RECENT FINDINGS: Optimal antibiotic treatment is challenging in critically ill patients with nosocomial pneumonia; most dosing guidelines do not consider the altered physiology and illness severity associated with severe lung infections. Antibiotic dosing can be guided by plasma drug concentrations, which do not reflect the concentrations at the site of infection. The application of aggressive dosing regimens, in accordance to the antibiotic's pharmacokinetic/pharmacodynamic characteristics, may be required to ensure rapid and effective drug exposure in infected lung tissues.
SUMMARY: Conventional antibiotic dosing increases the likelihood of therapeutic failure in critically ill patients with nosocomial pneumonia. Alternative dosing strategies, which exploit the pharmacokinetic/pharmacodynamic properties of an antibiotic, should be strongly considered to ensure optimal antibiotic exposure and better therapeutic outcomes in these patients.
METHODS: This review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic databases including MEDLINE, CINAHL, PubMed and EMBASE were searched up to September 2017 for relevant guidelines. Other databases such as NICE, Scottish Intercollegiate Guidelines Network (SIGN) and the websites of professional societies were also searched for relevant guidelines. The quality and reporting of included guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) instrument.
RESULTS AND DISCUSSION: Six guidelines were eligible for inclusion in our review. Among 6 domains of AGREE-II, "clarity of presentation" scored the highest (80.6%), whereas "applicability" scored the lowest (11.8%). All the guidelines supported the antibiotic de-escalation strategy, whereas the majority of the guidelines (5 of 6) recommended that empirical antibiotic therapy should be implemented in accordance with local microbiological data. All the guidelines suggested that for early-onset HAP/VAP, therapy should start with a narrow spectrum empirical antibiotic such as penicillin or cephalosporins, whereas for late-onset HAP/VAP, the guidelines recommended the use of a broader spectrum empirical antibiotic such as the penicillin extended spectrum carbapenems and glycopeptides.
WHAT IS NEW AND CONCLUSIONS: Expert guidelines promote the judicious use of antibiotics and prevent antibiotic overuse. The quality and validity of available HAP/VAP guidelines would be enhanced by improving their adherence to accepted best practice for the management of HAP and VAP.
MATERIALS & METHODS: This study was conducted in Hospital Kuala Lumpur, Malaysia from January 2016 to December 2017. A total of 303 isolates were included in this study which was obtained from 238 patients. The patients' microbiological worksheets and medical notes were reviewed to determine the antimicrobial susceptibility patterns, demographic data, classification of infection, and outcome (survival versus death).
RESULTS: Most of the patients were in the age group of one to less than five years old (41%) with 58% male and 85% Malay patients. Common causes of BSI were Staphylococcus aureus (17%), followed by Klebsiella pneumoniae (15%), Acinetobacter baumanii (10%), Pseudomonas aeruginosa (10%), and Escherichia coli (6%). Sixty percent of BSI episodes were caused by gram-negative bacteria, 34% by gram-positive bacteria, and 6% by fungi. Most of the infections were classified as hospital-acquired infections (72%), followed by healthcareassociated (20%) and community-acquired infections (8%). There were 33% of methicillin-resistant Staphylococcus aureus, 53% of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae, and 33% ESBL producing Escherichia coli. The overall case fatality rate (CFR) was 27% with the highest CFR caused by Serratia marcescens (53.3%).
CONCLUSIONS: The majority of paediatric bloodstream infections are hospital-acquired. Improvement in prevention strategies and revisions in antibiotic policies are important to overcome it.
Methods: A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality.
Results: Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL).
Conclusions: A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.
METHODS: The medical records of ICU patients receiving colistin therapy in Hospital Serdang and Hospital Sungai Buloh from 2010 to 2012 were retrospectively reviewed. Demographics data, treatment characteristic as well as culture result and creatinine level were documented. Nephrotoxicity was determined based on RIFLE criteria.
RESULTS: A total of 100 patients were included. Median daily dose, cumulative dose and duration of colistin therapy were 3.0 MIU (IQR: 4, range 1-12), 17.8 MIU (IQR: 31.5, range 2-180) and seven days (IQR: 4, range 1-30). Nephrotoxicity was found in 23% of the study population. All cases were reversible but marginally associated with higher mortality. No statistical association exist between age, gender and race as well as administration routes with nephrotoxicity by univariable analysis. The association of dose and duration with nephrotoxicity was also not significant by univariable analysis. After adjustment for confounders, statistical association between the independent variables and dependent variable remains not significant.
CONCLUSION: Lower dose and shorter duration in local settings contribute to lack of association between colistin therapy and nephrotoxicity in this study. Higher dosing regimen with loading dose application has been introduced in the latest National Antibiotic Guideline. Further evaluation of colistin-induced nephrotoxicity and potential risk factors is therefore warranted.
METHODS: This point prevalence survey (PPS) was conducted in 13 hospitals among 7 different cities of Pakistan. The survey included all inpatients receiving an antibiotic on the day of PPS. A web-based application was used for data entry, validation, and reporting as designed by the University of Antwerp (www.global-pps.com).
RESULTS: Out of 1954 patients, 1516 (77.6%) were treated with antibiotics. The top three most reported indications for antibiotic use were prophylaxis for obstetrics or gynaecological indications (16.5%), gastrointestinal indications (12.6%) and lower respiratory tract infections (12.0%). The top three most commonly prescribed antibiotics were ceftriaxone (35.0%), metronidazole (16.0%) and ciprofloxacin (6.0%). Out of the total indications, 34.2% of antibiotics were prescribed for community-acquired infections (CAI), 5.9% for healthcare-associated infections (HAI), and 57.4% for either surgical or medical prophylaxis. Of the total use for surgical prophylaxis, 97.4% of antibiotics were given for more than one day.
CONCLUSIONS: Unnecessary prophylactic antibiotic use is extremely high, and broad-spectrum prescribing is common among hospitals in Pakistan. There is an urgent need to work on the national action plan of Pakistan on antibiotic resistance to address this.