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Antimicrobial Agents and Chemotherapy Oct 2021Laboratories submit all carbapenem-resistant Enterobacter, Escherichia coli, and Klebsiella species to the Alameda County Public Health Department (ACPHD). ACPHD...
Laboratories submit all carbapenem-resistant Enterobacter, Escherichia coli, and Klebsiella species to the Alameda County Public Health Department (ACPHD). ACPHD evaluated 75 isolates submitted during 9 months for susceptibility to imipenem-relebactam (I-R) and, using whole-genome sequencing, identified β-lactamase genes. Of 60 (80%) isolates susceptible to I-R, 8 (13%) had detectable carbapenemase genes, including 4 KPC, two NDM, and two OXA-48-like; we described the relationship between the presence of β-lactamase resistance genes and susceptibility to I-R.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; Carbapenems; Drug Resistance, Bacterial; Gammaproteobacteria; Imipenem; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 34370572
DOI: 10.1128/AAC.02288-20 -
Antimicrobial Agents and Chemotherapy Nov 2020Combination therapy may enhance imipenem/cilastatin/relebactam's (I/R) activity against and suppress resistance development. Human-simulated unbound plasma...
Combination therapy may enhance imipenem/cilastatin/relebactam's (I/R) activity against and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible isolates in an pharmacodynamic model over 24 h. For I/R alone, the mean reductions in CFU ± the standard errors by 24 h were -2.52 ± 0.49, -1.49 ± 0.49, -1.15 ± 0.67, and -0.61 ± 0.10 log CFU/ml against isolates with MICs of 1/4, 2/4, 4/4, and 8/4 μg/ml, respectively. Amikacin alone also resulted in 24 h CFU reductions consistent with its MIC, while colistin CFU reductions did not differ. Resistant subpopulations were observed after 24 h in 1, 4, and 3 I/R-, colistin-, and amikacin-exposed isolates, respectively. The combination of I/R and colistin resulted in synergistic ( = 1) or additive ( = 2) interactions against three isolates with 24-h CFU reductions ranging from -2.62 to -4.67 log CFU/ml. The combination of I/R and amikacin exhibited indifferent interactions against all isolates, with combined drugs achieving -0.51- to -3.33-log CFU/ml reductions. No resistant subpopulations were observed during I/R and colistin combination studies, and when added to amikacin, I/R prevented the emergence of amikacin resistance. Against these six multidrug-resistant , I/R alone achieved significant CFU reductions against I/R-susceptible isolates. Combinations of I/R plus colistin resulted in additivity or synergy against some , whereas the addition of amikacin did not provide further antibacterial efficacy against these isolates.
Topics: Amikacin; Anti-Bacterial Agents; Azabicyclo Compounds; Cilastatin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 33139283
DOI: 10.1128/AAC.01764-20 -
BMJ Case Reports Mar 2016Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute...
Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid.
Topics: Adrenal Cortex Hormones; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Humans; Imipenem; Middle Aged; Pulmonary Eosinophilia; Treatment Outcome
PubMed: 26944380
DOI: 10.1136/bcr-2016-214804 -
American Journal of Veterinary Research Oct 2020To determine plasma pharmacokinetics of metronidazole and imipenem following administration of a single dose PO (metronidazole, 15 mg/kg) or IV (imipenem, 10 mg/kg) in...
Single-dose pharmacokinetics of orally administered metronidazole and intravenously administered imipenem in healthy horses and computer-based simulation of pleural fluid concentrations with multiple dosing.
OBJECTIVE
To determine plasma pharmacokinetics of metronidazole and imipenem following administration of a single dose PO (metronidazole, 15 mg/kg) or IV (imipenem, 10 mg/kg) in healthy Thoroughbreds and simulate pleural fluid concentrations following multiple dose administration every 8 hours.
ANIMALS
4 healthy Thoroughbreds.
PROCEDURES
Metronidazole and imipenem were administered, and samples of plasma and pleural fluid were collected at predetermined time points. Minimum concentrations of metronidazole and imipenem that inhibited growth of 90% of isolates (MIC), including 22 clinical isolates from horses with pleuropneumonia, were calculated. For the computer simulation, the target ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC for metronidazole was > 70, and the target percentage of time per day that the pleural fluid concentration of imipenem exceeded the MIC was > 50%.
