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Decoding carbapenem resistant organisms (CROs) causing lower respiratory tract infections & their antimicrobial susceptibility pattern
For correspondence: Dr Yasmin Muhammed, Department of Microbiology, Indian Naval Hospital Ship, Asvini, Colaba, Mumbai 400 005, Maharashtra, India e-mail: yasi.yas33@gmail.com
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Received: ,
Accepted: ,
Abstract
Background & objectives
Lower Respiratory Tract Infections (LRTIs) pose a significant global health problem. Emergence of Carbapenem Resistant Organism (CRO) has complicated the treatment of these infections. We conducted a retrospective analysis to identify the prevalence of CROs causing LRTI and their antimicrobial susceptibility patterns.
Methods
A total of 1041 respiratory samples received in the department of Microbiology, Armed Forces Medical College, Pune were immediately processed as per standard guidelines and antimicrobial susceptibility was carried out with Vitek 2 Compact, Biomerieux.
Results
Klebsiella pneumoniae sub spp pneumoniae was the most isolated CRO in our study. A high level of resistance was observed among commonly used antibiotics in LRTIs.
Interpretation & conclusions
The resistance pattern highlights the limited efficacy of many standard antibiotics against CROs. This emphasizes the urgent need for antimicrobial stewardship and importance of colistin as the primary therapeutic choice, albeit with the need for prudent application.
Keywords
Antimicrobial susceptibility
carbapenem resistant organisms
colistin
lower respiratory tract infection
Lower Respiratory Tract Infections (LRTI) pose a significant global health problem and are responsible for substantial hospital admissions particularly in developing countries. The pathogens responsible for LRTIs vary depending upon geographic locations, population and health conditions. In recent years, emergence of multidrug-resistant pathogens has complicated the treatment of these infections. One significant challenge in clinical practice is the rise of Carbapenem Resistant Organisms (CROs) particularly in Intensive Care Units (ICUs) and hospital settings1. Carbapenems are typically used as the last line of defence for treating severe bacterial infections, but increasing resistance has led to limited therapeutic options. The prevalence of CROs is largely attributed to their adaptive resistance mechanism, which include enzyme production, efflux pump activation and membrane permeability changes. These mechanisms allow CROs to resist multiple antibiotic classes beyond carbapenems, creating multidrug-resistant and even extensively drug-resistant profiles. Specifically, Acinetobacter baumannii and Pseudomonas aeruginosa are well known for their intrinsic and acquired resistance to multiple antibiotics, while Klebsiella spp and Escherichia coli exhibit varying levels of resistance depending upon geographic and clinical context1-4. In clinical practice this resistance means that standard treatment regimens often fail, forcing healthcare providers to rely on limited options like polymyxins or novel combinations, which themselves are associated with toxicity and the risk of developing further resistance5.This study provides an overview of CROs involved in LRTIs and their prevalence and antimicrobial susceptibility pattern against a range of antibiotics commonly used in LRTI treatment. This study was aimed to establish a comprehensive understanding of which antibiotics remain effective against these pathogens, providing clinicians with data to guide empirical therapy in suspected cases to help for their effective clinical management. The study also addresses a key knowledge gap by exploring local resistance patterns critical for infection control and therapeutic planning.
Materials & Methods
This retrospective study was carried out at the department of Microbiology, Armed Forces Medical College Pune, Maharashtra, India after obtaining the ethical approval from Institute Ethics Committee. We analysed the data of four years from January 1, 2020 to December 31, 2023. Respiratory samples [sputum, bronchoalveolar lavage (BAL), tracheal aspirate, lung biopsy] from patients of all age and sex were included in the study. Samples from In Patient Department (IPD), Outpatient Department (OPD) and Intensive Care Unit (ICU) were included. A total of 1041 samples were included in the analysis.
Methodology
The samples were subjected to direct Gram stain. Bartlett’s criteria were used to assess the adequacy of sputum samples. Semi quantitative analysis was done for bronchoalveolar lavage and tracheal aspirate. All satisfactory respiratory samples were processed for routine bacterial culture and susceptibility by inoculating onto five per cent Sheep blood agar, MacConkey agar and Chocolate agar (HiMedia Laboratories Pvt. Ltd,). Following which, identification and antimicrobial susceptibility was done as per laboratory standards using MALDI TOF Biomerieux and Vitek2 Compact, Biomerieux. Colistin susceptibility was determined using broth microdilution methods. Interpretation of antibiotic susceptibility was performed as per latest CLSI guidelines6.
Statistical analysis
Data were analysed using descriptive statistics. Prevalence of different pathogens and their antibiotic susceptibility profile were analysed. Data analysis was carried out with SPSS version 29 (IBM Corp., Armonk, New York, USA) Categorical variables were expressed as frequencies and percentages and association between them were assessed using Chi-square test. Age, being a continuous variable, was summarized using mean and range.
