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Journal of Biomaterials Applications Oct 2021The aims of the present study were the determination of antimicrobial and antibiofilm effects of meropenem-loaded mesoporous silica nanoparticles (MSNs) on carbapenem...
The aims of the present study were the determination of antimicrobial and antibiofilm effects of meropenem-loaded mesoporous silica nanoparticles (MSNs) on carbapenem resistant () and cytotoxicity properties . The meropenem-loaded MSNs had shown antibacterial and biofilm inhibitory activities on all isolates at different levels lower than MICs and BICs of meropenem. The viability of HC-04 cells treated with serial concentrations as MICs and BICs of meropenem-loaded MSNs was 92-100%. According to the obtained results, meropenem-loaded MSNs display the significant antibacterial and antibiofilm effects against carbapenem resistant and biofilm forming and low cell toxicity . Then, the prepared system can be an appropriate option for the delivery of carbapenem for further evaluation assays.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Drug Resistance, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Nanoparticles; Pseudomonas Infections; Pseudomonas aeruginosa; Silicon Dioxide
PubMed: 33722086
DOI: 10.1177/08853282211003848 -
International Journal of Antimicrobial... Aug 2023The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing...
Factors associated with meropenem pharmacokinetic/pharmacodynamic target attainment in septic critically ill patients treated with extended intermittent infusion or continuous infusion.
OBJECTIVES
The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII.
METHODS
The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models.
RESULTS
Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m (IQR 30, 84) vs. 79 mL/min/m (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001).
CONCLUSION
The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance.
Topics: Humans; Meropenem; Anti-Bacterial Agents; Retrospective Studies; Critical Illness; Prospective Studies
PubMed: 37244425
DOI: 10.1016/j.ijantimicag.2023.106868 -
Journal of Global Antimicrobial... Jun 2023Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp)...
Ceftazidime/avibactam-resistant meropenem-susceptible KPC-producing Klebsiella pneumoniae: Analysis of cases and evaluation of in vitro activity of fosfomycin-containing combinations.
OBJECTIVES
Little is known regarding outcomes and optimal therapeutic regimens of infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although susceptible to MEM in vitro, the possibility of developing MEM resistance overtime is a concern. We describe the clinical characteristics of patients with colonization/infection due to KPC variants with a focus on the in vitro activity of fosfomycin (FOS)-containing combinations.
METHODS
Patients with colonization/infection due to a KPC variant were included. Fosfomycin susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in vitro MEM resistance was also tested.
RESULTS
Eleven patients were included: eight with infection [four with ventilator-associated pneumonia and four with bloodstream infections] and three with colonization. Previous therapy with CZA was administered to all patients (with a mean cumulative duration of 23 days). All subjects with infection received meropenem, in monotherapy (n = 4) or with amikacin (n = 2) or fosfomycin (n = 2), and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in three patients (27.3%). Meropenem/vaborbactam (MVB) showed high in vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In vitro resistance to MEM was observed with maintenance of CZA resistance.
CONCLUSIONS
Detection of KPC variants may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may be a valuable combination option for KPC variants, while MVB may be considered in monotherapy. The detection of KPC variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is of concern, which may lead to therapeutic failure in clinical practice. In these cases, the addition of fosfomycin to meropenem, or a more potent antibiotic, such as meropenem/vaborbactam, may be valuable therapeutic options.
Topics: Humans; Ceftazidime; Meropenem; Fosfomycin; Klebsiella pneumoniae; Agar; Klebsiella Infections
PubMed: 37086891
DOI: 10.1016/j.jgar.2023.03.012 -
The Journal of Antimicrobial... Sep 2021Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among...
Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014-19).
OBJECTIVES
Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among other indications. Vaborbactam is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC) enzymes, but not class B or D carbapenemases. We analysed the activity of meropenem/vaborbactam and comparators against 6846 Enterobacterales and 3567 Pseudomonas aeruginosa isolates from patients hospitalized with pneumonia (PHP), including VAP.
METHODS
Isolates from PHP were consecutively collected during 2014-19 from 42 European hospitals located in 21 countries and susceptibility tested using the broth microdilution method. Carbapenem-resistant Enterobacterales (CRE) isolates were molecularly characterized to identify their carbapenem-resistance mechanisms. EUCAST (2020) interpretive criteria were used.
RESULTS
The most common Gram-negative pathogens isolated from PHP were P. aeruginosa (n = 3567), K. pneumoniae (n = 1877) and Escherichia coli (n = 1646). Overall, 98.0% of Enterobacterales and 82.1% of P. aeruginosa were susceptible to meropenem/vaborbactam, with 99.8% of Enterobacterales and 89.7% of P. aeruginosa in Western Europe (WE) and 92.7% of Enterobacterales and 69.1% of P. aeruginosa in Eastern Europe (EE). CRE were more common in EE (15.1%) than WE (2.1%). KPC was the most common carbapenemase in WE, while OXA-48-like was the most common carbapenemase in EE. Meropenem/vaborbactam susceptibility was 63.0% for all CRE (92.2% in WE and 51.5% in EE). Meropenem/vaborbactam inhibited 99.1% of KPC-producing isolates and 40.5% of OXA-48-like-producing isolates.
