ORIGINAL ARTICLE |
https://doi.org/10.5005/jp-journals-10071-24834 |
The Clinical Impression of NDM-producing Acinetobacter baumannii in Intensive Care Units of the University Referral Hospital in North India
1–4Department of Clinical Microbiology, King George’s Medical University, Lucknow, Uttar Pradesh, India
5Department of Medicine, King George’s Medical University, Lucknow, Uttar Pradesh, India
6Department of Critical Care Medicine, King George’s Medical University, Lucknow, Uttar Pradesh, India
Corresponding Author: Vimala Venkatesh, Department of Clinical Microbiology, King George’s Medical University, Lucknow, Uttar Pradesh, India, Phone: +91 9335912340, e-mail: vimalavenkatesh@gmail.com
How to cite this article: Singh S, Verma A, Venkatesh V, Verma S, Reddy DH, Agrawal A. The Clinical Impression of NDM-producing Acinetobacter baumannii in Intensive Care Units of the University Referral Hospital in North India. Indian J Crit Care Med 2024;28(11):1044–1049.
Source of support: Nil
Conflict of interest: None
Received on: 24 August 2024; Accepted on: 11 October 2024; Published on: 30 October 2024
ABSTRACT
Aims and background: Carbapenem-resistant Acinetobacter baumannii (CRAb), a major public health threat, causes severe infections in Intensive Care Unit (ICU) patients. It resists β-lactam antibiotics through mechanisms like New Delhi metallo-beta-lactamase (NDM).
Materials and methods: In ICU patients, 69 Acinetobacter species were isolated from 86 non-fermenting Gram-negative bacilli. Isolates were identified using biochemical methods and Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS), and carbapenem resistance detection was done by both phenotypic (mCIM and eCIM) and molecular methods.
Results: Out of 66 A. baumannii, 61 were carbapenem-resistant, with 20 confirmed as NDM producers. NDM-positive isolates exhibited higher resistance and were associated with significant mortality (75%).
Conclusion: NDM-positive Acinetobacter isolates are significant ICU pathogens with poor outcomes. Key risk factors include prolonged ICU stays, prior antimicrobial use, and inadequate therapy. Early detection and infection control are crucial.
Clinical significance: NDM-positive Acinetobacter infections in ICU patients are linked to poor outcomes, highlighting the need for early detection and control measures.
Keywords: Antimicrobial resistance, Bloodstream infection, Carbapenem-resistant Acinetobacter baumannii, Intensive care unit, New Delhi metallo-β-lactamases.
HIGHLIGHTS
Treating bloodstream infections in Intensive Care Unit (ICU) patients, especially those caused by metallo-β-lactamases (NDM)-positive Acinetobacter, is challenging because of their resistance patterns. Extended stays in the ICU, previous administration of antibiotics, and insufficient early treatment all contribute to unfavorable outcomes. Efficient management requires timely identification, control of infections, and tailored antimicrobial treatment plans to minimize occurrence and mortality.
INTRODUCTION
Carbapenem-resistant Acinetobacter baumannii (CRAb) is a major public health threat, and it is considered one of the top-priority pathogens (WHO).1 Carbapenem-resistant A. baumannii frequently causes infections in people who have been cared for in hospital facilities, particularly those who require invasive medical devices in intensive care units. In India, CRAb continues to be a major cause of morbidity in healthcare facilities, including bloodstream infections, ventilator-associated pneumonia (VAP), device-associated infections (DAI), wound or skin and soft-tissue infections (SSTI), urinary tract infections (UTI), intra-abdominal infection (IAI), and meningitis.2 The mechanisms of antibiotic resistance in Acinetobacter spp. are diverse. There are several reasons why some bacteria become resistant to β-lactam medicines. These include making more β-lactamase, having too many efflux pumps, and having less permeable outer membranes. But making too many carbapenem-hydrolyzing enzymes is still a big problem. Acinetobacter species usually become resistant to carbapenems by making NDM and oxacillinase-type carbapenemases.3 The novel NDM known as New Delhi metallo-β-lactamases (blaNDM-1) exhibit a high resistance to nearly all β-lactam antibiotics. Carbapenems are a crucial antimicrobial agent against NDM producers.4 In addition, NDM and other NDM like IMP and VIM have also been reported in CRAb.5 Carbapenem-resistant A. baumannii isolates have limited treatment options because of their widespread resistance to several antimicrobial drugs, including polymyxins, in addition to their resistance to carbapenem.6 Many countries, including China, the Middle East, Europe, the USA, and the Indian subcontinent, have reported infrequent cases of NDM-producing A. baumannii (NDMAb). Despite the ubiquitous presence of NDMAb, less is known regarding its epidemiology, clinical characteristics of infected patients, and transmission networks in hospital settings.7,8 The study aimed to identify potential risk factors and correlations between A. baumannii’s NDM gene presence and antimicrobial resistance in university hospitals ICU patients with bacteremia.
