Imipenem Resistance in Pseudomonas aeruginosa

2015 ◽  
pp. 240-244
Author(s):  
J. P. Quinn ◽  
D. Miyashiro ◽  
A. Darzins ◽  
R. Miller
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Imipenem Resistance

Imipenem Resistance in Pseudomonas aeruginosa Emergence, Epidemiology, and Impact on Clinical and Economic Outcomes

2010 ◽  
Vol 31 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Ebbing Lautenbach ◽  
Marie Synnestvedt ◽  
Mark G. Weiner ◽  
Warren B. Bilker ◽  
Lien Vo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Risk Factor ◽  
Hospital Stay ◽  
Hospital Cost ◽  
Independent Risk Factor ◽  
Multivariable Analysis ◽  
Economic Outcomes ◽  
Imipenem Resistance ◽  
Hospital Acquired ◽  
Control Study

Background.Pseudomonas aeruginosa is one of the most common gram-negative hospital-acquired pathogens. Resistance of this organism to imipenem complicates treatment.Objective.To elucidate the risk factors for imipenem-resistant P. aeruginosa (IRPA) infection or colonization and to identify the effect of resistance on clinical and economic outcomes.Methods.Longitudinal trends in prevalence of IRPA from 2 centers were characterized during the period from 1989 through 2006. For P. aeruginosa isolates obtained during the period from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRPA infection or colonization, and a cohort study was performed to identify the effect of IRPA infection or colonization on mortality, length of stay after culture, and hospital cost after culture.Results.From 1989 through 2006, the proportion of P. aeruginosa isolates demonstrating resistance to imipenem increased from 13% to 20% (P< .001, trend). During the period from 2001 through 2006, there were 2,542 unique patients with P. aeruginosa isolates, and 253 (10.0%) had IRPA isolates. Prior carbapenem use was independently associated with IRPA infection or colonization (adjusted odds ratio [OR], 7.92 [95% confidence interval {CI}, 4.78-13.11]). Patients with an IRPA isolate recovered had higher in-hospital mortality than did patients with an imipenem-susceptible P. aeruginosa isolate (17.4% vs 13.4%; P = .01). IRPA infection or colonization was an independent risk factor for mortality among patients with isolates recovered from blood (adjusted OR, 5.43 [95% CI, 1.72-17.10]; P = .004) but not among patients with isolates recovered from other anatomic sites (adjusted OR, 0.78 [95% CI, 0.51-1.21]; P = .27). Isolation of IRPA was associated with longer hospital stay after culture (P<.001) and greater hospital cost after culture (P<.001) than was isolation of an imipenem-susceptible strain. In multivariable analysis, IRPA infection or colonization remained an independent risk factor for both longer hospital stay after culture (coefficient, 0.20 [95% CI, 0.04-0.36]; P = .02) and greater hospital cost after culture (coefficient, 0.30 [95% CI, 0.06-0.54]; P = .02).Conclusions.The prevalence of IRPA infection or colonization has increased significantly, with important implications for both clinical and economic outcomes. Interventions to curb this continued increase and strategies to optimize therapy are urgently needed.

Imipenem Resistance Among Pseudomonas aeruginosa Isolates Risk Factors for Infection and Impact of Resistance on Clinical and Economic Outcomes

2006 ◽  
Vol 27 (9) ◽  
pp. 893-900 ◽  
Author(s):  
Ebbing Lautenbach ◽  
Mark G. Weiner ◽  
Irving Nachamkin ◽  
Warren B. Bilker ◽  
Angela Sheridan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Medical Center ◽  
Tertiary Care ◽  
Economic Outcomes ◽  
Control Group ◽  
Case Group ◽  
Tertiary Care Medical Center ◽  
Imipenem Resistance ◽  
The Impact

