HIV infection remains a major contributor to infectious morbidity and mortality worldwide despite major progress in the scale-up of antiretroviral therapy (ART). In 2024, approximately 630,000 people died from AIDS-related illnesses globally, underscoring persistent gaps in early diagnosis, treatment initiation, retention in care, and the management of advanced HIV disease [1][2]. People living with HIV (PLHIV) who are admitted to hospital frequently present with advanced HIV disease and multiple infectious complications [3]-[6]. Among these, severe bacterial infections remain leading causes of severe illness and death in patients with advanced HIV disease [3][4].

Non-tuberculous bacterial infections (NTBIs), particularly severe bacterial infections, represent an important but often under-characterized component of HIV-related morbidity in hospital settings. They may present as bloodstream infections, pneumonia, urinary tract infections, neuromeningeal infections, gastrointestinal infections, or skin and soft-tissue infections [3][4][7]. Compared with immunocompetent individuals, they occur at higher incidence, present with atypical features, progress more severely, and recur more frequently [3]. Their occurrence is favoured by impaired cellular and humoral immunity, mucosal barrier dysfunction, malnutrition, repeated healthcare exposure, prior antibiotic use, invasive procedures and delayed presentation to care [8]. In hospitalized PLHIV, these infections mimic tuberculosis, fungal infections, viral diseases or non-infectious inflammatory conditions [4][9]. This diagnostic uncertainty frequently leads to broad-spectrum empirical antibiotic therapy [6][10][11]. This treatment may be lifesaving when appropriately targeted but may also increase antimicrobial selection pressure when microbiological confirmation is delayed or unavailable [6][10].

The burden of these infections is further complicated by antimicrobial resistance (AMR), globally recognized as a major threat to patient survival. Sub-Saharan Africa is carrying one of the highest estimated burdens and western sub-Saharan Africa is showing the highest all-age death rate attributable to resistance in the 2019 global analysis [12]. The 2025 WHO Global Antibiotic Resistance Surveillance Report showed that approximately one in six laboratory-confirmed bacterial infections worldwide in 2023 were resistant to antibiotics, rising to nearly one in five in the African Region [13]. In PLHIV, available evidence suggests an increased risk of antimicrobial-resistant bacterial infections, including infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales [14] and methicillin-resistant Staphylococcusaureus [15]. These resistance patterns have direct implications for empirical antibiotic choices, antibiotic stewardship, infection prevention and control, and hospital outcomes [6][13][16].

In sub-Saharan Africa, the interplay between HIV, severe bacterial infections and AMR is amplified by late presentation to care, advanced immunosuppression at admission, limited access to rapid diagnostics, constrained microbiology laboratory capacity and restricted availability of last-line antibiotics [5][17]. In this context, local microbiological surveillance is essential to guide rational empirical therapy and improve patient outcomes [13]. However, data describing the clinical presentation, biological profile, bacterial spectrum, antimicrobial susceptibility patterns, resistance phenotypes and outcomes of non-tuberculous bacterial infections among hospitalized PLHIV remain limited in many West African tertiary hospitals.

In Senegal, HIV prevalence is relatively low compared with several countries in sub-Saharan Africa [1]. However, referral hospitals continue to manage patients with advanced HIV disease and severe infectious complications [4][18]. Previous studies from the Infectious and Tropical Diseases Department (Service des Maladies Infectieuses et Tropicales, SMIT) of Fann National University Hospital in Dakar have reported bacterial bloodstream infections among HIV-infected hospitalized patients, including Gram-positive and Gram-negative pathogens such as Escherichiacoli, Klebsiellapneumoniae and Staphylococcusaureus, with documented methicillin resistance and ESBL production [19]. Other local data have also shown that PLHIV admitted to this department frequently present with advanced disease and severe infectious conditions, including bacterial pneumonia and septicemia [18][20]. Earlier work on enterobacterial infections at Fann Hospital documented high levels of resistance to third-generation cephalosporins, aminoglycosides, ciprofloxacin and cotrimoxazole [21]. Nevertheless, these data remain fragmented and have generally focused on specific syndromes or bacterial groups rather than providing an integrated assessment of non-tuberculous bacterial infections in hospitalized PLHIV.

Therefore, this study aimed to describe the clinical presentation, to identify the bacterial species isolated, determine antimicrobial susceptibility patterns and resistance phenotypes, and estimate in-hospital case fatality of microbiologically documented non-tuberculous bacterial infections among PLHIV hospitalized in the Infectious and Tropical Diseases Department of Fann National University Hospital in Dakar, Senegal.