MATERIALS AND METHODS
A total of 69 isolates of Acinetobacter species were obtained from patients whose blood culture was positive for non-fermenting Gram-negative bacilli (GNNFB) isolates admitted in various ICUs and enrolled in this hospital-based observational study of King George’s Medical University, India. The study was conducted from September 2020 to October 2021 and was approved by the institutional ethics committee of King George’s Medical University, Lucknow (Ref No: 102nd ECM II B Thesis/P42). Informed written consent was obtained from all participants. This study included all ICU patients with bacteriemia that were confirmed by positive blood culture. Clinical details regarding demographic data, occupation, residential address, nature of work, history of previous hospitalization due to medical and surgical illness, duration of ICU admission, duration of subjection of antimicrobials, and any invasive procedure during ICU stay were collected.
Bacterial Isolates and Antimicrobial Susceptibility Tests
A total of 69 Acinetobacter species isolates were isolated from 86 non-fermenting GNNFB isolates from blood specimens collected from patients admitted in the ICU of the university hospital. The isolates were identified by conventional biochemical methods and MALDI-TOF. The Kirby–Bauer disc diffusion method was used to test all isolates for carbapenem resistance as per the Clinical and Laboratory Standards Institute recommendation 2020.9,10 The Kirby–Bauer disk diffusion method was performed with the following antibiotics: Piperacillin-tazobactam (10 μg), ceftazidime (30 μg), cefepime (30 μg), imipenem (10 μg), meropenem (10 μg), gentamicin (10 μg), tobramycin (10 μg), amikacin (30 μg) ciprofloxacin (5 μg), levofloxacin (5 μg), trimethoprim-sulfamethoxazole (1.25/23.75 μg). The minimum inhibitory concentration (MICs) of colistin were determined using the broth microdilution method as per CLSI recommendations. The breakpoints of colistin were as follows: isolates with MICs of 2–4 mg/mL were categorized as intermediate, and those with MICs of >4 mg/mL were categorized as resistant. Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as quality controls. All these strains were tested for susceptibility to meropenem (10 µg, Hi-media) by the disc diffusion method, and strains that showed reduced susceptibility to meropenem were further confirmed for carbapenem resistance by MICs for meropenem, obtained with the VITEK COMPACT 2MS system. Resistance of Acinetobacter species strains to carbapenem was reported if the MIC to meropenem was ≥16 μg/mL, possibly carbapenemase producers, and was characterized with both phenotypic as well as molecular tests for detection of carbapenemase.10
Phenotypic Test for Detection of Carbapenemase
A phenotypic detection test for OXA-48-like carbapenemases and Ambler classes A and B, known as the mCIM test, was conducted on all isolates of Acetobacter species. The eCIM phenotypic test was only performed on isolates that tested positive for the mCIM test, following the guidelines set by the Clinical and Laboratory Standard Institute (CLSI) in 2020.10
Molecular Investigations for Detection of Drug-resistant Genes (DNA Extraction and PCR for Carbapenemase Genes)
The most prevalent and clinically pertinent metallo beta-lactamases, New Delhi metallo-beta-lactamase (NDM), verona integron-encoded metallo-beta-lactamase (VIM), and imipenemase metallo-beta-lactamase (IMP), were detected and differentiated to verify the results of phenotypic assays regarding carbapenemase production. Conventional polymerase chain reaction (PCR) was used to evaluate the molecular profiles of 69 Acinetobacter species isolated in pure culture from blood samples. The DNA from the isolates was extracted using a cell lysis step and boiling method with the InstaGene Matrix (Bio-Rad Laboratories, USA) as per the manufacturer’s instructions. The primers utilized in this study were detailed in Table 1.
