SEARCH · PubMed Health

Results for “Meropenem”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed1998

Differential release of lipoteichoic and teichoic acids from Streptococcus pneumoniae as a result of exposure to beta-lactam antibiotics, rifamycins, trovafloxacin, and quinupristin-dalfopristin.

The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem, rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a concentration of 10 microg/ml, a rapid and intense release of LTA and TA occurred during exposure to ceftriaxone (3,248+/-1,688 ng/ml at 3 h and 3,827+/-2,133 ng/ml at 12 h) and meropenem (2,464+/-1,081 ng/ml at 3 h and 2,900+/-1,364 ng/ml at 12 h). Three hours after exposure to rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin, mean LTA and TA concentrations of less than 460 ng/ml were observed (for each group, P < 0.01 versus the concentrations after exposure to ceftriaxone). After 12 h of treatment, the LTA and TA concentrations were 463+/-126 ng/ml after exposure to rifampin, 669+/-303 ng/ml after exposure to rifabutin, and 1,236+/-772 ng/ml after exposure to quinupristin-dalfopristin (for each group, P < 0.05 versus the concentrations after exposure to ceftriaxone) and 1,745+/-1,185 ng/ml after exposure to trovafloxacin (P = 0.12 versus the concentration after exposure to ceftriaxone). At 10 microg/ml, bactericidal antibacterial agents that do not primarily affect cell wall synthesis reduced the amount of LTA and TA released during their cidal action against S. pneumoniae in comparison with the amount released after exposure to beta-lactams. Larger quantities of LTA and TA were released after treatment with low concentrations (1x the MIC and 1x the minimum bactericidal concentration) than after no treatment for all antibacterial agents except the rifamycins. This does not support the concept of using a low first antibiotic dose to prevent the release of proinflammatory cell wall components.

Anti-Bacterial Agents↗

PubMed1998

Outer membrane profiles of clonally related Klebsiella pneumoniae isolates from clinical samples and activities of cephalosporins and carbapenems.

Fifteen isolates of Klebsiella pneumoniae producing extended-spectrum beta-lactamases (ESBLs) isolated during a nosocomial outbreak were studied. The strains belonged to the same clonal type, as shown by pulsed-field gel electrophoretic analysis of chromosomal DNA. All the isolates were resistant to extended-spectrum cephalosporins, aztreonam, gentamicin, and fluoroquinolones and were susceptible to carbapenems, tobramycin, netilmicin, and amikacin. None of the isolates expressed the OmpK36 porin. Eight isolates, for which the MICs of cefoxitin were > or = 64 micrograms/ml, showed a diminished level or no expression of a 35-kDa porin. The MICs of meropenem, cefotaxime, and cefpirome were three to eight times higher for porin-deficient isolates than for isolates expressing the 35-kDa porin, but the MICs of imipenem increased two times for porin-deficient isolates compared to those for isolates expressing the porin. This MIC increase reverted to a level similar to that for the parental strain when porin-deficient isolates were transformed with the gene coding for the K. pneumoniae porin OmpK36. It is concluded that the high level of resistance to cefoxitin and the increase in the MICs of meropenem, cefotaxime, and cefpirome for the ESBL-producing K. pneumoniae isolates studied are associated with porin deficiency.

Bacterial Typing Techniques↗

PubMed1999

Efficacy of gatifloxacin in experimental Escherichia coli meningitis.

The effectiveness of gatifloxacin therapy (15 mg/kg every 5 h [q5h]) was compared with that of meropenem (75 mg/kg q5h) and cefotaxime (75 mg/kg q5h) therapy in experimental meningitis caused by a beta-lactamase-producing strain of Escherichia coli. Gatifloxacin therapy was more rapidly bactericidal than cefotaxime but similar to meropenem therapy (bacterial killing rates at 5 h, 0.83 +/- 0.26, 0. 46 +/- 0.3, and 0.73 +/- 0.17 CFU/ml/h, respectively; P = 0.03 for gatifloxacin versus cefotaxime). At 10 h, seven of eight animals treated with gatifloxacin had <10 CFU/ml in their cerebrospinal fluid, compared with one of seven treated with cefotaxime therapy (P = 0.01). Gatifloxacin was at least as effective as currently available antibiotics in this model of E. coli meningitis.

