Previous studies have shown that bacterial infections are a common complication in patients with seasonal viral respiratory tract infections due to virus-induced epithelial damage and immune down-regulation [29][32][34]–[36][37] and are associated with poor prognosis, increased risk of ICU admission and 29–55% mortality[14][16][38]. We report a 44.2% (53/120) prevalence of bacterial infections among COVID-19 patients admitted to KNH-IDU was 44.2% (53/120), similar to 41.8% reported among severe and critically ill COVID-19 patients at Aga Khan University Hospital, Kenya [39]. However, our study's bacterial prevalence is higher than reported elsewhere in Wuhan, China (19%) [40]and Bahrain (25%) [40] but lower than in Jiangsu Province, China (91.8%)[40][14] [14]. The discordance in these findings may suggest a geographical variation in bacterial etiologies occurrence and antimicrobial resistance. Since the prevalence of bacterial infections among COVID-19 patients before hospitalization is reportedly low ((≤ 3.5%)[41]–[43] [17] the high prevalence in our study suggests nosocomial transmission and is consistent with other reports [18], [19][44].
In our study, gram-negative bacteria (GNB) were the most dominant pathogens, with Klebsiella pneumoniae as the most prevalent bacterium in COVID-19 patients, findings consistent with similar studies done in Kenya [36], Egypt[45], Bahrain [46]and Italy [47]. The predominance of K. pneumoniae and GNB infections in COVID-19 patients is attributable to the microorganisms’ ability to acquire different resistance traits[46] and to cause infections in patients with invasive devices and mechanical ventilation during hospitalization [47]. The bacterial isolates profile was not a typical representation of the conventional community-acquired but rather nosocomial infections, suggesting low co-infections at the time of admission.
The prevalence of Gram-positive bacterial infection in our study population was 26.9%, with Enterococcus faecium and Staphylococcus aureus as the most common isolates; finding corroborating other studies among COVID-19[20] [39], [48], [49]and MERS patients[50], reflecting the pattern of infections in these pandemics. Pseudomonas aeruginosa and Acinetobacter baumanii were the dominant lower respiratory tract isolates, whereas Klebsiella pneumoniae was the most prevalent cause of GNB-associated bloodstream infections. These bacteria are well-known nosocomial pathogens [51] that cause ventilator-acquired pneumonia [52] and are often multidrug-resistant organisms [53]. Enterococcus faecium was the most common cause of bacteremia in our study population. The bacterium is a rare but emerging upper and lower respiratory tract pathogen, causing sinuses, trachea, bronchi, lung and pleural infections, and may worsen the clinical outcome in patients with impaired immunity [54]. Also, viral infection can alter the nasopharyngeal microbiota allowing bacteria in the nasopharynx to invade the lower respiratory tract and cause respiratory diseases and bacteremia[55].
We found that the male COVID-19 patients were significantly at risk of bacterial infection as compared to female patients, and this is consistent with other studies that found men to be at risk of having bacterial infections, consequently being severely ill and at increased risk of death[46][56][57]. Patients admitted to the critical care unit (CCU) had a significantly higher risk of death, and the finding corroborates those of Patone et al. (2021)[58]and Zali et al. (2020)[59]. Prolonged length of hospital stay was significantly associated with increased patients mortality, similar to other study reports in Africa and Asia [36][45][60], where the finding was due to frequent use of mechanical ventilators, treatment involving the combination of steroids (e.g., dexamethasone) and other immune-modulatory agents (e.g., infliximab), especially in the elderly patients admitted to the critical care unit. Non-vaccinated COVID-19 were at increased risk of death compared with vaccinated ones, corroborating other study findings on the effectiveness of COVID-19 vaccines on hospitalization outcomes [61], [62][63] and suggesting that the COVID-19 vaccines may attenuate disease severity among patients and reduce the risk of death thus the total benefits of vaccination exceed those estimated from the prevention of hospitalization alone. Elderly patients aged 60 years and above were also at increased risk of death compared with those aged between 25–40 years, similar to other study findings in COVID-19 across America and Asia [46][49][64][65] and MERS patients[66][67][68] whereby older age identified as an independent predictor of mortality in SARS and MERS pandemics. Age-dependent defects in T-cell and B-cell function and overproduction of type II cytokines could lead to a deficiency in the regulation of viral replication and prolonged inflammatory responses, possibly leading to poor outcomes [68].
Gram-negative bacteria (GNB) isolates were susceptible to Amikacin (AMK) but not Gentamicin (GEN), as opposed to Stephanini et al. (2020), who reported high resistance to amikacin among COVID-19 patients[47]. Aminoglycosides contain a defensin-mediated antiviral activity that, through retrocyclins, boosts immunity against SARS-CoV-2[69]. In this study, GNB resistant to beta-lactamase inhibitor-containing antibiotics, third-generation cephalosporins (cefotaxime and ceftriaxone), and fourth-generation cephalosporins, cefepime, were isolated. All these antibiotics are used in severe pneumonia management, with a possibility of overprescription, hence limiting their efficacy [47]. Acinetobacter calcoaceticus was resistant to all antibiotic classes, a phenomenon also observed in Italy among COVID-19 patients[47] and also in the general population [[70][71].
