Carbapenems represent a critical class of β-lactam antibiotics prized for their broad-spectrum activity against Gram-negative bacilli (GNB), including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. They remain a cornerstone for treating severe nosocomial infections, particularly hospital-acquired and ventilator-associated pneumonia [1]. However, the rapid global emergence of carbapenem-resistant Gram-negative bacilli (CR-GNB) poses a severe threat to public health, drastically limiting therapeutic options and contributing to high morbidity, mortality, prolonged hospital stays, and increased healthcare costs [2]. CR-GNB primarily arises through carbapenemase production (e.g., KPC, NDM, OXA-48, VIM, IMP), combined with mechanisms such as porin loss, efflux pump overexpression, and target modifications [3, 4]. Key pathogens include carbapenem-resistant Enterobacterales (CRE, notably Klebsiella pneumoniae and Escherichia coli), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPA). These organisms frequently cause respiratory tract infections in critically ill patients, especially those in intensive care units (ICUs) with mechanical ventilation, immunosuppression, or prior broad-spectrum antibiotic exposure [3, 4]. Globally, the burden is substantial. A meta-analysis reported a pooled CRKP prevalence of approximately 28.7% among K. pneumoniae infections, with South Asia showing the highest rates at over 66% [3]. In the United States, CRE infections caused significant morbidity, with rising incidence noted in recent years. Respiratory sources represent a major site for these pathogens in hospital settings, often linked to poorer outcomes compared to urinary tract infections [3, 5]. India faces one of the highest burdens of antimicrobial resistance (AMR) worldwide, driven by high infectious disease prevalence, widespread antibiotic misuse, and limited infection control in many healthcare facilities [6]. The Indian Council of Medical Research (ICMR) Antimicrobial Resistance Surveillance Network (AMRSN) consistently documents alarming carbapenem resistance rates [6, 7]. Recent reports indicate imipenem resistance around 28% in E. coli, 55% in K. pneumoniae, and up to 80-91% in A. baumannii, with NDM and OXA-type carbapenemases predominating [6-8]. High resistance extends to other classes, including fluoroquinolones, aminoglycosides, and β-lactams, leaving colistin and newer agents (where available and susceptible) as limited salvage options. Respiratory isolates often exhibit multidrug-resistant (MDR) or extensively drug-resistant (XDR) profiles [6-8]. Respiratory infections due to CR-GNB are particularly problematic because of biofilm formation (especially in P. aeruginosa and A. baumannii), device association (endotracheal tubes, tracheostomies), and diagnostic challenges in distinguishing colonization from infection [8]. Variations in resistance exist across sample types (sputum vs. bronchoalveolar lavage vs. endotracheal aspirates), influenced by patient acuity and acquisition setting (community vs. hospital). Institution-specific antibiograms are essential for guiding empirical therapy, as national or global data may not reflect local epidemiology. Despite growing awareness, gaps persist in Bihar’s tertiary care settings regarding comprehensive, species-specific prevalence, detailed antibiograms (including colistin), and comparisons across respiratory sample types [8, 9]. The primary research question of this study is: “What is the prevalence of carbapenem-resistant Gram-negative bacilli (CR-GNB) among Gram-negative isolates recovered from respiratory tract samples in a tertiary care hospital of Bihar?” The primary objective is to assess the prevalence of CR-GNB among respiratory isolates, while the secondary objectives are to determine the species-wise distribution of CR-GNB, including Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and other Enterobacteriaceae; evaluate their antimicrobial resistance profiles against β-lactams, fluoroquinolones, aminoglycosides, and carbapenems; identify the most effective therapeutic agents, particularly with respect to colistin susceptibility; compare resistance patterns across different respiratory sample types, including sputum, endotracheal secretions, bronchoalveolar lavage, and tracheostomy tube secretions; and generate institution-specific antibiogram data to support empirical antimicrobial therapy and strengthen antimicrobial stewardship.