Animals↗

PubMed2000

In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated in an intensive care unit outbreak.

Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 microg/ml), azithromycin (4 microg/ml), netilmicin (1 microg/ml), rifampin (8 microg/ml), polymyxin (0.8 U/ml), meropenem (4 microg/ml), trovafloxacin (4 microg/ml), and sulbactam (8 microg/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.

Acinetobacter↗

PubMed2000

OXA-24, a novel class D beta-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain.

Acinetobacter baumannii RYC 52763/97, a clinical isolate involved in a prolonged nosocomial outbreak at our hospital, was resistant to all beta-lactams tested, including imipenem and meropenem, which had MICs of 128 and 256 microg/ml, respectively. This strain synthesized three beta-lactamases: a plasmid-mediated TEM-1 beta-lactamase (pI 5.4), an AmpC-type chromosomal cephalosporinase (pI 9.4), and a novel, presumptively chromosomally mediated OXA-related enzyme (pI 9.0) named OXA-24. After cloning and sequencing, the deduced amino acid sequence of the OXA-24 beta-lactamase showed 40% homology with the OXA-10 (PSE-2) and OXA-7 beta-lactamases, 39% homology with the OXA-11 and OXA-5 enzymes, and 33% homology with the LCR-1 beta-lactamase. The amino acid sequence of the OXA-24 beta-lactamase contained the STFK motif found in serine beta-lactamases, but the typical class D triad KTG was replaced by KSG and the motif YGN was replaced by FGN. The OXA-24 beta-lactamase hydrolyzed benzylpenicillin and cephaloridine but lacked activity against oxacillin, cloxacillin, and methicillin. The enzymatic activity was inhibited by chloride ions and by tazobactam (50% inhibitory concentration [IC(50)], 0.5 microM), sulbactam (IC(50), 40 microM), and clavulanic acid (IC(50), 50 microM). Carbapenem MICs for an Escherichia coli transformant (pBMB-1) expressing the cloned OXA-24 enzyme had a fourfold increase. Relative V(max)/K(m) values of 13 and 6 were obtained with imipenem and meropenem, respectively, and a positive microbiological assay result with imipenem was obtained with a purified enzymatic extract of this transformant strain. Therefore, we consider this new beta-lactamase to be involved in the carbapenem resistance of A. baumannii RYC 52763/97.

Acinetobacter↗

PubMed2001

IMP-4, a novel metallo-beta-lactamase from nosocomial Acinetobacter spp. collected in Hong Kong between 1994 and 1998.

Between 1994 and 1998, 97 imipenem-resistant Acinetobacter isolates were identified at the Prince of Wales Hospital, Hong Kong, China. A bla(IMP) PCR product was obtained from 23 of 35 viable cultures; 12 isolates belonged to genomic DNA group 3, 8 belonged to group 2 (Acinetobacter baumannii), 2 belonged to group 13TU, and 1 belonged to group 1. The bla(IMP) homologues were sequenced from two isolates from genomic DNA group 2 and one isolate each from groups 3 and 13TU. The four sequences included an identical 738-bp open reading frame, predicted to encode a polypeptide of 246 amino acids, with 95.6% homology to IMP-1 and 89.3% homology to IMP-2. The new enzyme, designated IMP-4, was partially purified. It had a pI of 8.0 and was strongly active against imipenem and meropenem, with V(max) values 53 and 8% of that for penicillin G, respectively. Strong activity was also seen against oxyimino-aminothiazolyl cephalosporins but not against aztreonam. Hydrolytic activity was inhibited by EDTA but not by clavulanate or tazobactam. Carbapenem MICs for most bla(IMP)-positive isolates were 4 to 32 microg/ml, but one isolate with the intact gene was susceptible, with imipenem and meropenem MICs of 0.25 and 0.5 microg/ml, respectively. The latter isolate did not produce the band with a pI of 8.0, and gene expression was inferred to have been lost. None of the isolates studied in detail contained extrachromosomal DNA, and carbapenem resistance was not transmissible to Escherichia coli. Nevertheless, the presence of bla(IMP-4) in different genomic DNA groups implies horizontal transfer, and sequences resembling a GTTRRRY integrase-dependent recombination motif were identified in the flanking regions of bla(IMP-4).

