Antimicrobial Resistance in Salmonella Typhi Isolated From a Referral Hospital of Kathmandu, Nepal.

PURPOSE: The morbidity and mortality due to typhoid fever can be significantly reduced with the use of effective antibiotics. At present, fluoroquinolones, third generation cephalosporins, and azithromycin are widely used to treat typhoid fever. However, changing antibiotic susceptibility among Salmonella Typhi and Salmonella Paratyphi poses a particular challenge to the therapeutic management of enteric fever. The objective of this study was to assess the antibiotic susceptibility pattern of Salmonella Typhi isolates. PATIENTS AND METHODS: A total of 706 blood specimens were collected from febrile patients attending the outpatient department of Kathmandu Model Hospital during June to September, 2018. The antibiotic susceptibility testing for 11 different antibiotics (nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin, cefixime, ceftriaxone, cefotaxime, azithromycin, cotrimoxazole, chloramphenicol, and amoxicillin) was performed by disk diffusion method. Furthermore, minimum inhibitory concentration (MIC) values of ciprofloxacin, ofloxacin, and azithromycin were determined by agar dilution method. Mutation at gyrA ser83 associated with reduced susceptibility to fluoroquinolones was determined by PCR-RFLP. RESULTS: Out of 706 blood samples, 6.94% (n = 49) were culture positive for Salmonella enterica (S. Typhi, n = 46). It was revealed that 97.8% S. Typhi isolates were susceptible to conventional first-line antibiotics (ampicillin, chloramphenicol, and cotrimoxazole), 97.3% to cephalosporins and 95.7% to azithromycin. S. Typhi were either resistant or intermediately susceptible to fluoroquinolones: 97.8% to ciprofloxacin, 91.3% to ofloxacin, and 89.1% to levofloxacin. The MIC of ciprofloxacin, ofloxacin, and azithromycin for S. Typhi ranged from 0.008 to 32, 0.03 to 16, and 2 to 8 µg/mL, respectively. Out of 46 S. Typhi isolates, 44 (95.65%) had gyrA ser83 mutation. CONCLUSION: Fluoroquinolones have poor activity against Salmonella Typhi. The trends of increasing azithromycin MIC value among S. Typhi might limit its use for the treatment of typhoid fever. Effectiveness of conventional first-line antibiotics in vitro suggests considering their clinical use after large-scale studies.

Higher Prevalence of Extended Spectrum ß-Lactamase Producing Uropathogenic Escherichia coli Among Patients with Diabetes from a Tertiary Care Hospital of Kathmandu, Nepal.

This study aimed to determine the occurrence of antibiotic resistance genes for ß-lactamases; blaTEM and blaCTX-M in uropathogenic Escherichia coli isolates from urinary tract infection (UTI) suspected diabetic and nondiabetic patients. A hospital-based cross-sectional study was conducted in Kathmandu Model Hospital, Kathmandu, in association with the Department of Microbiology, GoldenGate International College, Kathmandu, Nepal, from June to December 2018. A total of 1,267 nonduplicate midstream urine specimens were obtained and processed immediately for isolation of uropathogens. The isolates were subjected to antibiotic susceptibility testing and extended spectrum ß-lactamase (ESBL) confirmation. In addition, blaTEM and blaCTX-M genes were detected using specific primers. The overall prevalence of UTI was 17.2% (218/1,267), of which patients with diabetes were significantly more infected; 32.3% (31/96) as compared with nonpatients with diabetes, 15.9% (187/1,171). A total of 221 bacterial isolates were obtained from 218 culture-positive specimens in which E. coli was the most predominant; 67.9% (150/221). Forty-four percent (66/150) of the total E. coli was multidrug resistant and 37.3% (56/150) were ESBL producers. Among 56 isolates, 92.3% (12/13) were from patients with diabetes, and 83.0% (44/53) were from nondiabetics. Furthermore, 84.9% of the screened ESBL producers were confirmed to possess either single or both of blaTEM and blaCTX-M genes. The blaTEM and blaCTX-M genes were detected in 53.6% and 87.5% of the phenotypically ESBL confirmed E. coli, respectively. Higher rates of ESBL producing uropathogenic E. coli are associated among patients with diabetes causing an alarming situation for disease management. However, second-line drugs with broad antimicrobial properties are still found to be effective drugs for multidrug resistance strains.