Primer name | Primer sequence | PCR product size |
---|---|---|
VIM-F | GATGGTGTTTGGTCGCATA | 390 bp |
VIM-R | CGAATGCGCAGCACCAG | |
IMP-F | GGAATAGAGTGGCTTAAYTCTC | 232 bp |
IMP-R | CCAAACYACTASGTTATCT | |
NDM-F | CACCTCATGTTTGAATTCGCC | 984 bp |
NDM-R | NDMr CTCTGTCACATCGAAATCGC |
RESULTS
Clinical Features of Carbapenem-resistant Acinetobacter Species
A total of 69/86 Acinetobacter species isolates were isolated by conventional biochemical methods as well as by MALDI-TOF method between September 2020 and October 2021 at a tertiary care hospital, King George’s Medical University, Lucknow. Out of 69 Acinetobacter species, 66 were A. baumannii, and three were Acinetobacter lwoffii. A total of 61/69 (88.40%) Acinetobacter species as carbapenem-resistant isolates were isolated by conventional tests by disk diffusion method and meropenem MICs by VITEK COMPACT 2MS system. We detected carbapenem-resistant genes, as mentioned in the Materials and Methods section, among all Acinetobacter species isolates. A total of 20/66 (30.30%) CRAb isolates were detected by conventional polymerase chain reaction (PCR) tests. We detected 20/66 (30.30%) isolates were NDM carbapenemase producers, and other metallo beta-lactamase carbapenem-resistant genes such as IMP and VIM were not found in these isolates. Out of 69, 49 Acinetobacter species isolates were negative for metallo beta Lactamase carbapenem-resistant genes like NDM, IMP, and VIM in conventional PCR tests.
A total of 20/61 (32.78%) NDM-detected A. baumannii isolates were also positive with m CIM and eCIM phenotypic test. Whereas 39/61 (63.93%) A. baumannii isolates were negative for carbapenem-resistant genes in PCR, but all were positive only for the mCIM phenotypic test none were positive for the eCIM phenotypic test.
Antimicrobial Susceptibility Patterns
All 20 CRAB isolates confirmed by the genotypic method were resistant to meropenem (100%), imipenem (100%), piperacillin/tazobactam (90%), and isolates had no susceptibility to amikacin (90%), gentamicin (80%), tobramycin (90%), levofloxacin (80%), ciprofloxacin (95%), piperacillin-tazobactam (90), trimethoprim-sulfamethoxazole (85%), cefepime (90%), cefoperazone (80%), and ceftriaxone (95%) whereas the non-susceptibility of NDM-positive A. baumannii to the tetracycline and ceftazidime antibiotics was 45 and 55%, respectively. In contrast, NDM-negative A. baumannii isolates had lower resistance to ceftazidime, tetracycline, cefoperazone, and aminoglycoside antibiotics of 60.08, 60.08, 76.08, and 80%, respectively. Conversely, all three isolates of Acinetobacter lwoffii isolates had no resistance to all the above antibiotics, and in these isolates, there was no metallo-beta-lactamase gene detected.
Acinetobacter baumannii isolate had the NDM gene and was resistant to most tested antimicrobials except colistin (Tables 2 and 3). However, colistin was observed (6/20, 12.24%) to be resistant in all NDM-positive A. baumannii isolates, whereas three isolates out of 46 (6.05%) of NDM-negative A. baumannii showed intermediate MIC for colistin.
Variables | NDM A. baumannii (N = 20) | Non NDM A. baumannii (N = 46) | p-value |
---|---|---|---|
Gender | |||
Male | 13 | 31 | 0.849 |
Female | 7 | 15 | |
Age | |||
20–40 | 9 | 20 | 0.089 |
>40–60 | 2 | 15 | |
>60 | 9 | 11 | |
History of prior surgery within 3 months | 5 | 22 | 0.083 |
Length of hospital stay prior to ICU admission (days), median (minimum-maximum) | 16 | 22 | 0.015 |
Exposure to broad-spectrum antibiotics during hospital stay before ICU admission | 17 | 23 | 0.007 |
History of prior hospital admission (<6 months) | 3 | 6 | 0.831 |
Ventilated | 10 | 21 | 0.744 |
Central venous catheter | 17 | 25 | 0.017 |
Urinary Foleys catheter | 17 | 32 | 0.187 |
Hypertension | 10 | 9 | 0.012 |
Diabetes | 12 | 15 | 0.037 |
Mortality | 15 | 18 | 0.007 |
Name of antibiotics | NDM A. baumannii (N = 20) | % of drug resistance | Non NDM A. baumannii (N = 46) | % of drug resistance |
---|---|---|---|---|
Cefepime (30 µg) | 18 | 90 | 43 | 88 |
Ceftazidime (30 µg) | 11 | 55 | 28 | 57 |
Tetracycline | 9 | 45 | 28 | 57 |
Cefoperazone (30 μg) | 16 | 80 | 35 | 71.5 |
Ceftriaxone (30 μg) | 19 | 95 | 45 | 91.83 |
Trimethoprim-sulfamethoxazole (1.25/23.75 μg) | 17 | 85 | 40 | 81.6 |
Piperacillin-tazobactam (10 µg) | 18 | 90 | 40 | 81.6 |
Ciprofloxacin (5 μg) | 19 | 95 | 42 | 85.7 |
Levofloxacin (5 μg) | 16 | 80 | 47 | 95.91 |
Imipenem (10 μg) | 20 | 100 | 45 | 91.83 |
Meropenem (10 μg) | 20 | 100 | 42 | 85.7 |
Tobramycin (10 μg) | 18 | 90 | 37 | 75.51 |
Gentamicin (10 μg) | 16 | 80 | 37 | 75.51 |
Amikacin (30 μg) | 18 | 90 | 37 | 75.51 |
Colistin* | 6 | 12.24 | 3 | 6.1 |
Risk Factor and Outcome
Both NDM-positive and NDM-negative Acinetobacter isolate-positive ICU patient groups exhibited equal demographic data on age and sex, with no discernible correlation. There was a strong positive association (p < 0.015) was seen with extended ICU stay (median ICU stay = 7 days), and patients with central venous catheters also had a significant positive correlation (17/20 vs 25/46 p < 0.017) for the occurrence of bloodstream infection caused by NDM-positive Acinetobacter isolates.
