Son 11 Yılda Haemophilus influenzae Direncindeki Eğilimler: Bir Üçüncü Basamak Hastanenin Deneyimi

Öz

Bu çalışmada on bir yıllık zaman diliminde üçüncü basamak bir hastane olan merkezimize başvuran hastaların klinik örneklerinde üreyen Haemophilus influenzae (H. influenzae) türlerinin değerlendirilmesi ve antimikrobiyal direnç paternlerinin incelenmesi amaçlanmıştır. 1 Ocak 2014-31 Aralık 2024 tarihleri arasında üreyen H. influenzae türleri retrospektif olarak değerlendirildi. H. influenzae türleri MALDİ-TOF MS (Bruker Daltonik GmbH, Bremen, Almanya) ile tanımlanmış olup Difco H. influenzae Type b antiserumu (Difco-BD®-USA) ile serotipleme yapıldı. H. influenzae izole edilen sadece 21 (%1,4) örnek (10 kan, 5 biyopsi, 3 BOS, 2 vitreus, 1 plevra) invaziv bölgeden olup non-invaziv örnekler içinde en yaygın örnek balgamdı (1179 suş, %81). H. influenzae izolatlarında ampisilin direnci %38,5 idi. Amoxicillin–Clavulanate (AMC) direnci %13,5, sefuroksim direnci %66,6, seftriakson direnci %45,7, kloramfenikol direnci %12,2, klaritromisin direnci %12,7, eritromisin direnci %14,3, levofloksasin direnci %11,5, meropenem direnci %21,2, rifampicin direnci %20,2, tetrasiklin direnci %21 ve Trimethoprim–Sulfamethoxazole (TMP-SMX) direnci %34,3 olarak tespit edildi. Non-Type B suşlarda ampisilin ve TMP-SMX direnci istatistiksel olarak daha yaygın saptandı. Non-invaziv örneklerde TMP-SMX direnci istatistiksel olarak daha yaygın saptandı. Yoğun bakım ünitesi (YBÜ)’nde yatan hastalardaki suşlar ampisilin ve seftriaksona istatistiksel olarak daha dirençli bulundu. Sonuç olarak, H. influenzae'nin antibiyotik direnç oranları ülkeye ve hatta ülke içindeki bölgelere göre zaman içinde değişiklik göstermektedir. Ayrıca antibiyotiklerin direnç durumunda yıllık dalgalanmalar göz önüne alındığında, sürekli güncel yerel ilaç direnci durumunun bilinmesi gereklidir. Bu çalışmada H. influenzae’nın etken olduğu enfeksiyonların tedavisinde ampisilin, seftriakson, sefuroksim ve TMP-SMX direnç oranlarının yüksekliği nedeni ile tedavi seçeneklerinin yeniden düzenlenmesi gerekliliğini ortaya kondu.

Anahtar Kelimeler

• Haemophilus influenzae
• ampisilin
• antibiyotik direnci

Trends in Haemophilus influenzae Resistance Over the Past 11 Years: A Tertiary Hospital Experience

Öz

This study aimed to evaluate retrospectively the species Haemophilus influenzae (H. influenzae) that was isolated from clinical specimens of patients admitted to our tertiary care hospital January 1, 2014, and December 31, 2024 and to investigate their antimicrobial resistance patterns. H. influenzae was identified using MALDI-TOF MS (Bruker Daltonik GmbH, Bremen, Germany) and serotyped using Difco H. influenzae Type b antiserum (Difco-BD®-USA). Only 21 (1.4%) samples (10 blood, 5 biopsy, 3 CSF, 2 vitreous, 1 pleural) isolated with H. influenzae were from invasive sites, and sputum was the most common sample among non-invasive samples (1179 strains,81%). Ampicillin resistance in H. influenzae isolates was 38.5%. Amoxicillin–Clavulanate (AMC) resistance was 13.5%, cefuroxime resistance was 66.6%, ceftriaxone resistance was 45.7%, chloramphenicol resistance was 12.2%, clarithromycin resistance was 12.7%, erythromycin resistance was 14.3%, levofloxacin resistance was 11.5%, meropenem resistance was 21.2%, rifampicin resistance was 20.2%, tetracycline resistance was 21%, and Trimethoprim–Sulfamethoxazole (TMP-SMX) resistance was 34.3%. Ampicillin and TMP-SMX resistance were statistically more prevalent in non-Type B strains. TMP-SMX resistance was statistically more prevalent in non-invasive samples. Strains from patients in the intensive care unit (ICU) were statistically more resistant to ampicillin and ceftriaxone. As a result, rates of antibiotic resistance for H. influenzae vary over time, depending on the country, and even within regions of the same country. Considering the annual fluctuations in antibiotic resistance, it is important to be aware of the current local drug resistance situation. This study revealed the need to reevaluate treatment options due to high resistance rates of ampicillin, ceftriaxone, cefuroxime, and TMP-SMX for treating infections caused by H. influenzae.

