enzymes over IMP-type enzymes (4:1). Although having an overall low prevalence (1.3%) and significant geographical differences, MBL-producing P. aeruginosa strains appeared to be widespread in Italy, with a notable diversity of clones, enzymes, and integrons carrying MBL gene cassettes.

Topics: Base Sequence; beta-Lactam Resistance; beta-Lactamases; Data Collection; DNA Primers; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Integrons; Italy; Molecular Epidemiology; Molecular Sequence Data

Hospitalized neonates are exposed to antibiotic-resistant bacterial pathogens and develop nosocomial infections. Limited data are available regarding the neonatal pharmacokinetics of meropenem, a broad spectrum carbapenem antibiotic.. Neonates <2 months of age received a single dose of meropenem at 10 or 20 mg/kg. Meropenem serum concentrations were measured at specified times during the 24 hours postinfusion. Population pharmacokinetics (PPK) were evaluated using NONMEM. Using Monte Carlo simulation (MCS), the probability of pharmacokinetic-pharmacodynamic target attainment was evaluated by computer modeling from predictions extrapolated from PPK data, using "virtual" dosing regimens of 10, 20, and 40 mg/kg administered every 8 or 12 hours against community- and hospital-acquired pathogens.. Thirty-seven neonates were enrolled, 22 were born at <36 weeks (range, 23-41 weeks) gestational age. Meropenem clearance was greater in neonates with older chronologic ages and in those born at later gestational ages. Serum creatinine and postconceptional age (PCA) were the best overall predictors of meropenem elimination: CL (L/h/kg) = 0.041 + 0.040/SCr + 0.003 x (PCA-35). MCS demonstrated that in infants during the first 2 weeks of life, a dosage of 20 mg/kg/dose every 8 hours achieved the desired PD target in 95% of preterm neonates and 91% of term neonates against Pseudomonas aeruginosa isolated from patients managed in adult and pediatric intensive care units in the United States.. MCS based on PPK determinations demonstrated that a meropenem dose of 20 mg/kg every 8 hours should provide adequate therapy for most nosocomial Gram-negative pathogens.

Topics: Age Factors; Anti-Bacterial Agents; Computer Simulation; Creatinine; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Male; Meropenem; Metabolic Clearance Rate; Monte Carlo Method; Serum; Thienamycins; United States

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

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

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

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

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

The Meropenem Yearly Susceptibility Test Information Collection Program is a 9-year-old antimicrobial resistance surveillance network of more than 100 medical centers worldwide, including 15 sites in the United States (US) that monitors the susceptibility of Gram-negative and Gram-positive bacterial pathogens especially to carbapenems. In 2005, the antimicrobial activity of 11 broad-spectrum agents was assessed against 2910 bacterial isolates (2493 Gram-negative and 417 staphylococci) submitted from the US medical centers to a reference laboratory using Clinical and Laboratory Standards Institute susceptibility testing methods and interpretative criteria. Meropenem continued to demonstrate 1) high potency with MIC(90) values 4- to 16-fold lower than imipenem against the Enterobacteriaceae, 2) equal activity against Pseudomonas aeruginosa, 3) 2-fold less activity compared with imipenem against Acinetobacter spp., and 4) 4- to 8-fold less activity compared with imipenem against the oxacillin-susceptible staphylococci. The wide spectrum of activity for carbapenems against Enterobacteriaceae (1657 strains) was confirmed by the overall rank order by percentage susceptibility at breakpoint criteria: imipenem (98.9%) > meropenem (98.7%) > cefepime (97.6%) > piperacillin/tazobactam (92.0%) > ceftriaxone (91.2%) > aztreonam (90.6%) > gentamicin = tobramycin (90.5%) > ceftazidime (90.4%) > levofloxacin (84.9%) > ciprofloxacin (83.9%). Against Acinetobacter spp. isolates, only tobramycin (92.0% susceptible) and carbapenems (92.0-85.6%) exhibited acceptable levels of activity. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin was observed with highest rates found among indole-positive Proteae species (36.5-33.3%) and Escherichia coli (21.6-20.4%) isolates, some documented by molecular typing methods as clonally related. Ongoing surveillance of meropenem and other broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against indicated Gram-negative and-positive pathogens causing serious infections in the hospital setting, and to detect the emergence of new or novel resistance mechanisms that could compromise clinical utility (serine and metallo-carbapenemases).