Non-tuberculous bacterial infections in hospitalized people living with HIV represent a major clinical challenge at the interface of advanced immunosuppression, delayed care, antimicrobial exposure and hospital-associated vulnerability. This study provides a focused description of non-tuberculous bacterial infections among hospitalized people living with HIV in a tertiary infectious diseases’ referral centre in Dakar, Senegal. Understanding the clinical spectrum, bacterial ecology, antimicrobial resistance patterns and outcomes is essential to inform empirical treatment strategies, optimize antimicrobial stewardship, and strengthen infection prevention practices in tertiary infectious diseases settings.

The clinical profile of this cohort strongly suggests that microbiologically documented non-tuberculous bacterial infections (NTBIs) frequently occurred in a context compatible with advanced HIV disease. CD4 count was available in only 10 patients (27.8%), among these tested patients, 90.0% of had CD4 counts below 200 cells/µL are highly consistent with advanced immunosuppression. This interpretation is aligned with the WHO definition of advanced HIV disease [4], and with WHO’s recognition that severe bacterial infections are among the common causes of severe illness and death in advanced HIV disease [3][22]. In practical terms, these data argue that bacterial infection in hospitalized PLHIV should not be viewed as an isolated infectious event, but as a potential marker of delayed diagnosis, treatment interruption, disengagement from HIV care, or insufficient screening for advanced HIV disease [4][23].

The long median duration of symptoms before admission, reaching 30 days, is clinically important. It suggests delayed consultation, delayed referral, or possible under-recognition of bacterial infection in immunocompromised patients. In advanced or poorly controlled HIV disease, bacterial infections may present with non-specific manifestations, overlapping with tuberculosis, fungal infections, viral reactivation, malignancy, or drug-related complications. The high frequency of fever, respiratory symptoms, digestive symptoms, asthenia, weight loss and altered consciousness in this cohort illustrates this diagnostic complexity [24]. However, the predominance of urinary and bloodstream infections indicates that systematic microbiological sampling remains essential, even when symptoms are not site-specific [11][24]. This is particularly relevant in settings where tuberculosis may dominate the diagnostic reasoning in PLHIV and potentially delay investigation for non-tuberculous bacterial infections [4].

Urinary tract infection was the leading documented site, and urine cultures had a high positivity rate among sampled patients. This urinary predominance is noteworthy, because much of the sub-Saharan African literature on severe bacterial infections among hospitalized PLHIV has historically focused on bloodstream and invasive bacterial infections, which are common and associated with substantial mortality [19][25]. Our finding may therefore reflect a true burden of urinary infection among hospitalized PLHIV, consistent with recent African data showing a high prevalence of UTI among PLHIV, particularly in patients with low CD4 cell counts [7]. However, it may also be influenced by sampling practices, catheter exposure, prior hospitalization, and the difficulty of distinguishing infection from colonization in some patients [26][27].

In our study, 58.3% of patients had bacteriological involvement of at least two anatomical sites. The high frequency of microbiological documentation should be interpreted cautiously. In immunocompromised patients, multiple positive cultures may reflect true concomitant infections, secondary bacterial dissemination, or colonization of non-sterile sites. Current guidance on advanced HIV disease and microbiology utilization emphasizes that bacterial culture results must be interpreted within the clinical syndrome and the quality and anatomical relevance of the specimen [4][28]. Therefore, isolates in this study were interpreted in relation to clinical presentation, anatomical plausibility, inflammatory markers and therapeutic decision-making, rather than culture positivity alone. However, given the retrospective design, residual misclassification between infection, colonization and contamination cannot be fully excluded [29].

A total of 57 bacterial isolates representing 16 species or taxa were recovered from 90 specimens. Gram-negative bacilli predominated (59.6%), driven by E.coli (26.3%) and K.pneumoniae (21.1%), while Gram-positive cocci accounted for 40.4%, led by S.aureus (19.3%) and S.saprophyticus (7.0%). This distribution is clinically relevant because E.coli, S.aureus and K.pneumoniae are among the leading bacterial pathogens contributing to the global burden of antimicrobial resistance [12]. This finding is also coherent with the WHO Bacterial Priority Pathogens List 2024, which places resistant Enterobacterales, including E.coli and K.pneumoniae, among critical-priority pathogens, and recognizes drug-resistant S.aureus as a high-priority pathogen [30]. The bacteriological distribution observed is also coherent with contemporary shifts in bacterial infections among PLHIV. Historically, invasive pneumococcal disease and non-typhoidal Salmonella were prominent in advanced HIV disease [31][32]. However, more recent literature suggests that Enterobacterales, S.aureus and healthcare-associated pathogens are increasingly important, especially in patients with prior hospital exposure and antibiotic pressure [3][4][15]. A recent review on sepsis and antimicrobial resistance in advanced HIV disease emphasized that bacterial infections are frequently underestimated as causes of death [33]. This review also points out that PLHIV have a substantially increased risk of bacterial bloodstream infection, particularly at low CD4 counts [33]. In the present study, E.coli and K.pneumoniae together accounted for nearly half of all isolates, while S.aureus represented almost one-fifth. This profile is consistent with the predominance of urinary tract infections, bacteremia, skin/soft tissue or suppurative infections, and possible healthcare-associated acquisition.

