-
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 -
European Journal of Hospital Pharmacy :... Nov 2022In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial...
Systematic review of the stability of antimicrobial agents in elastomeric devices for outpatient parenteral antimicrobial therapy services based on NHS Yellow Cover Document standards.
BACKGROUND
In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial agents to assign a product shelf-life. In the UK, the relevant standards for stability testing and shelf-life assignment are published in 'A Standard Protocol for Deriving and Assessment of Stability-Part 1 (Aseptic Preparations-Small Molecules), commonly called the Yellow Covered Document (YCD). A previous systematic review published in 2017 failed to identify data on the stability of antimicrobials in elastomeric devices for OPAT services that met YCD requirements in force at the time. The aim of this review was to update that search, following a subsequent change to YCD requirements in 2017 and 2019 and expand that dataset to identify progress made in providing assurance about the stability of antimicrobial agents for OPAT services.
METHODS
Searches were undertaken for papers relating to extended stability of antimicrobials. Citations were included when antimicrobial shelf-life was assessed using a stability-indicating method and considered a period of storage, either refrigerated or at room temperature, followed by in-use testing at a temperature at or above 32°C.
RESULTS
Of 267 initial citations, six met the inclusion criteria and underwent full text review for data extraction. Included antimicrobials were cefazolin, ceftazidime, piperacillin/tazobactam, flucloxacillin and ceftolozane/tazobactam. Of these, only flucloxacillin and piperacillin demonstrated YCD compliant stability over the 24-hour infusion period while cefazolin, ceftazidime and ceftolozane/tazobactam could be infused over 12-hour period.
CONCLUSIONS
Contrary to the position found in 2017 review, high-quality data are now available to support the use of a number of antimicrobial agents in extended infusion in elastomeric devices for OPAT services. There is a need to expand the dataset, as well as developing international consensus on the ideal parameters for stability assessment of such infusions in elastomeric devices.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Cefazolin; Ceftazidime; Floxacillin; Outpatients; Piperacillin; State Medicine; Tazobactam
PubMed: 33990388
DOI: 10.1136/ejhpharm-2021-002729 -
Open Forum Infectious Diseases Apr 2021In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a...
BACKGROUND
In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a systematic review and meta-analysis to assess the effect of restricting the use of specific antibiotic classes on the prevalence of resistant bacterial pathogens.
METHODS
We conducted a systematic literature search in Embase and PubMed/OVID MEDLINE. We included studies until June 4, 2020 in which a restrictive antibiotic policy was applied and prevalence of resistance and use of antibiotics were reported. We calculated the overall effect of antimicrobial resistance between postintervention versus preintervention periods using pooled odds ratios (ORs) from a mixed-effects model. We stratified meta-analysis by antibiotic-pathogen combinations. We assessed heterogeneity between studies using the I statistic and sources of heterogeneity using meta-regression.
RESULTS
We included 15 individual studies with an overall low quality of evidence. In meta-analysis, significant reductions in resistance were only observed with nonfermenters after restricting fluoroquinolones (OR = 0.77, 95% confidence interval [CI] = 0.62-0.97) and piperacillin-tazobactam (OR = 0.81, 95% CI = 0.72-0.92). High degrees of heterogeneity were observed with studies restricting carbapenem (Enterobacterales, I = 70.8%; nonfermenters, I = 81.9%), third-generation cephalosporins (nonfermenters, I = 63.3%), and fluoroquiolones (nonfermenters, I = 64.0%). Results were comparable when excluding studies with fewer than 50 bacteria. There was no evidence of publication bias for any of the antibiotic-pathogen combinations.
CONCLUSIONS
We could not confirm that restricting carbapenems or third-generation cephalosporins leads to decrease in prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria in hospitalized patients. Nevertheless, reducing fluoroquinolone and piperacilline-tazobactam use may decrease resistance in nonfermenters.
PubMed: 33880388
DOI: 10.1093/ofid/ofab070 -
Revista Do Instituto de Medicina... 2021The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the...
The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the clinical outcome of antibiotic therapy used to treat them. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with a systemic inflammatory response syndrome (SIRS) due to E. ramosum isolated from body fluids or tissues in which it is not normally present. Only reports identifying E. ramosum as the only microorganism isolated from a patient with SIRS were included. This systematic review included 15 studies reporting 19 individual cases in which E. ramosum caused invasive infections in various tissues, mainly in immunocompromised patients. E. ramosum was most often isolated by blood cultures and identified by specific biochemical tests. Severe infections caused by E. ramosum were in most cases effectively treated with antibiotics, except in two patients, one of whom died. More than one isolate of E. ramosum exhibited 100% susceptibility to metronidazole, amoxicillin/clavulanate and piperacillin/tazobactam. On the other hand, individual resistance of this bacterium to penicillin, ciprofloxacin, clindamycin, imipenem and ertapenem was reported. This systematic review confirmed the clinical relevance of E. ramosum as a cause of a number of severe infections mainly in immunocompromised inpatients. Metronidazole and meropenem appear to be the antibiotics of choice that should be used in combination or as monotherapy to treat E. ramosum infections, depending on the type and severity of the infection.
Topics: Anti-Bacterial Agents; Firmicutes; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests
PubMed: 33852713
DOI: 10.1590/S1678-9946202163030 -
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 -
Frontiers in Pediatrics 2020This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future...
This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Clearance and/or volume of distribution values were extracted from included studies. Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials ( = 13) and anticonvulsants ( = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. : CRD42019114881.
PubMed: 32670992
DOI: 10.3389/fped.2020.00260 -
BMC Infectious Diseases Jun 2020Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy.
METHODS
Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager.
RESULTS
Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28-1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55-0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (Mean Difference - 1.27, 95% Confidence Interval - 2.45-0.08, P = 0.04) in critically ill patients.
CONCLUSION
Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C/PI as a dosing strategy.
Topics: Adult; Anti-Bacterial Agents; Critical Illness; Humans; Length of Stay; Piperacillin, Tazobactam Drug Combination; Treatment Outcome
PubMed: 32563242
DOI: 10.1186/s12879-020-05149-6 -
The Brazilian Journal of Infectious... 2019Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte...
BACKGROUND
Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte and thought to be non-pathogenic to humans. Nevertheless, increasing number of reports of human infection have emerged in recent years, mostly in oncologic patients.
AIM
To report a case of a female patient with pyloric obstructive cancer with a catheter-related Papiliotrema laurentii blood stream infection and systematically review the available evidence on P. laurentii infection in humans.
METHODS
Retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually.
RESULTS
The search strategy retrieved 1703 references. In the final analysis, 31 references were included, with the description of 35 cases. Every patient but one had a previous co-morbidity - 48.4 % of patients had a neoplasm. Amphotericin B was the most used treatment and only a single case of resistance to it was reported. Most patients were cured of the infection.
CONCLUSION
P. laurentii infection in humans is usually associated to neoplasia and multiple co-morbidities, and amphotericin B seems to be a reliable agent for treatment.
Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Biopsy; Catheter-Related Infections; Cryptococcus; Female; Fluconazole; Humans; Piperacillin, Tazobactam Drug Combination; Stomach Neoplasms; Tomography, X-Ray Computed; Vancomycin
PubMed: 31738886
DOI: 10.1016/j.bjid.2019.10.005 -
Antimicrobial Agents and Chemotherapy Sep 2019Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this...
Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.
PubMed: 31591125
DOI: 10.1128/AAC.01572-19 -
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