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Longitudinal Studies; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Staphylococcal Infections; Staphylococcus; Thienamycins; United States

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Carbapenems; Cefepime; Cefoperazone; Cephalosporins; Ciprofloxacin; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Thienamycins; Turkey

The susceptibility of Gram-negative bacterial strains (n=620) isolated from clinical specimens of children hospitalized in a paediatric Intensive Care Unit between 2001 and 2005 was tested. Meropenem, imipenem and ciprofloxacin were most active (>90% susceptibility) against the tested isolates, with no observed reduction in activity over 5 years. A decrease in prevalence of extended-spectrum beta-lactamase and AmpC beta-lactamase producing Enterobacteriaceae from 56.3 to 34.1% was found.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Intensive Care Units, Pediatric; Meropenem; Microbial Sensitivity Tests; Poland; Thienamycins

Antibiotic restriction can be useful in maintaining bacterial susceptibility. The objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (NICU), would ameliorate broad-spectrum susceptibility of Gram-negative isolates. Nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: Group 1 (n=396) comprised patients admitted from January 2002 to December 2003, period in which cefepime was the most used broad-spectrum antibiotic. Patients in Group 2 (n=349) were admitted when piperacillin/tazobactam replaced cefepime (January to December 2004) and in Group 3 (n=250) when cefepime was reintroduced (January to September 2005). Meropenem was the alternative third-line antibiotic for all groups. Multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. Statistics involved Kruskal-Wallis, Mann-Whitney and logrank tests, Kaplan-Meier analysis. Groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. Ninety-eight Gram-negative isolates were analyzed. Patients were more likely to remain free of multiresistant isolates by Kaplan-Meier analysis in Group 2 when compared to Group 1 (p=0.017) and Group 3 (p=0.003). There was also a significant difference in meropenem resistance rates. Cefepime has a greater propensity to select multiresistant Gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cohort Studies; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Thienamycins; Time Factors

Ceftazidime and meropenem are frequently used in the empirical treatment of hospital-acquired cerebrospinal fluid (CSF) infections. Although their dispositions in CSF have been described, the ability of these agents to achieve critical pharmacodynamic targets against the array of nosocomial CSF Gram-negative bacteria encountered in practice has not been reported.. Serum and CSF pharmacokinetic data were obtained from hospital patients with external ventricular drains and who received ceftazidime or meropenem. Concentration-time profiles in serum and CSF were modelled using a three-compartment model with zero-order infusion and first-order elimination and transfer. The model parameters were identified using population pharmacokinetic analysis [Big Non-Parametric Adaptive Grid (BigNPAG)]. A Monte Carlo simulation (9999 subjects) estimated the probability of target attainment (PTA) for total drug CSF concentrations at 50% and 100% T(>MIC) for ceftazidime 2 g intravenously every 8 h and meropenem 2 g intravenously every 8 h. The Gram-negative infection isolates of the seven most prevalent Gram-negative bacilli from the Meropenem Yearly Susceptibility Test Information Collection Program were used as a measure of contemporary MIC distribution.. Post-Bayesian measures of bias and precision, observed-predicted plots and R(2) values were highly acceptable for both drugs. Although the PTA in CSF was approximately one dilution higher for ceftazidime compared with meropenem at a given MIC value, the cumulative fraction of response (CFR) in CSF against all Gram-negatives was markedly higher for meropenem when compared with ceftazidime secondary to the higher occurrence of lower MIC values for meropenem. Both agents had a low CFR against Pseudomonas aeruginosa.. The pharmacodynamics of meropenem was superior to that of ceftazidime against Gram-negative pathogens in the CSF.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftazidime; Central Nervous System Infections; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Models, Biological; Monte Carlo Method; Thienamycins

