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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 -
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 -
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 -
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 -
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 -
BJS Open May 2024Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend underlines the inadequacy of traditional antibiotic prophylaxis strategies. Hence, the aim of this meta-analysis was to assess the outcomes of antimicrobial prophylaxis, comparing piperacillin/tazobactam with traditional antibiotics.
METHODS
Upon registering in PROSPERO, the international prospective register of systematic reviews (CRD42023479100), a systematic search of various databases was conducted over the interval 2000-2023. This inclusive search encompassed a wide range of study types, including prospective and retrospective cohorts and RCTs. The subsequent data analysis was carried out utilizing RevMan 5.4.
RESULTS
A total of eight studies involving 2382 patients who underwent pancreatoduodenectomy and received either piperacillin/tazobactam (1196 patients) or traditional antibiotics (1186 patients) as antibiotic prophylaxis during surgery were included in the meta-analysis. Patients in the piperacillin/tazobactam group had significantly reduced incidences of surgical-site infections (OR 0.43 (95% c.i. 0.30 to 0.62); P < 0.00001) and major surgical complications (Clavien-Dindo grade greater than or equal to III) (OR 0.61 (95% c.i. 0.45 to 0.81); P = 0.0008). Subgroup analysis of surgical-site infections highlighted significantly reduced incidences of superficial surgical-site infections (OR 0.34 (95% c.i. 0.14 to 0.84); P = 0.02) and organ/space surgical-site infections (OR 0.47 (95% c.i. 0.28 to 0.78); P = 0.004) in the piperacillin/tazobactam group. Further, the analysis demonstrated significantly lower incidences of clinically relevant postoperative pancreatic fistulas (grades B and C) (OR 0.67 (95% c.i. 0.53 to 0.83); P = 0.0003) and mortality (OR 0.51 (95% c.i. 0.28 to 0.91); P = 0.02) in the piperacillin/tazobactam group.
CONCLUSION
Piperacillin/tazobactam as antimicrobial prophylaxis significantly lowers the risk of postoperative surgical-site infections, major surgical complications (complications classified as Clavien-Dindo grade greater than or equal to III), clinically relevant postoperative pancreatic fistulas (grades B and C), and mortality, hence supporting the implementation of piperacillin/tazobactam for surgical prophylaxis in current practice.
Topics: Humans; Pancreaticoduodenectomy; Antibiotic Prophylaxis; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Anti-Bacterial Agents; Piperacillin
PubMed: 38869238
DOI: 10.1093/bjsopen/zrae066 -
Medicina (Kaunas, Lithuania) Mar 2023: Vancomycin combined with piperacillin/tazobactam (vancomycin + piperacillin/tazobactam) has a higher risk of acute kidney injury (AKI) than vancomycin combined with... (Meta-Analysis)
Meta-Analysis Review
Evaluating the Nephrotoxicity of Area-under-the-Curve-Based Dosing of Vancomycin with Concomitant Antipseudomonal Beta-Lactam Antibiotics: A Systematic Review and Meta-Analysis.
: Vancomycin combined with piperacillin/tazobactam (vancomycin + piperacillin/tazobactam) has a higher risk of acute kidney injury (AKI) than vancomycin combined with cefepime or meropenem. However, it is uncertain if applying area under the curve (AUC)-based vancomycin dosing has less nephrotoxicity than trough-based dosing in these combinations. : We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to December 2022. We examined the odds ratio (OR) of AKI between vancomycin + piperacillin/tazobactam and the control group. The control group was defined as vancomycin combined with antipseudomonal beta-lactam antibiotics, except for piperacillin-tazobactam. : The OR for AKI is significantly higher in vancomycin + piperacillin/tazobactam compared with the control group (3 studies, 866 patients, OR of 3.861, 95% confidence interval of 2.165 to 6.887, < 0.05). In the sample population of patients who received vancomycin + piperacillin/tazobactam (2 studies, 536 patients), the risk of AKI (OR of 0.715, 95% CI of 0.439 to 1.163, = 0.177) and daily vancomycin dose (standard mean difference-0.139, 95% CI-0.458 to 0.179; = 0.392) are lower by AUC-based dosing than trough-based dosing, although it is not statistically significant. : Nephrotoxicity is higher when combined with piperacillin/tazobactam than other antipseudomonal beta-lactam antibiotics (cefepime or meropenem) using the AUC-based dosing. However, applying the AUC-based dosing did not eliminate the risk of AKI or significantly reduce thedaily vancomycin dose compared with the trough-based dosing in the available literature.