Results
During the study period, 2648 non repetitive samples from LRTIs were received. Out of these, 1041 samples (39.3%) yielded a significant pathogen. Out of these 39.3 per cent positive cultures, 75.2 per cent were male (n=783) and 24.8 per cent were female (n=258). Furthermore, of these 1041 samples, 98 samples showed polymicrobial infections. In the study, the mean age of the patients was 54 yr, with an age range of 19-87 yr. Age and gender distributions were not significantly associated with specific pathogen isolation (P>0.05). Most of the isolates were from ICU (653, 62.7%) followed by wards (265, 25.5%) and OPD (123, 11.8%). The most common isolated organisms were Klebsiella pneumonia (30.4%) and Pseudomonas aeruginosa (22.4%). Table shows the distribution of bacterial species causing LRTI. Carbapenem resistance was observed among 54.9 per cent of isolates (572/1041) and distribution of CROs (Fig. 1)
| Organism | n (%) |
|---|---|
| Klebsiella spp | 317 (30.4) |
| Pseudomonas spp | 234 (22.4) |
| Acinetobacter spp | 193 (18.5) |
| Escherichia coli | 88 (8.4) |
| Proteus | 38 (3.6) |
| Hemophilus spp | 26 (2.5) |
| Enterobacter spp | 19 (1.8) |
| Staphylococcus aureus | 16 (1.5) |
| Serratiamarcescens | 12 (1.1) |
| Staphylococcus hemolyticus | 12 (1.1) |
| Others | 86 (8.3) |
- Distribution of carbapenem resistant organisms (n=572).
Antimicrobial susceptibility pattern to various antibiotics of carbapenem resistant Gram-negative organisms are depicted in figures 2-5.
- Antimicrobial susceptibility pattern of carbapenem resistant Escherichia coli.
- Antimicrobial susceptibility pattern of carbapenem resistant Klebsiella pneumonia sub spp pneumoniae.
- Antimicrobial susceptibility pattern of carbapenem resistant Pseudomonas aeruginosa.
- Antimicrobial susceptibility pattern of carbapenem resistant Acinetobacter baumannii.
Carbapenem resistant Escherichia coli showed complete susceptibility to colistin, tigecycline and minocycline. However, it demonstrated no susceptibility to ceftazidime (0%) cefepime (0%) and low susceptibility to ciprofloxacin (7%), piperacillin tazobactam (10%), ceftazidime avibactam (30%) and amikacin (62%).
Carbapenem resistant Klebsiella spp exhibited high resistance across multiple antibiotics. Susceptibility was low for cefepime (1%), ceftazidime (1%), ciprofloxacin (3%), levofloxacin (4%), piperacillin tazobactam (20%), ceftazidime avibactam (24%), and amikacin (24%). Colistin retained 89 per cent susceptibility, while minocycline and tigecycline showed 80 per cent each.
Antibiotic sensitivity of carbapenem resistant Pseudomonas spp showed low susceptibility to ciprofloxacin (10%), ceftazidime (12%), cefepime (14%), levofloxacin (15%) piperacillin tazobactam (16%), ceftazidime avibactam (18%), amikacin (29%). Colistin showed higher susceptibility (63%).
Carbapenem resistant Acinetobacter baumannii exhibited low susceptibility to cefepime (1%), ceftazidime (1%), levofloxacin (4%), amikacin (16%), piperacillin tazobactam (30%). However, colistin and tigecycline retained higher susceptibility at 66 per cent and 40 per cent, respectively.
Discussion
The increasing prevalence of carbapenem resistant organisms (CROs) causing respiratory tract infections (RTIs) presents a growing challenge for clinicians, particularly in intensive care units (ICUs) where these pathogens are frequently encountered. Through our study we attempted to decode the resistance patterns of key respiratory pathogens with carbapenem resistance. The current study highlights significant concerns regarding the effectiveness of commonly used antibiotics, as well as the urgent need for alternative treatment strategies.
Similar to Makharita et al7, our study identified Klebsiella spp as the most common pathogen, followed by Pseudomonas spp, Acinetobacter baumanii, and Escherichia coli. The antibiotic susceptibility results in our study indicates the significant resistance trends, which can impact treatment options.
Escherichia coli isolates from respiratory tract infections exhibited concerning resistance patterns. It exhibited complete resistance to 3rd and 4th generation cephalosporins. Susceptibility was low to piperacillin tazobactam (10%) and fluoroquinolones. Ceftazidime avibactam showed only 30 per cent susceptibility, indicating limited but potential utility in select clinical scenarios. These findings are consistent with global reports that have documented high susceptibility of Escherichia coli to colistin, tigecycline, and minocycline8-10.
