Bacterial pulmonary infections in patients with HIV

INTRODUCTION — Bacterial pulmonary infections occur commonly in people with human immunodeficiency virus (HIV) [1]. However, incidence has been declining with the widespread use of antiretroviral therapy (ART). In resource-rich countries, bacterial pathogens account for a majority of respiratory infections in individuals with HIV, particularly as Pneumocystis jirovecii incidence has declined profoundly [2,3].

This topic discusses the epidemiology, risk factors, etiology, clinical manifestations, differential diagnosis, diagnostic evaluation, and treatment of bacterial pneumonia in patients with HIV. Pneumocystis pneumonia in patients with HIV and bacterial pneumonia in patients without HIV are discussed elsewhere. (See "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV" and "Treatment and prevention of Pneumocystis infection in patients with HIV" and "Evaluation of pulmonary symptoms in persons with HIV" and "Overview of community-acquired pneumonia in adults".)

EPIDEMIOLOGY — In resource-rich settings where antiretroviral therapy (ART) uptake is high, the annual incidence of bacterial pneumonia in patients with HIV is likely similar to that in patients without HIV. In a study of over 12,000 Swiss patients with HIV and follow up between 2008 and 2018, incidence of bacterial pneumonia decreased from 1.4 cases to 0.7 cases per 100 person years over the course of the decade [4]. This rate is comparable to the 0.7 to 1.0 percent incidence of bacterial pneumonia in patients without HIV [5-7].

In the preantiretroviral era, bacterial pneumonia incidence was higher among patients with HIV, at 5.5 to 29 percent annually [5,6,8]. The impact of ART on the risk of bacterial pneumonia is discussed further elsewhere. (See 'Effect of antiretroviral therapy (ART) on incidence of pneumonia' below.)

RISK FACTORS FOR PNEUMONIA — Although bacterial pneumonias can occur throughout the course of HIV infection, they occur more frequently in individuals with advanced immunosuppression [5,9]. Among patients with HIV, people who inject drugs, urban dwellers, smokers, and persons from resource-limited countries are at highest risk for bacterial pneumonias [4,5,8,10-12].

Immune status — A lower CD4 count has been associated with a higher incidence of bacterial pneumonia in patients with HIV. In one report, 4.9, 8.7, and 17.9 episodes occurred per 100 patient years with respective CD4 counts of >500, 200 to 500, and <200 cells/microL [6]. In another study, patients with CD4 counts <500 cells/microL were more likely to have bacterial pneumonia compared with patients with CD4 counts >500 cells/microL [4].

HIV infection is also a risk factor for recurrent pneumococcal pneumonia and bacteremia [13]. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults", section on 'Risk factors for invasive disease' and "Pneumococcal immunization in adults with HIV".)

Based upon these observations, the United States Centers for Disease Control and Prevention (CDC) added recurrent bacterial pneumonia as an acquired immunodeficiency syndrome (AIDS)-defining condition in 1992 [14].

Effect of antiretroviral therapy (ART) on incidence of pneumonia — The widespread use of effective ART has reduced the incidence of pneumonia [4,6,15]. In one study examining 1898 patients with HIV and CD4 counts <200 cells/microL from 1993 to 1998, use of ART was associated with a 45 percent reduction in the risk for bacterial pneumonia [16].

The benefit of ART has also been seen in patients with higher CD4 counts. As an example, in the Strategic Timing of Antiretroviral Treatment (START) study, patients with HIV and CD4 counts >500 cells/microL who received immediate ART had a 61 percent lower risk of serious bacterial infections (of which pneumonia was the most common manifestation) compared with participants who initiated ART when their CD4 count was <350 cells/microL (ie, deferred ART) [17].

Despite the benefits of ART, certain patients with HIV may still be at increased risk of pneumonia. In a Brazilian cohort study of patients with HIV on ART, a detectable viral load, a lower CD4 cell count, and cocaine use were significantly associated with a higher risk of bacterial pneumonia [18]. There are also conflicting data as to whether the incidence of invasive pneumococcal disease has declined with the use of effective ART [15,19-21].

The effect of ART on hospitalization has also been evaluated. An observational study of 3500 patients with HIV and 329,000 patients without HIV was conducted in Denmark from 1995 to 2007 to determine the incidence of hospitalization secondary to pneumonia during different time periods [22]. The incidence of hospitalizations in patients with HIV declined substantially from 51 per 1000 person-years during 1995 to 1996 to 20 per 1000 person-years during 2005 to 2007. Despite this decline, HIV remained a strong risk factor for hospitalization, even in persons with a CD4 cell count ≥500 cells/microL.

