{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:05:21Z","timestamp":1790737521053,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>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 <jats:italic>Streptococci pneumoniae \/<\/jats:italic> pneumococcus is very limited.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using <jats:italic>Streptococci pneumoniae<\/jats:italic> (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of the 252 enrolled HIV patients (mean age (37.38\u00b1 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of <jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> was 13.5% (95% CI: 8.4\u201315.6). 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\u20134.9) and gender (AOR: 2.5; 95% CI: 1.09\u20135.93) 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\u201336). 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0243054","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T22:03:03Z","timestamp":1607378583000},"page":"e0243054","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Does cotrimoxazole prophylaxis in HIV patients increase the drug resistance of pneumococci? A comparative cross-sectional study in southern Ethiopia"],"prefix":"10.1371","volume":"15","author":[{"given":"Mohammed","family":"Seid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Getnet","family":"Beyene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yared","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-0604","authenticated-orcid":true,"given":"Bereket","family":"Workalemahu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulugeta","family":"Delbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagimawie","family":"Taddesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gelila","family":"Biresaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-8093","authenticated-orcid":true,"given":"Aseer","family":"Manilal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"pone.0243054.ref001","volume-title":"Provisional WHO\/UNAIDS Secretariat Recommendations on the use of Trimethoprim-Sulfamethoxazole Prophylaxis in Adults and children living with HIV\/AIDS in Africa","author":"UNAIDS\/WHO","year":"2000"},{"key":"pone.0243054.ref002","unstructured":"WHO. Guidelines on Cotrimoxazole prophylaxis for HIV-related infections among children, adolescents and adults in resource-limited settings: recommendations for a public health approach. Geneva, 2006."},{"issue":"B","key":"pone.0243054.ref003","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/jac\/5.Supplement_B.221","article-title":"Co-trimoxazole for the treatment of serious infections","volume":"5","author":"AM Geddes","year":"1979","journal-title":"J Antimicrob. Chemother"},{"key":"pone.0243054.ref004","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/S0140-6736(98)07399-1","article-title":"Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, C\u00f4te d\u2019Ivoire: a randomised trial. Cotrimo-CI Study Group","volume":"353","author":"X Anglaret","year":"1999","journal-title":"Lancet Lond. Engl"},{"key":"pone.0243054.ref005","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/S0140-6736(99)03465-0","article-title":"Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, C\u00f4te d\u2019Ivoire: a randomised controlled trial","volume":"353","author":"SZ Wiktor","year":"1999","journal-title":"Lancet Lond. Engl"},{"key":"pone.0243054.ref006","first-page":"290","article-title":"Reconsidering empirical cotrimoxazole prophylaxis for infants exposed to HIV infection","volume":"82","author":"CJ Gill","year":"2004","journal-title":"Bull. World Health Organ"},{"issue":"9","key":"pone.0243054.ref007","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1093\/cid\/cir067","article-title":"Does Trimethoprim Sulfamethoxazole Prophylaxis for HIV Induce Bacterial Resistance to Other Antibiotic Classes?: Results of a Systematic Review","volume":"52","author":"EL Sibanda","year":"2011","journal-title":"Clin. Infect. Dis"},{"key":"pone.0243054.ref008","doi-asserted-by":"crossref","first-page":"929","DOI":"10.2471\/BLT.07.049668","article-title":"Effect of presumptive cotrimoxazole prophylaxis on pneumococcal colonization rates, seroepidemiology and antibiotic resistance in Zambian infants: a longitudinal cohort study","volume":"86","author":"CJ Gill","year":"2008","journal-title":"Bull. World Health Organ"},{"key":"pone.0243054.ref009","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3201\/eid0803.010192","article-title":"A European study on the relationship between antimicrobial use and antimicrobial resistance","volume":"8","author":"SL Bronzwaer","year":"2002","journal-title":"Emerg. Infect. Dis"},{"issue":"8","key":"pone.0243054.ref010","doi-asserted-by":"crossref","first-page":"e1007911","DOI":"10.1371\/journal.ppat.1007911","article-title":"Selective pressure: Rise of the non encapsulated pneumococcus","volume":"15","author":"JL Bradshaw","year":"2019","journal-title":"PLoS