This study also noted that previous exposure to broad-spectrum antimicrobial drugs before hospital admission was very likely significantly associated with acquiring bloodstream infection due to NDM-positive A. baumannii isolates (17/20 vs 23/46 p < 0.007). Comorbidities, such as hypertension (p < 0.012) and diabetes mellitus (p < 0.037) had significant risk factors associated with bloodstream infection caused by NDM-positive A. baumannii isolates.
A total of 33/69 (55.07%) deaths were observed in the study duration, out of which 15/20 (75%) deaths were observed in patients due to the presence of NDM A. baumannii isolate strains, and 18/46 (57.14%) deaths were observed in patients with non-NDM A. baumannii isolates with no detectable metallo beta-lactamase gene that is statistically significant (p < 0.007).
DISCUSSION
This was an observational hospital study to determine antimicrobial resistance patterns, risk factors, and outcomes for CRAB-associated bacteremia in ICU patients. Acinetobacter infections are commonly found in critically ill patients, especially in ICUs. Acinetobacter is a significant contributor to hospital-associated bloodstream infections, which can have severe consequences and often result in high morbidity and mortality rates.11,12 This pathogen demonstrates distinctive mechanisms of resistance to a range of antibiotics, such as carbapenems, and can last in challenging settings on non-living things within the hospital setting. Carbapenem-resistant Acinetobacter is becoming more widespread globally.13 There has been a significant increase in the resistance of Acinetobacter isolates to carbapenems in India, with rates ranging from 75 to 88%.14,15 In this study, we found that most of the Acinetobacter isolates (61 out of 69, or 88.4%) were carbapenem non-susceptible.
Another study in India also reported the carbapenem resistance of A. baumannii isolate 87.5%.16,17 Carbapenem resistance signifies a nationwide issue stemming from the indiscriminate and extensive utilization of these antibiotics. The issue of carbapenem resistance has escalated with the revelation of the NDM gene, which confers resistance to carbapenems, the ultimate antibiotics of last resort.18 It limited the capacity of all β-lactam antibiotic groups to treat infections caused by bacteria with resistance determinants.19 Our study’s most notable finding was the positivity of NDM-positive A. baumannii isolates (20/66; 30.30%) in bloodstream infection reported. Among the isolates studied for metallo beta-lactamase producers, 30.30% produced the NDM enzyme; no other metallo beta-lactamase enzyme-producing gene was detected. This shows that carbapenem resistance in A. baumannii was not only because of the presence of the NDM gene, but other underlying drug resistance mechanisms like naturally occurring oxacillinases, carbapenemases, and other ambler group genes were also involved. Carbapenem-resistant A. baumannii isolates typically resist the majority of current antibiotics such as tetracyclines and ceftazidime because of the combination of OXA enzymes, efflux pumps, and permeability abnormalities. However, this study found resistance to tetracyclines and ceftazidime in 45 and 55% of isolates, which may be due to local factors that may influence variations in resistance mechanisms. All CRAB strains do not exhibit uniform resistance; some may possess OXA enzymes without strong efflux activity, leading to partial sensitivity to agents such as tetracyclines or ceftazidime. Additionally, geographical differences in resistance profiles can affect drug efficacy, particularly in areas where certain antibiotics are less frequently used, reducing the percentage of resistance. The heterogeneity of clinical strains also contributes to varying resistance levels. The present study indicates that some CRAB strains remain susceptible to agents such as tetracyclines or ceftazidime despite carbapenem resistance, linked to efflux pump expression and target site mutations. To understand these atypical susceptibility patterns, further molecular investigations into the resistance mechanisms of isolates are essential, focusing on non-OXA-mediated factors like porin expression and efflux pump variations.20
The NDM-1 gene, linked to the Tn125 transposon, was hypothesized to originate from a specific strain of A. baumannii in a specific region of the world and be transferred to Enterobacteriaceae.21
Tn125 is likely the primary means by which NDM-1 genes are spread among strains of A. baumannii. The ISAba125 element is located upstream of the NDM-1 gene and is similarly involved in the horizontal transmission of NDM-1 in A. baumannii.22,23 The study reveals that carbapenem-resistant Acinetobacter spp. isolates exhibit a complex interaction of multiple resistance mechanisms, resulting in high phenotypic detection rates.