Smoking — Smoking, which is associated with a two- to fivefold increase in the risk of bacterial pneumonia and invasive pneumococcal disease in individuals with HIV, remains an important, modifiable risk factor in the ART era [4,6,19,23,24]. In smokers with HIV, decreases in absolute CD4 cell counts and percentages and suppression of IL-1 beta and TNF-alpha production within the lung may contribute to risk of infection.

Other factors — Other traditional risk factors that may be associated with pneumonia include pre-existing lung disease (eg, bronchiectasis or chronic obstructive pulmonary disease), heavy alcohol use, injection drug use, a prior episode of P. jirovecii pneumonia, neutropenia, corticosteroid therapy, or severe malnutrition [25,26]. A 2019 study from the Veterans Aging Cohort Study found that prescribed opioids were associated with increased community-acquired pneumonia risk in patients with and without HIV infection [27].

EFFECT OF PNEUMONIA ON THE PATIENT WITH HIV — The occurrence of bacterial pneumonia can have both short- and long-term consequences in this patient population:

●Acute bacterial pneumonia can transiently depress the CD4 count. One study of 30 antiretroviral-naive patients with HIV presenting with pneumococcal pneumonia found that the median CD4 count of 112 cells/microL on the day of admission increased to 270 cells/microL at one month follow-up without the use of antiretroviral therapy (ART) [28].

●The occurrence of bacterial pneumonia is associated with a permanent decline in pulmonary function [29] and a two- to fivefold increase in long-term mortality compared with CD4-matched controls [6,29,30].

ETIOLOGY

Community-acquired pneumonia — The bacterial pathogens reported to cause community-acquired pneumonia in patients with HIV are listed in the table (table 1) [5,10,11,31-40]. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are the most commonly isolated bacteria, with S. pneumoniae accounting for the majority of cases in which a bacterial pathogen is isolated [5,10,11,41-43]. In a prospective study of pulmonary infections in persons with HIV in Brazil that used enhanced diagnostics, an atypical pathogen (Mycoplasma pneumoniae or Chlamydia pneumoniae) was identified in nearly 10 percent of cases [44]. Legionella spp infection is uncommon and presents similarly in people with and without HIV [45]. Other uncommon infections include nocardia, pertussis, and Rhodococcus spp [35-37,46].

The risk of invasive pneumococcal disease is greater in patients with HIV than in the general population. In a United States Centers for Disease Control and Prevention (CDC)-sponsored study of pneumococcal disease using data from the Active Bacterial Core (ABC) surveillance and the National Health Interview Survey, the risk of invasive disease among risk groups was highest in adults with hematologic cancer or HIV [47]. Increased risk of invasive disease in patients with HIV may be partially explained by a predisposition for pneumococcal nasopharyngeal colonization. In a longitudinal cohort of 260 mother-infant pairs in Zambia, half of whom had HIV, HIV infection was associated with an increased risk of colonization, particularly with pediatric serotypes covered by the 7-valent conjugate vaccine (risk ratio 1.9, 95% CI 1.3-2.8) [48].

Community-onset methicillin-resistant S. aureus (CO-MRSA), usually harboring the Panton-Valentine leukocidin virulence factor, may cause rapidly progressive necrotizing pneumonia [49,50]. Although cases of pneumonia caused by CO-MRSA are relatively rare, they are characterized by high rates of morbidity and mortality. Risk factors for CO-MRSA colonization include HIV infection. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology".)

Pseudomonas aeruginosa, a nosocomial pathogen, is also implicated in community-acquired pneumonia in individuals with advanced HIV. Factors associated with Pseudomonas pneumonia include prior hospitalization, antibiotic exposure, neutropenia, and advanced immunosuppression [3,39,40,51-53]. Pseudomonal infection in patients with AIDS is associated with a 33 percent in-hospital mortality rate, poor one-year survival rates, and relapse of infection [39,40,51].

Several pathophysiologic mechanisms underlie the susceptibility to infection with encapsulated, pyogenic organisms [54-58]:

●Deficiencies in humoral immunity, including HIV-related B lymphocyte dysfunction with impaired antibody responses to S. pneumoniae and P. aeruginosa, and depressed IgA and IgG2 subclass antibody levels. These functional changes are seen despite the presence of polyclonal hyperglobulinemia.