Objectives.To identify risk factors for infection with imipenem-resistant Pseudomonas aeruginosa and determine the impact of imipenem resistance on clinical and economic outcomes among patients infected with P. aeruginosa.Designs.An ecologic study, a case-control study, and a retrospective cohort study.Setting.A 625-bed tertiary care medical center.Patients.All patients who had an inpatient clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000.Results.From 1991 through 2000, the annual prevalence of imipenem resistance among P. aeruginosa isolates increased significantly (P<.001 by the χ2 test for trend). Among 879 patients infected with P. aeruginosa during 1999-2000, a total of 142 had imipenem-resistant P. aeruginosa infection (the case group), whereas 737 had imipenem-susceptible P. aeruginosa infection (the control group). The only independent risk factor for imipenem-resistant P. aeruginosa infection was prior fluoroquinolone use (adjusted odds ratio, 2.52 [95% confidence interval {CI}, 1.61-3.92]; P<.001). Compared with patients infected with imipenem-susceptible P. aeruginosa, patients infected with imipenem-resistant P. aeruginosa had longer subsequent hospitalization durations (15.5 days vs 9 days; P = .02) and greater hospital costs ($81,330 vs $48,381; P<.001). The mortality rate among patients infected with imipenem-resistant P. aeruginosa was 31.1%, compared with 16.7% for patients infected with imipenem-susceptible P. aeruginosa (relative risk, 1.86 [95% CI, 1.38-2.51]; P<.001). In multivariable analyses, there remained an independent association between infection with imipenem-resistant P. aeruginosa and mortality.Conclusions.The prevalence of imipenem resistance among P. aeruginosa strains has increased markedly in recent years and has had a significant impact on both clinical and economic outcomes. Our results suggest that curtailing use of other antibiotics (particularly fluoroquinolones) may be important in attempts to curb further emergence of imipenem resistance.

scholarly journals Negative Regulation of the Pseudomonas aeruginosa Outer Membrane Porin OprD Selective for Imipenem and Basic Amino Acids

1999 ◽  
Vol 43 (5) ◽  
pp. 1085-1090 ◽  
Author(s):  
Martina M. Ochs ◽  
Matthew P. McCusker ◽  
Manjeet Bains ◽  
Robert E. W. Hancock
Keyword(s):  
Amino Acids ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Clinical Effectiveness ◽  
Multiple Antibiotic Resistance ◽  
Outer Membranes ◽  
Basic Amino Acids ◽  
Outer Membrane Porin ◽  
Strong Homology ◽  
Imipenem Resistance

ABSTRACT Pseudomonas aeruginosa OprD is a specific porin which facilitates the uptake of basic amino acids and imipenem, a carbapenem antibiotic. Resistance to imipenem due to the loss of OprD is an important mechanism for the loss of clinical effectiveness. To investigate the negative regulatory mechanisms influencingoprD expression, a gene upstream of the coregulatedmexEF-oprN efflux operon, designated mexT, was cloned. The predicted 304-amino-acid mature MexT protein showed strong homology to LysR-type regulators. When overexpressed it induced the expression of the mexEF-oprN efflux operon while decreasing the level of expression of OprD. The use of anoprD::xylE transcriptional fusion indicated that it acted by repressing the transcription ofoprD. Salicylate, a weak aromatic acid known to reduce porin expression and induce low levels of multiple antibiotic resistance in Escherichia coli, was able to induce imipenem resistance and reduce the expression of OprD but not multiple antibiotic resistance or OprN expression in P. aeruginosa. This was also demonstrated to occur at the level of transcription. Acetyl salicylate and benzoate, but not catechol, were also able to reduce the levels of OprD in the P. aeruginosa outer membranes. These OprD-suppressing compounds increased imipenem resistance even in a mexT-overexpressing andnfxC mutant backgrounds, suggesting that such resistance is independent of the MexT repressor and that oprD is influenced by more than a single mechanism of repression.

scholarly journals Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa

2009 ◽  
Vol 53 (11) ◽  
pp. 4783-4788 ◽  
Author(s):  
José-Manuel Rodríguez-Martínez ◽  
Laurent Poirel ◽  
Patrice Nordmann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Membrane Protein ◽  
Molecular Epidemiology ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Mechanisms Of Resistance ◽  
Genes Encoding ◽  
Imipenem Resistance

