MOLECULAR CHARACTERIZATION AND DETECTION OF MULTIDRUGRESISTANT GENE IN BACTERIAL ISOLATES CAUSING LOWER RESPIRATORY TRACT INFECTIONS (LRTI) AMONG HIV/AIDS PATIENTS ON HIGHLY ACTIVEANTIRETROVIRAL THERAPY (HAART) IN UYO, SOUTH-SOUTH NIGERIA

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R.S. Okon¹, I.A. Onwuezobe², E.N. Edem², S. Bonne³, E.N. Ekpenyong⁴, N.S. Uko⁵, G.M. Nworie², A. George⁶

1. Department of Biological Sciences, Akwa Ibom State Polytechnic, Ikot Osurua, Ikot Ekpene, Nigeria.
2. Dept. of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, University of Uyo, Nigeria.
3. Faculty of Medicine, McGill University, Canada
4. Dept. of Haematology and Blood Bank, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria
5. Department of Biochemistry, Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria.
6. Carelife Character Foundation, Uyo, Nigeria.

Abstract

Background: Antibiotic-resistant genes (ARGs) pose a significant challenge in modern medicine, rendering infections increasingly difficult to treat as bacteria acquire mechanisms to resist antibiotics. Addressing ARGs necessitates a multifaceted approach, encompassing surveillance efforts to monitor their presence and the development of strategies aimed at managing and curbing the spread of antibiotic resistance. Hence, this study characterized the genetic determinants of antibiotic resistance among isolates responsible for Lower Respiratory Tract Infections (LRTIs) in People Living with HIV/AIDS (PLWHA) in Uyo.

Methods: Sputum samples were collected from 61 LRTI suspects, with
bacterial isolates identified using VITEK-2 technology. Polymerase chain reaction assays were employed to detect resistance genes within the isolates.

Results: Results revealed a bacterial etiology in 39.3% of the samples, with a majority (79.2%) originating from St. Luke Hospital, Anua (SLHA), and the remainder (20.8%) from the University of Uyo Teaching Hospital (UUTH). Staphylococcus aureus emerged as the predominant isolate (46.6%), while resistance was notably high against Gentamicin and Sulphamethazole/ Trimethoprim. Conversely, Azithromycin, imipenem, clindamycin, erythromycin, and ceftriaxone displayed relatively lower resistance levels across all isolates. Notably, four resistance genes CTX-M, Aac, KPC, and MecA were identified, with CTX-M detected in all multidrug-resistant isolates. This underscores the predominantly community-acquired nature of resistance as conferred by CTX-M.

Conclusion: In conclusion, this study underscores the critical importance of continued vigilance and proactive measures in combating antibiotic esistance, particularly within vulnerable populations such as PLWHA. By elucidating the genetic mechanisms underlying antibiotic resistance, informed targeted interventions can be mitigated to curb threats posed by multidrug-resistant bacteria in clinical settings.

Keywords: Multidrug-resistant, Bacteria, Extensively drug-resistant, Antibiotics, Enterobacteriaceae, Pathogen

Introduction

The lower respiratory tract infections are the most frequent respiratory diseases among HIV infected patients, caused by diverse types of organisms including Gram positive and Gram negative bacteria which include Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, M. tuberculosis and Acinetobacter spp.¹ Effective treatment of LRTIs in People Living with HIV/AIDS (PLWHA) hinges upon accurate diagnosis,² viral load reduction through increased CD4 count, ¹ and appropriate antibiotic therapy. However, the emergence of antibiotic resistance poses a formidable obstacle to treatment efficacy, jeopardizing patient outcomes and exacerbating the threat of life threatening infections.³ This trend of antibiotic resistance is exacerbated by the widespread use of antimicrobials in human healthcare, veterinary medicine, and agriculture, fostering the proliferation of multidrug-resistant pathogens.^4,5,6

Some of the causes of HIV and LRTI co-infection include a weakened immune system from HIV’s attack on CD4 T cells, opportunistic infections from pathogens, environmental factors such as poor living conditions, and behavioral factors like smoking, drug use, and poor dental hygiene.⁷ The escalation of antibiotic resistance represents a complex interplay between bacterial adaptation and selective pressures imposed by antimicrobial agents. Bacteria exhibit remarkable resilience through genetic changes driven by horizontal gene transfer mechanisms, enabling the acquisition of antibiotic resistance genes (ARGs) hosted on mobile genetic elements (MGEs) like transposons and plasmids.⁸ These MGEs serve as vehicles for the dissemination of ARGs not only within pathogenic bacterial populations but also across diverse microbial communities, encompassing both benign and commensal species.⁹ Consequently, this horizontal transmission extends the spread of resistance traits to more virulent pathogens, exacerbating the challenge of antibiotic resistance propagation.¹⁰

In settings such as Nigeria, where antibiotic policies within healthcare institutions often lack rigor, individuals with compromised immune systems, such as People Living with HIV/AIDS (PLWHA), face heightened susceptibility to multidrug-resistant pathogens. This heightened vulnerability arises from limited treatment options due to the proliferation of resistant strains. Consequently, innovative strategies are imperative to combat infections effectively. Therefore, this study aimed to uncover the genetic basis of antibiotic resistance in isolates causing LRTIs in PLWHA in Uyo, with the goal of informing targeted interventions to enhance treatment efficacy in this vulnerable population.