Battling urinary tract infections: Unravelling the etiological spectrum and resistance repertoire of causative non-fermenting Gram-negative bacilli

Abstract

Objective: To ascertain the microbial landscape of uropathogenic non-fermenting Gram-negative bacilli (NFGNB) and their antimicrobial susceptibility profile in an Indian tertiary care hospital setting.
Methods: A retrospective observational study was conducted from May to October 2024, at a tertiary care hospital in India. Urine specimens were processed and bacterial identification was performed as per standard protocol. Antimicrobial susceptibility testing was performed in accordance with Clinical and Laboratory Standard Institute guidelines. The etiological and antimicrobial susceptibility profiles of the uropathogenic NFGNB isolates were retrieved from laboratory records and analyzed.
Results: Among the 24 286 urine specimens received during the study period, 12.3% (2 992/24 286) showed significant bacteriuria, of which 5.7% (171/2 992) were identified as NFGNB. The predominant NFGNB was Acinetobacter spp. (48.5%) followed by Pseudomonas spp. (48.0%, 82/171), with Acinetobacter baumannii being the most common NFGNB (42.1%, 72/171) isolated. Acinetobacter baumannii exhibited significantly lower susceptibility to carbapenems (38.9%–44.4%) compared to Pseudomonas aeruginosa (69.6%–75.4%) (P=0.001). Among the NFGNB, 56.5% were multidrug-resistant, 34.1% extensively drug-resistant and 15.9% pandrug-resistant. Multidrug-resistant and extensively drug-resistant rates were significantly higher in Acinetobacter species than in Pseudomonas species (P=0.001 and P=0.002, respectively) with inpatient isolates showing significantly lower antimicrobial susceptibility patterns.
Conclusions: The high prevalence of multidrug-resistant strains of uropathogenic NFGNB, especially in hospitalized patients, underscores the need for strengthened infection prevention and control practices and continuous ongoing surveillance activities to gain a more comprehensive understanding and improve clinical outcomes.

Keywords

Antimicrobial resistance / Multidrug resistance / Nonfermenting Gram-negative bacilli / Uropathogens

Conflict of interest statement

The authors claim there is no conflict of interest.

Funding

The study received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

Mitra S and Mehra B conceived the study, obtained ethical approval, validated, investigated, analyzed the data, reviewed for critical content and contributed in drafting and editing the manuscript. Aggarwal P was responsible for the organization, coordination and management of the study. Guleria A helped in management of the data. Saxena S provided general supervision, project administration and helped in final review and approval of the manuscript. All authors read and approved the final manuscript.

References

[1] Mancuso G, Midiri A, Gerace E, Marra M, Zummo S, Biondo C. Urinary tract infections: The current scenario and future prospects. Pathogens 2003; 12(4): 623.

[2] Grewal US, Bakshi R, Walia G, Shah PR. Antibiotic susceptibility profiles of non-fermenting Gram-negative Bacilli at a tertiary care hospital in Patiala, India. Niger Postgrad Med J 2017; 24(2): 121-125.

[3] Benachinmardi KK, Padmavathy M, Malini J, Naveneeth BV. Prevalence of non-fermenting Gram-negative bacilli and their in vitro susceptibility pattern at a tertiary care teaching hospital. J Sci Soc 2014; 41(3): 162-166.

[4] Gajdács M, Burián K, Terhes G. Resistance levels and epidemiology of non-fermenting Gram-negative bacteria in urinary tract infections of inpatients and outpatients (RENFUTI): A 10-year epidemiological snapshot. Antibiotics (Basel) 2019; 8(3): 143.

[5] Yadav SK, Jha UK, Sherchand JB. Urinary tract infection due to non-fermentative Gram-negative bacilli in Tribhuvan University teaching hospital, Kathmandu, Nepal. NUTA J 2020; 7(1-2): 71-78.

[6] Somily A, Balkhy HH, Enani MAS, Althawadi SI, Alawi M, Al Johani SM, et al. Antimicrobial resistance trends of non-fermenter Gram negative bacteria in Saudi Arabia: A six-year national study. J Infect Public Health 2021; 14(9): 1144-1150.

[7] Makkar A, Panda PS, Khan ID, Banerjee P, Kaira SS, Rajmohan KS. Non-fermenters as mysterious pathogens or contaminants-continuing dilemma. Saudi J Pathol Microbiol 2018; 3(9): 303-309.

[8] Lupo A, Haenni M, Madec JY. Antimicrobial resistance in Acinetobacter spp. and Pseudomonas spp. Microbiol Spectr 2018; 6(3): 10.1128/microbiolspec.arba-0007-2017.

[9] Di Pilato V, Willison E, Marchese A. The microbiology and pathogenesis of nonfermenting Gram-negative infections. Curr Opin Infect Dis 2023; 36(6): 537-544.