ABSTRACT The contributions of different mechanisms of resistance to carbapenems among a collection of imipenem- and meropenem-nonsusceptible Pseudomonas aeruginosa isolates were investigated. This screening included the recently reported extended-spectrum cephalosporinases (ESACs) weakly hydrolyzing carbapenems. Eighty-seven percent of the studied isolates were resistant to imipenem. Genes encoding metallo-β-lactamases or carbapenem-hydrolyzing oxacillinases were not identified. The main mechanism associated with imipenem resistance was the loss of outer membrane protein OprD. Identification of overexpressed ESACs and loss of OprD were observed for 65% of the isolates, all being fully resistant to imipenem. Resistance to meropenem was observed in 78% of the isolates, with all but one also being resistant to imipenem. Overexpression of the MexAB-OprM, MexXY-OprM, or MexCD-OprJ efflux systems was observed in 60% of the isolates, suggesting the contribution of efflux mechanisms in resistance to meropenem. The loss of porin OprD and the overproduction of ESACs were observed in 100% and 92% of the meropenem-resistant isolates, respectively. P. aeruginosa can very often accumulate different resistance mechanisms, including ESAC production, leading to carbapenem resistance.

scholarly journals Imipenem Resistance Mediated by blaOXA-913 Gene in Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1188
Author(s):  
Dong-Chan Moon ◽  
Abraham Fikru Mechesso ◽  
Hee-Young Kang ◽  
Su-Jeong Kim ◽  
Ji-Hyun Choi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Resistance Genes ◽  
Carbapenem Resistance ◽  
Rrna Genes ◽  
Whole Genome ◽  
Translation Initiation Region ◽  
Broth Microdilution Method ◽  
Imipenem Resistance

Treatment of infectious diseases caused by carbapenem-resistant Pseudomonas aeruginosa is becoming a greater challenge. This study aimed to identify the imipenem resistance mechanism in P. aeruginosa isolated from a dog. Minimum Inhibitory Concentration (MIC) was determined by the broth microdilution method according to the Clinical and Laboratory Standards Institute recommendations. We performed polymerase chain reaction and whole-genome sequencing to detect carbapenem resistance genes. Genomic DNA of P. aeruginosa K19PSE24 was sequenced via the combined analysis of 20-kb PacBio SMRTbell and PacBio RS II. Peptide-Peptide Nucleic Acid conjugates (P-PNAs) targeting the translation initiation region of blaOXA-913 were synthesized. The isolate (K19PSE24) was resistant to imipenem and piperacillin/tazobactam yet was susceptible to most of the tested antimicrobials. Whole-genome sequencing revealed that the K19PSE24 genome comprised a single contig amounting to 6,815,777 base pairs, with 65 tRNA and 12 rRNA genes. K19PSE24 belonged to sequence type 313 and carried the genes aph(3)-IIb, fosA, catB7, crpP, and blaOXA-913 (an allele deposited in GenBank but not described in the literature). K19PSE24 also carried genes encoding for virulence factors (exoenzyme T, exotoxin A, and elastase B) that are associated with adhesion, invasion, and tissue lysis. Nevertheless, we did not detect any of the previously reported carbapenem resistance genes. This is the first report of the blaOXA-913 gene in imipenem-resistant P. aeruginosa in the literature. Notably, no viable colonies were found after co-treatment with imipenem (2 µg/mL) and either of the P-PNAs (12.5 µM or 25 µM). The imipenem resistance in K19PSE24 was primarily due to blaOXA-913 gene carriage.

scholarly journals 2151. Biofilm and Metallo-β-Lactamase (MBL) Production Among Imipenem-Resistant Pseudomonas aeruginosa and Acinetobacter spp.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S729-S730
Author(s):  
Yang Metok ◽  
Supram Hosuru Subramanya ◽  
Upendra Thapa Shrestha ◽  
Leandro Reus Rodrigues Perez ◽  
Nabaraj Adhikari ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hospital Setting ◽  
Polymyxin B ◽  
Microtiter Plate ◽  
Multidrug Resistant ◽  
High Rate ◽  
Bacterial Strains ◽  
Microbiological Techniques ◽  
Acinetobacter Spp ◽  
Imipenem Resistance

