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PubMed2005

Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991-2003 at a university hospital in Taiwan.

This study was conducted to evaluate the relationship between antimicrobial resistance and antimicrobial use in a university hospital in Taiwan. Disk susceptibility data of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus spp., Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia and other non-fermentative Gram-negative bacilli causing nosocomial infections were evaluated. Data on annual patient-days and annual consumption (defined daily dose (DDD) per 1000 patient-days) of extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, flumoxef, cefepime and cefpirome), beta-lactam-beta-lactamase inhibitor combinations (ticarcillin/clavulanic acid and piperacillin/tazobactam), carbapenems (imipenem and meropenem), aminoglycosides (amikacin, gentamicin and tobramycin), fluoroquinolones (ciprofloxacin (oral and injectable) and oral levofloxacin and moxifloxacin) from 1991 to 2003 were analysed. Increasing trends of incidences of several of these bacteria causing all nosocomial infections or nosocomial bloodstream infections were noted from 1991 to 2003. The annual patient-days of the hospital significantly increased, from 360210 in 1991 to 672676 in 2002 (linear regression analysis, P < 0.05), but slightly decreased in 2003 (629168) owing to the severe acute respiratory syndrome epidemic in Taiwan. The rise in cefotaxime-resistant or ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa was significantly correlated with increased consumption of extended-spectrum cephalosporins, beta-lactam-beta-lactamase inhibitor combinations, carbapenems, fluoroquinolones and aminoglycosides (for ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa only) in the hospital (Pearson's correlation coefficient, r > 0.72 (or < -0.72) and P-value < 0.05). Increased ciprofloxacin-resistant K. pneumoniae and meropenem-resistant Acinetobacter spp. was significantly associated with the increased usage of extended-spectrum cephalosporins but not with the other four classes of antibiotics. This 13-year study in a hospital demonstrated significant changes in antimicrobial use, which may have affected antimicrobial resistance in certain Gram-negative bacteria at the hospital.

Aminoglycosides↗

PubMed2001

Antimicrobial resistance trends in medical centers using carbapenems: report of 1999 and 2000 results from the MYSTIC program (USA).

Trends in susceptibility to antimicrobials were assessed from United States participants using 4488 isolates in the MYSTIC Program, 1999 (10 centers) through 2000 (15 centers). Diverse types of hospitals (general service, university, cancer, federal, pediatric, cystic fibrosis) were enrolled from 13 states. In 2000, oxacillin-susceptible staphylococci were 100% susceptible to meropenem, imipenem, and cefepime; but only 88% of strains were susceptible to ceftazidime. Among Enterobacteriaceae, > or = 96% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem, imipenem, and cefepime; but ceftazidime, ceftriaxone, and piperacillin/tazobactam had 5-20% resistance rates. Extended-spectrum beta-lactamase resistance rates in Klebsiella spp. and Escherichia coli (6-7% and 3-5%, respectively) were stable over 2 years. Acinetobacter spp. were 78-81% susceptible to carbapenems but only 63-72% susceptible to ciprofloxacin. Meropenem, tobramycin, and piperacillin/tazobactam were the most active against Pseudomonas aeruginosa, but ciprofloxacin inhibited only 74% in 2000. Overall, meropenem remained the most potent agent, especially against ceftazidime- or piperacillin/tazobactam-resistant strains.

Academic Medical Centers↗

PubMed1995

Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus.

The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin. SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci. The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively. This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism. SM-17466 also showed bactericidal activity against methicillin-resistant S. aureus. In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis. SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S. aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml). This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S. aureus. SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and -resistant S. aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin. This activity was comparable to the in vitro activity of SM-17466. The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM-17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin. SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem.

Animals↗

PubMed1997

In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem.

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.

Animals↗

PubMed1999

Biochemical characterization of novel tetrahydrofuranyl 1beta-methylcarbapenems: stability to hydrolysis by renal dehydropeptidases and bacterial beta-lactamases, binding to penicillin binding proteins, and permeability properties.