While A. baumannii has OXA-51, a chromosomally encoded enzyme intrinsic to the species, most of the phenotypic resistance to carbapenems is caused by the predominant OXA-51. Ambler-class D beta-lactamases exhibit limited carbapenemase activity; they hydrolyze imipenem and ertapenem more effectively than meropenem.24,25 The incorporation of an insertion sequence (IS) element, such as ISAbaI and ISAba9, markedly enhances carbapenemase production, leading to clinical carbapenem resistance.26 In this study, only NDM genes were targeted, so other mechanisms of carbapenem resistance were not well explained, which led to the differences between phenotypic detection methods of metallo beta-lactamases. The extremely low quantity and permeability of porins in its outer membrane and multidrug efflux pumps contribute to Acinetobacter spp.’s overall antibiotic resistance. These bacteria can also swiftly pick up extra genetic elements from other bacterial species that confer resistance.26,27 The present study proved that all (20/20) Acinetobacter isolates expressing the NDM were completely resistant to carbapenems and all other tested antibiotics except colistin. The findings of this study are consistent with earlier Indian research that found that Acinetobacter isolates with coexisting blaNDM-1 exhibited considerably greater levels of carbapenem resistance than other blaNDM-1-negative isolates. Studies have observed that most Acinetobacter spp. that produce blaNDM-1 remain susceptible to colistin alone. However, when Acinetobacter isolates have both blaNDM-1 and blaOXA-23-like genes, the overexpression of these genes leads to heightened resistance to carbapenems and other antibiotics.
The policy of using antimicrobial drugs and the existence of drug-resistant clones in hospitals and ICUs are contributing to the problem of antibiotic resistance in A. baumannii isolates. In this study, we observed that most of the drugs were resistant in both NDM A. baumannii and non-NDM A. baumannii except colistin. Colistin is one of the few therapeutic choices available against CRAB infections, and due to increased use, the colistin resistance rate is progressively increasing globally, posing a healthcare concern. It was found that only 12.24% of Acinetobacter isolates showed resistance to colistin in NDM A. baumannii. This is consistent with previous studies in India where the resistance rate was low, ranging from 3 to 9.5%.28 The low resistance rate may be due to colistin being used as a reserve medication for multi-drug resistant pathogens. However, multiple studies have revealed that Pan Drug Resistance Acinetobacter has increased clinical importance, possibly because of the increase in the use of colistin; thus, resistance to it is also emerging.29,30
With a focus on NDM A. baumannii isolate-induced bloodstream infections, this study sought to determine the contributing factors to unfavorable patient outcomes.31 The results demonstrated that extended ICU stays and longer central venous catheter stays were important risk factors for infection by NDM-positive Acinetobacter isolates. A significant association was observed between prior medication use (17/20 vs 23/46; p = 0.007) and the acquisition of infections caused by blaNDM-1-positive Acinetobacter isolates.32 In this study, we also reported underlying comorbidities like hypertension and diabetes milletus are significant risk factors for bloodstream infection due to NDM A. baumannii. Antibiotic usage in the past has been shown to raise the risk of MDR-Acinetobacter bloodstream infection.33 Furthermore, Nhu et al. and Aneta et al. hypothesized that earlier carbapenem exposure may predispose individuals to later colonization and infection with resistant bacteria.33 Inappropriate empirical therapy for critical care patients is a significant predictor of mortality in ICUs.
