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Journal of Global Antimicrobial... Jun 2024To investigate the clinical distribution and changing trend of antibiotic resistance profiles of multidrug-resistant organisms (MDROs), a retrospective study was...
BACKGROUND
To investigate the clinical distribution and changing trend of antibiotic resistance profiles of multidrug-resistant organisms (MDROs), a retrospective study was undertaken.
METHODS
The characteristics of MDROs isolated from 2016 to March 2023 were retrospectively analysed. The detection rate of these MDROs was compared prior to COVID-19 (Period 1, 2016-2019), during the COVID-19 pandemic with restrictions (Period 2, 2020-2022), and after the end of zero-policy (Period 3, Jan-March, 2023). Antibiotic-resistant genes were detected.
RESULTS
The overall detection rates of CRPA, CRAB, CREC, CRKP, MRSA, and VREfm were 22.6%, 22.6%, 1.3%, 4.0%, 19.5%, and 3.1%, respectively. The detection rate of CRAB was significantly lower in Period 2 and 3 compared with Period 1 (P < 0.0001). The detection rate of CRPA and VREfm was significantly increased in Period 3 compared with Period 1 and 2 (P < 0.0001). The resistance rate to ticarcillin/clavulanic acid (TIM) and piperacillin/tazobactam (TZP) has gradually increased in CRPA since 2018. NDM and KPC were the most common carbapenemase genes identified in CREC (60.0%) and CRKP isolates (47.8%), respectively. All the 10 VREfm isolates carried the vanA gene.
CONCLUSIONS
The detection rate of CRAB has decreased since 2018, but a significantly increased prevalence of CRPA and VREfm was seen after the end of zero-policy. An increasing resistance rate to TIM and TZP was seen in CRPA. NDM, KPC, and vanA were the common genes harboured by CREC, CRKP, and VREfm, respectively. Ongoing surveillance after the COVID-19 era is suggested.
Topics: China; Humans; Hospitals, Teaching; COVID-19; Drug Resistance, Multiple, Bacterial; Retrospective Studies; SARS-CoV-2; Anti-Bacterial Agents; Male; Female; Middle Aged; Aged; Adult; Microbial Sensitivity Tests
PubMed: 38458536
DOI: 10.1016/j.jgar.2024.02.021 -
Pharmacotherapy Nov 2023The aim of this study was to compare the achievement of therapeutic pharmacokinetic-pharmacodynamic (PK-PD) exposure targets for beta-lactam antibiotics using product...
STUDY OBJECTIVE
The aim of this study was to compare the achievement of therapeutic pharmacokinetic-pharmacodynamic (PK-PD) exposure targets for beta-lactam antibiotics using product information dosing or guideline-based dosing for the treatment of serious infections.
DESIGN
In silico study.
DATA SOURCE
ID-ODS (Individually Designed Optimum Dosing Strategies).
PATIENTS AND INTERVENTION
None.
MEASUREMENTS AND MAIN RESULTS
In silico product information and guideline-based dosing simulations for cefepime, ceftazidime, flucloxacillin, meropenem, and piperacillin/tazobactam were performed using pharmacokinetic models from seriously ill patient populations. The median simulated concentration at 48 and 96 h was used to measure the probability of target attainment (PTA) to achieve predefined therapeutic and toxicity PK-PD targets. A multiple linear regression model was constructed to identify the effect of guideline-based dosing covariates on achieving pre-defined therapeutic targets. In total, 480 dosing simulations were performed. The PTA percentage with guideline-based dosing at 48 and 96 h was 80% and 68%, respectively, yielding significantly higher results when compared to product information dosing (48.45% and 49%, respectively), p < 0.001 at both time points. At 48 h, predefined toxicity thresholds were exceeded in 4.7% and 0% of simulations for guideline-based and product information-based dosing, respectively (p = 0.002). eGFR was significantly associated with the % PTA by guideline-based dosing, with eGFR values of 20 and 50 ml/min both statistically significant in leading to an increase in PTA.
CONCLUSIONS
Our study demonstrated that achievement of PK-PD exposures associated with an increased likelihood of effectiveness was more likely to occur with guideline-based dosing; especially at 48 h.