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

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

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

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

Shewanella putrefaciens is a facultatively anaerobic, non-motile, Gram-negative, non-fermentative bacterium. It is found in various environments and has been isolated worldwide. S. putrefaciens is a rare cause of brain abscesses and meningitis. This is a case report of a cerebellar abscess and meningitis caused by Shewanella putrefaciens and Klebsiella pneumoniae in a river trap fisherman.

Topics: Adult; Brain Abscess; Cerebellar Diseases; Gram-Negative Bacterial Infections; Head; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Otitis Media; Radiography; Shewanella putrefaciens; Thienamycins

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

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

Growing multiple drug resistance among gram-negative bacilli among hospitalized patients is a serious therapeutic problem, and the aim of the study was to assess the situation in our hospital.. Antimicrobial susceptibility testing with the disk method was carried out on 1,533 isolates of gram-negative bacilli from urine, pus, body fluid and blood from hospitalized patients.. Seventeen percent of isolates were susceptible only to meropenem and either to piperacillin + tazobactam, to cefoperazone + sulbactam or to both. Eleven percent of isolates were susceptible only to meropenem and 6% were resistant to all antimicrobial agents including meropenem.. Growing multiple drug resistance among gram-negative bacilli in hospital practice demands a rigid antibiotic policy and strict infection control measures.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitalization; Humans; India; Meropenem; Microbial Sensitivity Tests; Thienamycins

To study the in vitro activity of imipenem, meropenem and ertapenem against common pathogens isolated from patients in intensive care, haematology and dialysis/nephrology units at 7 Swedish university hospitals, a total of 788 isolates were collected during 2002-2003. The distribution of the isolates was as follows: Escherichia coli (n = 140), Klebsiella spp. (n = 132), Proteus spp. (n = 97), Enterobacter spp. (n = 113), Pseudomonas aeruginosa (n = 126), Acinetobacter spp. (n = 53) and Enterococcus faecalis (n = 127). The susceptibility to the 3 carbapenems was determined by E-test, and the MICs were interpreted according to SRGA criteria. All 3 carbapenems were highly active against Enterobacteriaceae. The overall susceptibility to imipenem, meropenem and ertapenem was 90%, 98% and 93%, respectively. Against Enterobacteriaceae, Enterobacter spp. excluded, ertapenem had an equal or lower MIC(90) than meropenem. Apart from being the most active carbapenem against Enterobacteriaceae, meropenem was also the most active carbapenem against P. aeruginosa, whereas imipenem was the most active drug against Acinetobacter spp. The carbapenems are still potent antibiotics. With the introduction of ertapenem, and an expected increase in the carbapenem consumption due to an increased prevalence of strains with extended-spectrum beta-lactamases, continuous surveillance of carbapenem resistance appears to be warranted, with special attention to P. aeruginosa, Enterobacter and Proteus spp.

Topics: Acinetobacter; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Carbapenems; Enterobacteriaceae; Ertapenem; Gram-Negative Bacterial Infections; Humans; Imipenem; Klebsiella; Meropenem; Microbial Sensitivity Tests; Proteus; Sweden; Thienamycins

A retrospective cohort study evaluated the effectiveness and nephrotoxicity of intravenous colistin monotherapy vs. colistin-meropenem combination therapy for patients with multidrug-resistant Gram-negative bacterial infections. Fourteen patients received intravenous colistin monotherapy and 57 received colistin-meropenem. No significant differences were found concerning clinical response of the infection (12/14 (85.7%) vs. 39/57 (68.4%), p 0.32) and development of nephrotoxicity (0/14 (0%) vs. 4/57 (7%), p 0.58). A favourable association was revealed between survival and treatment with colistin monotherapy compared to colistin-meropenem (0/14 (0%) vs. 21/57 (36.8%) deaths, p 0.007), even after adjusting for the variables for which significant differences were found.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Middle Aged; Retrospective Studies; Thienamycins; Treatment Outcome