The biochemical properties of tetrahydrofuranyl (THF) carbapenems, carbapenems with THF substituents, were evaluated with respect to enzyme stability, binding to penicillin-binding proteins (PBPs), and penetration into gram-negative organisms. THF carbapenems showed increased stability to hog renal dehydropeptidases (DHPs) compared to that of imipenem or meropenem and were more stable to human DHP than imipenem (<10% hydrolysis compared to that for imipenem). THF carbapenems were stable to hydrolysis by all serine beta-lactamases tested. CL 191,121, a prototype THF carbapenem, was more stable to hydrolysis by carbapenem-hydrolyzing serine beta-lactamases such as IMI-1 and Sme-1 than imipenem, with a relative k(cat) value of <20% for imipenem. Similar to imipenem and meropenem, THF carbapenems were not stable to the metallo beta-lactamases CcrA and L1. However, CL 191,121 bound to all Staphylococcus aureus PBPs at concentrations that were less than or equal to the MICs. The THF carbapenems bound to PBPs from Escherichia coli and Pseudomonas aeruginosa, with the highest affinities being for PBPs 2 and 4, as noted with imipenem. The affinities for PBPs 1a and 1b in E. coli were reduced for the THF carbapenems compared to that for imipenem, even though the MICs of the THF carbapenems for E. coli strains were lower than those of imipenem. The penetrability of the THF carbapenems into Serratia marcescens S6, which produces the Sme-1 carbapenem-hydrolyzing beta-lactamase, was 2.4 to 7.8 times less than that of imipenem. Compounds CL 190,294 and CL 188,624 showed good penetrability, with permeability coefficient values comparable to those of the rapidly penetrating agents cephaloridine, imipenem, meropenem, and biapenem. Decreased penetration into wild-type P. aeruginosa was suggested by the high MICs of the THF carbapenems (MICs, 16 to 32 microg/ml), despite equivalent or better binding to P. aeruginosa PBPs than that of imipenem. However, the MICs of the THF carbapenems for wild-type P. aeruginosa compared to that for an OprD2 mutant generally varied no more than 2-fold, but those of imipenem and other carbapenems differed 16-fold. These data indicated that THF carbapenems do not appear to enter through protein OprD2. In conclusion, the THF carbapenems exhibited stability to hydrolysis by renal DHPs and serine beta-lactamases, exhibited strong binding to essential PBPs from E. coli and S. aureus, and penetrated gram-negative enteric bacteria at rates comparable to those for meropenem and biapenem.

Animals↗

PubMed2026

Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

UNLABELLED: Detection of GES-type carbapenemases remains challenging because of their low prevalence and frequently weak hydrolytic activity against carbapenems. Carbapenem inactivation method (CIM)-based assays are widely used as phenotypic screening tools for carbapenemase detection; however, their performance in large collections of GES producers has not been systematically evaluated. We assessed the performance of CIM, modified CIM (mCIM), and CIM-Tris in a diverse collection of GES-producing clinical isolates, including 110 Enterobacterales and 108 Pseudomonas aeruginosa, recovered from Spanish hospitals (2010-2024), and 10 Acinetobacter baumannii isolates, mostly obtained from a hospital in Egypt. Whole-genome sequencing was carried out for species confirmation and resistome analysis. Meropenem MICs were determined by broth microdilution. Overall, 92.1% of isolates were GES-carbapenemase producers (CP), whereas 7.9% expressed GES-type extended-spectrum β-lactamases (ESBLs). In Enterobacterales (predominantly carrying blaGES-6), mCIM improved sensitivity compared with CIM (63.6% vs 40.0%), although many isolates remained undetected due to low meropenem MICs (MIC50, 0.5 µg/mL). In CP-P. aeruginosa (mainly blaGES-5), CIM, mCIM, and CIM-Tris showed sensitivities of 89.1%, 94.6%, and 100%, respectively; however, CIM-Tris yielded false-positive results in 50% of non-CP isolates (mostly blaGES-1 producers). Meropenem MICs in P. aeruginosa were higher (MIC50, >32 µg/mL). In A. baumannii, CIM-Tris improved sensitivity compared with CIM (100% vs 25.0%). These findings indicate that CIM-based methods can detect GES-type carbapenemases, but performance varies according to bacterial species and GES variant, and reduced specificity may occur in isolates producing GES-type ESBLs. Complementary molecular testing may therefore be necessary to ensure accurate detection of GES-type carbapenemases in routine clinical laboratories. IMPORTANCE: GES-type carbapenemases represent an important but underrecognized diagnostic challenge due to their low global prevalence, heterogeneous hydrolytic activity, and the limited performance data available for routine phenotypic detection methods. Although CIM-based assays are widely implemented in clinical microbiology laboratories for carbapenemase screening, their performance against GES-producing organisms has not been comprehensively evaluated across different bacterial genera and GES variants. In this study, we evaluated the performance of CIM, modified CIM (mCIM), and CIM-Tris in a large multicenter collection of well-characterized GES-producing clinical isolates, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our findings demonstrate substantial variability in assay performance according to bacterial species and GES variant. Notably, mCIM improved sensitivity among Enterobacterales with low meropenem MICs, whereas CIM-Tris achieved excellent sensitivity in P. aeruginosa and A. baumannii but at the expense of reduced specificity in isolates producing GES-type ESBLs. To the best of our knowledge, this is the first study directly comparing multiple CIM-based approaches in such a large and taxonomically diverse collection of GES-producing isolates.