Anahtar Kelimeler

• Haemophilus influenzae
• ampicilin
• antimicrobial resistance

Kaynakça

1. 1. Tristram S, Jacobs MR, Appelbaum PC. Antimicrobial resistance in Haemophilus influenzae. Clin Microbiol Rev. 2007 Apr;20(2):368-89. doi: 10.1128/CMR.00040-06. PMID: 17428889; PMCID: PMC1865592.
2. 2. Fuji N, Pichichero M, Kaur R. Haemophilus influenzae Prevalence, Proportion of Capsulated Strains and Antibiotic Susceptibility During Colonization and Acute Otitis Media in Children, 2019-2020. Pediatr Infect Dis J. 2021 Sep 1;40(9):792-796. doi: 10.1097/INF.0000000000003171. PMID: 34321442.
3. 3. Tønnessen R, García I, Debech N, Lindstrøm JC, Wester AL, Skaare D. Molecular epidemiology and antibiotic resistance profiles of invasive Haemophilus influenzae from Norway 2017-2021. Front Microbiol. 2022 Aug 29;13:973257. doi: 10.3389/fmicb.2022.973257. PMID: 36106084; PMCID: PMC9467436.
4. 4. Ilki A, Sağiroğlu P, Elgörmüş N, Söyletir G. Streptococcus pneumoniae ve Haemophilus influenzae izolatlarinin antibiyotik duyarlilik paternlerindeki değişim: dört yillik izlem [Trends in antibiotic susceptibility patterns of Streptococcus pneumoniae and Haemophilus influenzae isolates: four years follow up]. Mikrobiyol Bul. 2010 Apr;44(2):169-75. Turkish. PMID: 20549950.
5. 5. Kılıç H, Akyol S, Parkan ÕM, Dinç G, Sav H, Aydemir G. Molecular characterization and antibiotic susceptibility of Haemophilus influenzae clinical isolates. Infez Med. 2017 Mar 1;25(1):27-32. PMID: 28353452.
6. 6. Weinberger B. Vaccines for the elderly: current use and future challenges. Immun Ageing. 2018 Jan 22;15:3. doi: 10.1186/s12979-017-0107-2. PMID: 29387135; PMCID: PMC5778733.
7. 7. Whittaker R, Economopoulou A, Dias JG, Bancroft E, Ramliden M, Celentano LP; European Centre for Disease Prevention and Control Country Experts for Invasive Haemophilus influenzae Disease. Epidemiology of Invasive Haemophilus influenzae Disease, Europe, 2007-2014. Emerg Infect Dis. 2017 Mar;23(3):396-404. doi: 10.3201/eid2303.161552. PMID: 28220749; PMCID: PMC5382729.
8. 8. Çaycı YT, Avan T, Bilgin K, Birinci A. Alt solunum yolu örneklerinden izole edilen Streptococcus pneumoniae, Haemophilus influenzae ve Moraxella catarrhalis suşlarının antibiyotik duyarlılığının değerlendirilmesi. Turk J Clin Lab. 2019;10(3):277-82.