Abstract Background Pseudomonas aeruginosa and Acinetobacter spp. head the list of hospital-acquired infections. Resistance to carbapenem as reserve drug is under threat with the emergence of Metallo-β-lactamase (MBL) and biofilm producing bacterial strains. This study was thus undertaken to determine the rate of MBL and biofilm production among imipenem-resistant P. aeruginosa (IRPA) and imipenem-resistant Acinetobacter spp. (IRAS) isolates. Methods A total of 79 P. aeruginosa and 117 Acinetobacter spp. were isolated from different clinical specimens of patients visiting Manipal Teaching Hospital, Pokhara Nepal from July 2016 to January 2017. Isolation, identification and antibiotic susceptibility testing of the isolates were performed by standard microbiological techniques. Combined disc test and Epsilometer test (E-test) were employed to detect MBL in IRPA and IRAS isolates. Microtiter plate using crystal violet method was employed for detection of biofilm in imipenem-resistant isolates. Results 9 (11.4%) of P. aeruginosa and 49 (41.9%) of Acinetobacter spp. were Multidrug Resistant (MDR). Similarly, 22 (27.8%) of P. aeruginosa and 23 (19.7%) of Acinetobacter spp. were Extensively Drug Resistant (XDR). Imipenem resistance was detected among 15 (19%) P. aeruginosa and 57 (48.7%) Acinetobacter spp. isolates. 8 (53.3%) of IRPA and 22 (38.6%) of IRAS isolates were MBL producers while all (100%) of IRPA and 47 (82.5%) of IRAS were biofilm producers. All the biofilm producer IRPA isolates were XDR and 62.5% of XDR IRAS strains were moderate biofilm producers. However, 80% of IRPA, 49.1% of IRAS and 63% of both MBL producer isolates were weak biofilm formers. Polymyxin B and ampicillin-sulbactam showed a better degree of susceptibility against MBL cum biofilm producer IRPA and IRAS isolates respectively. Conclusion The study showed high propensity of IRPA and IRAS to form biofilm, which is strongly associated with higher drug resistance. Such high rate of MBL and biofilm producing P. aeruginosa and Acinetobacter spp. alarms the rapid spread of such strains in our hospital setting. Disclosures All authors: No reported disclosures.

scholarly journals Activity of imipenem/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases

2020 ◽  
Author(s):  
Shazad Mushtaq ◽  
Danièle Meunier ◽  
Anna Vickers ◽  
Neil Woodford ◽  
David M Livermore
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Middle East ◽  
Eastern Europe ◽  
Class A ◽  
Carbapenem Resistant ◽  
Class B ◽  
Agar Dilution ◽  
Imipenem Resistance ◽  
Esbl Producers

Abstract Background ESBL- and carbapenemase-producing Pseudomonas aeruginosa are prevalent in, for example, the Middle East, Eastern Europe and Latin America, though rarer elsewhere. Because P. aeruginosa readily mutate to become carbapenem resistant via loss of OprD, isolates producing ESBLs are often as broadly resistant as those producing carbapenemases. We hypothesized that: (i) relebactam might overcome class A carbapenemases directly in P. aeruginosa; and (ii) relebactam’s inhibition of AmpC, which gives a generalized potentiation of imipenem against the species, might restore imipenem susceptibility in OprD-deficient ESBL producers. Methods MICs were determined using CLSI agar dilution for P. aeruginosa isolates producing ESBLs, principally VEB types, and for those producing GES-5, KPC and other carbapenemases. Results Relebactam potentiated imipenem by around 4–8-fold for most P. aeruginosa isolates producing VEB and other ESBLs; however, MICs were typically only reduced to 4–16 mg/L, thus mostly remaining above EUCAST’s susceptible range and only partly overlapping CLSI’s intermediate range. Strong (approx. 64-fold) potentiation was seen for isolates producing KPC carbapenemases, but only 2-fold synergy for those with GES-5. Predictably, potentiation was not seen for isolates with class B or D carbapenemase activity. Conclusions Relebactam did potentiate imipenem against ESBL-producing P. aeruginosa, which are mostly imipenem resistant via OprD loss, but this potentiation was generally insufficient to reduce imipenem MICs to the clinical range. Imipenem resistance owing to KPC carbapenemases was reversed by relebactam in P. aeruginosa, just as for Enterobacterales.

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