beta-Lactamases↗

PubMed2000

Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa.

We developed a rapid in vitro antibiotic susceptibility test to screen double- and triple-antibiotic combinations for bactericidal activity against 75 multiresistant Pseudomonas aeruginosa isolates referred from 44 cystic fibrosis (CF) patients. When used alone, the most effective intravenous antibiotic, meropenem, was bactericidal against only 44% of the isolates. High-dose tobramycin (200 microg/ml; concentrations achievable by aerosol administration) was bactericidal against 72% of isolates. Adding a second antibiotic significantly improved bactericidal activity. The most effective double-antibiotic combinations contained high-dose tobramycin plus meropenem, piperacillin/tazobactam, or ciprofloxacin, and were bactericidal against 88 to 94% of the isolates. Excluding high-dose tobramycin, the most effective intravenous double-antibiotic combinations contained meropenem plus ciprofloxacin, tobramycin (4 microg/ml), or cefipime, and were bactericidal against 85%, 71%, and 70% of isolates, respectively. Adding a third antibiotic did not significantly improve inhibition in vitro. We conclude that double-antibiotic combinations containing meropenem or high-dose tobramycin show the best bactericidal activity in vitro against multiresistant strains of P. aeruginosa. Addition of a third antibiotic to these double-antibiotic combinations may be unnecessary.

Aminoglycosides↗

PubMedDate not supplied

Comparative in vitro activity of temocillin and other antimicrobial agents against Enterobacteriaceae isolated from patients admitted to five Belgian hospitals.

Temocillin, a methoxy-derivative of the broad-spectrum penicillin, ticarcillin, has been introduced into clinical practice in Belgium in 1988. Since then, not many surveys of its in vitro activity have been published. This study addresses this issue in a prospective collection of 300 consecutive Gram-negative isolates originating from in-patients in five general hospitals throughout Belgium. In addition to temocillin, seven common antibiotics were tested: amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime, aztreonam, meropenem, ciprofloxacin and amikacin. Meropenem appeared to exhibit the best activity overall, whereas amoxicillin-clavulanate scored the worst. Cumulative MIC plot for two subsets of organisms are given: temocillin, meropenem and cefotaxime are the most active on E. coli and Klebsiella spp., while a significant percentage is resistant to ciprofloxacin and amoxicillin-clavulanate. In the group of inducible Enterobacteriaceae, temocillin, meropenem and amikacin are the most active drugs, while the activity of amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime and ciprofloxacin is largely decreased. Taking this well preserved in vitro activity of temocillin into account, and looking at its convenient pharmacokinetics and low cost of acquisition, this drug may prove a useful alternative in the treatment of severe nosocomial infections.

Anti-Bacterial Agents↗

PubMed2005

Ertapenem: review of a new carbapenem.

The carbapenems are beta-lactam-type antibiotics with an exceptionally broad spectrum of activity. Ertapenem is a new carbapenem developed to address the pharmacokinetic shortcomings (short half-life) of imipenem and meropenem. Ertapenem shares similar structural features with meropenem, including its stability to dehydropeptidase-1, allowing it to be administered without a dehydropeptidase-1 inhibitor. Ertapenem, like imipenem and meropenem, demonstrates broad-spectrum antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes and is resistant to nearly all beta-lactamases, including extended-spectrum beta-lactamases and AmpCs. However, it differs from both imipenem and meropenem in demonstrating limited activity against Enterococcusspp., Pseudomonasaeruginosa and other nonfermentative Gram-negative bacteria commonly associated with nosocomial infections. The extensive protein binding of ertapenem extends the half-life and allows for once-daily dosing. Prospective, multicenter, randomized, double-blind, comparative clinical studies demonstrate similar clinical efficacy of ertapenem compared with other agents. Clinical trials of complicated intra-abdominal infection, acute pelvic infection, complicated skin and soft-structure infection, community-acquired pneumonia and complicated urinary tract infections demonstrated that ertapenem has equivalent efficacy and safety compared with ceftriaxone and piperacillin/tazobactam. Ertapenem is a promising new carbapenem with excellent efficacy and safety for the treatment of a variety of community-acquired infections. It also appears to be of great value as an outpatient parenteral antimicrobial therapy.