RESULTS
Mean ± SD pleural fluid concentrations of metronidazole and imipenem were 12.7 ± 3.3 μg/mL and 12.1 ± 0.9 μg/mL, respectively, 1 hour after administration and 4.9 ± 0.85 μg/mL and 0.3 ± 0.08 μg/mL, respectively, 8 hours after administration. For both antimicrobials, concentrations in the pleural fluid and plasma were similar. The ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC for metronidazole was 84.9, and the percentage of time per day the pleural fluid concentration of imipenem exceeded the MIC was 70.9%.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that administration of metronidazole (15 mg/kg, PO, q 8 h) or imipenem (10 mg/kg, IV, q 8 h) resulted in their accumulation in the pleural fluid in healthy horses and concentrations were likely to be effective for the treatment of pneumonia and pleuropneumonia caused by spp.
Topics: Animals; Anti-Infective Agents; Area Under Curve; Computer Simulation; Horses; Imipenem; Metronidazole
PubMed: 32969731
DOI: 10.2460/ajvr.81.10.783 -
Antimicrobial Agents and Chemotherapy Aug 2021Klebsiella pneumoniae is an opportunistic Gram-negative pathogen that employs different strategies (resistance and persistence) to counteract antibiotic treatments. This...
Enhanced Antibacterial Activity of Repurposed Mitomycin C and Imipenem in Combination with the Lytic Phage vB_KpnM-VAC13 against Clinical Isolates of Klebsiella pneumoniae.
Klebsiella pneumoniae is an opportunistic Gram-negative pathogen that employs different strategies (resistance and persistence) to counteract antibiotic treatments. This study aimed to search for new means of combatting imipenem-resistant and persister strains of K. pneumoniae by repurposing the anticancer drug mitomycin C as an antimicrobial agent and by combining the drug and the conventional antibiotic imipenem with the lytic phage vB_KpnM-VAC13. Several clinical K. pneumoniae isolates were characterized, and an imipenem-resistant isolate (harboring OXA-245 β-lactamase) and a persister isolate were selected for study. The mitomycin C and imipenem MICs for both isolates were determined by the broth microdilution method. Time-kill curve data were obtained by optical density at 600 nm (OD) measurement and CFU enumeration in the presence of each drug alone and with the phage. The frequency of occurrence of mutants resistant to each drug and the combinations was also calculated, and the efficacy of the combination treatments was evaluated using an infection model (Galleria mellonella). The lytic phage vB_KpnM-VAC13 and mitomycin C had synergistic effects on imipenem-resistant and persister isolates, both and The phage-imipenem combination successfully killed the persisters but not the imipenem-resistant isolate harboring OXA-245 β-lactamase. Interestingly, the combinations decreased the emergence of resistant mutants of both isolates. Combinations of the lytic phage vB_KpnM-VAC13 with mitomycin C and imipenem were effective against the persister K. pneumoniae isolate. The lytic phage-mitomycin C combination was also effective against imipenem-resistant K. pneumoniae strains harboring OXA-245 β-lactamase.
Topics: Anti-Bacterial Agents; Bacteriophages; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Mitomycin; beta-Lactamases
PubMed: 34228538
DOI: 10.1128/AAC.00900-21 -
Clinical Microbiology and Infection :... Nov 2022New antibiotics have been developed to treat multidrug-resistant Enterobacterales. We evaluated the impact of the inoculum size on minimal inhibitory concentrations...
OBJECTIVES
New antibiotics have been developed to treat multidrug-resistant Enterobacterales. We evaluated the impact of the inoculum size on minimal inhibitory concentrations (MICs) of recently commercialized antibiotics.
METHODS
We focused on 40 clinical carbapenemase-producing Enterobacterales and evaluated the impact of the inoculum size on the MICs to cefiderocol and to new β-lactams/β-lactamase inhibitors (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) at usual and high inocula (10 and 10 CFU/mL, respectively).
RESULTS
At usual inoculum, 15% were resistant to cefiderocol (n = 6), 30% to meropenem-vaborbactam (n = 12), 42.5% to ceftazidime-avibactam (n = 17), 55% to imipenem-relebactam (n = 22), and 90% to ceftolozane-tazobactam (n = 36). At higher inoculum, a switch from susceptible to resistant category was observed for 88% (n = 30/34; CI, 71.6-96.2), 75% (n = 3/4; CI, 21.9-98.7), 72% (n = 13/18; CI, 46.4-89.3), 50% (n = 14/28; CI, 31.1-68.9), and 8.7% (n = 2/23; CI, 1.5-29.5) isolates regarding cefiderocol, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam, and ceftazidime-avibactam, respectively.
