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Critical Care Medicine Jan 2018The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy.
DATA SOURCES
Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched.
STUDY SELECTION
Articles not in English, pediatric studies, and case reports were excluded.
DATA EXTRACTION
Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3.
DATA SYNTHESIS
Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11).
CONCLUSIONS
The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.
Topics: Acute Kidney Injury; Adult; Critical Care; Drug Therapy, Combination; Humans; Observational Studies as Topic; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic; Vancomycin
PubMed: 29088001
DOI: 10.1097/CCM.0000000000002769 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Possibly due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units. The last Cochrane Review was updated in 2004. Given the clinical importance, an updated systematic review assessing the effects of different antibiotic regimens for early-onset neonatal sepsis is needed.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for early-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2020, Issue 8); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for early-onset neonatal sepsis. We included participants from birth to 72 hours of life at randomisation.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (865 participants). All trials were at high risk of bias. The certainty of the evidence according to GRADE was very low. The included trials assessed five different comparisons of antibiotics. We did not conduct any meta-analyses due to lack of relevant data. Of the five included trials one trial compared ampicillin plus gentamicin with benzylpenicillin plus gentamicin; one trial compared piperacillin plus tazobactam with amikacin; one trial compared ticarcillin plus clavulanic acid with piperacillin plus gentamicin; one trial compared piperacillin with ampicillin plus amikacin; and one trial compared ceftazidime with benzylpenicillin plus gentamicin. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. Large RCTs assessing different antibiotic regimens in early-onset neonatal sepsis with low risk of bias are warranted.
Topics: Anti-Bacterial Agents; Bias; Cause of Death; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic
PubMed: 33998666
DOI: 10.1002/14651858.CD013837.pub2 -
British Journal of Clinical Pharmacology Sep 2022This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence. (Meta-Analysis)
Meta-Analysis Review
AIMS
This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence.
METHODS
This study assessed risk factors for vancomycin-associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Fifty-three studies were included in our meta-analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16-1.87), Caucasian (OR 0.72, 95% CI: 0.58-0.90) and obesity (OR 1.46, 95% CI: 1.12-1.90) were associated with an increase in vancomycin-associated AKIs. In terms of vancomycin-related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06-2.83), serum vancomycin trough level >15 μg/mL (OR 2.10, 95% CI: 1.43-3.07) and vancomycin trough level >20 μg/mL (OR 2.84, 95% CI: 1.48-5.44) increased the risks of vancomycin-associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51-3.17) showed the highest odds of vancomycin-associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44-7.87) showed the highest odds of vancomycin-associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39-7.46), vasopressors, loop diuretics, piperacillin-tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17-2.58) increased the odds of vancomycin-associated AKI.
CONCLUSION
Our results may help predict the risk of vancomycin-associated AKI in the clinical setting.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Retrospective Studies; Risk Factors; Vancomycin
PubMed: 35665530
DOI: 10.1111/bcp.15429 -
Antimicrobial Resistance and Infection... Sep 2020Clostridioides (Clostridium) difficile is an important pathogen of healthcare- associated diarrhea, however, an increase in the occurrence of C. difficile infection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clostridioides (Clostridium) difficile is an important pathogen of healthcare- associated diarrhea, however, an increase in the occurrence of C. difficile infection (CDI) outside hospital settings has been reported. The accumulation of antimicrobial resistance in C. difficile can increase the risk of CDI development and/or its spread. The limited number of antimicrobials for the treatment of CDI is matter of some concern.
OBJECTIVES
In order to summarize the data on antimicrobial resistance to C. difficile derived from humans, a systematic review and meta-analysis were performed.
METHODS
We searched five bibliographic databases: (MEDLINE [PubMed], Scopus, Embase, Cochrane Library and Web of Science) for studies that focused on antimicrobial susceptibility testing in C. difficile and were published between 1992 and 2019. The weighted pooled resistance (WPR) for each antimicrobial agent was calculated using a random- effects model.
RESULTS
A total of 111 studies were included. The WPR for metronidazole and vancomycin was 1.0% (95% CI 0-3%) and 1% (95% CI 0-2%) for the breakpoint > 2 mg/L and 0% (95% CI 0%) for breakpoint ≥32 μg/ml. Rifampin and tigecycline had a WPRs of 37.0% (95% CI 18-58%) and 1% (95% CI 0-3%), respectively. The WPRs for the other antimicrobials were as follows: ciprofloxacin 95% (95% CI 85-100%), moxifloxacin 32% (95% CI 25-40%), clindamycin 59% (95% CI 53-65%), amoxicillin/clavulanate 0% (0-0%), piperacillin/tazobactam 0% (0-0%) and ceftriaxone 47% (95% CI 29-65%). Tetracycline had a WPR 20% (95% CI 14-27%) and meropenem showed 0% (95% CI 0-1%); resistance to fidaxomicin was reported in one isolate (0.08%).