It was found that people who were infected with NDM-positive Acinetobacter isolates had significantly higher mortality (75% vs 57.14%, p = 0.007). According to other research, the mortality from an Acinetobacter bloodstream infection is between 26 and 68%.34 This high death rate, even with the right treatment, is because of MDR Acinetobacter isolates and poor empirical therapy.35
Limitations
One limitation of the study was that not all possible mechanisms of carbapenem were done, and one other major limitation was that it was carried out in a single center. In addition, the COVID-19 pandemic had a significant impact on healthcare settings, which likely influenced nosocomial infections like Acinetobacter in several ways, but we didn’t evaluate the impact of the COVID-19 pandemic on the study population.
CONCLUSION
Acinetobacter isolates containing the NDM gene, which resists carbapenems, cause most ICU infections. Acinetobacter isolates with the NDM gene conferring carbapenem resistance are among the major causes of infection in ICU patients. The most crucial information for guiding appropriate antibiotic therapy is an understanding of Acinetobacter resistance patterns, as managing this remains a challenge for doctors. This study emphasizes the risk factors associated with poor outcomes in bloodstream infection of ICU patients. The most important predictors of outcome were NDM-positive Acinetobacter isolate infection, longer hospital stay, intensive care unit stay of more than 7 days, history of antimicrobial agent exposure, and inadequate empirical therapy. Reducing incidence and mortality in hospitalized ICU patients requires early detection, infection control, antimicrobial policy, and preventive measures to control strain spread.
Clinical Significance
Bloodstream infections in ICU patients, particularly from NDM-positive Acinetobacter, are difficult to treat due to resistance patterns. Prolonged ICU stays, past antibiotic usage, and inadequate early therapy all contribute to poor outcomes. Effective management necessitates early detection, infection control, and customized antimicrobial regimens to limit incidence and death.
Ethical Approval
Ref No: 102nd ECM II B Thesis/P42
Authors’ Contributions
A Verma, S Singh, and V Venkatesh: Equally contributed to the conception of the work, design of the work, interpretation of data, and manuscript preparation. V Venkatesh, S Verma, D Himanshu, and A Agarwal: Equally contributed to the revision of the manuscript.
ORCID
Sangeeta Singh https://orcid.org/0009-0008-4655-6967
Anuragani Verma https://orcid.org/0000-0001-9874-0565
Vimala Venkatesh https://orcid.org/0000-0003-0322-4248
Sheetal Verma https://orcid.org/0000-0003-1766-4850
D Himanshu Reddy https://orcid.org/0000-0001-5627-4412
Avinash Agrawal https://orcid.org/0000-0003-0345-4166
REFERENCES
1. Jesudason T. WHO publishes updated list of bacterial priority pathogens. Lancet Microbe 202427:100940. DOI: 10.1016/j.lanmic.2024.07.003.
2. Rajni E, Kataria S, Garg V, Jorwal A, Bacchani D, Sharma R. Carbapenem resistant Acinetobacter baumannii: Current status of problem in a tertiary care hospital, Jaipur. Med J Dr. DY Patil Univ 2024;17(2):304–310. DOI: 10.4103/mjdrdypu.mjdrdypu_646_22.
3. Kyriakidis I, Vasileiou E, Pana ZD, Tragiannidis A. Acinetobacter baumannii antibiotic resistance mechanisms. Pathogens 2021;10(3):373. DOI: 10.3390/pathogens10030373.
4. Grewal AS, Thapa K, Sharma N, Singh S. New Delhi metallo-β-lactamase-1 inhibitors for combating antibiotic drug resistance: Recent developments. Med Chem Res 2020;29(8):1301–1320. DOI: 10.1007/s00044-020-02580.
5. Aruhomukama D, Najjuka CF, Kajumbula H, Okee M, Mboowa G, Sserwadda I, et al. Bla VIM-and bla OXA-mediated carbapenem resistance among Acinetobacter baumannii and Pseudomonas aeruginosa isolates from the Mulago hospital intensive care unit in Kampala, Uganda. BMC Infect Dis 2019;19:1–8 DOI: 10.1186/s12879-019-4510-5.
6. Lyu C, Zhang Y, Liu X, Wu J, Zhang J. Clinical efficacy and safety of polymyxins based versus non-polymyxins based therapies in the infections caused by carbapenem-resistant Acinetobacter baumannii: A systematic review and meta-analysis. BMC Infect Dis 2020;20:1–4. DOI: 10.1186/s12879-020-05026-2.