CONCLUSIONS
These in vitro data demonstrate that meropenem/vaborbactam has potent activity against isolates from PHP, including isolates producing KPC, and may be a useful treatment option for PHP, including VAP.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Boronic Acids; Carbapenems; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated; beta-Lactamases
PubMed: 34302173
DOI: 10.1093/jac/dkab252 -
Medicine Jul 2023This study aimed to investigate the clinical characteristics, management and prognosis of Bacillus cereus sepsis in premature neonates. The clinical information of 8...
This study aimed to investigate the clinical characteristics, management and prognosis of Bacillus cereus sepsis in premature neonates. The clinical information of 8 premature neonates with B cereus sepsis who were treated in Shanghai Children Hospital from January 2015 to December 2019 was retrospectively collected from the medical records and analyzed. The neurodevelopment related conditions were collected at follow up visits at corrected age of 6 months and 12 months. Five patients developed meningitis, and cerebral magnetic resonance image showed abnormal in 5 patients. After treatment with meropenem and vancomycin, 1 patient died, and 7 patients survived and were smoothly discharged. At follow up visits, 1 patient was diagnosed with hydrocephalus and showed severely delayed neurodevelopment, 2 patients had mild delayed neurodevelopment, and the neurodevelopment was basically normal in remaining 4 patients. B cereus infection can cause severe complications of central nervous system, and affect neurodevelopmental outcome. Antibiotic treatment with meropenem and vancomycin is proven to be effective. Refreshing the central catheters is helpful for the prevention of B cereus sepsis and cerebral magnetic resonance image may be employed for the prognosis assessment.
Topics: Infant, Newborn; Child; Humans; Infant; Vancomycin; Bacillus cereus; Meropenem; Retrospective Studies; China; Sepsis; Prognosis; Infant, Newborn, Diseases
PubMed: 37443518
DOI: 10.1097/MD.0000000000034261 -
Microbial Drug Resistance (Larchmont,... Aug 2023We examined the susceptibility of meropenem-nonsusceptible Enterobacterales, , and complex isolates from five consecutive annual SIDERO-WT surveillance studies...
We examined the susceptibility of meropenem-nonsusceptible Enterobacterales, , and complex isolates from five consecutive annual SIDERO-WT surveillance studies (2014-2019) to cefiderocol and comparator agents in the context of their carbapenemase carriage. 1,003 Enterobacterales, 1,758 , and 2,809 complex isolates from North America and Europe that were meropenem nonsusceptible (CLSI M100, 2022) were molecularly characterized for β-lactamase content by PCR followed by Sanger sequencing or by whole genome sequencing. Among Enterobacterales, 91.5% of metallo-β-lactamase (MBL)-producing, 98.4% of KPC-producing, 97.3% of OXA-48 group-producing, and 98.7% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among , 100% of MBL-producing, 100% of GES carbapenemase-producing, and 99.8% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among complex, 60.0% of MBL-producing, 95.6% of OXA-23 group-producing, 89.5% of OXA-24 group-producing, 100% of OXA-58 group-producing, and 95.5% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Cefiderocol was inactive against complex isolates carrying a PER or VEB β-lactamase ( = 103; 15.5% susceptible). Ceftazidime-avibactam and ceftolozane-tazobactam were inactive against MBL-carrying and complex isolates; ceftolozane-tazobactam was also inactive against serine carbapenemase-carrying Enterobacterales and . In summary, cefiderocol was highly active against Gram-negative isolates carrying MBLs and serine carbapenemases, as well as carbapenemase-negative, meropenem-nonsusceptible isolates.
Topics: Meropenem; Anti-Bacterial Agents; Microbial Sensitivity Tests; Gram-Negative Bacteria; Tazobactam; beta-Lactamases; Pseudomonas aeruginosa; Azabicyclo Compounds; Cefiderocol
PubMed: 37253158
DOI: 10.1089/mdr.2022.0279 -
Antimicrobial Agents and Chemotherapy Oct 2022Xeruborbactam (formerly QPX7728) is a cyclic boronate inhibitor of numerous serine and metallo-beta-lactamases. At concentrations generally higher than those required...