9. 9. Uskudar Guclu A, Altay Kocak A, Akcil Ok M, Tutluoglu B, Basustaoglu AC; Respiratory Study Group. Antibacterial Resistance in Lower Respiratory Tract Bacterial Pathogens: A Multicenter Analysis from Turkey. J Infect Dev Ctries. 2021 Mar 7;15(2):254-262. doi: 10.3855/jidc.12599. PMID: 33690209.
10. 10. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0. 2021. Available from: https://www.eucast.org/clinical_breakpoints/
11. 11. Szabo BG, Lenart KS, Tirczka T, Ostorhazi E. Clinical and microbiological characteristics of adult invasive Haemophilus influenzae infections: results of a 14-year single-center experience from Hungary. Infection. 2018 Dec;46(6):855-860. doi: 10.1007/s15010-018-1213-6. Epub 2018 Sep 6. PMID: 30191513.
12. 12. Bae S, Lee J, Lee J, et al. Antimicrobial resistance in Haemophilus influenzae respiratory tract isolates in Korea: results of a nationwide acute respiratory infections surveillance. Antimicrob Agents Chemother. 2010 Jan;54(1):65-71. doi: 10.1128/AAC.00966-09. Epub 2009 Nov 2. PMID: 19884366; PMCID: PMC2798543.
13. 13. Giufrè M, Cardines R, Caporali MG, Accogli M, D’Ancona F, Cerquetti M. Ten years of Hib vaccination in Italy: prevalence of non-encapsulated Haemophilus influenzae among invasive isolates and the possible impact on antibiotic resistance. Vaccine. 2011 May 31;29(22):3857-62. doi: 10.1016/j.vaccine.2011.03.010. PMID:21443963.
14. 14. Jalalvand F, Riesbeck K. Update on non-typeable Haemophilus influenzae-mediated disease and vaccine development. Expert Rev Vaccines. 2018 Jun;17(6):503-512. doi: 10.1080/14760584.2018.1484286. Epub 2018 Jun 18. PMID: 29863956.
15. 15. Sener B, Tunçkanat F, Ulusoy S, et al. A survey of antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae in Turkey, 2004 2005. J Antimicrob Chemother. 2007 Sep;60(3):587-93. doi: 10.1093/jac/dkm232. Epub 2007 Jun 26. PMID: 17597058.
16. 16.Alışkan H, Karakeçe E, Yaylı G, et al. Antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae isolated from respiratory tract specimens. Cukurova Med J.2016;41(2):201-7. doi: 10.17826/cutf.196127.
17. 17.Vaez H, Sahebkar A, Pourfarzi F, Yousefi-Avarvand A, Khademi F. Prevalence of Antibiotic Resistance of Haemophilus Influenzae in Iran- A Meta-Analysis. Iran JOtorhinolaryngol. 2019 Nov;31(107):349-357. doi:10.22038/ijorl.2019.34363.2137. PMID: 31857979; PMCID:PMC6914328.
18. 18.Zhou M, Fu P, Fang C, et al. Antimicrobial resistance ofHaemophilus influenzae isolates from pediatric hospitals in Mainland China: Report from the ISPED program, 2017-2019. Indian J Med Microbiol. 2021 Oct-Dec;39(4):434-438. doi: 10.1016/j.ijmmb.2021.09.001. Epub 2021 Sep 21. PMID:34556347.
19. 19.Abavisani M, Keikha M, Karbalaei M. First global report about the prevalence of multi-drug resistant Haemophilus influenzae: a systematic review and meta-analysis. BMC Infect Dis. 2024Jan 15;24(1):90. doi: 10.1186/s12879-023-08930-5. PMID:38225571; PMCID: PMC10789054.
20. 20.Wang J, Wang R, Jing C, Xiang Y, Xiong Z, Liu F. Shifts in Epidemiology and Antibiotic Resistance of HaemophilusInfluenzae in Children From Chongqing (2019-2024): Pre-,During, and Post-COVID-19. Infect Drug Resist. 2025 Aug 28;18:4461-4470. doi: 10.2147/IDR.S535755. PMID:40904903; PMCID: PMC12402710.
21. 21.Yuluğ DP, Öztürk B, Toprak OB, et al. Physicians’ irrational attitudes on the antibiotic prescribing for the treatment of COVID-19 in Turkey: A multicenter survey. BMC Health Serv Res 24, 650 (2024). https://doi.org/10.1186/s12913-024-11110-z
22. 22.Önal U, Tüzemen Ü, Kazak E, et al. Effects of COVID-19pandemic on healthcare-associated infections, antibiotic resistance and consumption rates in intensive care units. Infez Med. 2023 Jun 1;31(2):195-203. doi: 10.53854/liim-3102-7. PMID: 37283640; PMCID: PMC10241394.
23. 23.Hacıseyitoğlu D, Sümerkan B. Klinik örneklerden izole edilenHaemophilus influenzae suşlarının serotiplendirilmesi ve bazıantimikrobiyallere duyarlılık durumlarının araştırılması. Ortadogu Tıp Derg 2019; 11(4): 497-503.https://doi.org/10.21601/ortadogutipdergisi.544493
24. 24.McElligott M, Meyler K, Bennett D, Mulhall R, Drew RJ, Cunney R. Epidemiology of Haemophilus influenzae in the Republic of Ireland, 2010-2018. Eur J Clin Microbiol Infect Dis. 2020 Dec;39(12):2335-2344. doi: 10.1007/s10096-020-03971-z. Epub 2020 Jul 14. PMID: 32666480.
25. 25.Kiedrowska M, Foryś WJ, Gołębiewska A, et al. Antimicrobial resistance among Haemophilus influenzae isolates responsible for lower respiratory tract infections in Poland, 2005-2019. EurJ Clin Microbiol Infect Dis. 2022 Jun;41(6):961-969. doi: 10.1007/s10096-022-04457-w. Epub 2022 May 18. PMID:35585442.
26. 26.Ulanova M, Tsang RSW, Lo T, et al. Epidemiology of invasiveHaemophilus influenzae disease in northwestern Ontario: comparison of invasive and noninvasive isolates. Can JMicrobiol. 2023;69(8):605-616. doi:10.1139/cjm-2019-0210.
27. 27.World Health Organization. Global Antimicrobial Resistanceand Use Surveillance System (GLASS) Report: 2024. Geneva,Switzerland: WHO; 2025. Accessed December 10, 2025.https://www.who.int/publications/i/item/9789240108127.