Burden of carbapenem-resistant Acinetobacter baumannii involved in ventilator-associated pneumonia

INTRODUCTION

Ventilator-associated pneumonia (VAP) is defined as nosocomial pneumonia in patients who have been on ventilator support through an endotracheal (ET) tube or a tracheostomy for more than 48 h during intensive care unit (ICU) stay, excluding microbes that were present or incubating at the time of ICU admission.^[1] The most significant class of antibiotics that is recommended as the first line of treatment for VAP patients is carbapenems.^[2] Since carbapenems inhibit peptidoglycan cross-linking, causing cell lysis and death, they are regarded as bactericidal agents. However, the misjudiciary use of carbapenems leads to the emergence of Gram-negative bacteria that are resistant to them.^[3]

Among the Gram-negative bacilli, carbapenem-resistant non-fermenters Pseudomonas aeruginosa and Acinetobacter baumannii both are highlighted as “pathogens of concern” by the World Health Organization.^[4,5] Both are an opportunistic pathogen that are generally inhabited the hospital environment. By producing biofilm, acquiring and overexpressing various resistance genes, they can survive in harsh conditions, and typically infect only those patients who are mechanically ventilated or immunocompromised.^[6,7] The most recent data from the Indian Council of Medical Research Antimicrobial Resistance surveillance network state that 80% of A. baumannii isolates were found imipenem-resistant.

Based on this, the present study was focused on the following objectives:

1. Phenotypic identification and characterization of A. baumannii involved in VAP by VITEK 2

2. Assessment of the antimicrobial susceptibility profile of the A. baumannii by VITEK 2.

MATERIAL AND METHODS

RESULTS

In the present study out of two hundred ET/BAL suspected samples, 17 samples (8.5%) were positive for A. baumannii isolates.

Age and gender wise distribution of patients infected by A. baumannii

There were 17 A. baumannii isolates from suspected ET/BAL samples, in which seven samples were from female patients (41.17%), and ten samples were obtained from male patients (58.82%). Out of the seven female patients, BAL sample was collected from only 1 patient (14.28%), ET samples were received from 6 female patients (85.71%), whereas in the male group, all ten ET samples were obtained from male patients (100%).

Table 1 shows percentage-wise ratio of males and female infected with A. baumannii according to different age group interval. Highest number of patients (58.82%) were seen in the age group between 51 and 75 years, whereas least were seen in the age group between 76 and 100 years, followed by 0–25 years (11.76%). Among the 17 patients infected with A. baumannii, there were 7 female patients (41.17%) and 10 male patients (58.82%). In the age group interval between 0 and 25 years, 2 female patients (28.57%), out of seven female patients, were infected with A. baumannii, whereas in age group between 51 and 75 years, 5 female patients (71.42%) were found to be infected with A. baumannii. In age groups 26–50 years, and 56–100 years, no female patient was seen infected with it. Among ten male patients, in the age group between 0 and 25 years, no male patient was suspected, in the age group 26–50 years, 4 male patients (40%) out of ten were infected with A. baumannii. In the age group 56–75 years, 5 male patients (50%) were infected with A. baumannii. In the age group between 76 and 100 years, only one male patient was suspected. These results indicate that patients in the age group 51–75 years are more prone to get A. baumannii infections in both sexes [Figure 1].

Table 1: Percentage-wise distribution of male-female patients infected with A. baumannii (n=17).

Age-group (in years)	Female (n=7)(%)	Male (n=10) (%)	Total (n=17)
0–25	2 (28.57)	0	2 (11.76%)
26–50	0	4 (40)	4 (23.52%)
51–75	5 (71.42)	5 (50)	10 (58.82%)
76–100	0	1 (10)	1 (5.88%)
Total	7 (41.17)	10 (58.82)	17

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Figure 1:

Age group-wise distribution of ventilator-associated pneumonia patients infected with Acinetobacter baumannii.