Topics: Adult; Humans; Anti-Bacterial Agents; Lactams; Meropenem; Cefepime; Ceftazidime; Critical Illness; Microbial Sensitivity Tests
PubMed: 36567467
DOI: 10.1002/phar.2753 -
International Journal of Clinical... Aug 2023In Europe, Serbia occupies a high position in antibiotic utilization and antimicrobial resistance (AMR).
BACKGROUND
In Europe, Serbia occupies a high position in antibiotic utilization and antimicrobial resistance (AMR).
AIM
The aim was to analyse utilization trends of meropenem, ceftazidime, aminoglycosides, piperacillin/tazobactam and fluoroquinolones (2006-2020), and the reported AMR in Pseudomonas aeruginosa (2013-2020) in Serbia and to compare with data from eight European countries (2015-2020).
METHOD
Joinpoint regression was used to analyse antibiotic utilization data (2006-2020) and the reported AMR in Pseudomonas aeruginosa (2013-2020). Data sources were relevant national and international institutions. Antibiotic utilization and AMR in Pseudomonas aeruginosa data in Serbia were compared with eight European countries.
RESULTS
There was a significantly increased trend for ceftazidime utilization and reported resistance in Pseudomonas aeruginosa, Serbia (p < 0.05) (2018-2020). For ceftazidime, piperacillin/tazobactam, and fluoroquinolones resistances in Pseudomonas aeruginosa an increased trend was observed, Serbia (2013-2020). A decrease in both the utilization of aminoglycosides, Serbia (p < 0.05) (2006-2018) and contemporaneous Pseudomonas aeruginosa resistance (p > 0.05) was detected. Fluoroquinolone utilization (2015-2020) was highest in Serbia compared to Netherlands and Finland, 310 and 305% higher, similar compared to Romania, and 2% less compared to Montenegro. Aminoglycosides (2015-2020) were 2550 and 783% more used in Serbia compared to Finland and Netherlands, and 38% less regarding Montenegro. The highest percentage of Pseudomonas aeruginosa resistance was in Romania and Serbia (2015-2020).
CONCLUSION
The use of piperacillin/tazobactam, ceftazidime and fluoroquinolones should be carefully monitored in clinical practice due to increased Pseudomonas aeruginosa resistance. The level of utilization and AMR in Pseudomonas aeruginosa is still high in Serbia compared to other European countries.
Topics: Humans; Ceftazidime; Pseudomonas aeruginosa; Serbia; Pseudomonas Infections; Anti-Bacterial Agents; Anti-Infective Agents; Aminoglycosides; Fluoroquinolones; Piperacillin, Tazobactam Drug Combination
PubMed: 37284904
DOI: 10.1007/s11096-023-01603-y -
Antibiotics (Basel, Switzerland) Nov 2023Antimicrobial resistance (AMR), a serious global public health challenge, may have accelerated development during the COVID-19 pandemic because antibiotics were...
Antimicrobial resistance (AMR), a serious global public health challenge, may have accelerated development during the COVID-19 pandemic because antibiotics were prescribed for COVID-19. This study aimed to assess antibiotics use before and during the pandemic and correlate the results with the rate of resistant microorganisms detected in hospitalized patients during the study period. This single-center study looked retrospectively at four years of data (2018-2021) from Royal Hospital, Muscat, which is the biggest hospital in Oman with approximately 60,000 hospital admissions yearly. The consumption rate of ceftriaxone, piperacillin tazobactam, meropenem, and vancomycin was presented as the antibiotic consumption index, the ratio of defined daily dose (DDD) per 100 bed days. Analyses were performed using the nonparametric test for trend across the study period. Correlation between antibiotic consumption indexes and the isolated microorganisms in the four-year study period was performed using Spearman's rank correlation coefficient. We compared data from the pre-COVID-19 to the COVID-19 period. Though more patients were admitted pre-COVID-19 (132,828 versus 119,191 during COVID-19), more antibiotics were consumed during the pandemic (7350 versus 7915); vancomycin and ceftriaxone had higher consumption during than before the pandemic (-values 0.001 and 0.036, respectively). Vancomycin-resistant Enterococcus (VRE) and were detected more during the COVID-19 period with -values of 0.026 and 0.004, respectively. Carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant spp., and were detected more often during the pandemic with -values of 0.011, 0.002, and 0.03, respectively. Significant positive correlations between antibiotic consumption and drug-resistant isolates were noted. This study confirms that the overuse of antibiotics triggers the development of bacterial resistance; our results emphasize the importance of antibiotic control.