A retrospective, observational, hospital-based study was conducted over a period of 3 months in the Department of Microbiology, in collaboration with the Departments of Medicine, Pulmonary Medicine, and Critical Care of a tertiary care teaching hospital in Bihar, India. Data were obtained from respiratory clinical samples received in the Clinical Microbiology Laboratory for routine aerobic bacterial culture and antimicrobial susceptibility testing, along with relevant demographic and clinical information retrieved from hospital information system records, case sheets, and laboratory requisition forms. Study Population The study population comprised patients aged 18 years or older from both inpatient and outpatient departments who had clinically significant Gram-negative bacilli isolated from respiratory samples, including sputum, endotracheal aspirates, bronchoalveolar lavage (BAL) fluid, and tracheostomy tube secretions. The organisms included Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and other Enterobacteriaceae associated with clinical features suggestive of respiratory tract infection. Isolates showing resistance to at least one carbapenem, namely imipenem or meropenem, by disk diffusion or automated susceptibility testing were considered for detailed CR-GNB analysis. Gram-positive and fungal isolates, duplicate isolates from the same patient within 30 days, contaminated or poor-quality samples, and isolates considered colonizers without clinical correlation were excluded. Sample Size The minimum sample size was calculated using the standard formula for estimation of a single population proportion, based on a prevalence of carbapenem resistance of 25.62% reported by Santra R et al. (2026) [10], in which 92 of 359 Gram-negative respiratory isolates were carbapenem-resistant. With an expected prevalence (p) of 0.2562, a 95% confidence level (Z = 1.96), and an absolute precision of 5%, the calculated minimum sample size was 293 Gram-negative respiratory isolates. Outcome Parameters The primary outcome parameter was the prevalence of carbapenem-resistant Gram-negative bacilli among Gram-negative respiratory isolates. Secondary outcome parameters included the species-wise distribution of CR-GNB, antimicrobial susceptibility patterns against β-lactams, fluoroquinolones, aminoglycosides, carbapenems, and colistin, and the percentage susceptibility to colistin and other relevant last-resort antimicrobial agents. Resistance rates were also compared across different respiratory sample types, including sputum, endotracheal secretions, BAL fluid, and tracheostomy tube secretions. The study further aimed to generate institution-specific antibiogram data to support empirical antimicrobial selection and antimicrobial stewardship. Methodology Respiratory samples were processed using standard microbiological procedures. Samples were inoculated onto Blood agar, Chocolate agar, and MacConkey agar and were incubated aerobically at 37°C for 18–24 hours. Bacterial identification was performed using automated identification systems, including VITEK 2 Compact or MALDI-TOF MS, wherever available, supplemented by conventional biochemical tests when required. Antimicrobial susceptibility testing was performed using the Kirby–Bauer disk diffusion method and/or automated susceptibility testing by VITEK 2, in accordance with the applicable Clinical and Laboratory Standards Institute (CLSI) 2024 recommendations. Carbapenem resistance was assessed using imipenem and meropenem 10-µg disks or the corresponding automated susceptibility results. Colistin susceptibility was determined by broth microdilution according to CLSI recommendations. Appropriate quality-control procedures were followed using standard American Type Culture Collection (ATCC) reference strains. Demographic and laboratory variables, including age, sex, ward or ICU admission, sample type, date of sample