Acinetobacter↗

PubMed2002

Comparative stability studies of antipseudomonal beta-lactams for potential administration through portable elastomeric pumps (home therapy for cystic fibrosis patients) and motor-operated syringes (intensive care units).

The stability of antipseudomonal beta-lactams in concentrated solutions was examined in view of their potential administration by continuous infusion with external pumps (for intensive care patients) or with portable pumps carried under clothing (for cystic fibrosis patients). Aztreonam (100 g/liter), piperacillin (128 g/liter, with tazobactam), and azlocillin (128 g/liter) remained 90% stable for up to more than 24 h at 37 degrees C (mezlocillin [128 g/liter] was stable at 25 degrees C but not at 37 degrees C). Ceftazidime (120 g/liter), cefpirome (32 g/liter), and cefepime (50 g/liter) remained 90% stable for up to 24, 23.7, and 20.5 h at 25 degrees C but only for 8, 7.25, and 13 h at 37 degrees C, respectively. The control of temperature therefore appears to be critical for all three cephalosporins that cannot be recommended for use in portable pumps carried under clothes for prolonged periods for reasons of stability. Cefpirome and cefepime solutions developed an important color change (from light yellow to dark red) upon exposure when stored at 30 degrees C or higher. Degradation of ceftazidime was accompanied by the liberation of pyridine which, at 37 degrees C, was in excess of what is allowed by the U.S. Pharmacopeia, i.e., 1.1 mg/liter, after 8 and 12 h for drug concentrations of 12 and 8.3%, respectively. Imipenem and meropenem are too unstable (10% degradation at 25 degrees C after 3.5 and 5.15 h, respectively) to be recommended for use by continuous infusion. Faropenem, examined in comparison with imipenem and meropenem, proved as stable as aztreonam or piperacillin.

Anti-Bacterial Agents↗

PubMed2003

Bacteremia due to Bacteroides fragilis group: distribution of species, beta-lactamase production, and antimicrobial susceptibility patterns.

A retrospective analysis of susceptibility data on 542 blood isolates of the Bacteroides fragilis group tested from 1987 to 1999 by the same NCCLS-recommended broth microdilution method throughout is presented. Metronidazole, beta-lactam-beta-lactamase inhibitor combinations, carbapenems, and trovafloxacin were the most active agents (susceptibility of >or=93%). Among the cephalosporin-cephamycins, the order of activity was cefoxitin > ceftizoxime > cefotetan = cefotaxime = cefmetazole > ceftriaxone. All isolates were resistant to penicillin G, and 22% were resistant to clindamycin. The susceptibility rates to piperacillin-tazobactam, imipenem, and meropenem were affected least among isolates resistant to cefoxitin or clindamycin. Except for piperacillin-tazobactam, imipenem, and meropenem, the B. fragilis species was more susceptible than were the non-B. fragilis species. These data underscore the importance of susceptibility testing of the B. fragilis group and can serve as a guide in the choice of empirical antimicrobial therapy.

Anti-Bacterial Agents↗

PubMed2004

Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp. with characterized beta-lactamases.

