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European Journal of Hospital Pharmacy :... Dec 2023Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical...
BACKGROUND
Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)', which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world.
METHODS
Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022.
RESULTS
We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.This review has not been registered under PROSPERO.
Topics: Humans; Anti-Bacterial Agents; beta Lactam Antibiotics; Inpatients; Temperature; Ceftazidime
PubMed: 37848286
DOI: 10.1136/ejhpharm-2023-003855 -
Pharmacotherapy Nov 2023Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of... (Review)
Review
Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: (1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, (2) evaluate the quality of evidence supporting these data, and (3) propose dosing recommendations based on the synthesis of these data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction were conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recommendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials, and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.
Topics: Humans; Adult; Intermittent Renal Replacement Therapy; Critical Illness; Anti-Bacterial Agents; Anti-Infective Agents; Vancomycin; Renal Replacement Therapy
PubMed: 37596844
DOI: 10.1002/phar.2861 -
Frontiers in Medicine 2023Carbapenem-resistant (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment...
, and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant and multidrug-resistant isolates or infections: a scoping review.
INTRODUCTION
Carbapenem-resistant (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate , and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections.
METHODS
We systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded.
RESULTS
22 , 7 and 20 clinical studies were evaluated. studies showed reliable synergy between CZA and aztreonam against metallo-β-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer or studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies.
DISCUSSION
The benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552.
PubMed: 37727767
DOI: 10.3389/fmed.2023.1249030 -
Infectious Diseases & Clinical... Sep 2023This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes. (Review)
Review
OBJECTIVE
This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes.
MATERIALS AND METHODS
It was conducted according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using the keywords "Pancrea AND carbapenem OR imipenem OR ertapenem OR meropenem OR doripenem." Primer outcomes were mortality, surgical intervention, and pancreatic and non-pancreatic infection. Subgroup analyses were also performed to reduce the risk of bias.
RESULTS
Ten studies with 4038 patients were included in the meta-analyses. While eight of ten were randomized controlled trials, two were observational studies. The prophylactic use of carbapenems had no statistically significant effect on mortality (OR=0.82, 95% CI=0.65-1.04, I²=0%) and surgical intervention. (OR=0.81, 95% CI=0.57-1.17, I²=0%). However, the real impact of prophylaxis on reducing the incidence of mortality and surgical intervention was uncertain due to the insufficient sample size. The prophylactic use of carbapenems was significantly associated with a lower risk of peripancreatic (OR=0.37, 95% CI=0.25-0.55, I²=61%) and non-pancreatic infection risk (OR=0.60, 95% CI=0.46-0.78, I²=65%). The definitions of infection in the articles were not clear, and the diagnostic approach to infection was based on subjective criteria. In addition, there was inadequate collateral damage and safety assessments. In high-quality studies with a low risk of bias, prophylactic carbapenems had no effect on peripancreatic infection (RR=1.54, 95% CI=0.65-3.47, I²=0%) and non-pancreatic infection (RR=0.72, 95% CI=0.48-1.07, I²=0%).
CONCLUSION
Although there is a reduction in the infection risk, routine carbapenem use in acute pancreatitis cases should not be recommended based on current evidence. Cooperation with Infectious Disease specialists and developing diagnostic algorithms are required instead of routine prophylaxis to prevent infection, especially non-pancreatic infection.
PubMed: 38633556
DOI: 10.36519/idcm.2023.239 -
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 -
JAC-antimicrobial Resistance Jun 2024Antimicrobial resistance (AMR) is a serious threat to global health systems. is a major cause of urinary tract infections (UTIs). Understanding the AMR patterns of... (Review)
Review
BACKGROUND
Antimicrobial resistance (AMR) is a serious threat to global health systems. is a major cause of urinary tract infections (UTIs). Understanding the AMR patterns of uropathogenic (UPEC) is crucial for effective public health interventions worldwide.
OBJECTIVES
This systematic review and meta-analysis aimed to consolidate existing research and provide a comprehensive information on AMR UPEC in Ethiopia.