Xeruborbactam (formerly QPX7728) is a cyclic boronate inhibitor of numerous serine and metallo-beta-lactamases. At concentrations generally higher than those required for beta-lactamase inhibition, xeruborbactam has direct antibacterial activity against some Gram-negative bacteria, with MIC/MIC values of 16/32 μg/mL and 16/64 μg/mL against carbapenem-resistant and carbapenem-resistant Acinetobacter baumannii, respectively (the MIC/MIC values against Pseudomonas aeruginosa are >64 μg/mL). In Klebsiella pneumoniae, inactivation of OmpK36 alone or in combination with OmpK35 resulted in 2- to 4-fold increases in the xeruborbactam MIC. In A. baumannii and P. aeruginosa, AdeIJK and MexAB-OprM, respectively, affected xeruborbactam's antibacterial potency (the MICs were 4- to 16-fold higher in efflux-proficient strains). In Escherichia coli and K. pneumoniae, the 50% inhibitory concentrations (ICs) of xeruborbactam's binding to penicillin-binding proteins (PBPs) PBP1a/PBP1b, PBP2, and PBP3 were in the 40 to 70 μM range; in A. baumannii, xeruborbactam bound to PBP1a, PBP2, and PBP3 with ICs of 1.4 μM, 23 μM, and 140 μM, respectively. Treating K. pneumoniae and P. aeruginosa with xeruborbactam at 1× and 2× MIC resulted in changes of cellular morphology similar to those observed with meropenem; the morphological changes observed after treatment of A. baumannii were consistent with inhibition of multiple PBPs but were unique to xeruborbactam compared to the results for control beta-lactams. No single-step xeruborbactam resistance mutants were obtained after selection at 4× MIC of xeruborbactam using wild-type strains of E. coli, K. pneumoniae, and A. baumannii; mutations selected at 2× MIC in K. pneumoniae did not affect antibiotic potentiation by xeruborbactam through beta-lactamase inhibition. Consistent with inhibition of PBPs, xeruborbactam enhanced the potencies of beta-lactam antibiotics even against strains that lacked beta-lactamase. In a large panel of KPC-producing clinical isolates, the MIC values of meropenem tested with xeruborbactam (8 μg/mL) were at least 4-fold lower than those in combination with vaborbactam at 64 μg/mL, the concentration of vaborbactam that is associated with complete inhibition of KPC. The additional enhancement of the potency of beta-lactam antibiotics beyond beta-lactamase inhibition may contribute to the potentiation of beta-lactam antibiotics by xeruborbactam.
Topics: Meropenem; Penicillin-Binding Proteins; Escherichia coli; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Microbial Sensitivity Tests; Klebsiella pneumoniae; Carbapenems; Monobactams; Pseudomonas aeruginosa; Serine
PubMed: 36102663
DOI: 10.1128/aac.00879-22 -
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 -
Future Microbiology Sep 2022The authors aimed to determine the efficacy of frequently used antibiotics, alone or in combination, against biofilms of ventilator-associated pneumonia isolates. The...
The authors aimed to determine the efficacy of frequently used antibiotics, alone or in combination, against biofilms of ventilator-associated pneumonia isolates. The authors determined the MICs, minimum biofilm inhibitory concentrations and minimum biofilm eradication concentrations of meropenem, ciprofloxacin and colistin as well as their combinations against planktonic forms and biofilms of , and clinical isolates. Generally, the minimum biofilm inhibitory concentrations and minimum biofilm eradication concentrations of the antibiotics were 1000-fold higher than their MICs, and synergy was provided by different concentrations of meropenem-colistin and meropenem-ciprofloxacin combinations with checkerboard and time-kill curve methods. The combination of meropenem and ciprofloxacin seems to be a good candidate for the treatment of biofilm-associated infections; none of the concentrations obtained as a result of the synergy test were clinically significant.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Biofilms; Ciprofloxacin; Colistin; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Ventilator-Associated
PubMed: 35796076
DOI: 10.2217/fmb-2021-0305 -
Microbial Drug Resistance (Larchmont,... Jul 2022Colistin-based antibiotic therapies have been recommended for the treatment of multidrug-resistant infections. During colistin treatment, persister cells that tolerate...
Colistin-based antibiotic therapies have been recommended for the treatment of multidrug-resistant infections. During colistin treatment, persister cells that tolerate antibiotics may arise. Here we designed an study to assess the killing activity of colistin, meropenem, and amikacin on colistin-induced persisters in comparison with starvation-induced persisters. Colistin-induced persisters were generated under exposure to 10 × minimum inhibitory concentration dose of colistin, whereas starvation-induced persisters were produced by limitation of nutrients. In colistin-induced persisters, amikacin totally inhibited cell growth in 6 hours, whereas 98% of the cell population was inhibited by meropenem, and total eradication with meropenem was observed after 24 hours. Both antibiotics also inhibited metabolic activity >88%. The lack of killing effect under colistin exposure suggested to us that these cells could protect themselves from further colistin stress. There was no significant permeabilization change in the cellular membrane with all antibiotics. There was no killing effect on starvation-induced persister cells with the exposure to all antibiotics. In 6 hours, the metabolic activity of the persisters with meropenem and colistin increased 99% and 40%, respectively, whereas there was no increase with amikacin. The sustained inhibition with amikacin was an important finding for antipersister effect of amikacin. Amikacin had rapid and sustained antipersister activity on colistin-induced persister cells. During the colistin treatment of infection, the addition of amikacin to the regimen seems to be an effective approach to prevent a recurrence.
Topics: Amikacin; Anti-Bacterial Agents; Colistin; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests
PubMed: 35759379
DOI: 10.1089/mdr.2021.0207