Doripenem (S-4661), a new parenteral carbapenem, was tested against over 250 clinical isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp., selected or derived for their beta-lactamase expression characteristics. Imipenem, meropenem, and ertapenem were tested as comparators, along with cephalosporins and piperacillin-tazobactam, by using National Committee for Clinical Laboratory Standards agar dilution methodology. Doripenem MICs were from 0.03 to 0.25 microg/ml for Klebsiella isolates, irrespective of the presence of extended-spectrum beta-lactamases (ESBLs) or plasmid-mediated AmpC or hyperproduced K1 beta-lactamase. Similarly, MICs of doripenem for both AmpC-inducible and -derepressed Enterobacter isolates were 0.06 to 0.5 microg/ml. ESBL production did not raise the MICs of doripenem for Escherichia coli transconjugants, and studies with known expression mutants confirmed that neither inducible nor depressed AmpC beta-lactamase expression was protective in Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, or Morganella morganii. In all of these respects, doripenem resembled meropenem and imipenem, whereas the MICs of ertapenem were raised (but still < or =1 microg/ml) for many ESBL-producing klebsiellas and AmpC-derepressed E. cloacae and C. freundii strains. Resistance to all carbapenems, including doripenem (MICs of mostly 16 to 64 microg/ml, compared with 0.25 to 1 microg/ml for typical strains), was seen in Acinetobacter isolates with metallo-beta-lactamases or OXA-carbapenemases. Isolates of Klebsiella and Serratia spp. with IMP, KPC, and SME beta-lactamases also were resistant to doripenem (MICs, 8 to >64 microg/ml) and to other carbapenems, although the continued apparent susceptibility (MICs, < or =0.5 microg/ml) of E. coli derivatives with cloned IMP-1 and NMC-A beta-lactamases suggested that carbapenem resistance might require other factors besides the enzymes.

Acinetobacter↗

PubMed2004

Optimizing pharmacodynamic target attainment using the MYSTIC antibiogram: data collected in North America in 2002.

The OPTAMA Program is intended to examine typical antimicrobial regimens used in the treatment of common nosocomial pathogens and the likelihood of these regimens attaining appropriate pharmacodynamic exposure in different parts of the world. A 5,000-subject Monte Carlo simulation was used to estimate pharmacodynamic target attainment for meropenem, imipenem, ceftazidime, cefepime, piperacillin-tazobactam, and ciprofloxacin against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Standard dosing regimens from North America were used. Pharmacokinetic parameter variability was derived from existing healthy volunteer data, and MIC data came from the 2002 MYSTIC Program. Ciprofloxacin displayed the lowest target attainment against all bacterial species (41 to 46% for A. baumannii, 53 to 59% for P. aeruginosa, and 80 to 85% for the Enterobacteriaceae). Increasing the dose to 400 mg every 8 h did not significantly increase target attainment against nonfermenters. Piperacillin-tazobactam target attainments were similar to that of ceftazidime against all pathogens. Higher doses of both compounds were needed to achieve better target attainments against P. aeruginosa. Overall, meropenem, imipenem, and cefepime attained the highest probabilities of attainment against the Enterobacteriaceae (99 to 100%). The carbapenems appear to be the most useful agents against A. baumannii (88 to 92%), and these agents, along with higher doses of any of the beta-lactams, would be the most appropriate choices for empirical therapy for P. aeruginosa infection. Given the lack of agreement between percent susceptibility and probability of target attainment for certain antimicrobial regimens, a methodology employing stochastic pharmacodynamic analyses may be a more useful tool for differentiating the most-optimal compounds and dosing regimens in the clinical setting of initial empirical therapy.

Algorithms↗

PubMed2004

Doripenem versus Pseudomonas aeruginosa in vitro: activity against characterized isolates, mutants, and transconjugants and resistance selection potential.

Doripenem is a broad-spectrum parenteral carbapenem under clinical development in Japan and North America. Its activities against (i) Pseudomonas aeruginosa isolates with graded levels of intrinsic efflux-type resistance, (ii) mutants with various combinations of AmpC and OprD expression, (iii) PU21 transconjugants with class A and D beta-lactamases, and (iv) P. aeruginosa isolates with metallo-beta-lactamases were tested by the agar dilution method of the National Committee for Clinical Laboratory Standards. Selection of resistant P. aeruginosa mutants was investigated in single- and multistep procedures. Doripenem MICs for isolates without acquired resistance mostly were 0.12 to 0.5 microg/ml, whereas meropenem MICs were 0.25 to 0.5 microg/ml and imipenem MICs were 1 to 2 microg/ml. The MICs of doripenem, meropenem, ertapenem, and noncarbapenems for isolates with increased efflux-type resistance were elevated, whereas the MICs of imipenem were less affected. The MICs of doripenem were increased by the loss of OprD but not by derepression of AmpC; nevertheless, and as with other carbapenems, the impermeability-determined resistance caused by the loss of OprD corequired AmpC activity and was lost in OprD- mutants also lacking AmpC. The TEM, PSE, PER, and OXA enzymes did not significantly protect P. aeruginosa PU21 against the activity of doripenem, whereas MICs of > or =16 microg/ml were seen for clinical isolates with VIM and IMP metallo-beta-lactamases. Resistant mutants seemed to be harder to select with doripenem than with other carbapenems (or noncarbapenems), and the fold increases in the MICs were smaller for the resistant mutants. Single-step doripenem mutants were mostly resistant only to carbapenems and had lost OprD; multistep mutants had broader resistance, implying the presence of additional mechanisms, putatively including up-regulated efflux. Most mutants selected with aminoglycosides and quinolones had little or no cross-resistance to carbapenems, including doripenem.