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

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

To compare the pharmacodynamics of two beta-lactams--ceftazidime and meropenem--in healthy subjects versus patients.. Monte Carlo simulation based on published pharmacokinetic studies.. One hundred and ninety-seven participants (75 healthy volunteers and 122 patients) from published pharmacokinetic studies of ceftazidime or meropenem.. Data on total body clearance and volume of distribution for ceftazidime and meropenem in healthy subjects and patients were obtained from published studies. Monte Carlo simulations were performed based on the pharmacokinetics from each study for ceftazidime 1000 mg every 8 hours and meropenem 1000 mg every 8 hours against isolates of Escherichia coli , Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa collected from North and South America. We calculated the likelihood of obtaining bactericidal exposures (50% time above the minimum inhibitory concentration [MIC] for ceftazidime and 40% time above the MIC for meropenem) for each combination of pharmacokinetic study data and MIC distribution. Linear regression was used to compare target attainments for healthy subjects versus patients. Only three drug-pathogen combinations differed in target attainment between healthy subjects and patients: ceftazidime against P. aeruginosa in North America and meropenem against E. coli and P. aeruginosa in South America. The regression line of target attainment for patients versus healthy subjects had a slope of 1.04 (95% confidence interval [CI] 0.983-1.093) and a y intercept of -3.73 (95% CI -8.265-0.827, r2 = 0.992). The beta values for slope and intercept did not differ to a statistically significant extent between the regression line and the line of identity (p=0.264).. The pharmacodynamic target attainment calculated with healthy subject pharmacokinetic data was predictive of patient target target attainment for ceftazidime and meropenem.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Ceftazidime; Clinical Trials as Topic; Drug Resistance, Bacterial; Escherichia coli; Female; Gram-Negative Bacterial Infections; Half-Life; Humans; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; North America; Pseudomonas aeruginosa; Reference Values; South America; Thienamycins

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. In 2004 (year six), the antimicrobial activity of 12 broad-spectrum agents was assessed against 2,799 Gram-negative bacterial isolates submitted from 15 United States (USA) medical centers using Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) recommended methods. Meropenem continued to demonstrate a high potency with MIC90 values 4- to 32-fold lower than imipenem against the Enterobacteriaceae. The wide spectrum of activity for meropenem against all Gram-negative isolates was demonstrated by the overall rank order of percentage susceptibility at CLSI breakpoints: amikacin (96.5%) > meropenem (96.0%) > imipenem (95.8%) > piperacillin/tazobactam (91.5%) > tobramycin (91.4%) > cefepime (91.2%) > ceftazidime (89.0%) > gentamicin (88.0%) > aztreonam (81.5%) > levofloxacin (80.5%) > ciprofloxacin (80.2%) > ceftriaxone (69.1%). Only the aminoglycosides (84.5%) and carbapenems (76.1-83.8%) exhibited acceptable levels of susceptibility against the Acinetobacter spp. isolates as this species group became more resistant to all antimicrobial classes. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin over the six years was observed, most alarming among Escherichia coli (20.2-20.7%) and indole-positive Proteus species (34.4-42.2%) isolates, some documented as clonal. Continued surveillance of these broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against Gram-negative pathogens causing serious infections and the emergence of new or novel resistance mechanisms that could compromise carbapenem therapy.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; Longitudinal Studies; Meropenem; Microbial Sensitivity Tests; Population Surveillance; Thienamycins

Antibiotic surveillance studies lack consideration of pharmacodynamics and provide little information about optimal dosing. By using minimum inhibitory concentration (MIC) data derived from a global surveillance study and Monte Carlo simulation, the Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram (OPTAMA) Program was established to impart greater understanding of the ability to attain pharmacodynamic exposure for specific dosing regimens and their relationship with percent susceptibility. Early OPTAMA studies focused on determining the cumulative fraction of response (CFR) for various antibiotics against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa regionally in Europe and the Americas. Later reports considered the prevalence of specific bacteria causing infections to estimate the CFR for empiric therapy of pneumonia, bloodstream, complicated skin/skin structure, and intra-abdominal infections. Collectively, the approach of the OPTAMA Program provides a novel tool that complements susceptibility data to help in the selection of appropriate empirical antibiotic therapy at the national, regional, and institutional level.