METHODS
We systematically searched databases such as PubMed, Web of Science, and Science Direct, along with including articles from Google Scholar. Data were extracted into Microsoft Excel and analysed using STATA 17.0. Cohen's kappa was computed to assess reviewer agreement, while the I statistic evaluated heterogeneity. Egger's tests were conducted to detect publication bias, and random-effects models were utilized to estimate the pooled resistance, with AMR rates for each antibiotic pooled separately.
RESULTS
UPEC showed resistance rates, ranging from 3.64% (95% CI: -4.38% to 11.67%) for amikacin to 85.32% (95% CI: 78.6%-92.04%) for ampicillin. Highest resistance was to ampicillin (85.32%), followed by amoxicillin at 82.52% (95% CI: 74.3%-90.74%), tetracycline at 60.67% (95% CI: 51.53%-69.81%) and trimethoprim/sulfamethoxazole at 57.17% (95% CI: 49.93%-64.42%). Conversely, resistance rates were lower for amikacin at 3.64% and meropenem at 5.26% (95% CI: 2.64%-7.88%). UPEC demonstrated a pooled MDR rate of 79.17% (95% CI: 70.32%-88.01%) and a pooled ESBL production rate of 29.16% (95% CI: 22.36%-38.55%).
CONCLUSIONS
High levels of AMR were observed in UPEC strains, highlighting a critical public health issue requiring urgent action through robust antimicrobial stewardship and surveillance to preserve effective UTI treatment options.
PubMed: 38716402
DOI: 10.1093/jacamr/dlae068 -
Annals of Clinical Microbiology and... Mar 2024Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge.
AIM
The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies.
METHOD
A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis.
RESULT
Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010.
CONCLUSIONS
Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Minocycline; Stenotrophomonas maltophilia; Microbial Sensitivity Tests; Anti-Bacterial Agents; Cefiderocol; Drug Resistance, Microbial; Gram-Negative Bacterial Infections
PubMed: 38504262
DOI: 10.1186/s12941-024-00685-4 -
Antimicrobial Resistance and Infection... Apr 2024Antimicrobial resistance (AMR) is a pressing global health concern, particularly pronounced in low-resource settings. In Ethiopia, the escalating prevalence of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antimicrobial resistance (AMR) is a pressing global health concern, particularly pronounced in low-resource settings. In Ethiopia, the escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) poses a substantial threat to public health.
METHODS
A comprehensive search of databases, including PubMed, Scopus, Embase, Hinari, and Google Scholar, identified relevant studies. Inclusion criteria encompassed observational studies reporting the prevalence of meropenem-resistant P. aeruginosa in Ethiopia. Quality assessment utilized JBI checklists. A random-effects meta-analysis pooled data on study characteristics and prevalence estimates, with subsequent subgroup and sensitivity analyses. Publication bias was assessed graphically and statistically.
RESULTS
Out of 433 studies, nineteen, comprising a total sample of 11,131, met inclusion criteria. The pooled prevalence of meropenem-resistant P. aeruginosa was 15% (95% CI: 10-21%). Significant heterogeneity (I = 83.6%) was observed, with the number of P. aeruginosa isolates identified as the primary source of heterogeneity (p = 0.127). Subgroup analysis by infection source revealed a higher prevalence in hospital-acquired infections (28%, 95% CI: 10, 46) compared to community settings (6%, 95% CI: 2, 11). Geographic based subgroup analysis indicated the highest prevalence in the Amhara region (23%, 95% CI: 8, 38), followed by Addis Ababa (21%, 95% CI: 11, 32), and lower prevalence in the Oromia region (7%, 95% CI: 4, 19). Wound samples exhibited the highest resistance (25%, 95% CI: 25, 78), while sputum samples showed the lowest prevalence. Publication bias, identified through funnel plot examination and Egger's regression test (p < 0.001), execution of trim and fill analysis resulted in an adjusted pooled prevalence of (3.7%, 95% CI: 2.3, 9.6).