Evaluation of an Antimicrobial Stewardship Program for Wound and Burn Care in Three Hospitals in Nepal.

Antimicrobial stewardship (AMS) programs can decrease non-optimal use of antibiotics in hospital settings. There are limited data on AMS programs in burn and chronic wound centers in low- and middle-income countries (LMIC). A post-prescription review and feedback (PPRF) program was implemented in three hospitals in Nepal with a focus on wound and burn care. A total of 241 baseline and 236 post-intervention patient chart data were collected from three hospitals. There was a significant decrease in utilizing days of therapy per 1000 patient days (DOT/1000 PD) of penicillin (p = 0.02), aminoglycoside (p < 0.001), and cephalosporin (p = 0.04). Increases in DOT/1000 PD at post-intervention were significant for metronidazole (p < 0.001), quinolone (p = 0.01), and other antibiotics (p < 0.001). Changes in use of antibiotics varied across hospitals, e.g., cephalosporin use decreased significantly at Kirtipur Hospital (p < 0.001) and Pokhara Academy of Health Sciences (p = 0.02), but not at Kathmandu Model Hospital (p = 0.59). An independent review conducted by infectious disease specialists at the Henry Ford Health System revealed significant changes in antibiotic prescribing practices both overall and by hospital. There was a decrease in mean number of intravenous antibiotic days between baseline (10.1 (SD 8.8)) and post-intervention (8.8 (SD 6.5)) (t = 3.56; p < 0.001), but no difference for oral antibiotics. Compared to baseline, over the 6-month post-intervention period, we found an increase in justified use of antibiotics (p < 0.001), de-escalation (p < 0.001), accurate documentation (p < 0.001), and adherence to the study antibiotic prescribing guidelines at 72 h (p < 0.001) and after diagnoses (p < 0.001). The evaluation data presented provide evidence that PPRF training and program implementation can contribute to hospital-based antibiotic stewardship for wound and burn care in Nepal.

Summary of the International Patient Safety Conference, June 28-29, 2019, Kathmandu, Nepal.

Globally, medical errors are associated with an estimated $42 billion in costs to healthcare systems. A variety of errors in the delivery of healthcare have been identified by the World Health Organization and it is believed that about 50% of all errors are preventable. Initiatives to improve patient safety are now garnering increased attention across a range of countries in all regions of the world. From June 28--29, 2019, the first International Patient Safety Conference (IPSC) was held in Kathmandu, Nepal and attended by over 200 healthcare professionals as well as hospital, government, and non-governmental organization leaders. During the conference, presentations describing the experience with errors in healthcare and solutions to minimize future occurrence of adverse events were presented. Examples of systems implemented to prevent future errors in patient care were also described. A key outcome of this conference was the initiation of conversations and communication among important stakeholders for patient safety. In addition, attendees and dignitaries in attendance all reaffirmed their commitment to furthering actions in hospitals and other healthcare facilities that focus on reducing the risk of harm to patients who receive care in the Nepali healthcare system. This conference provides an important springboard for the development of patient-centered strategies to improve patient safety across a range of patient care environments in public and private sector healthcare institutions.

Evaluation of a Hospital-Based Post-Prescription Review and Feedback Pilot in Kathmandu, Nepal.

Capacity building is needed in low- and middle-income countries (LMICs) to combat antimicrobial resistance (AMR). Stewardship programs such as post-prescription review and feedback (PPRF) are important components in addressing AMR. Little data are available regarding effectiveness of PPRF programs in LMIC settings. An adapted PPRF program was implemented in the medicine, surgery, and obstetrics/gynecology wards in a 125-bed hospital in Kathmandu. Seven "physician champions" were trained. Baseline and post-intervention patient chart data were analyzed for changes in days of therapy (DOT) and mean number of course days for intravenous and oral antibiotics, and for specific study antibiotics. Charts were independently reviewed to determine justification for prescribed antibiotics. Physician champions documented recommendations. Days of therapy per 1,000 patient-days for courses of aminoglycoside (P < 0.001) and cephalosporin (P < 0.001) decreased. In the medicine ward, data indicate increased justified use of antibiotics (P = 0.02), de-escalation (P < 0.001), rational use of antibiotics (P < 0.01), and conforming to guidelines in the first 72 hours (P = 0.02), and for definitive therapy (P < 0.001). Physician champions documented 437 patient chart reviews and made 138 recommendations; 78.3% of recommendations were followed by the attending physician. Post-prescription review and feedback can be successfully implemented in LMIC hospitals, which often lack infectious disease specialists. Future program adaptation and training will focus on identifying additional stewardship programming and support mechanisms to optimize antibiotic use in LMICs.

Antimicrobial Sensitivity Trend in Blood Culture Positive Enteric Fever.

BACKGROUND: For diagnosis of enteric fever, the culture of the organism from different body fluids is the gold standard. After diagnosis, it is important to treat with the right antibiotic before any complications can occur. The retrospective study is designed to explore the antibiotic sensitivity trend in blood culture positive typhoid fever cases and the extent of drug resistance before treatment is administered. METHODS: A retrospective study was carried out for culture isolated enteric fever patients admitted in Kathmandu Model Hospital. The discharged records from January 2012 to December 2016 were analyzed. The patients above 15 years and with culture isolated enteric fever were included in the study. RESULTS: One hundred fifty-nine strains of Salmonella typhi and paratyphi were isolated from Jan 2012 to Dec 2016 at Kathmandu Model Hospital. Out of 159 isolated, 125 (78.6%) were Salmonella typhi and 34 (21.4%) were paratyphi. Among them co-trimoxazole, chloramphenicol, ceftriaxone, cefotaxime, cefixime, and ofloxacin demonstrated 100% sensitivity. Similarly, amoxicillin sensitivity was 98.1% (n=156) while ciprofloxacin was sensitive in 6.3% (n=10), intermediately sensitive in 49.1% (n=78) and resistance in 44.7% (n=71).The newer quinolone levofloxacin showed 78.5% (n=11) sensitivity. Azithromycin was sensitive in 99.2% (n=132) of total isolated Salmonella species both typhi and paratyphi. CONCLUSIONS: A high degree of sensitivity was noted to chloramphenicol and co-trimoxazole, showing sensitivity has returned to conventional antibiotics. The drug-like ofloxacin is still the best responding drug in our contest whereas ciprofloxacin resistance is still high, but five years patterns show a trend of rollback of sensitivity.

Antibiotic Susceptibility Pattern of Gram-negative Isolates of Lower Respiratory Tract Infection.

BACKGROUND: Lower respiratory tract infection is a common cause of morbidity and mortality worldwide. A cross-sectional study was carried out with an objective to study the antibiogram of Gram-negative isolates of patients with lower respiratory tract infection visiting Kathmandu Model Hospital. METHODS: A total of 274 specimens including sputum, endotracheal aspirates, suction tips were cultured as per standard microbiological technique. Antibiotic susceptibility and detection of Extended-spectrum beta- lactamases (ESBLs) were performed following Clinical Laboratory Standard Institute (CLSI 2014) guidelines. RESULTS: Respiratory pathogens were recovered from 24.6% (n=65) cases. Klebsiella pneumoniae (40%) was the commonest isolates. The highest prevalence of multidrug-resistance (69.23%) was observed in Acinetobacter calcoaceticus baumannii complex. Extended-spectrum beta- lactamases were detected in Escherichia coli (n=4), Klebsiella pneumoniae (n=4) and Acinetobacter calcoaceticus baumannii complex (n=1). CONCLUSIONS: High prevalence of multidrug-resistance and extended- spectrum beta- lactamase producers were observed in respiratory isolates. For effective management of lower respiratory tract infections, an ultimate and detailed microbiological diagnosis and susceptibility testing is required.