collection, organism identified, and antimicrobial susceptibility results, were recorded in a structured data-collection proforma and entered into a Microsoft Excel spreadsheet using coded patient identifiers. Statistical Analysis The collected data were analysed using IBM SPSS Statistics version 26.0 and/or R statistical software. Categorical variables were expressed as frequencies and percentages. The prevalence of CR-GNB was calculated as a proportion of the total Gram-negative respiratory isolates, with corresponding 95% confidence intervals. The Chi-square test or Fisher’s exact test, as appropriate, was used to compare antimicrobial resistance patterns between bacterial species and different respiratory sample types. A p-value of <0.05 was considered statistically significant. Descriptive statistical methods were used to summarize the species distribution and antimicrobial susceptibility patterns and to prepare the institution-specific antibiogram. Ethical Consideration The study protocol was submitted to and approved by the Institutional Ethics Committee of the participating tertiary care hospital before commencement. As the study involved retrospective analysis of routinely collected laboratory samples and clinical records without any additional intervention, a waiver of written informed consent was obtained where permitted by the Institutional Ethics Committee

Of the 293 Gram-negative respiratory isolates, 115 (39.2%) were carbapenem-resistant, indicating a substantial burden of CR-GNB. Among 115 patients with CR GNB respiratory isolates, the largest group was aged 61–80 years (39.1%), followed by 41–60 years (32.2%). Patients aged 18–40 years and >80 years comprised 15.7% and 13.0%, respectively. Males predominated (67.0%) compared to females (33.0%). Most isolates were from ICU patients (59.1%), followed by general wards (33.9%), while only 7.0% were from outpatients. Sputum was the most common specimen (39.1%), followed by endotracheal secretions (37.4%). BAL fluid (12.2%) and tracheostomy secretions (11.3%) contributed smaller proportions [Table 1]. Table 1. Demographic and clinical characteristics of patients with CR-GNB isolates (n = 115) Characteristic Category n (%) Age group 18–40 years 18 (15.7) 41–60 years 37 (32.2) 61–80 years 45 (39.1) >80 years 15 (13.0) Sex Male 77 (67.0) Female 38 (33.0) Patient location ICU 68 (59.1) General ward 39 (33.9) Outpatient 8 (7.0) Respiratory sample Sputum 45 (39.1) Endotracheal secretion 43 (37.4) BAL fluid 14 (12.2) Tracheostomy secretion 13 (11.3) Of 293 Gram negative respiratory isolates, Klebsiella pneumoniae was most frequent (35.8%), followed by Acinetobacter baumannii (28.0%), Pseudomonas aeruginosa (20.8%), and other Enterobacteriaceae (15.4%). Carbapenem resistance was highest in A. baumannii (62.2%), followed by K. pneumoniae (36.2%), P. aeruginosa (27.9%), and other Enterobacteriaceae (20.0%). Overall, 115 isolates (39.2%) were carbapenem resistant. The difference across species was statistically significant (χ² = 28.82, p < 0.0001) [Table 2]. Table 2. Distribution of Gram-negative respiratory isolates and prevalence of CR-GNB Organism Total isolates, n (%) Carbapenem-resistant isolates, n (%) Carbapenem-susceptible isolates, n (%) Klebsiella pneumoniae 105 (35.8) 38 (36.2) 67 (63.8) Acinetobacter baumannii 82 (28.0) 51 (62.2) 31 (37.8) Pseudomonas aeruginosa 61 (20.8) 17 (27.9) 44 (72.1) Other Enterobacteriaceae 45 (15.4) 9 (20.0) 36 (80.0) Total 293 (100.0) 115 (39.2) 178 (60.8) Chi-square test: χ² = 28.82, p <0.0001 Sputum accounted for 48.5% of samples, followed by endotracheal secretions (30.4%), BAL fluid (13.0%), and tracheostomy tube secretions (8.2%). CR GNB proportion was highest in tracheostomy secretions (54.2%), followed by endotracheal secretions (48.3%), BAL fluid (36.8%), and sputum (31.7%). Overall, 115 of 293 isolates (39.2%) were carbapenem resistant. The association between