CONCLUSION
The noteworthy prevalence of meropenem resistance among P. aeruginosa isolates in Ethiopia, particularly in healthcare settings, underscores the urgency of implementing strict infection control practices and antibiotic stewardship. Further research is imperative to address and mitigate the challenges posed by antimicrobial resistance in the country.
Topics: Humans; Anti-Infective Agents; Ethiopia; Meropenem; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Drug Resistance, Bacterial
PubMed: 38600535
DOI: 10.1186/s13756-024-01389-2 -
Antibiotics (Basel, Switzerland) Feb 2024Optimizing antibiotic therapy is imperative with rising bacterial resistance and high infection mortality. Extended infusion defined as a continuous infusion (COI) or... (Review)
Review
Optimizing antibiotic therapy is imperative with rising bacterial resistance and high infection mortality. Extended infusion defined as a continuous infusion (COI) or prolonged infusion (PI) of beta-lactams and glycopeptides might improve efficacy and safety compared to their intermittent administration (IA). This study aimed to evaluate the efficacy and safety of extended infusion in pediatric patients. Adhering to Cochrane standards, we conducted a systematic review with meta-analysis investigating the efficacy and safety of COI (24 h/d) and PI (>1 h/dose) compared to IA (≤1 h/dose) of beta-lactams and glycopeptides in pediatrics. Primary outcomes included mortality, clinical success, and microbiological eradication. Five studies could be included for the outcome mortality, investigating meropenem, piperacillin/tazobactam, cefepime, or combinations of these. The pooled relative risk estimate was 0.48 (95% CI 0.26-0.89, = 0.02). No significant differences between the administration modes were found for the outcomes of clinical success, microbiological eradication (beta-lactams; glycopeptides), and mortality (glycopeptides). No study reported additional safety issues, e.g., adverse drug reactions when using COI/PI vs. IA. Our findings suggest that the administration of beta-lactams by extended infusion leads to a reduction in mortality for pediatric patients.
PubMed: 38391550
DOI: 10.3390/antibiotics13020164 -
Acta Anaesthesiologica Scandinavica Aug 2023Piperacillin/tazobactam or meropenem are often used to treat patients with severe bacterial infections. We aimed to compare the desirable and undesirable effects of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Piperacillin/tazobactam or meropenem are often used to treat patients with severe bacterial infections. We aimed to compare the desirable and undesirable effects of empirical and/or definitive piperacillin/tazobactam versus carbapenems in patients with severe bacterial infections.
METHODS
We searched PubMed, Embase, CENTRAL, Epistemonikos, and trial registers for randomised clinical trials of empirical and/or definitive piperacillin/tazobactam versus carbapenems in adult patients with severe bacterial infection (i.e., any bacterial infection requiring hospitalisation). The primary outcome was all-cause short-term mortality within 90 days. Secondary outcomes were all-cause long-term mortality, adverse events, quality of life, days alive without or duration of life support, secondary infections, selection of fungi or resistant bacteria, and days alive and out of hospital or hospital length of stay. We calculated relative risks (RRs) using random effects and fixed effect meta-analyses along with trial sequential analyses.
RESULTS
We included 31 trials (n = 8790 patients) with overall high risk of bias. The RR for all-cause short-term mortality was 1.16 (95% confidence interval [CI]: 0.94-1.43, low certainty evidence), for adverse events 1.00 (98% CI: 0.96-1.04, moderate certainty evidence), for secondary infections 1.13 (98% CI: 0.76-1.68, very low certainty evidence), and for selection of fungi or resistant bacteria 1.61 (98% CI: 0.89-2.89, very low certainty evidence). There were no or limited data for the remaining outcomes.
CONCLUSIONS
Based on very low or low certainty evidence, piperacillin/tazobactam may be associated with less favourable outcomes in patients with severe bacterial infections as compared with carbapenems, but the information size for a robust conclusion has not been reached.
Topics: Adult; Humans; Carbapenems; Coinfection; Quality of Life; Piperacillin, Tazobactam Drug Combination; Bacterial Infections; Bacteria
PubMed: 36919866
DOI: 10.1111/aas.14239