Animals↗

PubMed2001

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

Anti-Bacterial Agents↗

PubMed2003

Utilization of restricted antibiotics in a university hospital in Thailand.

Antibiotic resistance, a major negative consequence of antibiotic overuse, is an important problem worldwide. Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information. The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital. Antimicrobial agents, likely to be abused namely ceftazidime, cefepime, cefoperazone/sulbactam, imipenem/cilastatin, meropenem, ciprofloxacin, netilmicin, vancomycin, azithromycin and clarithromycin, were selected for evaluation. A simple AOF with educational information was used as a mean to follow up the treatment. The investigator collected data from the filled AOF and the patient's charts of the Department of Internal Medicine from June to November 2000; all relevant data were assessed. The appropriateness of antibiotic use, assessed according to the criteria specified in the AOF, showed that 74% of these antibiotics were prescribed appropriately; this may prove the effectiveness of the system used in the present study. However, 348 of the 430 prescriptions (80.9%) were prescribed empirically at the initial stage for treatment of nosocomial infections in patients with serious conditions like pneumonia, sepsis and febrile neutropenia. Drugs that were frequently used empirically were ceftazidime (37.9%), imipenem/cilastatin or meropenem (19.3%), and cefoperazone/sulbactam (12.1%) respectively. Ceftazidime and imipenem/cilastatin or meropenem were also frequently used inappropriately among 111 prescriptions that were classified as an inappropriate prescribing. The most common misuses were prescriptions of the drug that did not follow the specified indications (70 prescriptions), no dosage adjustment in patients with renal impairment (39 prescriptions), improper dose (12 prescriptions) and improper dosing interval (9 prescriptions). The results suggested overuse of certain antibiotics remain to be an unsolved problem. Better monitoring and strict controlled use of the problematic antibiotics, ie ceftazidime, imipenem/cilastatin or meropenem and vancomycin are essential to promote rational drug use as well as to reduce the frequency of drug resistance.

Anti-Bacterial Agents↗

PubMed2006

[The roles of active efflux system overexpression and outer membrane protein OprD deficiency or loss in carbapenem resistance of Pseudomonas aeruginosa].

OBJECTIVE: To investigate the mechanisms of carbapenem resistance in Pseudomonas aeruginosa (PA). METHODS: Forty-nine strains of PA were isolated from surgical intensive care unit during a period of 3 years. The levels of outer membrane protein OprD and OprN were measured by Western blotting. RT-PCR was used to measure the transcription levels of mexA gene. The metallo-beta-lactamase genes IMP and VIM and the negative regulator gene mexR for mexAB-OprM operon were amplified. The DNA fragments were sequenced by automated ABI PRISM 3700 sequencer. RESULTS: 42 of the 49 strains were resistant to carbapenem. 23 of the 42 strains showed loss of OprD and were all resistant to imipenem, but only one strain was resistant to meropenem. 18 of the 42 strains had a decreased OprD expression, 17 of which were resistant to Imipenem, and 3 were resistant to meropenem as well. 7 strains expressed OprD, all of which were sensitive to carbapenem. 27 strains overexpressed the mexAB-OprM. The resistant rate to imipenem of the mexAB-OprM overexpression group was 86.4%, not significantly different from that of the mexAB-OprM low expression group (81.5%, chi(2) = 0.005, P = 0.943). But the resistant rate to meropenem of the mexAB-OprM overexpression group was 44.4%, statistically higher than that of mexAB-OprM low expression group (13.6%, chi(2) = 5.417, P = 0.020). Nucleotide sequences and deduced amino acid sequences analysis revealed that eight strains overexpressed mexAB-OprM carried mutations in mexR gene, 7 of which had amino acid substitutions in MexR protein, and one of which had terminal code at the position of amino acid 32. 14 strains were found expressing OprN. Neither IMP gene nor VIM gene was found in the isolates. CONCLUSION: In the clinical strains from SICU, the imipenem resistance is mainly mediated by OprD deficiency or loss. Overexpression of MexAB-OprM is the primary mechanism of meropenem resistance, which is upregulated by mutations in mexR gene. Metallo-beta-lactamases IMP and VIM are rarely seen.