●Decreased serum and bronchoalveolar opsonic activity against pneumococcal capsular polysaccharides [59,60].

●Alveolar macrophage and neutrophil dysfunction.

Tracheitis and bronchitis — Bacterial tracheitis and recurrent bronchitis, often associated with bronchiectasis, have also been reported in individuals with HIV. The isolated bacterial pathogens are similar to those causing pneumonia and include S. pneumoniae, H. influenzae, S. aureus, and P. aeruginosa [35-37].

Nosocomial pneumonia — Nosocomial pneumonia in patients with HIV is most commonly caused by S. aureus and gram-negative organisms, including P. aeruginosa, Klebsiella pneumoniae, and Enterobacter species. These infections tend to occur late in the course of HIV infection and in patients with additional host factors predisposing to bacterial infections, such as neutropenia [11,61].

CLINICAL MANIFESTATIONS — The clinical presentation of bacterial pneumonia in the patients with HIV is similar to that in patients without HIV. Many patients have an abrupt onset of fever, chills, cough with sputum production, dyspnea, and pleuritic chest pain [62,63]. The leukocyte count is generally elevated except in advanced immunosuppression. Bacteremia is frequently associated with pneumonia, with rates as high as 60 percent reported with S. pneumoniae infection [62,64,65].

Bronchitis with bronchiectasis often presents in a similar fashion with fever and copious purulent sputum production [66,67] (see "Clinical manifestations and diagnosis of bronchiectasis in adults"). In comparison, bacterial tracheitis may present with signs and symptoms of upper airway obstruction [68].

IMAGING — The most common chest roentgenographic manifestation of bacterial pneumonia in patients with HIV is segmental or lobar consolidation, although diffuse reticulonodular infiltrates and patchy lobar infiltrates may also be seen [2,10]. Certain patterns have been associated with specific infections, although such associations are of minimal diagnostic predictive value when assessing an individual patient:

●Rhodococcus equi, an unusual gram-positive pathogen, has been reported as a cause of pneumonia in patients with HIV, generally in the setting of advanced immunosuppression. R. equi pneumonia is characterized by an indolent course with cavitary infiltrates, often in the upper lobes, mimicking tuberculosis [37,69].

●Upper lobe consolidation with cavitation has also been observed in pulmonary nocardiosis. Other radiographic findings described in association with Nocardia infection include diffuse interstitial infiltrates, reticulonodular infiltrates, pleural effusions, and solitary masses [35].

Computed tomography (CT) of the chest is helpful in defining the nature of the infiltrate, particularly in identifying subtle diffuse or "ground-glass" infiltrates that suggest P. jirovecii, a viral, or atypical bacterial pneumonia (eg, Chlamydia pneumoniae). In a South African study, in which 49 subjects with HIV and pulmonary symptoms were evaluated with both chest radiograph and high resolution computed tomography (HRCT), 40 subjects (82 percent) had lesions identified on HRCT that were not identified on chest radiograph, including "ground-glass" infiltrates, mediastinal lymphadenopathy, and pleural effusions [70].

Chest radiographs in patients with bronchitis and bronchiectasis are usually normal or may show only increased bronchovascular markings [66,67]. The presence of bronchiectasis can be confirmed by CT scan.

DIFFERENTIAL DIAGNOSIS — A common clinical dilemma is determining whether a patient with HIV presenting with pulmonary complaints has bacterial pneumonia, viral pneumonia (eg, coronavirus disease 2019 [COVID-19], influenza), P. jirovecii, or tuberculosis. (See 'Clinical manifestations' above and "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV" and "Pulmonary tuberculosis: Clinical manifestations and complications" and "COVID-19: Clinical features" and "COVID-19: Clinical features", section on 'Clinical manifestations' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Pneumonia and respiratory tract complications'.)

Although considerable overlap exists, simple clinical factors can be helpful. Admitting notes were reviewed in a retrospective study of 229 patients with HIV and verified hospital discharge diagnoses of P. jirovecii, bacterial pneumonia, or tuberculosis [71]. Symptoms for less than seven days and a lobar infiltrate on chest radiograph had 94 percent specificity for typical bacterial pneumonia.