Bacterial Outer Membrane Proteins↗

PubMed2005

In vitro and in vivo antibacterial activities of CS-023 (RO4908463), a novel parenteral carbapenem.

CS-023 (RO4908463, formerly R-115685) is a novel 1beta-methylcarbapenem with 5-substituted pyrrolidin-3-ylthio groups, including an amidine moiety at the C-2 position. Its antibacterial activity was tested against 1,214 clinical isolates of 32 species and was compared with those of imipenem, meropenem, ceftazidime, ceftriaxone, ampicillin, amikacin, and levofloxacin. CS-023 exhibited a broad spectrum of activity against gram-positive and -negative aerobes and anaerobes, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae (PRSP), beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, and Pseudomonas aeruginosa. CS-023 showed the most potent activity among the compounds tested against P. aeruginosa and MRSA, with MICs at which 90% of isolates tested were inhibited of 4 microg/ml and 8 microg/ml, respectively. CS-023 was stable against hydrolysis by the beta-lactamases from Enterobacter cloacae and Proteus vulgaris. CS-023 also showed potent activity against extended-spectrum beta-lactamase-producing Escherichia coli. The in vivo efficacy of CS-023 was evaluated with a murine systemic infection model induced by 13 strains of gram-positive and -negative pathogens and a lung infection model induced by 2 strains of PRSP (serotypes 6 and 19). Against the systemic infections with PRSP, MRSA, and P. aeruginosa and the lung infections, the efficacy of CS-023 was comparable to those of imipenem/cilastatin and vancomycin (tested against lung infections only) and superior to those of meropenem, ceftriaxone, and ceftazidime (tested against P. aeruginosa infections only). These results suggest that CS-023 has potential for the treatment of nosocomial bacterial infections by gram-positive and -negative pathogens, including MRSA and P. aeruginosa.

Animals↗

PubMed2006

Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates.

Carbapenems are important agents for the therapy of infections due to multidrug-resistant Pseudomonas aeruginosa; the development of carbapenem resistance hampers effective therapeutic options. To assess the mechanisms leading to resistance, 33 clinical isolates with differing degrees of carbapenem susceptibility were analyzed for the expression of the chromosomal beta-lactamase (ampC), the porin that is important for the entry of carbapenems (oprD), and the proteins involved in four efflux systems (mexA, mexC, mexE, and mexX). Real-time reverse transcriptase PCR was performed using primers and fluorescent probes for each of the target genes. The sequencing of regulatory genes (ampR, mexR, nalC, nalD, mexT, and mexZ) was also performed. Diminished expression of oprD was present in all imipenem- and meropenem-resistant isolates but was not required for ertapenem resistance. Increased expression of ampC was not observed in several isolates that were overtly resistant to carbapenems. Increased expression of several efflux systems was observed in many of the carbapenem-resistant isolates. Increased efflux activity correlated with high-level ertapenem resistance and reduced susceptibility to meropenem and aztreonam. Most isolates with increased expression of mexA had mutations affecting nalC and/or nalD. Two isolates with mutations leading to a premature stop codon in mexZ had markedly elevated mexX expressions, although mutations in mexZ were not a prerequisite for overexpression. beta-Lactam resistance in clinical isolates of P. aeruginosa is a result of the interplay between diminished production of oprD, increased activity of ampC, and several efflux systems.

Anti-Bacterial Agents↗

PubMed2001

Identification and antimicrobial susceptibility of Alcaligenes xylosoxidans isolated from patients with cystic fibrosis.