sample type and CR GNB was significant (χ² = 8.803, p = 0.032) [Table 3]. Table 3. Distribution of respiratory sample types and CR-GNB Respiratory sample type Total isolates, n (%) CR-GNB, n (%) Non-CR-GNB, n (%) Sputum 142 (48.5) 45 (31.7) 97 (68.3) Endotracheal secretions 89 (30.4) 43 (48.3) 46 (51.7) Bronchoalveolar lavage 38 (13.0) 14 (36.8) 24 (63.2) Tracheostomy tube secretions 24 (8.2) 13 (54.2) 11 (45.8) Total 293 (100.0) 115 (39.2) 178 (60.8) Chi-square test: χ² = 8.803, p = 0.0320 Resistance to carbapenems was very high: 93.0% to imipenem and 94.8% to meropenem, with no susceptible isolates. Resistance was also high to cefepime (80.9%), ceftazidime (79.1%), piperacillin–tazobactam (76.5%), and ciprofloxacin (77.4%). Amikacin showed lower resistance (65.2%) compared to gentamicin (69.6%). Colistin retained the highest activity, with 87.8% of isolates susceptible [Table 4]. Table 4. Antimicrobial susceptibility pattern of CR-GNB isolates (n = 115) Antimicrobial agent Susceptible, n (%) Intermediate, n (%) Resistant, n (%) Imipenem 0 (0.0) 8 (7.0) 107 (93.0) Meropenem 0 (0.0) 6 (5.2) 109 (94.8) Piperacillin–tazobactam 18 (15.7) 9 (7.8) 88 (76.5) Cefepime 14 (12.2) 8 (7.0) 93 (80.9) Ceftazidime 17 (14.8) 7 (6.1) 91 (79.1) Ciprofloxacin 21 (18.3) 5 (4.3) 89 (77.4) Amikacin 34 (29.6) 6 (5.2) 75 (65.2) Gentamicin 28 (24.3) 7 (6.1) 80 (69.6) Colistin 101 (87.8) — 14 (12.2) Susceptibility varied across species. Piperacillin–tazobactam activity ranged from 5.9% in A. baumannii to 29.4% in P. aeruginosa. Cefepime susceptibility ranged from 3.9% in A. baumannii to 29.4% in P. aeruginosa. Ciprofloxacin susceptibility was highest in other Enterobacteriaceae (44.4%) and lowest in A. baumannii (7.8%). Amikacin showed better activity against other Enterobacteriaceae (55.6%) and P. aeruginosa (47.1%), but had a limited effect in A. baumannii (15.7%). Colistin remained the most effective agent, with susceptibility ranging from 82.4% in A. baumannii to 94.7% in K. pneumoniae [Table 5]. Table 5. Species-wise antimicrobial susceptibility of CR-GNB isolates Antimicrobial agent K. pneumoniae (n=38) n (%) A. baumannii (n=51) n (%) P. aeruginosa (n=17) n (%) Other Enterobacteriaceae (n=9) n (%) Piperacillin–tazobactam 8 (21.1) 3 (5.9) 5 (29.4) 2 (22.2) Cefepime 6 (15.8) 2 (3.9) 5 (29.4) 1 (11.1) Ciprofloxacin 7 (18.4) 4 (7.8) 6 (35.3) 4 (44.4) Amikacin 13 (34.2) 8 (15.7) 8 (47.1) 5 (55.6) Gentamicin 11 (28.9) 7 (13.7) 6 (35.3) 4 (44.4) Colistin 36 (94.7) 42 (82.4) 15 (88.2) 8 (88.9)

The present study demonstrated a substantial burden of carbapenem-resistant Gram-negative bacilli (CR-GNB) among respiratory isolates in a tertiary care hospital in Bihar. The overall prevalence of CR-GNB in the present study (39.2%) was higher than the 25.62% reported by Santra et al. (2026) from a tertiary care hospital in Navi Mumbai. Santra et al. examined 359 Gram-negative respiratory isolates and found 92 carbapenem-resistant isolates, with K. pneumoniae being the predominant organism and sputum being the most frequent source [10]. The predominance of K. pneumoniae and sputum in their study is consistent with the present findings, where K. pneumoniae constituted 35.8% of all Gram-negative isolates and sputum accounted for 48.5% of samples. However, the present study demonstrated a substantially greater contribution of A. baumannii, which represented 28.0% of all isolates and had the highest carbapenem resistance rate (62.2%). Importantly, both studies identified extensive multidrug resistance and found colistin to retain the greatest activity, supporting its continuing importance as a potential salvage agent against highly resistant respiratory pathogens. The species-specific distribution in the present study also differed from several international reports. In our study, K. pneumoniae was the most common Gram-negative respiratory isolate, while A. baumannii showed the highest resistance