Topics: Humans; Vancomycin; Anti-Bacterial Agents; Cefepime; Meropenem; Drug Therapy, Combination; Retrospective Studies; Piperacillin, Tazobactam Drug Combination; Monobactams; Acute Kidney Injury
PubMed: 37109649
DOI: 10.3390/medicina59040691 -
Journal of Clinical and Experimental... Oct 2022Patients with odontogenic infections are commonly prescribed antimicrobials on an experiential base without knowing the precise microorganisms implicated. The aim of... (Review)
Review
BACKGROUND
Patients with odontogenic infections are commonly prescribed antimicrobials on an experiential base without knowing the precise microorganisms implicated. The aim of this systematic scoping review is to evaluate the prevalence and proportions of antimicrobial-resistant species in patients with odontogenic infections.
MATERIAL AND METHODS
A systematic scoping review of scientific evidence was accomplished involving different databases.
RESULTS
Eight randomized clinical trials and 13 prospective observational studies were included. These investigations analyzed 1506 patients. The species that showed higher levels of resistance included aerobic and facultative anaerobe such as , and . In obligate anaerobes sampled were Peptostreptococcos spp., Bacteroides spp., and Prevotella spp. Staphylococcus showed resistance to ampicillin, piperacillin, clindamycin, amoxicillin, metronidazole, and penicillin. Streptococcus had resistance to metronidazole, clindamycin, doxycycline, penicillin, and amoxicillin. Peptostreptococcus spp. presented resistance to penicillin, amoxicillin, erythromycin, and cefalexin. Gram-negative microorganisms had resistance to tetracycline, ciprofloxacin, azithromycin, amoxicillin, erythromycin, and penicillin. Bacteroides spp. exhibited resistance to penicillin, erythromycin, and gentamicin. Prevotella spp. showed resistance to penicillin, amoxicillin, erythromycin, clindamycin, levofloxacin, and imipenem. Finally, Klebsiella spp. displayed resistance to ampicillin, amoxicillin, moxifloxacin, and cefalexin. Interestingly, one clinical trial showed that after therapy there was a reduction in sensitivity of 18% for azithromycin and 26% for spiramycin.
CONCLUSIONS
Most of the microorganisms had resistance to diverse groups of antimicrobials. Suitable antimicrobials must be prescribed founded on the microbial samples, culture susceptibility, and clinical progression of the odontogenic infection. Furthermore, it was observed high levels of resistance to antimicrobials that have been used in local and systemic therapy of oral cavity infections. A preponderance of anaerobic microorganisms over aerobic ones was observed. Antibiotic resistance, odontogenic infections, efficacy, microorganisms, scoping review.
PubMed: 36320675
DOI: 10.4317/jced.59830 -
Frontiers in Pharmacology 2022β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing...
β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.
PubMed: 36210807
DOI: 10.3389/fphar.2022.964005 -
The Journal of Hospital Infection May 2024Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can... (Review)
Review
Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can appear to be many times more resistant to antibiotics or disinfectants. This systematic review explores the prevalence and microbial profile associated with biofilm production of bacteria isolated from endotracheal tubes and its associations with antimicrobial resistance. A comprehensive search was performed on databases PubMed, Embase, and Google Scholar for relevant articles published between 1 January 2000 and 31 December 2022. The relevant articles were exported to Mendeley Desktop 1.19.8 and screened by title and abstract, followed by full text screening based on the eligibility criteria of the study. Quality assessment of the studies was performed using the Newcastle-Ottawa Scale (NOS) customized for cross-sectional studies. Furthermore, the prevalence of antimicrobial resistance in biofilm-producers isolated from endotracheal tube specimens was investigated. Twenty studies encompassing 981 endotracheal tubes met the eligibility criteria. Pseudomonas spp. and Acinetobacter spp. were predominant isolates among the biofilm producers. These biofilms provided strong resistance against commonly used antibiotics. The highest resistance rate observed in Pseudomonas spp. was against fluoroquinolones whereas the least resistance was seen against piperacillin-tazobactam. A similar trend of susceptibility was observed in Acinetobacter spp. with a very high resistance rate against fluoroquinolones, third-generation cephalosporins and carbapenems. In conclusion, endotracheal tubes were associated with colonization by biofilm forming bacteria with varying levels of antimicrobial resistance. Biofilms may promote the occurrence of recalcitrant infections in endotracheal tubes which need to be managed with appropriate protocols and antimicrobial stewardship. Research focus should shift towards meticulous exploration of biofilm-associated infections to improve detection and management.
Topics: Biofilms; Humans; Intubation, Intratracheal; Drug Resistance, Bacterial; Anti-Bacterial Agents; Bacteria
PubMed: 38522561
DOI: 10.1016/j.jhin.2024.03.004