Bacterial Outer Membrane Proteins↗

PubMed1998

Postantibiotic effect of some antibiotics on the metabolism of Pseudomonas aeruginosa.

The influence of the postantibiotic effects (PAEs) of ciprofloxacin, pefloxacin, imipenem, meropenem and amikacin in the suprainhibitory concentrations (2 x and 4 x MIC) on the metabolic processes of P. aeruginosa was studied. The synthesis of macromolecules was expressed by influencing of the incorporation rate of [14C] adenine and [14C] leucine. Remarkable affecting of both biosynthetic processes evoked the suprainhibitory concentration 4 x MIC of meropenem by inhibition of the nucleic acids synthesis to 76.1% and proteins synthesis to 61.1% against the control. The suprainhibitory concentration 4 x MIC of both pefloxacin and ciprofloxacin affected the highest suppression of the endogenous respiration to 16.5% and to 20.3%, respectively. The respiration was influenced the least after the effect of meropenem in the both suprainhibitory concentrations tested. According to our knowledge, this is first report about the evaluation of the endogenous respiration after PAE. In this study we demonstrated the inhibitory effects of 4 x MIC concentration of antibiotics studied on the metabolic processes of P. aeruginosa. The results suggest a multiple mechanism for the PAE.

Adenine↗

PubMed2006

Prevalence and mechanisms of decreased susceptibility to carbapenems in Klebsiella pneumoniae isolates.

In this study, we examined the prevalence of and mechanisms of decreased susceptibility to either imipenem or meropenem in Klebsiella pneumoniae isolates. A total of 230 clinical isolates of K. pneumoniae were collected from 13 clinical laboratories from a nationwide distribution. The MICs of imipenem and meropenem were determined by the agar dilution method. To characterize the isolates with decreased susceptibility to carbapenems (MICs of >2 microg/mL), we performed polymerase chain reaction amplification of a variety of beta-lactamase genes, isoelectric focusing, and outer membrane profile analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. Three isolates (BD6, BD8, and KN16) exhibited decreased susceptibility to carbapenems with imipenem MICs of 1, 4, and 8 microg/mL and meropenem MICs of 4, 8, and 4, respectively. Isolate BD6 produced bla(TEM-1), bla(SHV-12), and bla(OXA-17); isolate BD8 produced bla(GES-3), bla(SHV-12), and bla(OXA-17); and isolate KN16 produced bla(TEM-11), bla(SHV-12), and bla(DHA-1). In all the 3 isolates, OmpK35 porin was not expressed, and in 1 isolate (KN16), OmpK36 was not expressed either. The prevalence of decreased susceptibility to carbapenems was low (1.3%), and none of them showed overt resistance to carbapenems. Decreased susceptibility to carbapenems can occur in K. pneumoniae when bla(GES-3), bla(TEM-11), bla(SHV-12), bla(OXA-17), and/or bla(DHA-1) are produced in combination with porin loss. In addition, to our knowledge, this is the 1st report of bla(OXA-17) in Enterobacteriaceae.

Amino Acid Sequence↗

PubMed2004

Metallo-beta-lactamase expressing multi-resistant Acinetobacter baumannii transmitted in the operation area.