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DISCUSSION

VAP is the most prevalent nosocomial infection in the ICU, especially in immunocompromised patients requiring mechanical ventilation for extended periods of time.^[9] Patients who are older and immunosensecence are more vulnerable to VAP, due to lowered antibody responses, decreased T-cell function, and dysregulated inflammatory responses.^[10,11] A. baumannii, P. aeruginosa, and Stenotrophomonas maltophilia are among the carbapenem-resistant non-fermenting Gram-negative bacilli that have caused a significant increase in VAP burden in India in the preceding 5 years.^[12,13] According to Alnimr (2023), the mortality rate for VAP brought on by carbapenem-resistant A. baumannii (CRAB) strains was more than 50%, which happens to be much greater than the mortality rate of strains susceptible to this antibiotic.^[14] Hospitals frequently get endemic, due to the multidrug-resistant A. baumannii. Porins, capsules, as well as proteins are a few of the virulence factors involved in pathogenesis.^[15] By virtue of its resilience, A. baumannii can withstand hostile environments, which can result in serious infections. Because A. baumannii has a unique ability to retain a multidrug-resistant phenotype, major antibiotic classes become less efficient.^[16] Eight to fourteen percentages of VAP in the US and Europe are caused A. baumannii ; however, in Asia, Latin America, and several Middle Eastern countries, this bacterium is linked to greater rates (19–>50%) according to Ayoub Moubareck and Hammoudi Halat (2020).^[17] Saleem et al., 2022 in their 2 years prospective study, reported high prevalence of XDR A. baumannii (9%) involved in VAP.^[18]

In the present study, A. baumannii isolates were found to be resistant against almost all the 12 antibiotics. Similar findings were reported by Kumari et al., 2021.^[19] Maximum effective drug was minocycline. In this study, almost 82.35% isolates were susceptible to this antibiotic, whereas Yang et al. (2022) reported that 55% carbapenem isolates were susceptible to minocycline.^[20] Beheshti et al. (2020) mentioned in their findings that 71% A. baumannii isolates were susceptible to minocycline.^[21] Srivastava et al. (2024) demonstrated that minocycline is more effective antimicrobial than beta-lactam antibiotics.^[22] Adukauskiene et al. (2022) reported that almost 90% A. baumannii strains were resistant to carbapenem, cephalosporin, and piperacillin/tazobactam.^[9] These findings are similar to the results obtained in the present study where more than 88.23% isolates were resistant to these antimicrobials. Sharma et al. (2022) demonstrated that more than 90% A. baumannii isolates were resistant to ceftazidime, cefepime, levofloxacin, ciprofloxacin, cotrimoxazole, and piperacillin/tazobactam.^[23]

A unique outer membrane protein called OprD, which permits the antibiotic to enter the cell, has been lost in A. baumannii making it resistant to carbapenem antibiotics A. baumannii is capable of producing changes in the structure of bacterial cells that hinder the ability of the antibiotic to fuse to its target and carbapenemases, which degrade carbapenem drugs. Minocycline is a type of tetracycline that is able to bind with bacterial ribosomes which, thus, inhibit protein synthesis.^[20] It may produce antimicrobial peptides and inhibit the formation of bacterial cell wall. Its lengthy half-life, low minimum inhibitory concentration, and high concentration within tissues are among its pharmacodynamic characteristics. The evidence supporting minocycline’s efficacy against CRAB is, however, weak, and more research is required to validate its efficacy, track resistance, and ascertain its usefulness in combination therapy.^[8,24]

CONCLUSION

Although in the present study, a low prevalence (8.5%) of A. baumannii causing VAP was seen due to effective infection control measures implemented by the infection control committee of the Adesh Hospital, Bathinda, almost all strains were found to be carbapenem resistant, which is a worrisome situation. Thus, an effective infection control, including an interdisciplinary approach with microbiologists, is required to implement resistance surveillance in ICUs. The present study emphasizes the relevance of strictly adhering to “reserve antibiotics,” so carbapenems should be strictly avoided as an empirical treatment. Patients who are found positive for carbapenem-resistant pathogens should be isolated to avoid the dissemination. Antibiotic stewardship and awareness programs should be implemented by various stakeholders.