Antimicrobial resistance among uropathogens in the Asia-Pacific region: a systematic review.

BACKGROUND: Antimicrobial resistance (AMR) in urinary tract infections (UTI) is a global public health problem. However, estimates of the prevalence of AMR, required for empirical treatment guidelines, are lacking for many regions. OBJECTIVES: To perform a systematic review and summarize the available information about AMR prevalence among urinary Escherichia coli and Klebsiella pneumoniae, the two priority uropathogens, in the Asia-Pacific region (APAC). METHODS: PubMed, EBSCO and Web of Science databases were searched for articles (2008-20), following PRISMA guidelines. The prevalence of resistance was calculated and reported as point estimate with 95% CI for antimicrobial drugs recommended in WHO treatment guidelines. Data were stratified by country and surveillance approach (laboratory- or population-based surveillance). The quality of included articles was assessed using a modified Newcastle-Ottawa Quality Assessment Scale. RESULTS: Out of 2400 identified articles, 24 studies, reporting on 11 (26.8%) of the 41 APAC countries, met the inclusion criteria. Prevalence of resistance against trimethoprim/sulfamethoxazole, ciprofloxacin, and ceftriaxone ranged between 33% and 90%, with highest prevalence reported from Bangladesh, India, Sri Lanka and Indonesia. Resistance against nitrofurantoin ranged between 2.7% and 31.4%. Two studies reported data on fosfomycin resistance (1.8% and 1.7%). Quality of reporting was moderate. CONCLUSIONS: We show very high prevalence estimates of AMR against antibiotics commonly used for the empirical treatment of UTI, in the limited number of countries in the APAC for which data are available. Novel feasible and affordable approaches that facilitate population-based AMR surveillance are needed to increase knowledge on AMR prevalence across the region.

Appropriateness of diagnosis and antibiotic use in sepsis patients admitted to a tertiary hospital in Indonesia.

OBJECTIVE: To evaluate the diagnostic and antibiotic treatment strategies for patients suspected of sepsis, in a tertiary hospital in Indonesia. This can identify areas for improvement in care provided, and inform diagnostic and antimicrobial stewardship activities within the hospital. METHODS: Retrospective review of medical records with regards to the diagnosis and management of adult patients with sepsis admitted to a tertiary hospital in Indonesia. We assessed the diagnostic process, and whether or not the antibiotic treatment provided was appropriate for the diagnosis. Appropriateness of antibiotic treatment was classified as being definite appropriate, probable appropriate, inappropriate, or unknown. RESULTS: The study included 535 adult patients, of whom 295 (55%) were diagnosed with a community-acquired sepsis, and 240 (45%) with a hospital-acquired sepsis. A specimen for culture and antimicrobial susceptibility testing was collected from three out of four patients (392/535). All but 10 patients had information on antibiotic treatment at the time of sepsis diagnosis. Of those, nearly 50% (257/525) of the patients received antibiotic treatment with unknown appropriateness because no cultures were taken (n = 141) or all cultures were negative (n = 116). Just 3.4% and 9.1% of the patients received definite or probable appropriate antibiotic treatment, respectively. CONCLUSIONS: There is a clear need in encouraging attending physicians to obtain the much-required blood cultures, or cultures from the suspected source of infection before empirical antibiotic treatment is started. This will improve the use of appropriate antibiotic treatment strategies, and contribute to antimicrobial stewardship.

Laboratory-based versus population-based surveillance of antimicrobial resistance to inform empirical treatment for suspected urinary tract infection in Indonesia.

Surveillance of antimicrobial resistance (AMR) enables monitoring of trends in AMR prevalence. WHO recommends laboratory-based surveillance to obtain actionable AMR data at local or national level. However, laboratory-based surveillance may lead to overestimation of the prevalence of AMR due to bias. The objective of this study is to assess the difference in resistance prevalence between laboratory-based and population-based surveillance (PBS) among uropathogens in Indonesia. We included all urine samples submitted to the laboratory growing Escherichia coli and Klebsiella pneumoniae in the laboratory-based surveillance. Population-based surveillance data were collected in a cross-sectional survey of AMR in E. coli and K. pneumoniae isolated from urine samples among consecutive patients with symptoms of UTI, attending outpatient clinics and hospital wards. Data were collected between 1 April 2014 until 31 May 2015. The difference in percentage resistance (95% confidence intervals) between laboratory- and population-based surveillance was calculated for relevant antibiotics. A difference larger than +/- 5 percent points was defined as a biased result, precluding laboratory-based surveillance for guiding empirical treatment. We observed high prevalence of AMR ranging between 63.1% (piperacillin-tazobactam) and 85% (ceftriaxone) in laboratory-based surveillance and 41.3% (piperacillin-tazobactam) and 74.2% (ceftriaxone) in population-based surveillance, except for amikacin and meropenem (5.7%/9.8%; 10.8%/5.9%; [laboratory-/population-based surveillance], respectively). Laboratory-based surveillance yielded significantly higher AMR prevalence estimates than population-based surveillance. This difference was much larger when comparing surveillance data from outpatients than from inpatients. All point estimates of the difference between the two surveillance systems were larger than 5 percent points, except for amikacin and meropenem. Laboratory-based AMR surveillance of uropathogens, is not adequate to guide empirical treatment for community-based settings in Indonesia.