In the past decade, potential pathogens, including Alcaligenes species, have been increasingly recovered from cystic fibrosis (CF) patients. Accurate identification of multiply antibiotic-resistant gram-negative bacilli is critical to understanding the epidemiology and clinical implications of emerging pathogens in CF. We examined the frequency of correct identification of Alcaligenes spp. by microbiology laboratories affiliated with American CF patient care centers. Selective media, an exotoxin A probe for Pseudomonas aeruginosa, and a commercial identification assay, API 20 NE, were used for identification. The activity of antimicrobial agents against these clinical isolates was determined. A total of 106 strains from 78 patients from 49 CF centers in 22 states were studied. Most (89%) were correctly identified by the referring laboratories as Alcaligenes xylosoxidans. However, 12 (11%) strains were misidentified; these were found to be P. aeruginosa (n = 10), Stenotrophomonas maltophilia (n = 1), and Burkholderia cepacia (n = 1). Minocycline, imipenem, meropenem, piperacillin, and piperacillin-tazobactam were the most active since 51, 59, 51, 50, and 55% of strains, respectively, were inhibited. High concentrations of colistin (100 and 200 microg/ml) inhibited 92% of strains. Chloramphenicol paired with minocycline and ciprofloxacin paired with either imipenem or meropenem were the most active combinations and inhibited 40 and 32%, respectively, of strains. Selective media and biochemical identification proved to be useful strategies for distinguishing A. xylosoxidans from other CF pathogens. Standards for processing CF specimens should be developed, and the optimal method for antimicrobial susceptibility testing of A. xylosoxidans should be determined.

Alcaligenes↗

PubMed2001

Evaluation of the VITEK 2 system for the identification and susceptibility testing of three species of nonfermenting gram-negative rods frequently isolated from clinical samples.

VITEK 2 is a new automatic system for the identification and susceptibility testing of the most clinically important bacteria. In the present study 198 clinical isolates, including Pseudomonas aeruginosa (n = 146), Acinetobacter baumannii (n = 25), and Stenotrophomonas maltophilia (n = 27) were evaluated. Reference susceptibility testing of cefepime, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin, tobramycin, levofloxacin (only for P. aeruginosa), co-trimoxazole (only for S. maltophilia), and ampicillin-sulbactam and tetracycline (only for A. baumannii) was performed by microdilution (NCCLS guidelines). The VITEK 2 system correctly identified 91.6, 100, and 76% of P. aeruginosa, S. maltophilia, and A. baumannii isolates, respectively, within 3 h. The respective percentages of essential agreement (to within 1 twofold dilution) for P. aeruginosa and A. baumannii were 89.0 and 88.0% (cefepime), 91.1 and 100% (cefotaxime), 95.2 and 96.0% (ceftazidime), 98.6 and 100% (ciprofloxacin), 88.4 and 100% (gentamicin), 87.0 and 92.0% (imipenem), 85.0 and 88.0% (meropenem), 84.2 and 96.0% (piperacillin), and 97.3 and 80% (tobramycin). The essential agreement for levofloxacin against P. aeruginosa was 86.3%. The percentages of essential agreement for ampicillin-sulbactam and tetracycline against A. baumannii were 88.0 and 100%, respectively. Very major errors for P. aeruginosa (resistant by the reference method, susceptible with the VITEK 2 system [resistant to susceptible]) were noted for cefepime (0.7%), cefotaxime (0.7%), gentamicin (0.7%), imipenem (1.4%), levofloxacin (2.7%), and piperacillin (2.7%) and, for one strain of A. baumannii, for imipenem. Major errors (susceptible to resistant) were noted only for P. aeruginosa and cefepime (2.0%), ceftazidime (0.7%), and piperacillin (3.4%). Minor errors ranged from 0.0% for piperacillin to 22.6% for cefotaxime against P. aeruginosa and from 0.0% for piperacillin and ciprofloxacin to 20.0% for cefepime against A. baumannii. The VITEK 2 system provided co-trimoxazole MICs only for S. maltophilia; no very major or major errors were obtained for co-trimoxazole against this species. It is concluded that the VITEK 2 system allows the rapid identification of S. maltophilia and most P. aeruginosa and A. baumannii isolates. The VITEK 2 system can perform reliable susceptibility testing of many of the antimicrobial agents used against P. aeruginosa and A. baumannii. It would be desirable if new versions of the VITEK 2 software were able to determine MICs and the corresponding clinical categories of agents active against S. maltophilia.