The antimicrobial resistance profile is one of the strongest findings of the study. These resistance findings should be interpreted at the isolate level, as they reflect the susceptibility profiles of tested bacterial isolates rather than the prevalence of resistance among patients. The high resistance levels to amoxicillin, amoxicillin-clavulanate, cotrimoxazole, ceftriaxone and ciprofloxacin indicate that many commonly used empirical options may be unreliable in this population. This concern is especially relevant in settings where third-generation cephalosporins and fluoroquinolones remain widely used for empirical management of severe bacterial infections. The 61.3% ESBL rate among Enterobacterales is particularly alarming. This proportion exceeds the pooled ESBL prevalence reported in a recent systematic review among HIV-positive individuals, which estimated an overall prevalence of ESBL-producing Enterobacterales of approximately 20.3%, with marked heterogeneity across regions and study populations [14]. It also aligns with Senegalese AMR surveillance data showing moderately high resistance to third-generation cephalosporins among Enterobacterales and high MRSA rates [16]. These findings are consistent with, and at the upper bound of, the ESBL prevalence recently reported across Senegalese clinical Enterobacterales isolates [34]. Our data thus are consistent with the general upward trend in ESBL and third-generation cephalosporin resistance documented across sub-Saharan Africa [35]. These results are also coherent with documented risk factors such as previous cephalosporin or carbapenem exposure, comorbidities, invasive devices and healthcare exposure [36].

The resistance profile has direct therapeutic implications. Ceftriaxone was the leading empirical antibiotic in this cohort, yet ceftriaxone resistance among tested isolates was 71.4%. This discrepancy is not simply a microbiological observation; it is a stewardship warning. In a setting where ESBL-producing Enterobacterales are frequent, empirical ceftriaxone may be inadequate for a substantial proportion of severely ill PLHIV, especially those with recent hospitalization, prior antibiotic exposure, severe sepsis, urinary source, or suspected bloodstream infection. This interpretation is consistent with IDSA guidance on the treatment of antimicrobial-resistant Gram-negative infections [37] and with Surviving Sepsis Campaign treatment recommendation for multidrug-resistant pathogens [11]. However, the solution is not indiscriminate escalation to carbapenems. Although carbapenems remain preferred agents for severe ESBL-producing Enterobacterales infections outside the urinary tract and for critically ill patients, unnecessary carbapenem exposure should be minimized to preserve their activity and reduce selection pressure for carbapenem-resistant organisms [37]. The rational approach is risk-stratified empirical therapy, systematic sampling before antibiotics, early reassessment at 48 - 72 hours, and strict de-escalation once susceptibility results are available [11][38].

The observed use of imipenem after susceptibility testing reflects the microbiological pressure exerted by ESBL-producing Enterobacterales. Carbapenem resistance remained relatively limited overall, but its presence in K.pneumoniae is a serious signal. K.pneumoniae is a well-recognized hospital-adapted pathogen with strong epidemic potential, especially in high-risk wards, intensive care settings and immunocompromised patients [39]. The Senegal AMR report similarly observed lower rates of carbapenem resistance than third-generation cephalosporin resistance [16]. This report also emphasized the need for infection prevention measures, hand hygiene, standard and contact precautions, and minimization of invasive devices to limit spread of resistant Enterobacterales [16]. In this context, even a small number of carbapenem-resistant isolates should trigger institutional vigilance, because hospital transmission can rapidly transform a sporadic finding into an endemic problem.

The high cotrimoxazole resistance also requires a balanced interpretation. Cotrimoxazole remains clinically important in HIV care because of its preventive role against several opportunistic and bacterial infections in eligible PLHIV. WHO guidance continues to recognize cotrimoxazole preventive therapy for adults with severe or advanced HIV disease as a survival-improving intervention [4]. However, high resistance among bacterial isolates limits its value as treatment for documented bacterial infections and may reflect cumulative selective pressure from prophylactic and therapeutic use. Studies in sub-Saharan Africa have reported very high cotrimoxazole resistance among E.coli isolates of 70.86% from people with HIV, including among those receiving cotrimoxazole prophylaxis [40]. Therefore, cotrimoxazole prophylaxis should not be interpreted as protection against all bacterial infections, and suspected severe bacterial infection in advanced HIV disease still requires microbiological documentation and locally adapted empirical treatment [37].