[10] Matar GM. Pseudomonas and Acinetobacter: From drug resistance to pathogenesis. Front Cell Infect Microbiol 2018; 8: 68.

[11] Jiménez-Guerra G, Heras-Cañas V, Gutiérrez-Soto M, Aznarte-Padial MDP, Expósito-Ruiz M, Navarro-Marí JM, et al. Urinary tract infection by Acinetobacter baumannii and Pseudomonas aeruginosa: Evolution of antimicrobial resistance and therapeutic alternatives. J Med Microbiol 2018; 67(6): 790-797.

[12] Asif M, Alvi IA, Rehman SU. Insight into Acinetobacter baumannii: Pathogenesis, global resistance, mechanisms of resistance, treatment options, and alternative modalities. Infect Drug Resist 2018; 11: 1249-1260.

[13] Brooke JS. Advances in the microbiology of Stenotrophomonas maltophilia. Clin Microbiol Rev 2021; 34(3): e0003019.

[14] Karakonstantis S, Kritsotakis EI, Gikas A. Pandrug-resistant Gram-negative bacteria: A systematic review of current epidemiology, prognosis and treatment options. J Antimicrob Chemother 2020; 75(2): 271-282.

[15] Dougnon V, Assogba P, Anago E, Déguénon E, Dapuliga C, Agbankpè J, et al. Enterobacteria responsible of urinary infections: A review about pathogenicity, virulence factors and epidemiology. J Appl Biol Biotech 2020; 8: 117-124.

[16] Bologna E, Licari LC, Manfredi C, Ditonno F, Cirillo L, Fusco GM, et al. Carbapenem-resistant Enterobacteriaceae in urinary tract infections: From biological insights to emerging therapeutic alternatives. Medicina (Kaunas) 2024; 60(2): 214.

[17] Collee JG, Marr W. Culture of bacteria. In: Collee JG, Fraser AG, Marmion BP, Simmons A (Eds). Mackie & McCartney Practical medical microbiology. 14th ed. London: Churchill Livingstone; 2006, pp. 113-130.

[18] Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing, CLSI Supplement M100-Ed34. 34th ed. PA: Wayne; 2024.

[19] Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.

[20] Berwal A, Shobha KL, Gupta R, Gupta K, Ashraf A, Balakumar AK, et al. Non-fermenting gram negative bacteria as uropathogens in causing urinary tract infection and its antimicrobial susceptibility pattern at a tertiary care centre of South India. J Pure Appl Microbiol 2020; 14(3): 2033-2038.

[21] Rodriguez-Mañas L. Urinary tract infections in the elderly: A review of disease characteristics and current treatment options. Drugs Context 2020; 9: 2020-4-13.

[22] Parajuli NP, Acharya SP, Mishra SK, Parajuli K, Rijal BP, Pokhrel BM. High burden of antimicrobial resistance among Gram negative bacteria causing healthcare associated infections in a critical care unit of Nepal. Antimicrob Resist Infect Control 2017; 6: 67.

[23] Koulenti D, Vandana KE, Rello J. Current viewpoint on the epidemiology of nonfermenting Gram-negative bacterial strains. Curr Opin Infect Dis 2023; 36(6): 545-554.

[24] Mahajan R, Mahajan B. Isolation and identification of non fermenting gram negative bacilli in a tertiary care hospital. Sch J Appl Med Sci 2016; 4: 872-876.

[25] Indian Council of Medical Research (ICMR). Annual Report January 2023 to December 2023. Antimicrobial resistance research and surveillance network. [Online] Available on: https://www.icmr.gov.in/icmrobject/uploads/Documents/1725536060_annual_report_2023.pdf. [Accessed on 15 March 2025].

[26] Pragasam AK, Veeraraghavan B, Anandan S, Narasiman V, Sistla S, Kapil A, et al. Dominance of international high-risk clones in carbapenemase-producing Pseudomonas aeruginosa: Multicentric molecular epidemiology report from India. Indian J Med Microbiol 2018; 36(3): 344-351.

[27] World Health Organization. WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. [Online] Available from: https://www.who.int/publications/i/item/9789240093461. [Accessed on 15 March 2025].

[28] Namaei MH, Yousefi M, Askari P, Roshanravan B, Hashemi A, Rezaei Y. High prevalence of multidrug-resistant non-fermentative Gram-negative bacilli harboring blaIMP-1 and blaVIM-1 metallo-beta-lactamase genes in Birjand, south-east Iran. Iran J Microbiol 2021; 13(4): 470-479.

[29] Gheorghe I, Czobor I, Chifiriuc MC, Borcan E, Ghiţă C, Banu O, et al. Molecular screening of carbapenemase-producing gram-negative strains in Romanian intensive care units during a one year survey. J Med Microbiol 2014; 63: 1303-1310.