CONCLUSION
Resistance to metronidazole, vancomycin, fidaxomicin, meropenem and piperacillin/tazobactam is reported rarely. From the alternative CDI drug treatments, tigecycline had a lower resistance rate than rifampin. The high-risk antimicrobials for CDI development showed a high level of resistance, the highest was seen in the second generation of fluoroquinolones and clindamycin; amoxicillin/clavulanate showed almost no resistance. Tetracycline resistance was present in one fifth of human clinical C. difficile isolates.
Topics: Anti-Bacterial Agents; Clindamycin; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests
PubMed: 32977835
DOI: 10.1186/s13756-020-00815-5 -
Clinical Pharmacokinetics Feb 2020Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target...
BACKGROUND
Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.
METHODS
Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life.
RESULTS
50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles.
CONCLUSION
The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.
Topics: Acute Kidney Injury; Adolescent; Aminoglycosides; Anti-Bacterial Agents; Area Under Curve; Carbapenems; Cephalosporins; Child; Child, Preschool; Critical Illness; Drug Monitoring; Female; Half-Life; Humans; Infant; Infusions, Intravenous; Male; Penicillins; Vancomycin; Young Adult
PubMed: 31432468
DOI: 10.1007/s40262-019-00813-w -
The Journal of Infection Dec 2019Antibiotics change the composition of the intestinal microbiota. The magnitude of the effect of antibiotics on the microbiota and whether the effects are short-term or...
OBJECTIVE
Antibiotics change the composition of the intestinal microbiota. The magnitude of the effect of antibiotics on the microbiota and whether the effects are short-term or persist long-term remain uncertain. In this review, we summarise studies that have investigated the effect of antibiotics on the composition of the human intestinal microbiota.
METHODS
A systematic search was done to identify original studies that have investigated the effect of systemic antibiotics on the intestinal microbiota in humans.
RESULTS
We identified 129 studies investigating 2076 participants and 301 controls. Many studies reported a decrease in bacterial diversity with antibiotic treatment. Penicillin only had minor effects on the intestinal microbiota. Amoxicillin, amoxcillin/clavulanate, cephalosporins, lipopolyglycopeptides, macrolides, ketolides, clindamycin, tigecycline, quinolones and fosfomycin all increased abundance of Enterobacteriaea other than E. coli (mainly Citrobacter spp., Enterobacter spp. and Klebsiella spp.). Amoxcillin, cephalosporins, macrolides, clindamycin, quinolones and sulphonamides decreased abundance of E. coli, while amoxcillin/clavulante, in contrast to other penicillins, increased abundance of E. coli. Amoxicllin, piperacillin and ticarcillin, cephalosporins (except fifth generation cephalosporins), carbapenems and lipoglycopeptides were associated with increased abundance of Enterococcus spp., while macrolides and doxycycline decreased its abundance. Piperacillin and ticarcillin, carbapenems, macrolides, clindamycin and quinolones strongly decreased the abundance of anaerobic bacteria. In the studies that investigated persistence, the longest duration of changes was reported after treatment with ciprofloxacin (one year), clindamycin (two years) and clarithromycin plus metronidazole (four years). Many antibiotics were associated with a decrease in butyrate or butryrate-producing bacteria.
CONCLUSION
Antibiotics have profound and sometimes persisting effects on the intestinal microbiota, characterised by diminished abundance of beneficial commensals and increased abundance of potentially detrimental microorganisms. Understanding these effects will help tailor antibiotic treatment and the use of probiotics to minimise this 'collateral damage'.
Topics: Anti-Bacterial Agents; Gastrointestinal Microbiome; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbiota
PubMed: 31629863
DOI: 10.1016/j.jinf.2019.10.008 -
Revista Do Instituto de Medicina... 2021The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were...
The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with systemic inflammatory response syndrome, harboring C. striatum isolated from body fluids or tissues in which it is not normally present. C. striatum had to be identified as the only causative agent of the invasive infection, and its isolation from blood, body fluids or tissues had to be confirmed by one of the more advanced diagnostic methods (biochemical methods, mass spectrometry and/or gene sequencing). This systematic review included 42 studies that analyzed 85 individual cases with various invasive infections caused by C. striatum. More than one isolate of C. striatum exhibited 100% susceptibility to vancomycin, linezolid, teicoplanin, piperacillin-tazobactam, amoxicillin-clavulanate and cefuroxime. On the other hand, some strains of this bacterium showed a high degree of resistance to fluoroquinolones, to the majority majority of β-lactams, aminoglycosides, macrolides, lincosamides and cotrimoxazole. Despite the antibiotic treatment, fatal outcomes were reported in almost 20% of the patients included in this study. Gene sequencing methods should be the gold standard for the identification of C. striatum, while MALDI-TOF and the Vitek system can be used as alternative methods. Vancomycin should be used as the antibiotic of choice for the treatment of C. striatum infections, in monotherapy or in combination with piperacillin-tazobactam. Alternatively, linezolid, teicoplanin or daptomycin may be used in severe infections, while amoxicillin-clavulanate may be used to treat mild infections caused by C. striatum.
