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.
METHODS: Demographic data, underlying diseases, procedures and details on polymyxin B therapy were retrospectively analyzed in a cohort of 84 patients who received intravenous polymyxin B in an intensive care unit from 2010 to 2014.
RESULTS: Polymyxin B was used to treat bacteremia (46.4% of cases) and pneumonia (53.6%). Majority of the pathogens isolated were Acinetobacter spp. (96.4%). The mortality rate was 48.8%, of which 82.9% was attributed to polymyxin B treatment failure. The independent predictors of treatment failure were low doses of polymyxin B (p = 0.002), shorter duration of therapy (p = 0.009), not combining with cefoperazone/sulbactam (p = 0.030), female gender (p = 0.004), administered for treatment of bacteremia (p = 0.023) and renal impairment (p = 0.021). Low polymyxin B doses (p = 0.007), not combining with cefoperazone/sulbactam (p = 0.024), female gender (p = 0.048) and renal impairment (p = 0.022) were also significant predictors for in-hospital mortality.
CONCLUSIONS: To the best of our knowledge, this is the first report on the association of inadequate dose of polymyxin B (<15,000 units/kg/day) with poor outcome in critically ill patients. Besides that, further clinical studies are warranted to evaluate the use of cefoperazone/sulbactam as second antibiotic in the combination therapy.
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.