Rethinking Antimicrobial Resistance Surveillance: A Role for Lot Quality Assurance Sampling.

Global surveillance of antimicrobial resistance (AMR) is a key component of the 68th World Health Assembly Global Action Plan on AMR. Laboratory-based surveillance is inherently biased and lacks local relevance due to aggregation of data. We assessed the feasibility, sensitivity, and affordability of a population-based AMR survey using lot quality assurance sampling (LQAS), which classifies a population as having a high or low prevalence of AMR based on a priori defined criteria. Three studies were carried out in Medan and Bandung, Indonesia, between April 2014 and June 2017. LQAS classifications for 15 antibiotics were compared with AMR estimates from a conventional population-based survey, with an assessment of the cost of a single LQAS classification using microcosting methodology, among patients suspected of urinary tract infection at 11 sites in Indonesia. The sensitivity of LQAS was above 98%. The approach detected local variation in the prevalence of AMR across sites. Time to reach LQAS results ranged from 47 to 138 days. The average cost of an LQAS classification in a single facility was US$466. The findings indicate that LQAS-based AMR survey is a feasible, sensitive, and affordable strategy for population-based AMR surveys, providing essential data to inform local empirical treatment guidelines and antimicrobial stewardship efforts.

Predictive value of the urinary dipstick test in the management of patients with urinary tract infection-associated symptoms in primary care in Indonesia: a cross-sectional study.

OBJECTIVE: To assess the test characteristics of a urine dipstick test in predicting a positive urine culture in an outpatient setting in Indonesia. DESIGN: Cross-sectional study. SETTING: Two outpatient clinics in Medan, Indonesia. PARTICIPANTS: 616 consecutively enrolled participants suspected of having a urinary tract infection. OUTCOME MEASURES: The primary outcome is the estimates of accuracy (sensitivity, specificity, predictive values) where urine culture is the reference test. The secondary outcome is the post-test probability of a positive urine culture. RESULTS: The optimal test characteristics were obtained when index test positivity was defined as any leucocyte esterase reaction and/or a nitrite reaction and reference test positivity was defined as a urine culture with a growth of at least 103 colony-forming units/mL (sensitivity: 88.2% (95% CI 81.6 to 93.1), negative predictive value: 93.0% (95% CI 88.9 to 95.9)). The post-test probability of a positive urine culture after a negative urinary dipstick test was 7% in the obstetric/gynaecology clinic and 8% in the internal medicine clinic. CONCLUSION: The use of a urine dipstick test in a rule-out strategy can reduce the need for urine culture and avoid the prescription of (ineffective) antibiotics in a non-urology outpatient setting.

Antimicrobial resistance in uropathogens and appropriateness of empirical treatment: a population-based surveillance study in Indonesia.

Objectives: Urinary tract infections (UTIs) are a common reason for empirical treatment with broad-spectrum antibiotics worldwide. However, population-based antimicrobial resistance (AMR) prevalence data to inform empirical treatment choice are lacking in many regions, because of limited surveillance capacity. We aimed to assess the prevalence of AMR to commonly used antimicrobial drugs in Escherichia coli and Klebsiella pneumoniae isolated from patients with community- or healthcare-associated UTIs on two islands of Indonesia. Methods: We performed a cross-sectional patient-based study in public and private hospitals and clinics between April 2014 and May 2015. We screened patients for symptoms of UTIs and through urine dipstick analysis. Urine culture and susceptibility testing were supported by telemicrobiology and interactive virtual laboratory rounds. Surveillance data were entered in forms on mobile phones. Results: Of 3424 eligible patients, 3380 (98.7%) were included in the final analysis, and yielded 840 positive cultures and antimicrobial susceptibility data for 657 E. coli and K. pneumoniae isolates. Fosfomycin was the single oral treatment option with resistance prevalence <20% in both E. coli and K. pneumoniae in community settings. Tigecycline and fosfomycin were the only options for treatment of catheter-associated UTIs with resistance prevalence <20%, whilst the prevalence of resistance to meropenem was 21.3% in K. pneumoniae . Conclusions: Patient-based surveillance of AMR in E. coli and K. pneumoniae causing UTIs indicates that resistance to the commonly available empirical treatment options is high in Indonesia. Smart AMR surveillance strategies are needed to inform policy makers and to guide interventions.