Outbreaks of Acinetobacter baumannii demonstrating multiple antibiotic resistance, including meropenem resistance, have been described as severe therapeutic problems. Here we describe a monoclonal outbreak of infection and colonization with multidrug-resistant A. baumannii over a two-month period. Resistance to meropenem was mediated by expression of a metallo-beta-lactamase enzyme. Four of 14 patients showed clinical signs of infection and two died. Contamination of the environment, water, or instruments were excluded as causes of the outbreak. All patients, except one, underwent surgery in a specific operation theatre where surgery of contamination class IV (infected, dirty) was performed. Although individual surgeon error was eliminated, analyses of the patients' histories suggested that bacterial transmission had occurred during surgery. Five patients showed signs of A. baumannii infection and two of these patients suffered from large abdominal wounds infected with a high density of A. baumannii requiring repeated revisions. Presumably, these revisions favoured the transmission of A. baumannii, which is remarkably resistant to various environmental stresses including soaps, disinfectants and dry conditions. No case of meropenem-resistant A. baumannii had been observed in the hospital before the outbreak. Interestingly, the resistant bacteria appear to have been imported by a patient returning from West Africa. This indicates that, similar to MRSA, multiresistant A. baumannii may be introduced by patients from foreign hospitals. The outbreak was stopped in the following months by reinforcing standard procedures and by taking all necessary precautions such as patient isolation, and finally only one new case was detected.

Acinetobacter Infections↗

PubMed1998

Selecting therapy for serious infections in children: maximizing safety and efficacy.

Serious infections in children represent unique challenges for the treating physician. For the pediatric patient, considerations of drug toxicity are especially critical to avoid potential long-term complications of therapy. There are several advantages associated with using single, broad-spectrum, empiric antibiotic therapy, including reduced potential for drug-mediated toxicity or drug interactions and facilitation of home therapy. Of the antibiotics available for monotherapy, the carbapenems have the broadest spectrum of activity. However, a major obstacle toward the use of the carbapenems in pediatrics has been the risk of seizures occurring during therapy with imipenem/cilastatin. In clinical studies of meningitis and other infections in children, no drug-related seizures were reported when treated with the carbapenem meropenem. Meropenem monotherapy has been shown to be similar to ceftriaxone- and cefotaxime-based single or multiple antibiotic regimens, in terms of clinical and microbiologic efficacy and tolerability. Thus, meropenem represents a favorable treatment choice for the seriously ill child, either as empiric monotherapy or as definitive therapy of polymicrobial or nosocomial infections.

Child↗

PubMed2003

In vitro susceptibility, tolerance and MLS resistance phenotypes of Group C and Group G streptococci isolated in Turkey between 1995 and 2002.

A total of 105 clinical strains of Group C and Group G streptococci were examined for their susceptibility to penicillin, cefotaxime, erythromycin, meropenem and vancomycin using a broth microdilution method. Minimum bactericidal concentrations of the antimicrobial agents and phenotypes of strains resistant to erythromycin were also evaluated. No resistance to penicillin, cefotaxime, meropenem and vancomycin was found in years 1995-2002, but there was 6.7% resistance to erythromycin. No tolerance was seen for penicillin and vancomycin, but there were strains tolerant to cefotaxime, erythromycin and meropenem. The resistance phenotypes of erythromycin-resistant isolates were determined by the double disc test with erythromycin and clindamycin which showed inducible MLS (57.1%) and M phenotype (42.8%) resistance. This in vitro finding shows that classical antimicrobial agents used for the treatment of GCS and GGS have good activity against clinically significant isolates, but the presence of macrolide resistance and tolerant isolates suggests that careful surveillance of the streptococcal isolates should be carried out.

Anti-Bacterial Agents↗

PubMed1997

Differential antibiotic-induced endotoxin release and interleukin-6 production by human umbilical vein endothelial cells (HUVECs): amplification of the response by coincubation of HUVECs and blood cells.

The activation of human vascular endothelial cells (ECs), as assessed by interleukin (IL)-6 production, was investigated in response to antibiotic-induced lipopolysaccharide release from Escherichia coli. Antibiotic-induced killing of E. coli resulted in the activation of human umbilical vein endothelial cells (HUVECs). Imipenem and meropenem induced faster killing of E. coli than ceftriaxone at 2 and 6 h. However, imipenem-induced bacterial killing resulted in significantly less IL-6 release compared with meropenem or ceftriaxone. When HUVECs were coincubated with diluted (4%) human blood, bacterial killing-induced total IL-6 release was significantly higher than that produced by HUVECs or by 4% blood cells alone. These observations suggest that antibiotic-induced lipopolysaccharide release activates both endothelial cells and monocytes and that the effect is significantly amplified when endothelial cells and monocytes are coincubated. Imipenem, which has a greater affinity for penicillin-binding protein (PBP) 2, induced less IL-6 release from blood and endothelial cells than did PBP 3-specific ceftriaxone and meropenem.

Anti-Bacterial Agents↗