Gram-positive bacteria (GPB), except for one S. aureus isolate (17%), were resistant to erythromycin, an antibiotic with a similar spectrum of activity as Azithromycin, which was widely prescribed for COVID-19[72][73] management and overused as a repurposed drug in many African countries, possibly exerting a positive selection pressure hence the observed resistance in our study [72][73][74][34]. The rationale of increased prescription for antibiotics was to avert bacterial co-infections and to the fact that there has been no specific treatment for COVID-19. Enterococcus faecalis isolates showed 100% resistance to levofloxacin in the current study, corroborating other study findings that showed the ineffectiveness of fluoroquinolones in SARS-CoV-2 and MERS-CoV infections' management [47][75]. Consistent with Ayobami et al. (2022) and Huang et al. (2019)[76][77]. We found no vancomycin-resistant E. faecalis or E. Faecium. Therefore, the empirical cover for resistant Gram-positive pathogens (e.g., vancomycin) may not be warranted.
The majority of bacteria isolates (64.3%) were multidrug-resistant (MDR), attributable to GNB (69.6%), and this agrees with the findings of Saeed et al. (2021) [46], who reported a 65.8% MDR rate among the GNB in patients infected with SARS-CoV-2. In our study, the predominant MDR phenotypes were those observed in Klebsiella pneumonia, Enterococcus cloacae complex, and Escherichia coli, similar to those documented by Ramadan et al. (2020) in Egypt [45], were the pathogens carrying diverse antimicrobial resistance genes. Several studies, especially from the United States, Italy, and Germany, have reported increased bacterial infections with high multidrug-resistance rates during the COVID-19 pandemic [78][79][80]]. Weak antimicrobial policies, allowing improper consumption of the World Health Organization (WHO) Watch and Reserve antibiotics category [30] and prolonged hospital stay [81], among other varying contextual factors as observed and documented in other LMICs[30][82], could be implicated in increasing resistance and are likely to exacerbate the antimicrobial resistance (AMR) menace[27][26][28]. The indiscriminate use of antibiotics in COVID-19 pandemics may promote the selection of resistant strains and is likely to exacerbate the antimicrobial resistance (AMR) menace[26] [27] [28]. High resistance of these pathogens insinuates a near-patient environmental source, indicating compromised hand hygiene besides non-adherence to device-related bundle care practices [30]. A possible additional cause of multidrug resistance is the wide use of biocidal agents for individual and environmental decontamination outside hospital settings because some biocides exposure can predispose resistance and heighten the risk of cross-resistance to many antibiotics, especially those that are effective in treating GNB [83]. We may have another pandemic of AMR on top of the COVID-19 pandemic, as reported in a recent report where AMR caused more than 30,000 deaths in Europe alone in the year 2020[79]. AMR has both health and economic blows, remarkably in low resource settings, where there is low availability and high costs of some of the laboratory tests routinely conducted in high-income countries to manage AMR [82]. We therefore highly recommend carrying out appropriate microbiological culture tests, testing for specific biomarkers, improved surveillance and antibiotic de-escalation in the spirit of supporting antibiotic stewardship. Antibiotics use should be highly discouraged not unless there is supported bacterial infection evidence or the presence of signs of haemodynamic instability.
Some limitations to our study is that, first, it was a monocentre study performed in a tertiary level hospital with potentially high dominance of MDR bacteria. Therefore, the AST profiles observed in our study may not be a representation of other hospitals, thus limiting the generalization of our findings. With this study, we aim to highlight the need for strengthening antimicrobial stewardship programmes especially during the COVID-19 pandemic. This study was also conducted at the peak of the COVID-19 wave when the infection rate was very high and the findings may allude that there was over-prescription of antibiotics at the time. In addition, most of the isolates were not from sterile sites, (respiratory tract specimens), and may be more of colonization which might be pathogenic when the immunity of the COVID-19 patients is compromised rather than true infection. Furthermore, it is well known that steroids (e.g. dexamethasone) and other immune-modulatory agents (e.g. infliximab) which may have been used in treating of COVID-19 patients, (though we did not manage to evaluate the impact of these agents in our study), have been known to predispose such patient to bacterial infections[40]. However, our study specifically focused on bacterial infections during hospitalization and assessed the risk factors of acquiring these infections among COVID-19 infected patients, and this may have underrated the incidence of fungal and other viral infections in COVID-19 infected patients unlike other studies, which described superinfections and co-infections in COVID-19 patients. In spite of these limitations, we put focus on a critical need to scale up and rally culture-based and rationalized antibiotic prescription practices in our IDU and the hospital at large. Our findings are imperative in outlining the role of antibiotic therapy and stewardship strategies in COVID-19 patients to attain optimal therapeutic outcomes in future waves and pandemics.