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 USED TO CONDUCT THE REVIEW: This review was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendation. Electronic databases including MEDLINE, CINAHL, PubMed, Embase, Cochrane Databases and Cochrane Central Register of Controlled Trials were searched up to March 2017 for relevant trials. The methodological quality of included trials was assessed by using a modified version of the Newcastle-Ottawa Quality Assessment Scale for Case-Control and Cohort Studies. A meta-analysis was conducted using the random-effect model to combine the rate of mortality and length of stay outcomes.
FINDINGS OF THE REVIEW: Nine observational trials involving 2128 patients were considered eligible for inclusion. Although based on low quality evidence, there was a statistically significant difference in favour of the impact of de-escalation on hospital stay but not mortality (MD -5.96 days; 95% CI -8.39 to -3.52).
INTERPRETATIONS AND IMPLICATIONS OF THE FINDINGS: This review highlights the need for more rigorous studies to be carried out before a firm conclusion on the benefit of de-escalation therapy is supported.
PATIENT CONCERNS: An 18-year-old woman who had an underlying mitral valve prolapse without mitral regurgitation presented to our hospital with low-grade fever, left leg weakness, and left abdominal pain. She was diagnosed with brain infarction and microabscess as well as IE. The patient totally recovered after the 6-week course of intravenous antibiotics.
DIAGNOSIS: Brain magnetic resonance imaging revealed brain infarction and microabscess. Abdominal computed tomography revealed splenic and left renal infarction. Three sets of blood culture were positive for S anginosus. Transthoracic echocardiogram identified mitral valve prolapse with moderate eccentric mitral valve regurgitation, and a 0.3 × 0.6-cm vegetation was found on the left mitral valve. All of these results meet the modified Duke criteria.
INTERVENTIONS: The abdominal pain and left leg weakness were improving after 2 weeks of intravenous antibiotics treatment. No neurological sequelae were noted after completing the 6-week course of medical treatment.
OUTCOMES: The patient was successfully treated and discharged after completing the 6-week intravenous antibiotics treatment.
LESSONS: IE should be considered in young patients with native valve disease who have prolonged fever. Though S anginosus commonly causes invasive pyogenic infection, patients with native valve disease should be checked for IE.
METHODS: There were 5 patients, with a median age of 1.75 (range 0.1-6.25) years, a median weight of 10.7 (2.9-21.5) kg, and a median creatinine clearance of 179 (44-384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20-0.21) million international units/kg, equivalent to 6.8 (6.5-6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.
RESULTS: The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41-3.50 mg/L), even though all patients received the same body weight-based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.
CONCLUSIONS: The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.
OBJECTIVES: This study explores the pattern of antibiotic use and practices in a Malaysian community and identifies the variables associated with a likelihood of non-compliance with a course of antibiotic treatment.
SETTING: The study was conducted in Cheras, a community located to the south-east of Kuala Lumpur, the capital city of Malaysia.
METHOD: A cross-sectional survey was conducted with 250 individuals, using an interviewer-administered questionnaire in Cheras, Kuala Lumpur, Malaysia.
MAIN OUTCOME MEASURES: Frequency of antibiotic use, sources of antibiotics, use of antibiotics without prescription, discontinuation of antibiotic treatment, antibiotic resistance awareness, handling of unused antibiotics, and association between respondents characteristics and compliance with a course of antibiotic treatment.
RESULTS: Approximately 36 % of the participants (n = 91) had taken antibiotics in the year of the study. The majority (66.8 %) obtained antibiotics from clinics. Almost 80 % of the participants had never obtained antibiotics without a doctor's prescription. Nearly 55 % discontinued the course of antibiotics once symptoms disappeared. The most common method of disposing leftover antibiotics was throwing them into the household rubbish bin (78.8 %). Only 6.4 % of participants returned leftover antibiotics to the pharmacist or doctor. Univariate analysis revealed that male gender (p = 0.04), lack of knowledge of antibiotic functions (p < 0.0001), and lack of awareness of antibiotic resistance (p < 0.0001) were all significantly associated with a greater likelihood of non-compliance with a full course of prescribed antibiotic treatment.
CONCLUSION: Most individuals in the Malaysian community obtained antibiotics through prescription. Non-completion of a course of antibiotic treatment and improper disposal of unused antibiotics need to be addressed to prevent AMR. Male gender, lack of knowledge and awareness of antibiotics and resistance were significantly associated with a greater likelihood of non-compliance with a full course of prescribed antibiotic treatment. Therefore, patient education and counselling about antibiotics and antibacterial resistance is very important to enhance compliance to antibiotic therapy.