proportion. This contrasts with Chen et al. (2022), who studied 690 critically ill patients with CRGNB-associated nosocomial pneumonia in Taiwan and reported A. baumannii in 78.7% and P. aeruginosa in 13.0% of cases. Chen et al. also demonstrated that prolonged hospitalization, greater SOFA scores, and vasopressor requirement independently predicted mortality, highlighting the clinical severity associated with CRGNB infections [11]. Although mortality and clinical severity were not evaluated in the present study, the predominance of CR-GNB among ICU patients (59.1%) similarly suggests an important association with critically ill populations. The high resistance observed in the present study is also broadly consistent with findings from Agarwal et al. (2017) [12]. Their Indian ICU-based study reported A. baumannii as the predominant non-fermenting Gram-negative bacillus and documented very high resistance to imipenem and meropenem, particularly among A. baumannii [12]. In the present study, resistance to imipenem and meropenem among all CR-GNB was 93.0% and 94.8%, respectively, with no isolate classified as susceptible to either agent. Thus, both studies demonstrate that carbapenem resistance is particularly problematic among healthcare-associated respiratory Gram-negative organisms in Indian hospitals. The pattern observed in the present study differs from the older findings of Gladstone et al. (2005), who reported a carbapenem resistance prevalence of 12.2% among non-fermenting Gram-negative bacilli isolated from ICU respiratory specimens. P. aeruginosa constituted the largest proportion of resistant isolates in their study [13]. In contrast, the present study found 39.2% carbapenem resistance among all Gram-negative respiratory isolates, with A. baumannii demonstrating the highest species-specific resistance. Similarly, Cai et al. (2017) reported a considerably lower overall carbapenem resistance rate of 4.5% among 292,742 Gram-negative infections across 206 US hospitals. Their resistant isolates were predominantly non-glucose-fermenting organisms, particularly P. aeruginosa and A. baumannii, which together accounted for most carbapenem-resistant infections [14]. Although sputum was the most common specimen, the proportion of CR-GNB was highest in tracheostomy tube secretions (54.2%), followed by endotracheal secretions (48.3%), compared with 31.7% in sputum and 36.8% in BAL fluid. These findings are clinically relevant because endotracheal and tracheostomy-associated samples are commonly obtained from patients with prolonged hospitalization, mechanical ventilation, or airway instrumentation, conditions that may facilitate colonization and infection by resistant organisms. The findings are broadly compatible with Agarwal et al. (2017), in which endotracheal aspirates constituted 64.5% of respiratory samples from ICU patients with lower respiratory tract infections [12]. However, direct numerical comparison should be made cautiously because their study was restricted to ICU patients and focused on non-fermenters. The antimicrobial susceptibility pattern observed in the present study is particularly concerning. Resistance exceeded 75% for piperacillin–tazobactam, cefepime, ceftazidime, and ciprofloxacin, while resistance to amikacin and gentamicin was 65.2% and 69.6%, respectively. This broadly agrees with Santra et al. (2026), who also reported extensive resistance across β-lactams, fluoroquinolones, aminoglycosides, and carbapenems [10]. Species-wise, A. baumannii demonstrated particularly poor susceptibility in the present study, with only 5.9% susceptible to piperacillin–tazobactam, 3.9% to cefepime, 7.8% to ciprofloxacin, 15.7% to amikacin, and 13.7% to gentamicin. Conversely, P. aeruginosa and other Enterobacteriaceae generally demonstrated somewhat better susceptibility to several agents. Colistin emerged as the most active antimicrobial in the present