Klebsiella pneumoniae isolates demonstrated significant resistance to commonly used antibiotics, with notably low susceptibility to piperacillin-tazobactam (20%), ceftazidime (1%), and cefepime (1%), suggestive of widespread beta-lactam resistance. Amikacin (24%), ciprofloxacin (3%) and levofloxacin (4%) showed poor susceptibility. Colistin retained the highest susceptibility at 89 per cent supporting its role as last resort agent when used with caution. Both tigecycline and minocycline demonstrated susceptibility of 80 per cent each, offering viable alternative treatment options for carbapenem-resistant Klebsiella spp. Ceftazidime-avibactam, a novel beta lactam/beta lactamse inhibitor combination, showed only 24 per cent susceptibility, highlighting the need for careful interpretation of its role in treatment. These results align with studies by Lorenzi et al9, Arnold et al11, and Ali et al12 all of which reported high sensitivity of Klebsiella spp to colistin, tigecycline, and minocycline, further emphasizing the potential of these antibiotics in managing multidrug-resistant Klebsiella infections. The consistency of these findings across different studies highlights the importance of these agents as part of the therapeutic arsenal against carbapenem-resistant pathogens and underscores the need for ongoing surveillance of resistance patterns9,11,12.
The findings for Pseudomonas aeruginosa show limited resistance to commonly used antibiotics like third generation cephalosporins, piperacillin tazobactam, ceftazidime avibactam, fluoroquinolones and aminoglycosides. It calls for caution when relying on these agents. Interestingly, colistin show relatively higher level of susceptibility of 61 per cent, suggesting that it may still be viable options for Pseudomonas aeruginosa infection. Studies conducted by Ali et al12 and Chaudhary et al13 also observed comparable resistance pattern.
In the present study, Acinetobacter baumannii demonstrated high resistance to cephalosporins, aminoglycosides and fluoroquinolones. However, only 66 per cent of the isolates were susceptible to colistin. The emergence of these strains is considered as public health threat. These findings align with global reports on the high level of multi drug resistance in Acinetobacter baumannii, underscoring colistin’s critical role as last resort option. However, the reliance on colistin calls for cautious use to mitigate the risk of future resistance. The low resistance to amikacin (16%) suggests that aminoglycosides could still play a role in the treatment of Acinetobacter spp infections. Studies conducted by Ghasemian et al14, Afhami et al15 and Aljindhan et al16 also observed comparable resistance pattern.
These resistance pattern underline the urgent need for local antimicrobial stewardship, with careful consideration of sensitivity results to guide empirical treatment. In particular, the findings emphasize the role of colistin as a cornerstone for treating CROs related LRTIs. The resistance profiles observed in our study highlight the limited therapeutic options for treating respiratory infections caused by CROs. The increasing resistance to first-line antibiotics, including beta-lactams, fluroquinolones and aminoglycosides emphasizes the need for rapid identification of pathogens and their susceptibility patterns, particularly in critically ill patients. Given the high resistance rates, colistin and tigecycline remain key option for treating multidrug resistance infections especially in the case of Escherichia coli where both antibiotics showed 100 per cent susceptibility. However, the rising resistance to these last-resort agents necessitates careful use, informed by antimicrobial stewardship programmes.
The study has several limitations that should be considered when interpreting the results. First, smoking history, which is a known factor for LRTIs and antibiotic resistance, was not recorded in the patient data. Second, biofilms formation by CROs was not assessed, although this mechanism is known to influence antibiotic resistance, especially in carbapenem resistant Pseudomonas aeruginosa and carbapenem resistant Klebsiella spp. Third, molecular characterization of resistance mechanisms, including carbapenemase gene detection or efflux pump profiling, was not performed due to logistical constraints. Fourth, this study did not stratify resistance data by gender or age group, although demographics were reported descriptively. Finally, the study was conducted in a tertiary care centre, which may limit the generalization of the findings to other regions or institutions.
This study highlights the escalating challenge posed by carbapenem-resistant organisms (CROs) in treating respiratory tract infections. The resistance patterns observed emphasize the pressing need for alternative treatment options and the discovery of novel antibiotics. Furthermore, robust infection control practices such as strict contact precautions, cohorting of colonized patients, environmental disinfection, and hand hygiene as per standard hospital protocols. These practices when combined with antimicrobial stewardship efforts, are critical in limiting the spread of CROs and safeguarding clinical outcomes. Future research should focus on unravelling the genetic mechanisms behind antibiotic resistance with molecular methods such as polymerase chain reaction (PCR), for resistance gene detection, plasmid profiling and whole genome sequencing (WGS) to identify carbapenemase genes and mobile genetic elements involved in resistance dissemination. Strengthening surveillance systems and updating local antibiograms will be key to guiding optimal treatment. The findings from this study may contribute to shaping local antibiotic policies and stewardship strategies aimed at preserving the efficacy of last-line antibiotics such as colistin and tigecycline.
Financial support & sponsorship
None.
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
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