DISCUSSION
Cefiderocol and meropenem-vaborbactam were the most efficient against carbapenemase-producing Enterobacterales at usual inoculum. When increasing inoculum to 10 CFU/mL, all of the molecules were impacted, particularly cefiderocol and imipenem-relebactam, while others, such as ceftazidime-avibactam, remain mildly affected. Our in vitro results deserved to be confirmed in vivo.
Topics: Humans; Anti-Bacterial Agents; Meropenem; beta-Lactamase Inhibitors; Carbapenems; Tazobactam; Imipenem; Cefiderocol
PubMed: 35777602
DOI: 10.1016/j.cmi.2022.06.018 -
Journal of Global Antimicrobial... Jun 2022Gram-negative bacilli (GNB) are currently the predominant bacterial pathogens in patients with cancer. Many GNB have become problematic due to the widespread emergence...
OBJECTIVES
Gram-negative bacilli (GNB) are currently the predominant bacterial pathogens in patients with cancer. Many GNB have become problematic due to the widespread emergence of resistance. Imipenem/relebactam (IMI/REL) is a combination of the carbapenem imipenem with relebactam, a non-β-lactam β-lactamase inhibitor. It is active against most pathogenic GNB including many that are resistant to other agents. We compared its in vitro activity to six other agents against 490 GNB recovered exclusively from patients with cancer because such data are scarce.
METHODS
Clinical and Laboratory Standards Institute (CLSI) microbroth dilution methods were used for susceptibility testing. Whole genome sequencing (Illumina MiSeq) was performed on 30 selected isolates.
RESULTS
IMI/REL was active against 98% of Enterobacterales and 87% of non-Enterobacterales isolates (excluding Stenotrophomonas maltophilia). It had potent activity against extended spectrum β-lactamase-producing Escherichia coli, Klebsiella pneumoniae, and other Enterobacterales (Enterobacter cloacae, Citrobacter Spp., and Serratia Spp.) and moderate activity against carbapenem-resistant Enterobacterales. IMI/REL had potent activity against Achromobacter Spp., non-multidrug resistant Pseudomonas aeruginosa, and Sphingomonas paucimobilis and moderate activity against multidrug resistant P. aeruginosa. Overall, IMI/REL was associated with the lowest number of nonsusceptible isolates compared with six other agents (imipenem, meropenem, cefepime, piperacillin/tazobactam, amikacin, and tigecycline) commonly used in patients with cancer. Whole genome sequencing performed on 30 resistant isolates (10 each of E. coli, K. pneumonia, and P. aeruginosa) did not reveal any predominant mechanism of resistance to IMI/REL.
CONCLUSION
Its in vitro activity indicates that IMI/REL might have a role to play in the treatment of Gram-negative infections in patients with cancer.
Topics: Anti-Bacterial Agents; Carbapenems; Escherichia coli; Gram-Negative Bacteria; Humans; Imipenem; Microbial Sensitivity Tests; Neoplasms; Pseudomonas aeruginosa
PubMed: 35121163
DOI: 10.1016/j.jgar.2022.01.020 -
Journal of Comparative Effectiveness... Mar 2023This study evaluates the cost-effectiveness of imipenem/cilastatin/relebactam (IMI/REL) for treating hospital-acquired bacterial pneumonia and ventilator-associated...
This study evaluates the cost-effectiveness of imipenem/cilastatin/relebactam (IMI/REL) for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in an 'early adjustment prescribing scenario'. An economic model was constructed to compare two strategies: continuation of empiric piperacillin/tazobactam (PIP/TAZ) versus early adjustment to IMI/REL. A decision tree was used to depict the hospitalization period, and a Markov model used to capture long-term outcomes. IMI/REL generated more quality-adjusted life years than PIP/TAZ, at an increased cost per patient. The incremental cost-effectiveness ratio of $17,529 per QALY is below the typical US willingness-to-pay threshold. IMI/REL may represent a cost-effective treatment for payers and a valuable option for clinicians, when considered alongside patient risk factors, local epidemiology, and susceptibility data.