The Gram-positive findings are also clinically relevant. MRSA represented 36.4% of S.aureus isolates, and MLSB, quinolone and cotrimoxazole resistance were frequent. This proportion is broadly compatible with Senegalese surveillance estimates reporting MRSA rates between 28% and 42% in available datasets [16]. The absence of vancomycin resistance is reassuring, but it should not lead to complacency, particularly because national Senegalese AMR surveillance did not include estimates for vancomycin-resistant or vancomycin-intermediate staphylococci [16]. In resource-limited settings, vancomycin use is constrained by availability, renal monitoring requirements, therapeutic drug monitoring limitations and nephrotoxicity risks, especially in patients with anemia, renal dysfunction or severe sepsis. In practice, suspected invasive MRSA infection in PLHIV requires early source control, blood culture documentation, susceptibility-guided therapy and close renal monitoring [41][42].

The high case fatality proportion, 33.3%, is one of the most important findings of this work. This mortality is higher than that reported in a recent Dakar tertiary-hospital study of bacterial infections in internal medicine and infectious diseases departments, where the death rate was 15% [43]. However, that study was not restricted to PLHIV with culture-documented bacterial infection and severe immunosuppression markers. The excess mortality in the present cohort is biologically plausible: patients combined delayed presentation, anemia, lymphopenia, frequent multi-site infection, bloodstream involvement, high inflammatory burden, prior hospitalization and high AMR pressure. These factors should be interpreted as a cluster of severity markers rather than as independent causal determinants, because the sample size does not allow robust multivariable modelling. The median interval from admission to death of 20 days suggests that mortality was not solely due to immediate fulminant sepsis. It may also reflect persistent infection, delayed effective therapy, complications or organ dysfunction, opportunistic coinfections, or underlying advanced HIV-related frailty. Recent Senegalese data identified anemia as strongly associated with death among hospitalized patients with bacterial infections [43]. More broadly, anemia is a recognized prognostic marker in HIV and is linked with poor outcomes [44][45]. In the present study, anemia and lymphopenia should be discussed as severity markers that may contribute to poor outcomes, even if the sample size does not allow robust multivariable modelling.

This study has several limitations. Its retrospective design exposes it to missing data, particularly for CD4 count, viral load, ART adherence, procalcitonin measures, prior microbiological colonization and timing of antibiotic exposure. The relatively small sample size also limited the statistical power and prevented reliable identification of mortality associated factors. The lack of admission-to-culture timing prevented classification of infections as community-onset or hospital-onset, limiting interpretation of the high antimicrobial resistance burden. In addition, prior antibiotic exposure may have reduced culture yield, especially for blood and cerebrospinal fluid cultures. Another limitation is the absence of molecular characterization of resistance mechanisms, which prevented confirmation of resistance genes This study was conducted in a tertiary infectious diseases’ referral centre, then the findings may not be generalizable to all PLHIV in Senegal, particularly outpatient populations or district-level hospitals.

Despite these limitations, the study has clear clinical and public health value. It documents a high-risk profile of hospitalized PLHIV with microbiologically documented NTBIs, combining delayed presentation, severe immunosuppression among tested patients, high ESBL burden, substantial MRSA prevalence, prolonged hospital stay and high mortality. These findings call for systematic advanced HIV disease assessment in PLHIV admitted with suspected severe infection. They also support the need to revise empirical antibiotic protocols in infectious diseases referral centres according to local AMR patterns and individual risk factors for ESBL-producing Enterobacterales and MRSA.

This study describes microbiologically documented non-tuberculous bacterial infections among hospitalized PLHIV in a Senegalese infectious diseases referral centre. These infections were marked by frequent urinary and bloodstream involvement, predominance of Enterobacterales and Staphylococcusaureus, high ESBL burden, clinically relevant MRSA and substantial multidrug resistance. These infections mainly affected severely immunocompromised patients, although advanced HIV disease could not be fully assessed across the cohort. The high in-hospital case-fatality proportion underscores the clinical consequences of the intersection between advanced immunosuppression, delayed presentation, severe bacterial infection and antimicrobial resistance. These findings support the need for systematic advanced HIV disease assessment, early microbiological documentation, locally adapted and risk-stratified empirical antibiotic protocols, timely de-escalation, antimicrobial stewardship and strengthened infection prevention and control. In West Africa, tertiary infectious disease units should be leveraged as sentinel platforms for surveillance of severe bacterial infections and antimicrobial resistance among PLHIV.