Topics: Anti-Bacterial Agents; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Thienamycins

The treatment of gram-negative infection of the central nervous system (CNS) presents a clinical challenge due to antibiotic resistance and difficulties with penetration into the cerebrospinal fluid (CSF). Two patients with gram-negative CNS infections were treated successfully with high-dose, prolonged infusions of meropenem. The CSF meropenem concentrations exceeded the minimum inhibitory concentration of the pathogen for virtually the entire dosing interval in both cases. Our experience demonstrates that dosage modification to maximize pharmacodynamic targets and bactericidal activity may be practically applied to optimize antibiotic treatment for difficult-to-treat CNS infections.

Topics: Adult; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Pseudomonas aeruginosa; Serratia marcescens; Thienamycins; Time Factors

Comamonas testosteroni, a lesser-known member of the genus, has shown little apparent capacity for causing infections in humans. We here present a case of purulent meningitis due to C. testosteroni, which occurred in a patient who had recurrent cholesteatoma. Ceftriaxone treatment was not effective in this patient even though in vitro the bacteria were susceptible to the drug. The patient responded well to meropenem therapy.

Topics: Anti-Bacterial Agents; Cefotaxime; Cholesteatoma; Comamonas testosteroni; Gram-Negative Bacterial Infections; Humans; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Thienamycins

We describe a case of empyema with infected ascites caused by Stenotrophomonas maltophilia, which has rarely been reported as pathogenic. The source was determined to a disinfectant solution. The isolate was sensitive to a newer carbapenem-meropenem, and the patient was treated successfully. This case represents a novel dual presentation of a nosocomial infection by the isolate in question.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Disinfectants; Female; Gram-Negative Bacterial Infections; Humans; India; Meropenem; Stenotrophomonas maltophilia; Thienamycins

Although there are ever increasing reports of extraintestinal human infections caused by Aeromonads, in both immunocompromised and immunocompetent patients, respiratory tract infections remain uncommon. We describe a case of aspiration pneumonia in an immunocompetent patient with multiple sclerosis, caused by a community acquired, multidrug resistant strain of Aeromonas hydrophila sensitive only to meropenem. The case highlights the clinical significance of Aeromonas hydrophila as a respiratory pathogen, as well as the community origin of multidrug resistance and the utility of newer carbapenems in such cases.

Topics: Adolescent; Aeromonas hydrophila; Drug Resistance, Microbial; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Humans; Meropenem; Pneumonia, Aspiration; Thienamycins

Topics: Carbapenems; Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Humans; Imipenem; Meropenem; Methylobacterium; Microbial Sensitivity Tests; Phenotype; Thienamycins

Topics: Adult; Animals; Anti-Bacterial Agents; Bites and Stings; Capnocytophaga; Dogs; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Myocardial Infarction; Thienamycins

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

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

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

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

Topics: Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Hydrolysis; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins

Meropenem was compared in vitro with imipenem as well as with several other contemporary beta-lactams, ciprofloxacin, and gentamicin against a group of highly antibiotic resistant members of the family Enterobacteriaceae and a collection of oxidase-positive and/or glucose-nonfermentative gram-negative bacilli. In this study, meropenem was more active than imipenem against isolates of Enterobacter, Klebsiella, Morganella, Providencia, Alcaligenes, Aeromonas, and Pasteurella.

Topics: Drug Resistance, Microbial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins