OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.
METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.
RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1).
CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.
Materials and Methods: We used three online databases, i.e., PubMed, ScienceDirect, and Cochrane Central Registry of Clinical Trials. Randomized controlled trials (RCTs) on the use of prophylactic chemotherapeutic agents used in treating nonpregnant women with recurrent urinary tract infections (RUTIs) published between 2002 and 2016 were selected. Only published papers in English were assessed for study quality, and meta-analyses were performed using fixed-effects model with NetMetaXL.
Results: Six RCTs fulfilled the criteria. When all three variables, i.e., efficacy, adverse effects and cost were considered, nitrofurantoin 50 mg once daily for 6 months appears to rank high for prophylaxis against RUTI. When efficacy was the only factor, fosfomycin had the highest superiority compared to D-mannose, nitrofurantoin, estriol, trimethoprim-sulfamethoxazole, and cranberry juice, respectively. However, fosfomycin was also ranked highest by adverse events. When cost alone is considered, nitrofurantoin appeared the most cost-effective agent while placed third for efficacy alone.
Conclusion: Selecting appropriate chemotherapeutic agents for RUTI will need to factor in effectiveness, adverse effects, and cost. While it is difficult to select an ideal drug, evaluation using network analysis may guide choice of medication for best practice.
Aim: This study was designed to determine whether the phenotypic antibiotic resistance pattern of B. pseudomallei is associated with the source of isolates and the genotype.
Materials and Methods: A collection of 111 B. pseudomallei isolates from veterinary cases of melioidosis and the environments (soil and water) were obtained from stock cultures of previous studies and were phylogenetically characterized by multilocus sequence typing (ST). The susceptibility to five antibiotics, namely meropenem (MEM), imipenem, ceftazidime (CAZ), cotrimoxazole (SXT), and co-amoxiclav (AMC), recommended in both acute and eradication phases of melioidosis treatment were tested using minimum inhibitory concentration antibiotics susceptibility test.
Results: Majority of isolates were susceptible to all antibiotics tested while few resistant strains to MEM, SXT, CAZ, and AMC were observed. Statistically significant association was found between resistance to MEM and the veterinary clinical isolates (p<0.05). The likelihood of resistance to MEM was significantly higher among the novel ST 1130 isolates found in veterinary cases as compared to others.
Conclusion: The resistance to MEM and SXT appeared to be higher among veterinary isolates, and the novel ST 1130 was more likely to be resistant to MEM as compared to others.
METHOD: Electronic search (PubMed, Scopus and Google scholar) was conducted using the following search terms: "MRSA OR Methicillin Resistant Staphylococcus aureus AND Nigeria." Reference list of selected studies was scanned to identify more studies. Studies published between 2007 and 2017 that tested at least 30 non-duplicate S. aureus isolates were selected. An independent reviewer extracted data from the studies using a standardized form.
RESULTS: Twelve studies were included in this review. Overall, prevalence of MRSA infection increased from 18.3% (2009) to 42.3% (2013). The prevalence of MRSA infection was less than 50% in all the regions during the period under review. There was a decline in the prevalence of MRSA infection in the North-East (from 12.5% to 8.0%) between 2007 and 2012, and an increase in the South-West (from 20.2% to 47.4%) between 2006 and 2010. Wound, blood and urine specimens had the highest proportion of MRSA isolates. Non-susceptibility of MRSA strains to cotrimoxazole and tetracycline was greater than 85%.
CONCLUSION: Prevalence of MRSA infection in Nigeria is rising, albeit regional variations. Non-susceptibility to commonly prescribed, orally available and inexpensive antibiotics was high. Antimicrobial resistance surveillance system, infection control, and antimicrobial stewardship interventions are recommended.
METHODS: From 2014 to 2017, a total of 245 invasive S. pneumoniae isolates from children ≤5 years of age were received from hospitals all around Malaysia. All isolates were identified and subjected to serotyping and antimicrobial susceptibility testing.
RESULTS: Of the 245 isolates, 117 (48.0%) were from children aged <1year, 46 (19.05%) were from children aged 1-2 years, and 82 (33.0%) were from children aged 2-5 years. The most common serotypes were 14 (26.9%), 6B (19.6%), 19A (11.8%), 6A (10.6%), and 19F (6.9%) and vaccine coverage was 88.2% for PCV13, 64.1% for PCV10, and 63.3% for PCV7. Resistance to penicillin was 0.2% for non-meningitis cases and 22.2% for meningitis cases; erythromycin resistance was reported in 42.9%, co-trimoxazole in 35.9%, and tetracycline in 42.9%.
CONCLUSIONS: Serotypes 14, 6B, 19A, 6A, and 19F were the most common serotypes isolated from children with IPD in Malaysia during this pre-vaccination era. The lack of reports on the serotype distribution has limited action for the implementation of PCV in the national immunization programme (NIP). The information from this study may benefit future policies for the introduction of PCV in the Malaysian NIP and ultimately may reduce the morbidity and mortality among children in Malaysia.
METHODS: Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.
RESULTS: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.
CONCLUSIONS: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.
CASE PRESENTATION: Here, we report two cases of melioidosis from Nepal. Both of them were diabetic male who presented themselves with fever, multiple abscesses and developed sepsis. They were treated with multiple antimicrobial agents including antitubercular drugs before being correctly diagnosed as melioidosis. Consistent with this, both patients were farmer by occupation and also reported travelling to Malaysia in the past. The diagnosis was made consequent to the isolation of B. pseudomallei from pus samples. Accordingly, they were managed with intravenous meropenem followed by oral doxycycline and cotrimoxazole.
CONCLUSION: The case reports raise serious concern over the existing unawareness of melioidosis in Nepal. Both of the cases were left undiagnosed for a long time. Therefore, clinicians need to keep a high index of suspicion while encountering similar cases. Especially diabetic-farmers who present with fever and sepsis and do not respond to antibiotics easily may turn out to be yet another case of melioidosis. Ascertaining the travel history and occupational history is of utmost significance. In addition, the microbiologist should be trained to correctly identify B. pseudomallei as it is often confused for other Burkholderia species. The organism responds only to specific antibiotics; therefore, correct and timely diagnosis becomes crucial for better outcomes.