DIAGNOSTIC EVALUATION AND TREATMENT — The initial inpatient evaluation of a patient with HIV and suspected pneumonia should include a chest radiograph, sputum examination, white blood cell count, and blood cultures. In addition, testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be routinely performed during the COVID-19 pandemic. Urinary antigen testing for S. pneumoniae and Legionella spp and testing for other respiratory viruses may also be useful, if available. Diagnostic evaluation can help determine if the presence of a particular pathogen may alter the initial choice of treatment (eg, P. aeruginosa in a patient with advanced AIDS). (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

Given the increased incidence of tuberculosis in patients with HIV, the diagnosis of tuberculosis should always be considered as well when evaluating the patient's history, risk factors, and chest x-ray findings [26]. (See 'Differential diagnosis' above.)

Routine diagnostic workup is optional in a patient who is well enough to be treated as an outpatient [26].

Sputum — Expectorated sputum should be sent for Gram stain and bacterial culture. In patients with HIV who have tuberculosis risk factors (eg, homelessness, substance abuse, history of tuberculosis exposure) or whose symptoms have been present longer than seven days, we also send sputum specimen for acid-fast bacilli smear, nucleic acid amplification testing, and mycobacterial culture to evaluate for pulmonary tuberculosis. Testing for respiratory viruses is appropriate if the diagnosis is unclear or to assess whether a prior viral infection has led to bacterial superinfection. If the patient is at risk for P. jirovecii (eg, because of low CD4 cell count), an induced sputum should be requested, as well as serum testing for 1,3-beta-D-glucan. (See "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV", section on 'Evaluation and diagnosis'.)

Blood cultures — S. pneumoniae can be isolated in blood cultures in up to 60 percent of patients with HIV and pneumococcal pneumonia [62]. In patients with pneumonia and high-grade bacteremia, gram-positive diplococci may occasionally be seen on Gram stain of the buffy coat.

Thoracocentesis — A diagnostic thoracentesis should be considered in any patient with a pleural effusion, particularly if there is a concern regarding empyema.

TREATMENT — In general, the treatment of bacterial pneumonia in patients with HIV is the same as those without HIV [26,72]. In patients presenting with typical symptoms of bacterial pneumonia plus focal consolidation on chest radiograph, initial antibiotic regimen should be directed at the most common community-acquired pathogens. However, clinicians should also take into account current antibiotic prophylaxis (eg, trimethoprim-sulfamethoxazole for Pneumocystis pneumonia prophylaxis) when making decisions about administering empiric treatment for intercurrent bacterial infections. In addition, the diagnosis of tuberculosis should be considered before initiating fluoroquinolone therapy, since patients with tuberculosis may initially respond clinically to fluoroquinolone therapy leading to a delay in the diagnosis of tuberculosis and to the emergence of fluoroquinolone resistance in Mycobacterium tuberculosis [73]. The decision to treat as an outpatient or inpatient depends on the clinical status and the reliability of the individual. (See "Overview of community-acquired pneumonia in adults", section on 'Treatment'.)

Outpatients — Patients with HIV who present with suspected bacterial infection with single lobar involvement and good respiratory status may be considered for outpatient therapy. Recommendations for treatment are presented separately. (See "Treatment of community-acquired pneumonia in adults in the outpatient setting".)

Inpatients — Patients with HIV who have evidence of severe disease or severe immunocompromise should be admitted to the hospital for initial management. (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care".)

Respiratory isolation should be considered for possible COVID-19, influenza, or tuberculosis until appropriate tests can be performed to rule out these conditions. Treatment of community-acquired pneumonia in patients who require hospitalization begins with empiric therapy directed against the most common pathogens. If alternative diagnoses are also being considered, such as infection with P. jirovecii, empiric therapy should cover such pathogens. (See "Treatment of community-acquired pneumonia in adults who require hospitalization" and "Treatment and prevention of Pneumocystis infection in patients with HIV".)

Proceeding to bronchoscopy may be necessary in those patients who fail to respond to empiric therapy or in patients who are at risk for P. jirovecii or tuberculosis. Combination therapy directed at bacterial as well as opportunistic infections may be necessary while awaiting the results of diagnostic testing. (See "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV" and "Treatment and prevention of Pneumocystis infection in patients with HIV" and "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy".)

When culture results are available, specific pathogen-directed therapy should be provided. See the appropriate topics reviews for treatment recommendations for specific pathogens.