study, with 87.8% overall susceptibility. Species-wise susceptibility remained high across K. pneumoniae (94.7%), A. baumannii (82.4%), P. aeruginosa (88.2%), and other Enterobacteriaceae (88.9%). This finding is consistent with Santra et al. (2026) and supports the continued role of colistin as a potential treatment option for highly resistant infections when susceptibility is demonstrated [10]. However, Wang et al. (2021) showed that clinical outcomes in critically ill patients with CRGNB-associated pneumonia were not significantly different between colistin plus carbapenem and colistin plus tigecycline regimens, while nephrotoxicity remained frequent in both groups [15]. Therefore, although the high in-vitro susceptibility to colistin in the present study is encouraging, susceptibility results should not automatically be equated with clinical efficacy, and treatment decisions should consider toxicity, infection severity, site of infection, and individual patient factors. The clinical significance of CRGNB is further supported by McCann et al. (2020) and Tabak et al. (2020) [16, 17]. McCann et al. demonstrated substantial mortality, readmission, prolonged hospitalization, and economic burden among patients with carbapenem-nonsusceptible respiratory infections, particularly when infection was hospital-onset or associated with mechanical ventilation and ICU-level illness [16]. Tabak et al. similarly showed increased length of stay and healthcare costs associated with carbapenem-nonsusceptible respiratory infections, particularly in hospital-onset cases [17]. Finally, Babiker et al. (2021) demonstrated that CRGNB isolation increased over an 18-year period, although overall 30-day mortality declined, emphasizing that improved recognition and management can potentially mitigate adverse outcomes despite persistent antimicrobial resistance [18]. Their finding that ICU residence was a strong predictor of mortality is particularly relevant to the present study, where nearly three-fifths of CR-GNB isolates were obtained from ICU patients. The study has several limitations. Its retrospective, single-centre design and short 3-month study period may limit the generalizability of the findings to other hospitals and regions. The study primarily evaluated microbiological resistance patterns and did not assess clinical outcomes such as treatment response, mortality, duration of hospital stay, or prior antibiotic exposure. Furthermore, molecular characterization of carbapenem-resistance mechanisms was not performed, limiting interpretation of the underlying resistance mechanisms.

Overall, the present study confirms the substantial and locally important burden of carbapenem resistance in respiratory Gram-negative isolates in a tertiary-care hospital in Bihar. The high resistance to carbapenems and most conventional antibiotics, combined with significant variation according to species and specimen type, highlights the need for regular institutional antibiograms, judicious antimicrobial prescribing, early microbiological diagnosis, and strengthened infection-control measures. The relatively high susceptibility to colistin provides a potential therapeutic option, but its use should be guided strictly by susceptibility testing and antimicrobial stewardship principles.

1. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011 Nov;55(11):4943-60. doi: 10.1128/AAC.00296-11. 2. Werth BJ. Carbapenems. MSD Manual Professional Edition. Updated May 2024. Accessed August 23, 2026. https://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-medications/carbapenems 3. Lin XC, Li CL, Zhang SY, Yang XF, Jiang M. The Global and Regional Prevalence of Hospital-Acquired Carbapenem-Resistant Klebsiella pneumoniae Infection: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2023 Dec 19;11(2):ofad649. doi: 10.1093/ofid/ofad649. 