Pathog"},{"issue":"3","key":"pone.0243054.ref011","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3201\/eid1003.030252","article-title":"Harbarth S: Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes","volume":"10","author":"WC Albrich","year":"2004","journal-title":"Emerg. Infect. Dis"},{"key":"pone.0243054.ref012","unstructured":"USAIDS \/WHO Global burden of HIV\/AIDS. 2018 https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/unaids-data-2018_en.pdf"},{"key":"pone.0243054.ref013","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s40249-019-0594-9","article-title":"Trend and spatial distribution of HIV prevalence in Ethiopia","volume":"8","author":"GD Kibret","year":"2019","journal-title":"Infect. Dis. Poverty"},{"issue":"3","key":"pone.0243054.ref014","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4269\/ajtmh.2008.79.320","article-title":"Does Cotrimoxazole Prophylaxis for the Prevention of HIV-Associated Opportunistic Infections Select for Resistant Pathogens in Kenyan Adults?","volume":"79","author":"MJ Hamel","year":"2008","journal-title":"Am. J. Trop. Med. Hyg"},{"key":"pone.0243054.ref015","first-page":"134","article-title":"Resistance of Commensal Intestinal Escherichia Coli and Other Enteric to Cotrimoxazole and Commonly Used Antibiotics in HIV\/AIDS Patients","volume":"3","author":"KD Mwambete","year":"2013","journal-title":"Clin. Microbial"},{"issue":"9","key":"pone.0243054.ref016","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1128\/AAC.01409-09","article-title":"Impact of Co-trimoxazole on Carriage and Antibiotic Resistance of Streptococcus pneumoniae and Haemophilus influenzae in HIV-Infected Children in Zambia","volume":"54","author":"DM Mwenya","year":"2010","journal-title":"Antimicrob. Agents Chemother"},{"issue":"2","key":"pone.0243054.ref017","first-page":"156","article-title":"Effect of trimethoprim-sulfamethoxazole prophylaxis on faecal carriage rates of resistant isolates of Escherichia coli in HIV-infected adult patients in Lagos","volume":"10","author":"C Egwuatu","year":"2016","journal-title":"Infect. Dis"},{"key":"pone.0243054.ref018","article-title":"Resistance to Cotrimoxazole and Other Antimicrobials among Isolates from HIV\/AIDS and Non-HIV\/AIDS Patients at Bugando Medical Centre, Mwanza, Tanzania","author":"J Karol","year":"2015","journal-title":"AIDS Res. Ther"},{"key":"pone.0243054.ref019","article-title":"Cotrimoxazole Prophylaxis Specifically Selects for Cotrimoxazole Resistance in Streptococcus mutans and Streptococcus sobrinus with Varied Polymorphisms in the Target Genes folA and folP","author":"B William","year":"2012","journal-title":"Int J Microbiol"},{"key":"pone.0243054.ref020","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1099\/jmm.0.000503","article-title":"Molecular mechanisms and epidemiology of resistance in Streptococcus pneumoniae in the Middle East region","volume":"66","author":"El Moujaber","year":"2017","journal-title":"J. Med. Microbiol"},{"key":"pone.0243054.ref021","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/infdis\/175.3.590","article-title":"Colonization by Streptococcus pneumoniae among human immunodeficiency virus-infected adults: prevalence of antibiotic resistance, impact of immunization, and characterization by polymerase chain reaction with BOX primers of isolates from persistent S. pneumoniae carriers","volume":"175","author":"MC Rodriguez-Barradas","year":"1997","journal-title":"Lancet Infect. Dis"},{"key":"pone.0243054.ref022","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.diagmicrobio.2006.08.021","article-title":"Prevalence, serotypes, and risk factors for pneumococcal carriage among HIV-infected adults","volume":"57","author":"C Nicoletti","year":"2007","journal-title":"Diagn. Microbiol. Infect. Dis"},{"key":"pone.0243054.ref023","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1086\/420933","article-title":"Invasive pneumococcal disease in patients infected with HIV: still a threat in the era of highly active antiretroviral therapy","volume":"38","author":"Q Jordano","year":"2004","journal-title":"Clin. Infect. Dis"},{"key":"pone.0243054.ref024","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1097\/00002030-200207050-00013","article-title":"Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival","volume":"16","author":"SB Gordon","year":"2002","journal-title":"AIDS"},{"issue":"11","key":"pone.0243054.ref025","doi-asserted-by":"crossref","first-page":"e27929","DOI":"10.1371\/journal.pone.0027929","article-title":"Persistent high burden of invasive pneumococcal disease in South African HIV-infected adults in the era of an antiretroviral treatment program","volume":"6","author":"MC Nunes","year":"2011","journal-title":"PLoS One,"},{"issue":"14","key":"pone.0243054.ref026","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1097\/QAD.0000000000000755","article-title":"Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi: a cohort