Topics: Aminoglycosides; Anti-Bacterial Agents; Corynebacterium; Corynebacterium Infections; Humans; Microbial Sensitivity Tests
PubMed: 34161555
DOI: 10.1590/S1678-9946202163049 -
Antimicrobial Resistance and Infection... 2018Identifying risk factors predicting acquisition of resistant will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Identifying risk factors predicting acquisition of resistant will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic therapy. We conducted a systematic review examining risk factors of acquisition of resistant among hospitalized patients.
METHODS
MEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant , among hospitalized patients. Random effects model meta-analysis was conducted when at least three or more studies were sufficiently similar.
RESULTS
Of the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR) and 26 publications (29 studies) examined resistant The acquisition of MDR , as compared with non-MDR , was significantly associated with intensive care unit (ICU) admission (3 studies: summary adjusted odds ratio [OR] 2.2) or use of quinolones (4 studies: summary adjusted OR 3.59). Acquisition of MDR or XDR compared with susceptible was significantly associated with prior hospital stay (4 studies: summary adjusted OR 1.90), use of quinolones (3 studies: summary adjusted OR 4.34), or use of carbapenems (3 studies: summary adjusted OR 13.68). The acquisition of MDR compared with non- was significantly associated with prior use of cephalosporins (3 studies: summary adjusted OR 3.96), quinolones (4 studies: summary adjusted OR 2.96), carbapenems (6 studies: summary adjusted OR 2.61), and prior hospital stay (4 studies: summary adjusted OR 1.74). The acquisition of carbapenem-resistant compared with susceptible , was statistically significantly associated with prior use of piperacillin-tazobactam (3 studies: summary adjusted OR 2.64), vancomycin (3 studies: summary adjusted OR 1.76), and carbapenems (7 studies: summary adjusted OR 4.36).
CONCLUSIONS
Prior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant . These findings provide guidance in identifying patients that may be at an elevated risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.
Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cephalosporins; Critical Care; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Quinolones; Risk Factors; Vancomycin
PubMed: 29997889
DOI: 10.1186/s13756-018-0370-9 -
Hospital Pharmacy Dec 2023Simultaneous administration of vancomycin and piperacillin-tazobactam (VPT) poses significant challenges related to physical and chemical compatibility, as well as... (Review)
Review
Simultaneous administration of vancomycin and piperacillin-tazobactam (VPT) poses significant challenges related to physical and chemical compatibility, as well as clinical practice. A systematic review of available literature related to VPT Y-site compatibility was performed. Data was collected from primary and tertiary sources. Seven articles were included in addition to one internal assessment and one review article and information from tertiary drug databases. The literature supports the simultaneous administration via Y-site of piperacillin-tazobactam 33.75 mg/mL in normal saline (NS) and vancomycin 4 to 8 mg/mL in NS. The same drug products at differing concentrations, diluents, storage conditions, or preparations outside of this recommendation should be considered incompatible.
PubMed: 38560538
DOI: 10.1177/00185787231169455 -
Clinical Infectious Diseases : An... Mar 2017Concomitant vancomycin and piperacillin/tazobactam may be associated with increased acute kidney injury (AKI) compared to vancomycin without piperacillin/tazobactam. A... (Review)
Review
Concomitant vancomycin and piperacillin/tazobactam may be associated with increased acute kidney injury (AKI) compared to vancomycin without piperacillin/tazobactam. A systematic search of Medline, Cochrane Library, and Scopus through October 2016 using ["vancomycin" and "piperacillin" and "tazobactam"] and ["AKI" or "acute renal failure" or "nephrotoxicity"] and registered meta-analysis (PROSPERO: CRD42016041646) with relevant scenarios was performed. From 307 results, fourteen observational studies totaling 3549 patients were analyzed. Concomitant vancomycin and piperacillin/tazobactam was associated with AKI in unadjusted (odds ratio (OR) 3.12, 95% confidence interval (CI) 2.04-4.78) and adjusted (aOR 3.11, 95% CI 1.77-5.47) analyses. Similar findings were seen assessing studies in adults (aOR 3.15, 95% CI 1.72-5.76), children (OR 4.55, 95% CI 2.71-10.21), and when <50% of patients received care in an intensive care unit (aOR 3.04, 95% CI 1.49-6.22) but not ≥50% (aOR 2.83, 95% CI 0.74-10.85). Increased AKI with concomitant vancomycin and piperacillin/tazobactam should be considered when determining beta-lactam therapy.
PubMed: 27940946
DOI: 10.1093/cid/ciw811