PubMed: 38136699
DOI: 10.3390/antibiotics12121665 -
PLoS Pathogens Jun 2024Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the...
Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales. Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In37 have been "harvested" by insertion sequence IS26 as a transposon that is widely disseminated among the Enterobacterales. This transposon encodes the enzymes AAC(6')-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS26/In37-derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.
Topics: Humans; Anti-Bacterial Agents; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Piperacillin; Amikacin; Microbial Sensitivity Tests; Enterobacteriaceae Infections; Enterobacteriaceae; Integrons; Bacteremia
PubMed: 38843111
DOI: 10.1371/journal.ppat.1012235 -
Frontiers in Microbiology 2023Gram-negative bacilli are one of the most common causes of various infections in clinical. The emergence and global spread of multi-drug resistant gram-negative bacilli...
Distribution and antimicrobial resistance analysis of gram-negative bacilli isolated from a tertiary hospital in Central China: a 10-year retrospective study from 2012 to 2021.
BACKGROUND
Gram-negative bacilli are one of the most common causes of various infections in clinical. The emergence and global spread of multi-drug resistant gram-negative bacilli has become a major challenge in the global public health field.
METHODS
A total of 51,189 non-repetitive strains of gram-negative bacilli were isolated in clinical settings. The antimicrobial susceptibility testing was conducted by using the automated VITEK 2 compact system and the matched AST susceptibility test card, complemented by the disk diffusion method. The antimicrobial susceptibility results were interpreted by CLSI. Rates of MDR and XDR in , , and were investigated. Used the chi-square test to determine whether the antimicrobial resistance rates of four major gram-negative bacilli isolated from ICU and non-ICU department have statistical differences.
RESULTS
(31.4%), spp. (21.2%), spp. (13.8%), and (11.0%) were the most frequently isolated gram-negative bacilli. was the top one organism isolated from urinary tract (68.4%), bloodstream (39.9%), body fluid (33.2%), wound and pus (37%), except for respiratory tract (8.8%). Whereas and were the major isolated organisms from respiratory tract. showed high resistance to fluoroquinolones, β-lactam/β-lactamase inhibitor combinations class, ceftazidime, cefepime, imipenem, and meropenem, the resistance rates reached more than 70%. Ceftazidime showed a lower resistance rate to than ceftriaxone. For , fluoroquinolones showed a high resistance rate (ciprofloxacin 61.36% and levofloxacin 53.97%), whereas amikacin, carbapenems exhibited a lower resistance rate fluctuating at 2%. and showed rapid increases in carbapenem resistance whereas had the lowest resistance rate and remain stable at 2%. exhibited the highest rate of MDR and XDR, reaching 60-80 and 45-55%, respectively. Compared to non-ICU departments, the resistance rates of four major gram-negative bacilli in the ICU department were much higher and the differences were statistically significant ( < 0.05).
CONCLUSION
Amikacin, carbapenems, and piperacillin/tazobactam exhibited relatively high sensitivity, whereas fluoroquinolones showed high resistance rate whether they can be the first-line antimicrobials for empirical treatment of UTI should take more consideration. The gram-negative bacilli in ICU were more resistance than that in non-ICU. These findings are helpful for clinicians using antimicrobials reasonably.
PubMed: 38111644
DOI: 10.3389/fmicb.2023.1297528 -
In Vivo (Athens, Greece) 2024Pharmacovigilance data and clinical studies have indicated a risk of acute kidney injury (AKI) associated with concomitant administration of vancomycin and...
BACKGROUND/AIM
Pharmacovigilance data and clinical studies have indicated a risk of acute kidney injury (AKI) associated with concomitant administration of vancomycin and piperacillin-tazobactam. However, no pharmacovigilance studies have evaluated time-to-onset and outcomes of AKI related to this combination. Therefore, this study used a pharmacovigilance database to investigate the incidence, time-to-onset, and outcomes of AKI in patients treated with intravenous vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics.