7. Adler A, Ghosh H, Gross A, Rechavi A, Lasnoy M, Assous MV, et al. Clinical and molecular features of NDM-producing Acinetobacter baumannii in a multicenter study in Israel. Ann Clin Microbiol Antimicrob 2023;22(1):52. DOI: 10.1186/s12941-023-00607-w.
8. Ayoub Moubareck C, Hammoudi Halat D. Insights into Acinetobacter baumannii: A review of microbiological, virulence, and resistance traits in a threatening nosocomial pathogen. Antibiotics 2020;9(3):119. DOI: 10.3390/antibiotics9030119.
9. Humphries R, Bobenchik AM, Hindler JA, Schuetz AN. Overview of changes to the clinical and laboratory standards institute performance standards for antimicrobial susceptibility testing, M100. J Clin Microbiol 2021;59(12):10–128. DOI: 10.1128/jcm.00213-21.
10. Weinstein MP, Lewis JS. The Clinical and Laboratory Standards Institute Subcommittee on antimicrobial susceptibility testing: Background, organization, functions, and processes. J Clin Microbiol 2020;58(3):e01864–19. DOI: 10.1128/JCM.01864-19.
11. Cavallo I, Oliva A, Pages R, Sivori F, Truglio M, Fabrizio G, et al. Acinetobacter baumannii in the critically ill: Complex infections get complicated. Front Microbiol 2023;14:1196774. DOI: 10.3389/fmicb.2023.1196774.
12. Piri Gharaghie T, Doosti A, Mirzaei SA. Prevalence and antibiotic resistance pattern of Acinetobacter spp. infections in Shahrekord medical centers. Development Biol 2021;13(4):35–46. DOI: 10.30495/jdb.2021.686587.
13. Papadopoulou M, Deliolanis I, Polemis M, Vatopoulos A, Psichogiou M, Giakkoupi P. Characteristics of the genetic spread of carbapenem-resistant Acinetobacter baumannii in a Tertiary Greek Hospital Genes 2024;15(4):458. DOI: 10.3390/genes15040458.
14. Prayag PS, Patwardhan SA, Joshi RS, Panchakshari SP, Rane T, Prayag AP, et al. Enzyme patterns and factors associated with mortality among patients with carbapenem resistant Acinetobacter baumannii (CRAB) Bacteremia: Real world evidence from a Tertiary Center in India. Indian J Crit Care Med 2023;27(9):663. DOI: 10.5005/jp-journals-10071-24534.
15. Pragasam AK, Vijayakumar S, Bakthavatchalam YD, Kapil A, Das BK, Ray P, et. al. Molecular characterisation of antimicrobial resistance in Pseudomonas aeruginosa and Acinetobacter baumannii during 2014 and 2015 collected across India. Indian J Med Microbiol 2016;34(4):433–441. DOI: 10.4103/0255-0857.195376.
16. Rout BP, Dash SK, Otta S, Behera B, Praharaj I, Sahu KK. Colistin resistance in carbapenem non-susceptible Acinetobacter baumanii in a tertiary care hospital in India: Clinical characteristics, antibiotic susceptibility and molecular characterization. Mol Biol Rep 2024;51(1):357. DOI: 10.1007/s11033-023-08982-5.
17. Rout BP, Dash SK, Otta S, Behera B, Praharaj I, Sahu KK. Molecular epidemiology of carbapenem and colistin resistant Acinetobacter baumanii. DOI: 10.21203/rs.3.rs-3339579/v1.
18. Yohei Doi, Treatment options for Carbapenem-resistant Gram-negative bacterial infections. Clinical Infect Dis 2019;69(Supplement_7):S565–S575. DOI: 10.1093/cid/ciz830.
19. Bose P, Rangnekar A, Desikan P. NDM-beta-lactamase-1: Where do we stand?. Indian J Med Res 2022;155(2):243–252. DOI: 10.4103/ijmr.IJMR_685_19.
20. Serapide F, Guastalegname M, Gullì SP, Lionello R, Bruni A, Garofalo E, et al. Antibiotic treatment of Carbapenem-resistant Acinetobacter baumannii infections in view of the newly developed β-Lactams: A narrative review of the existing evidence. Antibiotics (Basel) 2024;13(6):506. DOI: 10.3390/antibiotics13060506.
21. Bonnin RA, Poirel L, Nordmann P. New Delhi metallo-β-lactamase-producing Acinetobacter baumannii: A novel paradigm for spreading antibiotic resistance genes. Future Microbiol 2014;9(1):33–41. DOI: 10.2217/fmb.13.69.