4. Jean S-S, Harnod D, Hsueh P-R. Global threat of carbapenem-resistant Gram-negative bacteria. Front Cell Infect Microbiol. 2022;12:823684. doi:10.3389/fcimb.2022.823684 5. Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenemresistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc. 2011;86(3):250-259. 6. Rajni E, Bairwa K, Galav H, Upadhyaya H, Gajjar D. An update on carbapenem-resistant Enterobacterales: A prospective study from Western India. J Postgrad Med. 2025 Apr 1;71(2):61-67. doi: 10.4103/jpgm.jpgm_558_24. 7. Walia K, Madhumathi J, Veeraraghavan B, Chakrabarti A, Kapil A, Ray P, Singh H, Sistla S, Ohri VC. Establishing Antimicrobial Resistance Surveillance & Research Network in India: Journey so far. Indian J Med Res. 2019 Feb;149(2):164-179. doi: 10.4103/ijmr.IJMR_226_18. 8. Azad MS, Kumari N, Sinha R, Saurabh K, Shahi SK. Multi-drug resistant Gram-negative bacilli in lower respiratory tract infections at IGIMS, Patna: a tertiary care hospital. J Indira Gandhi Inst Med Sci. 2020 Jan–Jun;6(1):50-3. 9. Kumari N, Kumar M, Katiyar A, Kumar A, Priya P, Kumar B, Biswas NR, Kaur P. Genome-wide identification of carbapenem-resistant Gram-negative bacterial (CR-GNB) isolates retrieved from hospitalized patients in Bihar, India. Sci Rep. 2022 May 19;12(1):8477. doi: 10.1038/s41598-022-12471-3. 10. Santra R, Swaminathan R, Joshi SA. Prevalence and antibiogram of carbapenem-resistant Gram-negative bacilli isolated from respiratory samples using an automated system in a tertiary care hospital, Navi Mumbai. IP Int J Med Microbiol Trop Dis. 2026;12(2):307-12. doi:10.18231/j.ijmmtd.15348.1774261743. 11. Chen CY, Yang KY, Peng CK, Sheu CC, Chan MC, Feng JY, et al. Clinical outcome of nosocomial pneumonia caused by Carbapenem-resistant gram-negative bacteria in critically ill patients: a multicenter retrospective observational study. Sci Rep. 2022 May 7;12(1):7501. Available from: https://doi.org/10.1038/s41598-022-11061-7 12. Agarwal S, Kakati B, Khanduri S, Gupta S. Emergence of Carbapenem Resistant Non-Fermenting Gram-Negative Bacilli Isolated in an ICU of a Tertiary Care Hospital. J Clin Diagn Res. 2017 Jan 1;11(1):DC04–7. Available from: https://doi.org/10.7860/JCDR/2017/24023.9317 13. Gladstone P, Rajendran P, Brahmadathan KN. Incidence of carbapenem resistant nonfermenting gram negative bacilli from patients with respiratory infections in the intensive care units. Indian J Med Microbiol. 2005 Jul–Sep;23(3):189–191. Available from: https://doi.org/10.1016/S0255-0857(21)02593-7 14. Cai B, Echols R, Magee G, Ferreira JCA, Morgan G, Ariyasu M, et al. Prevalence of Carbapenem-Resistant Gram-Negative Infections in the United States Predominated by Acinetobacter baumannii and Pseudomonas aeruginosa. Open Forum Infect Dis. 2017 Aug 16;4(3):ofx176. Available from: https://doi.org/10.1093/ofid/ofx176 15. Wang SH, Yang KY, Sheu CC, Chen WI, Chan MC, Feng JY, et al. Efficacies of Colistin–Carbapenem versus Colistin–Tigecycline in Critically Ill Patients with CR-GNB-Associated Pneumonia: A Multicenter Observational Study. Antibiotics. 2021 Sep 7;10(9):1081. Available from: https://doi.org/10.3390/antibiotics10091081 16. McCann E, Sung AH, Ye G, Vankeepuram L, Tabak YP. Contributing Factors to the Clinical and Economic Burden of Patients with Laboratory-Confirmed Carbapenem-Nonsusceptible Gram-Negative Respiratory Infections. Infect Drug Resist. 2020 Mar 9;13:761–71. Available from: https://doi.org/10.2147/IDR.S236026 17. Tabak YP, Sung A, Ye G, Vankeepuram L, Gupta V, McCann E. Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections. PLoS One. 2020 Feb 21;15(2):e0229393. Available from: https://doi.org/10.1371/journal.pone.0229393 18. Babiker A, Clarke LG, Saul M, Gealey JA, Clancy CJ, Nguyen MH, et al. Changing Epidemiology and Decreased Mortality Associated With Carbapenem-resistant Gram-negative Bacteria, 2000–2017. Clin Infect Dis. 2021 Dec 1;73(11):e4521–30. Available from: https://doi.org/10.1039/cid/ciaa1464.