Does cotrimoxazole prophylaxis in HIV patients increase the drug resistance of pneumococci? A comparative cross-sectional study in southern Ethiopia

Abstract

Background Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited. Objective This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia. Materials and methods A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis. Results Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4–15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05–4.9) and gender (AOR: 2.5; 95% CI: 1.09–5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3–36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant. Conclusion The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.

Frequent shedding of multi-drug resistant pneumococci among adults living with HIV on suppressive antiretroviral therapy in Malawi

“…In Malawi, as part of standard HIV clinical management, PLHIV are put on daily co-trimoxazole prophylaxis 17, 18 . Consistent with purifying selection and in agreement with previous studies 44, 45 , there was higher prevalence of co-trimoxazole resistant carriage isolates in PLHIV than HIV-uninfected participants. Considering that co-trimoxazole is a broad-spectrum antimicrobial and its resistance is associated with penicillin resistance 45, 46 , it could differentially alter the microbiota in the oropharyngeal and nasopharyngeal compartments, resulting in stronger selection for multi-drug resistant pneumococci.…”

High Fecal Carriage of Multidrug Resistant Bacteria in the Community among Children in Northwestern Tanzania

“…A total of 399 children below five years of age were enrolled with a median [interquartile range [IQR] age of 19 [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] months and 212 (53%) were males. The gender distribution was almost equal between two groups ( p = 0.463).…”

“…HIV infection has been reported to be a risk factor for colonization with MDR pathogens [ 12 ]; this has partly been attributed to trimethoprim/sulfamethoxazole prophylaxis that is routinely given to prevent opportunistic infections [ 13 , 14 ]. The high prevalence of HIV and the emergence of MDR complicate efforts to control bacterial infections in many LMIC settings.…”

Antibiotic prescribing patterns and carriage of antibiotic-resistant Escherichia coli and Enterococcus species in healthy individuals from selected communities in Lusaka and Ndola districts, Zambia

“… 48 The use of co-trimoxazole for prophylaxis of opportunistic infections in people living with HIV (PLWHIV) might also promote selective pressure, hence the high levels of resistance noted. 49 A study in southern Ethiopia revealed that co-trimoxazole prophylaxis increased the risk of resistance to co-trimoxazole, and this was statistically associated with co-resistance to penicillin. 49 …”

“… 49 A study in southern Ethiopia revealed that co-trimoxazole prophylaxis increased the risk of resistance to co-trimoxazole, and this was statistically associated with co-resistance to penicillin. 49 …”