Acinetobacter↗

PubMed2004

Antimicrobial susceptibility testing of Acinetobacter spp. by NCCLS broth microdilution and disk diffusion methods.

Although both broth microdilution (BMD) and disk diffusion (DD) are listed by NCCLS as acceptable methods for testing Acinetobacter spp. for antimicrobial susceptibility, few studies have compared the results generated by the two methods. We tested 196 isolates of Acinetobacter spp. from nine U.S. hospitals and from the Centers for Disease Control culture collection by using BMD and DD and clinically appropriate antimicrobial agents. Categorical results for amikacin, ciprofloxacin, gatifloxacin, gentamicin, imipenem, levofloxacin, meropenem, tobramycin, and trimethoprim-sulfamethoxazole were comparable for the two methods: there was only one very major (VM) error, with tobramycin, and only one major (M) error, with meropenem, when DD results were compared with BMD results. However, VM errors were frequent with the beta-lactams and beta-lactam-beta-lactam inhibitor combinations, while M errors were often observed with tetracyclines. For BMD, tests frequently exhibited subtle growth patterns that were difficult to interpret, especially for beta-lactams. If subtle growth (i.e., granular, small button, or "starry" growth) was considered positive, error rates between BMD and DD were unacceptably high for ampicillin-sulbactam (VM error, 9.8%; minor [m] error, 16.1%), piperacillin (VM error, 5.7%; m error, 13.5%), piperacillin-tazobactam (VM error, 9.3%; m error, 12.9%), ceftazidime (VM error, 6.2%; m error, 11.4%), cefepime (VM error, 6.2%; m error, 13.0%), cefotaxime (m error, 21.2%), ceftriaxone (m error, 23.3%), tetracycline (M error, 11.4%; m error, 32.1%), and doxycycline (M error, 2.6%). When subtle growth patterns were ignored, the agreement still did not achieve acceptable levels. To determine if the problems with BMD testing occurred in other laboratories, we sent frozen BMD panels containing beta-lactam drugs and nine isolates to six labs with experience in performing BMD and DD. Among these laboratories, cefepime MICs ranged from < or =8 to > or =32 microg/ml for four of the nine strains, confirming the problem in interpreting BMD results. Discrepancies between the categorical interpretations of BMD and DD tests were noted primarily with cefepime and piperacillin, for which the BMD results were typically more resistant. Clinical laboratories should be aware of these discrepancies. At present, there are no data to indicate which method provides more clinically relevant information.

Acinetobacter↗

PubMed2024

Antibiotic resistance genotype, phenotype, and clinical outcomes in patients with Gram-negative infections at Rabin Medical Center in Israel.