PREVENTION — Preventive strategies against bacterial pneumonia include immunizations, prophylactic antibiotics, and smoking cessation counseling.

Pneumococcal vaccine — Pneumococcal vaccination is recommended for all patients with HIV. A detailed discussion on vaccine administration and when to immunize is found elsewhere. (See "Pneumococcal immunization in adults with HIV", section on 'Vaccine recommendations'.).

Prophylactic antibiotics — Antibiotics used for prevention of opportunistic infections in patients with HIV may also have the effect of preventing bacterial pneumonia. However, antibiotics for the specific purpose of preventing bacterial pneumonia is not formally recommended.

Trimethoprim-sulfamethoxazole, when used as Pneumocystis pneumonia (PCP) prophylaxis, has been shown to decrease the risk for bacterial infections [5,6,74,75]. In one report, for example, patients receiving trimethoprim-sulfamethoxazole had a 67 percent reduction in the incidence of confirmed episodes of bacterial pneumonia [5]. For those patients receiving other forms of PCP prophylaxis not expected to have antibacterial activity (eg, dapsone or aerosolized pentamidine), antimicrobial prophylaxis with another antibiotic is not recommended.

The safety of discontinuing trimethoprim-sulfamethoxazole for PCP prophylaxis when immune reconstitution has been achieved is well established [26], although such patients may subsequently be at increased risk for bacterial pneumonia. A Swiss study reported similarly low rates of bacterial pneumonia in patients who discontinued prophylaxis compared to those who had not following immune reconstitution with antiretroviral therapy (ART) [76]. However, in a randomized placebo-controlled trial of patients with HIV in Uganda who were stably treated with ART and had a CD4 cell count ≥250 cells/microL, discontinuation of trimethoprim-sulfamethoxazole resulted in a 57 percent increased risk of trimethoprim-sulfamethoxazole preventible infections, most of which were bacterial pneumonias [77]; hematologic adverse events were higher with trimethoprim-sulfamethoxazole continuation.

Smoking cessation counseling — Cigarette smoking is highly prevalent in individuals with HIV, is a strong risk factor for bacterial pneumonia, and is linked to all-cause mortality among patients with HIV [78]. Thus, multifaceted approaches to smoking cessation are warranted. (See "Overview of smoking cessation management in adults" and "Behavioral approaches to smoking cessation".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opportunistic infections in adults with HIV".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – In patients with HIV who are on antiretroviral therapy (ART), the incidence of bacterial pneumonia is similar to that of those without HIV. (See 'Epidemiology' above.)

●Risk factors – Risk factors for bacterial pneumonia in individuals with HIV include degree of immunosuppression, uncontrolled HIV, smoking, alcohol and injection drug use, underlying lung disease, history of Pneumocystis jirovecii pneumonia (PCP), malnutrition, or other causes of immunosuppression (eg, neutropenia, corticosteroid therapy). (See 'Risk factors for pneumonia' above.)

●Etiology – Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are the most commonly isolated bacterial pathogens associated with community-acquired pneumonia in this patient population. (See 'Etiology' above.)

●Clinical manifestations – The clinical presentation of bacterial pneumonia in patients with HIV is similar to that in patients without HIV. Many patients have an abrupt onset of fever, chills, cough with sputum production, dyspnea, and pleuritic chest pain. (See 'Clinical manifestations' above.)

●Imaging – The most common chest roentgenographic manifestation of bacterial pneumonia in patients with HIV is segmental or lobar consolidation, although diffuse reticulonodular infiltrates and patchy lobar infiltrates may also be seen. (See 'Imaging' above.)

●Diagnostic evaluation – The initial inpatient evaluation of a patient with HIV and suspected pneumonia should include a chest radiograph, sputum examination, white blood cell count, and blood cultures. (See 'Diagnostic evaluation and treatment' above.)

●Respiratory isolation – Respiratory isolation should be considered for possible COVID-19, influenza or tuberculosis until appropriate tests can be performed to rule out these conditions. (See 'Inpatients' above.)

●Treatment – Treatment of bacterial pneumonia in a patient with HIV is the same as in patients without HIV. However, clinicians should consider PCP and tuberculosis in the differential diagnosis in patients with certain risk factors (eg, CD4 cell count <200 cells/microL, tuberculosis risk factors). Special attention should also be given to any antibiotic prophylaxis the patient is taking when deciding on an empiric antibiotic regimen. (See 'Treatment' above.)

ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.