study","volume":"29","author":"E Heinsbroek","year":"2015","journal-title":"AIDS"},{"key":"pone.0243054.ref027","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/cid\/cis842","article-title":"Defective pneumococcal-specific Th1 responses in HIV-infected adults precedes a loss of control of pneumococcal colonization","volume":"56","author":"SJ Glennie","year":"2013","journal-title":"Clin. Infect. Dis"},{"issue":"3","key":"pone.0243054.ref028","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jinf.2007.12.003","article-title":"Impact of cotrimoxazole on non-susceptibility to antibiotics in Streptococcus pneumonia carriage isolates among HIV-infected mineworkers in South Africa","volume":"56","author":"L Pemba","year":"2008","journal-title":"J. Infect"},{"issue":"7","key":"pone.0243054.ref029","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1086\/528806","article-title":"Impact of Human Immunodeficiency Virus Infection on Streptococcus pneumoniae Colonization and Seroepid emiology among Zambian Women","volume":"197","author":"CJ Gill","year":"2008","journal-title":"J. Infect. Dis"},{"issue":"5","key":"pone.0243054.ref030","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.jiph.2016.01.004","article-title":"Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia","volume":"9","author":"K Harimurti","year":"2016","journal-title":"J. Infect. Public Health"},{"key":"pone.0243054.ref031","first-page":"3632","article-title":"Cross-sectional study of nasopharyngeal carriage of Streptococcus pneumoniae in human immunodeficiency virus-infected adults in the conjugate vaccine era","author":"C Onwubiko","year":"2008","journal-title":"J. Clin. Microbiol"},{"issue":"9","key":"pone.0243054.ref032","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1080\/21645515.2016.1172758","article-title":"Nasopharyngeal pneumococcal carriage rates among HIV-infected adults following widespread pediatric use of conjugate pneumococcal vaccine-13","volume":"12","author":"D. Feola Theresa","year":"2016","journal-title":"Hum. Vaccin. Immunother"},{"issue":"1","key":"pone.0243054.ref033","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/INF.0b013e31814da70c","article-title":"The descriptive epidemiology of Streptococcus pneumoniae and Haemophilus influenzae nasopharyngeal carriage in children and adults in Kilifi District, Kenya","volume":"27","author":"O Abdullahi","year":"2008","journal-title":"Pediatr. Infect. Dis. J"},{"key":"pone.0243054.ref034","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1097\/00006454-199907000-00017","article-title":"Nasopharyngeal colonization with Streptococcus pneumoniae in children receiving trimethoprim-sulfamethoxazole prophylaxis","volume":"18","author":"N Abdel-Haq","year":"1999","journal-title":"Pediatr. Infect. Dis. J"},{"key":"pone.0243054.ref035","unstructured":"World Health Organization. Manual for the Laboratory Identification and Antimicrobial Susceptibility Testing of Bacterial Pathogens of Public Health Importance in the Developing World, 2003. https:\/\/apps.who.int\/iris\/handle\/10665\/68554"},{"key":"pone.0243054.ref036","volume-title":"CLSI supplement M100","author":"CLSI","year":"2018","edition":"28"},{"issue":"6","key":"pone.0243054.ref037","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ijid.2006.05.010","article-title":"Oropharyngeal colonization by Streptococcus pneumoniae among HIV-infected adults in Uganda: assessing prevalence and antimicrobial susceptibility","volume":"10","author":"DB Blossom","year":"2006","journal-title":"Int. J. Infect. Dis"},{"key":"pone.0243054.ref038","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12879-015-1312-2","article-title":"High Streptococcus pneumoniae colonization prevalence among HIV-infected Kenyan parents in the year before pneumococcal conjugate vaccine introduction","volume":"16","author":"LM Conklin","year":"2016","journal-title":"BMC Infect. Dis"},{"key":"pone.0243054.ref039","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1186\/s40064-015-1056-x","article-title":"Bacteriological profile and antimicrobial susceptibility patterns of blood culture isolates among febrile patients in Mekelle Hospital, Northern Ethiopia","volume":"4","author":"AG Wasihun","year":"2015","journal-title":"Springerplus"},{"issue":"1","key":"pone.0243054.ref040","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1186\/s12879-017-2713-1","article-title":"Antimicrobial resistance in Africa: a systematic review","volume":"17","author":"BT Tadesse","year":"2017","journal-title":"BMC Infect Dis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T22:03:34Z","timestamp":1607378614000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0243054"}},"subtitle":[],"editor":[{"given":"Grzegorz","family":"Wo\u017aniakowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,7]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0243054","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,7]]}}}