PATIENTS AND METHODS
From data in the Japanese Adverse Drug Event Report (JADER) database, we calculated the reporting odds ratios (RORs) and 95% confidence intervals (CIs), time-to-onset, and outcomes of AKI following intravenous administration of vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics and with other vancomycin regimens, including monotherapy.
RESULTS
The JADER database contained 4,471 reports of intravenous vancomycin treatment, including 517 reports of AKI. The adjusted RORs (95%CIs) of AKI in cases with co-administration of intravenous vancomycin and piperacillin-tazobactam was 2.58 (2.06-3.24). The median time-to-onset for AKI in vancomycin plus piperacillin-tazobactam was 6.0 (interquartile range=3.0-10.3). Weibull shape parameter analysis showed that the pattern of onset of AKI in vancomycin plus piperacillin-tazobactam represented a wear out failure, predicting an increasing hazard with time. For the outcome of AKI, there was no significant difference between all vancomycin regimen and the piperacillin-tazobactam combination groups.
CONCLUSION
Concomitant use of intravenous vancomycin and piperacillin-tazobactam may increase the incidence of AKI but may not affect the outcome. This combination does not necessarily have to be avoided, but long-term use is not advisable.
Topics: Vancomycin; Acute Kidney Injury; Humans; Piperacillin, Tazobactam Drug Combination; Male; Female; Anti-Bacterial Agents; Middle Aged; Aged; Drug Therapy, Combination; Adult; Incidence; Pharmacovigilance; Databases, Factual; Aged, 80 and over; Risk Factors
PubMed: 38688650
DOI: 10.21873/invivo.13586 -
Clinical Microbiology and Infection :... Sep 2023To analyse carbapenemases in Proteus mirabilis and assess the performance of carbapenemase detection assays.
OBJECTIVES
To analyse carbapenemases in Proteus mirabilis and assess the performance of carbapenemase detection assays.
METHODS
Eighty-one clinical P. mirabilis isolates with high-level resistance at least to ampicillin (>32 mg/L) or previous detection of carbapenemases were selected and investigated by three susceptibility testing methods (microdilution, automated susceptibility testing, and disk diffusion), six phenotypic carbapenemase assays (CARBA NP, modified carbapenemase inactivation method [CIM], modified zinc-supplemented CIM, simplified CIM, faropenem, and carbapenem-containing agar), two immunochromatographic assays, and whole-genome sequencing.
RESULTS
Carbapenemases were detected in 43 of 81 isolates (OXA-48-like [n = 13]; OXA-23 [n = 12]; OXA-58 [n = 12]; New Delhi metallo-β-lactamase (NDM) [n = 2]; Verona integron-encoded metallo-β-lactamase (VIM) [n = 2]; Imipenemase (IMP) [n = 1]; Klebsiella pneumoniae carbapenemase (KPC) [n = 1]). Carbapenemase-producing Proteus were frequently susceptible to ertapenem (26/43; 60%), meropenem (28/43; 65%), ceftazidime (33/43; 77%), and some even to piperacillin-tazobactam (9/43; 21%). Sensitivity/specificity of phenotypic tests were 30% (CI: 17-46%)/89% (CI: 75-97%) for CARBA NP, 74% (CI: 60-85%)/82% (CI: 67-91%) for faropenem, 91% (CI: 78-97%)/82% (CI: 66-92%) for simplified CIM, and 93% (CI: 81-99%)/100% (CI: 91-100%) for modified zinc-supplemented CIM. An algorithm for improved detection was developed, which demonstrated sensitivity/specificity of 100% (CI: 92-100%)/100% (CI: 91-100%) on the 81 isolates, and 100% (CI: 29-100%)/100% (CI: 96-100%) in a prospective analysis of additional 91 isolates. Interestingly, several OXA-23-producing isolates belonged to the same clonal lineage reported previously from France.