22. Wang J, Ning Y, Li S, Wang Y, Liang J, Jin C, et al. Multidrugresistant Acinetobacter baumannii strains with NDM1: Molecular characterization and in vitro efficacy of meropenembased combinations. Exp TherMed 2019;18(4):2924–2932. DOI: 10.3892/etm.2019.7927.
23. Acman M, Wang R, van Dorp L, Shaw LP, Wang Q, Luhmann N, et al. Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla NDM. Nat Commun 2022;13(1):1131. DOI: 10.1038/s41467-022-28819-2.
24. Mitteregger D, Wessely J, Barišić I, Bedenić B, Kosak D, Kundi M. A variant carbapenem inactivation method (CIM) for Acinetobacter baumannii group with shortened time-to-result: rCIM-A. Pathogens 2022;11(4):482. DOI: 10.3390/pathogens11040482.
25. Singh V, Agarwal J, Nath SS, Sharma A. Evaluation of direct antimicrobial susceptibility testing from positive flagged blood cultures in sepsis patients. Indian J Crit Care Med 2024;28(4):387–392. DOI: 10.5005/jp-journals-10071-24687.
26. Blackwell GA, Hamidian M, Hall RM. IncM plasmid R1215 is the source of chromosomally located regions containing multiple antibiotic resistance genes in the globally disseminated Acinetobacter baumannii GC1 and GC2 clones. MSphere 2016;1(3):10–128. DOI: 10.1128/msphere.00117-16.
27. Vila J, Martí S, Sanchez-Céspedes J. Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. J Antimicrob Chemother 2007;59(6):1210–1215. DOI: 10.1093/jac/dkl509.
28. Bardhan T, Chakraborty M, Bhattacharjee B. Prevalence of colistin-resistant, carbapenem-hydrolyzing proteobacteria in hospital water bodies and out-falls of West Bengal, India. Int J Environ Res Public Health 2020;17(3):1007. DOI: 10.3390/ijerph17031007.
29. Papazachariou A, Tziolos RN, Karakonstantis S, Ioannou P, Samonis G, Kofteridis DP. Treatment strategies of colistin resistance Acinetobacter baumannii infections. Antibiotics 2024;13(5):423. DOI: 10.3390/antibiotics13050423.
30. Mathai AS, Oberoi A, Madhavan S, Kaur P. Acinetobacter infections in a tertiary level intensive care unit in northern India: Epidemiology, clinical profiles and outcomes. J Infect Public Health 2012;5(2):145–152. DOI: 10.1016/j.jiph.2011.12.002.
31. Diep DT, Tuan HM, Ngoc KM, Vinh C, Dung TT, Phat VV, et al. The clinical features and genomic epidemiology of carbapenem-resistant Acinetobacter baumannii infections at a tertiary hospital in Vietnam. J Global Antimicrob Resist 2023;33:267–275. DOI: 10.1016/j.jgar.2023.04.007.
32. Jiang Y, Ding Y, Wei Y, Jian C, Liu J, Zeng Z. Carbapenem-resistant Acinetobacter baumannii: A challenge in the intensive care unit. Frontiers in microbiology 2022;13:1045206. DOI: 10.3389/fmicb.2022.1045206.
33. Nhu NT, Lan NP, Campbell JI, Parry CM, Thompson C, Tuyen HT, et al. Emergence of carbapenem-resistant Acinetobacter baumannii as the major cause of ventilator-associated pneumonia in intensive care unit patients at an infectious disease hospital in southern Vietnam. J Med Microbiol 2014;63(10):1386–1394. DOI: 10.1099/jmm.0.076646-0.
34. Srikanth D, Joshi SV, Shaik MG, Pawar G, Bujji S, Kanchupalli V, Chopra S, Nanduri S. A comprehensive review on potential therapeutic inhibitors of nosocomial Acinetobacter baumannii superbugs. Bioorg Chem 2022;124:105849. DOI: 10.1016/j.bioorg.2022.105849.
35. Abarca-Coloma L, Puga-Tejada M, Nuñez-Quezada T, Gómez-Cruz O, Mawyin-Muñoz C, Barungi S, et al. Risk factors associated with mortality in Acinetobacter baumannii infections: Results of a prospective cohort study in a Tertiary Public Hospital in Guayaquil, Ecuador. Antibiotics 2024;13(3):213. DOI: 10.3390/antibiotics13030213.
________________________
© The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.