Topics: Humans; Cost-Benefit Analysis; Imipenem; Cilastatin; Drug Combinations; Piperacillin, Tazobactam Drug Combination; Pneumonia, Bacterial; Ventilators, Mechanical; Hospitals; Anti-Bacterial Agents
PubMed: 36688591
DOI: 10.2217/cer-2022-0113 -
Diagnostic Microbiology and Infectious... Aug 2023Antibiotic resistance surveillance may be essential to identify patterns of antibiotic resistance and guide treatment choices. Therefore, this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Antibiotic resistance surveillance may be essential to identify patterns of antibiotic resistance and guide treatment choices. Therefore, this systematic review and meta-analysis aimed to evaluate amikacin resistance and susceptibility in children with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). From inception to September 5, 2022, relevant studies were searched via PubMed, Embase, Cochrane Library, and Web of Science databases. A network meta-analysis was conducted to explore the sequencing of resistance rates in amikacin and other antibiotics. Totally, 26 studies with 2582 clusters of bacterial isolates were included. The resistance rate of amikacin in children with ESBL-PE was 10.1%, higher than the resistance rate of tigecycline (0.0%), ertapenem (0.4%), meropenem (0.7%), and imipenem (3.0%). For the drug susceptibility rate in children with ESBL-PE, the susceptibility rate of amikacin (89.7%) was lower than tigecycline (99.6%), imipenem (96.8%), meropenem (97.3%), and ertapenem (95.6%). Amikacin showed a low drug resistance and a high drug resistance in children with ESBL-PE infection, making it a good option for the treatment of the infection caused by ESBL-PE.
Topics: Child; Humans; Amikacin; Ertapenem; Meropenem; Tigecycline; Escherichia coli; Klebsiella pneumoniae; Anti-Bacterial Agents; Imipenem; beta-Lactamases; Drug Resistance; Microbial Sensitivity Tests
PubMed: 37290259
DOI: 10.1016/j.diagmicrobio.2023.115956 -
Journal of Global Antimicrobial... Sep 2020The aim of this study was to investigate the molecular mechanisms of imipenem resistance in Enterobacteriaceae and to assess the antimicrobial activities of...
Genetic diversity and in vitro activity of ceftazidime/avibactam and aztreonam/avibactam against imipenem-resistant Enterobacteriaceae isolates in Southwest China: A single-centre study.
OBJECTIVES
The aim of this study was to investigate the molecular mechanisms of imipenem resistance in Enterobacteriaceae and to assess the antimicrobial activities of ceftazidime/avibactam (CAZ/AVI) and aztreonam/avibactam (ATM/AVI) against imipenem-resistant clinical isolates in a tertiary hospital in China.
METHODS
A total of 91 imipenem-resistant Enterobacteriaceae were collected and genes encoding carbapenemases, ESBLs, AmpC β-lactamases and porins were detected using PCR. MICs and susceptibility were determined using in-house-prepared broth microdilution panels and were interpreted according to CLSI breakpoints.
RESULTS
Imipenem-resistant isolates comprising 54 Klebsiella pneumoniae, 18 Escherichia coli, 8 Enterobacter cloacae, 6 Serratia marcescens, 3 Klebsiella oxytoca and 2 Klebsiella aerogenes were collected independently. Five different carbapenemase genes were identified, namely bla (n = 60), bla (n = 14), bla (n = 11), bla (n = 4) and bla (n = 1). Among the 91 carbapenem-resistant Enterobacteriaceae (CRE), 85 isolates harboured at least one ESBL and/or AmpC gene, including 5 strains without carbapenemase-encoding genes. Moreover, 31 K. pneumoniae carried ompK35 and/or ompK36 mutations. MLST results showed that the K. pneumoniae belonged to 12 different STs, with ST11 being predominant (29/54; 53.7%). Overall, 17.6%, 25.3%, 41.8%, 65.9% and 100% of the CRE strains were susceptible to amikacin, trimethoprim/sulfamethoxazole, tetracycline, CAZ/AVI and ATM/AVI, respectively.
CONCLUSION
This study revealed that CRE isolates differ significantly in their species, STs, porins and carbapenemase genes in a single Chinese hospital. ATM/AVI exhibited potent activity against CRE isolates, even for the most notorious double-carbapenemase-producers with porin defects, whereas CAZ/AVI was active against all the non-metallo-β-lactamase-producing isolates.
Topics: Azabicyclo Compounds; Aztreonam; Ceftazidime; China; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Genetic Variation; Imipenem; Multilocus Sequence Typing
PubMed: 32387260
DOI: 10.1016/j.jgar.2020.04.023