UNLABELLED: Antibiotic resistance is a major cause of morbidity and mortality. However, a better understanding of the relationship between bacterial genetic markers, phenotypic resistance, and clinical outcomes is needed. We performed whole-genome sequencing on five medically important pathogens (Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) to investigate how resistance genes impact patient outcomes. A total of 168 isolates from 162 patients with Gram-negative infections admitted to Beilinson Hospital at Rabin Medical Center in Israel were included for final analysis. Genomes were analyzed for resistance determinants and correlated with microbiologic and clinical data. Thirty-day mortality from time of culture was 26.5% (43/162). Twenty-nine patients had carbapenem-resistant isolates (29/168, 17.2%), while 63 patients had multidrug-resistant isolates (63/168, 37.5%). Albumin levels were inversely associated with mortality and length of stay, while arrival from a healthcare facility and cancer chemotherapy predicted having a multidrug-resistant isolate. Sequencing revealed possible patient-to-patient transmission events. blaCTX-M-15 was associated with multidrug-resistance in E. coli (OR = 3.888, P = 0.023) on multivariate analysis. Increased blaOXA-72 copy number was associated with carbapenem-resistance in A. baumannii (P = 0.003) and meropenem minimum inhibitory concentration (P = 0.005), yet carbapenem-resistant isolates retained sensitivity to cefiderocol and sulbactam-durlobactam. RJX84154 was associated with multidrug-resistance across all pathogens (P = 0.0018) and in E. coli (P = 0.0024). Low albumin levels were associated with mortality and length of stay in this sample population. blaCTX-M-15 was correlated with multidrug-resistance in E. coli, and blaOXA-72 depth predicted meropenem minimum inhibitory concentration in A. baumannii. RJX84154 may play a role in multidrug-resistance. IMPORTANCE: While there have been several studies that attempt to find clinical predictors of outcomes in patients hospitalized with bacterial infections, less has been done to combine clinical data with genomic mechanisms of antibiotic resistance. This study focused on a hospitalized patient population in Israel with infections due to medically important bacterial pathogens as a way to build a framework that would unite clinical data with both bacterial antibiotic susceptibility and genomic data. Merging both clinical and genomic data allowed us to find both bacterial and clinical factors that impact certain clinical outcomes. As genome sequencing of bacteria becomes both rapid and commonplace, near real-time monitoring of resistance determinants could help to optimize clinical care and potentially improve outcomes in these patients.

Humans↗

PubMedDate not supplied

Antibiotic susceptibility testing (agar disk diffusion and agar dilution) of clinical isolates of Enterococcus faecalis and E. faecium: comparison of Mueller-Hinton, Iso-Sensitest, and Wilkins-Chalgren agar media.

Forty-two isolates of Enterococcus faecalis and 56 isolates of Enterococcus faecium, including 8 vancomycin-resistant strains, were examined for comparative susceptibility to 27 antimicrobial drugs with the agar dilution method, employing Mueller-Hinton (MHA), Iso-Sensitest (ISTA), and Wilkins-Chalgren (WCA) agar. The Bauer-Kirby agar disk diffusion method was used to comparatively test 24 of the agents in parallel. The enterococci yielded better growth on ISTA and WCA. However, WCA completely antagonized co-trimoxazole and, though less, fosfomycin. Importantly, WCA slightly reduced the activities of teicoplanin (minimal inhibitory concentrations, MICs, raised up to twofold) and vancomycin (MICs raised two- to fourfold) against enterococci and staphylococcal quality control strains. Therefore, WCA was judged unsuitable for susceptibility testing of enterococci. For E. faecalis no discrepancies between agar dilution MICs and inhibition zone diameters were encountered with augmentin, ampicillin, ampicillin-sulbactam, chloramphenicol, mupirocin, oxacillin, teicoplanin, and co-trimoxazole. Overall, MHA yielded fewer very major (category I) and major (category II) discrepancies than ISTA. However, numerous minor (category III), slight (category IV), minimal (category V), and/or negligible (category VI) discrepancies were encountered with ciprofloxacin, doxycycline, erythromycin, fosfomycin, fusidic acid, meropenem, ofloxacin and rifampin. With respect to E. faecium, only cefotaxime, mupirocin, oxacillin, and teicoplanin yielded nondiscrepant results. Several very major (I) and major (II) discrepancies were observed with augmentin, ampicillin, ampicillin-sulbactam, doxycycline, fusidic acid, imipenem, and penicillin G. Minor discrepancies (categories III-VI) were particularly numerous with augmentin, chloramphenicol, ciprofloxacin, doxycycline, and piperacillin. The largest numbers of negligible (VI) discrepancies were noted with fosfomycin, fusidic acid, and ofloxacin. It is recommended to test one cephalosporin (cefuroxime or the like) in parallel for educational purposes and to exclude fosfomycin, fusidic acid, and rifampin from test batteries because of the wide scatter of test results. The large number of minimal (V) discrepancies of ciprofloxacin against E. faecalis, the numerous minor (III) and slight (IV) discrepancies of chloramphenicol against E. faecium, and the not insignificant number of very major (I) and minor (III) discrepancies observed with meropenem against isolates of E. faecalis necessitated proposals for new disk intermediate susceptibility criteria.

Agar↗