DISCUSSION
Current susceptibility testing methods and phenotypic tests frequently fail to detect carbapenemases in P. mirabilis, which could result in inadequate antibiotic treatment. In addition, the non-inclusion of bla in many molecular carbapenemase assays further impedes their detection. Therefore, the prevalence of carbapenemases in P. mirabilis is likely underestimated. With the herein proposed algorithm, carbapenemase-producing Proteus can be easily identified.
Topics: Humans; Proteus mirabilis; Bacterial Proteins; beta-Lactamases; Anti-Bacterial Agents; Algorithms; Zinc; Microbial Sensitivity Tests
PubMed: 37271195
DOI: 10.1016/j.cmi.2023.05.032 -
PloS One 2023Multi-drug resistant (MDR) globally disseminated extraintestinal pathogenic high-risk Escherichia coli (ExPEC) clones are threatening the gains in bacterial disease...
Resistome and virulome of high-risk pandemic clones of multidrug-resistant extra-intestinal pathogenic Escherichia coli (ExPEC) isolated from tertiary healthcare settings in Uganda.
Multi-drug resistant (MDR) globally disseminated extraintestinal pathogenic high-risk Escherichia coli (ExPEC) clones are threatening the gains in bacterial disease management. In this study, we evaluated the genomic structure including the resistome and virulome of the E. coli isolates from extraintestinal infections using whole genome sequencing (WGS). The results highlight that isolates were highly resistant (≥ 90.0%) to commonly used antibiotics (Ampicillin, Trimethoprim-Sulfamethoxazole, Nalidixic acid, and Piperacillin) and were less (<14%) resistant to last resort antibiotics; Imipenem (10.94%) and Meropenem (10.20%). A greater proportion of the E. coli isolates belonged to phylogroup B2 (30.52%) and phylogroup A (27.37%). The sequence types ST131 of phylogroup B2 (21.05%) and ST648 of phylogroup F (9.3%) were the dominant pandemic high-risk clones identified in addition to the ST1193, ST410, ST69, ST38, ST405, and ST10. Many of the isolates were MDR and most (64.58%) carried the blaCTX-M-15 gene for extended-spectrum β-lactamases. There was a high correlation between phylogroups and the occurrence of both antimicrobial resistance and virulence genes. The cephalosporin-resistance gene blaEC-5 was only found in phylogroup B2 while blaEC-8 and blaEC-19, were only found within phylogroup D and phylogroup F respectively. Aminoglycoside gene (aadA1) was only associated with phylogroups D and C. The isolates were armed with a broad range of virulence genes including adhesins, toxins, secreted proteases, iron uptake genes, and others. The yfcv, chuA, and kpsE genes preferentially occurred among isolates of phylogroup B2. The study underlines the predominance of MDR internationally disseminated high-risk ExPEC clones with a broad range of virulence genes known to be highly transmissible in healthcare and community settings.
Topics: Humans; Escherichia coli; Extraintestinal Pathogenic Escherichia coli; Escherichia coli Infections; Tertiary Healthcare; Uganda; Pandemics; Genotype; Anti-Bacterial Agents; Virulence Factors; beta-Lactamases; Membrane Transport Proteins; Escherichia coli Proteins
PubMed: 37992119
DOI: 10.1371/journal.pone.0294424 -
Antibiotics (Basel, Switzerland) Dec 2023Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal... (Review)
Review
BACKGROUND
Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population.
METHODS
We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients. We extracted and synthetized data on drug regimens and their ability to attain adequate PK/PD targets.
RESULTS
We selected 35 studies for analysis. Overall, studies showed that both high doses and the continuous infusion (CI) of broad-spectrum beta-lactams were needed to achieve internationally-recognized PK/PD targets, ideally with therapeutic drug monitoring guidance. The most extensive evidence concerned meropenem, but similar conclusions could be drawn about piperacillin-tazobactam, ceftazidime, cefepime, imipenem-clinastatin and aztreonam. Insufficient data were available about new beta-lactam-beta-lactamase inhibitor combinations, ceftaroline, ceftobiprole and cefiderocol.
CONCLUSIONS
Both high doses and CI of broad-spectrum beta-lactams are needed when treating burn patients due to the peculiar changes in the PK/PD of antibiotics in this population. Further studies are needed, particularly about newer antibiotics.
PubMed: 38136771
DOI: 10.3390/antibiotics12121737