Nosocomial pulmonary infections in HIV-positive patients

PURPOSE OF REVIEW: Nosocomial infections (NI) constitute a significant public health problem and contribute to prolonged hospitalization, additional healthcare costs, and excess morbidity and mortality. Immunocompromised patients, including HIV-infected individuals, are at increased risk for NI, and 15-18.3% of them are represented by lower respiratory tract infections. Nosocomial pulmonary infections (NPI) appear to be more common in patients with acquired immunodeficiency syndrome (AIDS), as a result of the degree of immunosuppression, prior use of antibiotics, and exposure to invasive procedures. RECENT FINDINGS: This article reviews the epidemiologic and clinical evidences and reports on the occurrence of NPI in HIV-infected inpatients. SUMMARY: Although underestimated, NI occur commonly in HIV-infected patients, and among them nosocomial pneumonia, including tuberculosis and bacterial pneumonia, are associated with significant morbidity and mortality. The improvement of antiretroviral therapeutic options in developed countries has resulted in a decreased hospitalization rate of HIV-infected individuals. Healthcare delivery in the in- and outpatient setting represents a potential for infections, including lower respiratory tract ones, according to the degree of immunosuppression and the intensity of invasive procedures. To minimize the risk of acquisition of healthcare associated low respiratory tract infections, adherence of healthcare workers to common infection practices, specific respiratory precautions, and early identification of persons who have tuberculosis or are at high risk for active tuberculosis, should be strengthened.     

Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smear-negative HIV-positive patients with atypical chest X-ray in Ethiopia

Pneumocystis pneumonia (PCP) has been considered a rare disease in sub-Saharan Africa. However, a rising prevalence has been noted recently. The objective of this study was to determine the relative prevalence of PCP and other pulmonary opportunistic diseases in patients infected with HIV in Ethiopia. 131 consecutive patients with respiratory symptoms and atypical chest X-ray, who were sputum smear-negative for AFB and seroreactive for HIV, underwent clinical evaluation and investigation for Pneumocystis jiroveci and Mycobacterium tuberculosis from sputum and bronchoalveolar lavage (BAL), and fungal and bacterial pathogens from BAL alone. Bacterial infections, Pneumocystis pneumonia (PCP) and pulmonary tuberculosis (PTB) occurred in 44 (33.6%), 39 (29.7%) and 31 (23.7%) patients, respectively. Pulmonary Kaposi sarcoma and non-specific interstitial pneumonitis occurred in 4 patients each. In a multivariate regression model, predictors of PCP were typical chest X-ray and low CD4 count while purulent sputum predicted bacterial infection. The sensitivity of physicians and chest X-ray diagnosis was particularly low for PTB and bacterial infections. We conclude that chronic bacterial infection and Pneumocystis pneumonia are important differential diagnoses in HIV-infected, smear-negative PTB patients presenting with atypical chest X-ray. We therefore need to escalate the use of preventive and highly active antiretroviral (HAART) treatment in order to prevent a PCP epidemic.     

Opportunistic and other infections in HIV-infected children in Latin America compared to a similar cohort in the United States

Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U.S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.     

Non-tuberculosis opportunistic infections and other lung diseases in HIV-infected infants and children.

The diagnosis and management of human immunodeficiency virus (HIV) infected infants and children who do not respond to recommended empiric therapy for acute or chronic pneumonia is a frequent clinical challenge, especially as the greatest burden of childhood HIV-related lung disease occurs in low-income regions where options for investigation and treatment are limited. Lung disease is due to a wider spectrum of causes in HIV-infected than non-infected children. Bacterial pneumonia, viral pneumonia and pulmonary tuberculosis (TB) are common in children throughout the developing world, and the added impact of HIV infection on the incidence and outcome of these diseases is covered in companion articles. This review focuses on lung diseases that are more specifically HIV-related. Pneumocystis jirovecii pneumonia (PJP) is a major cause of pneumonia and death in HIV-infected infants, especially in regions where maternal HIV status is often not known and the provision of PJP prophylaxis for HIV-exposed infants is unusual. Cytomegalovirus is commonly found in the lungs of HIV-infected infants, with implications for the use of corticosteroids for PJP. Lymphoid interstitial pneumonitis, a common cause of persistent respiratory symptoms in HIV-infected children, must be differentiated from pulmonary or miliary TB. The incidence of uncommon causes such as fungal pneumonia or HIV-related pulmonary malignancy varies among regions. The burden of lung disease due to opportunistic infections would be significantly reduced by more widely applying available measures that reduce mother-to-child HIV transmission, by providing cotrimoxazole prophylaxis for HIV-exposed infants, and by increasing the availability of antiretroviral therapy.     

Causes of death in hospitalized adults with a premortem diagnosis of tuberculosis: an autopsy study

OBJECTIVE: To ascertain the immediate and underlying causes of death in adults who died in hospital with a premortem diagnosis of tuberculosis. DESIGN: Causes of death were assessed independently by internists and pathologists in 50 adults admitted to two Soweto hospitals who died 24 h or more after admission. Detailed record reviews and complete autopsies, including HIV tests when not performed premortem, were performed. In addition, a variety of postmortem microbiological tests were performed. RESULTS: Forty-seven patients had HIV infection; all were antiretroviral naive. Their median age was 34.5 years, median CD4 cell count was 48 cells/microl and median length of hospitalization before death was 6 days. Autopsy confirmed the premortem diagnosis of tuberculosis in 37 HIV-infected patients (79%), whereas 10 (21%) did not demonstrate tuberculosis. Bronchopneumonia and cytomegalovirus pneumonitis were the leading pathologies in these 10 patients. In 47 HIV-infected cadavers immediate or contributory causes of death were: extensive pulmonary tuberculosis, 32 (68%); disseminated tuberculosis, 28 (60%); bacterial pneumonia, 13 (26%); cytomegalovirus pneumonitis in seven (15%); cytomegalovirus DNA was found in 31 (66%) and Pneumocystis pneumonia was found in five cadavers (11%). The lung, followed by lymph nodes, liver and kidney, were the commonest sites of tuberculosis. Mycobacterium tuberculosis was cultured from 19 spleens, one of which was multidrug resistant, and Salmonella spp. was cultured from 11 splenic specimens. CONCLUSION: We demonstrated disseminated, extensive tuberculosis associated with advanced HIV disease. Severe bacterial infections, including salmonellosis, were the leading co-morbidity, suggesting that hospitalized HIV-infected adults in whom tuberculosis is suspected may benefit from broad-spectrum antibiotic therapy.     

Tuberculosis in HIV-infected persons in the context of wide availability of highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) greatly reduces the risk of developing tuberculosis for HIV-infected persons. Nonetheless, HIV-associated tuberculosis continues to occur in countries where HAART is widely used. To identify the characteristics of HIV-infected persons who develop tuberculosis in the context of the availability of HAART, the current authors analysed data taken from 271 patients diagnosed, in Italy, during 1999-2000. These patients represent 0.7% of the 40,413 HIV-infected patients cared for in the clinical units participating in this current study. From the data it was observed that 20 patients (7.4%) had a previous episode of tuberculosis whose treatment was not completed. Eighty-one patients (29.9%) were diagnosed with HIV at tuberculosis diagnosis, 108 (39.8%) were aware of their HIV status but were not on antiretroviral treatment and 82 (30.3%) were on antiretroviral treatment. Patients on antiretroviral treatment were significantly less immunosuppressed than patients with HIV diagnosed concurrently with tuberculosis, or other patients not on antiretrovirals (median CD4 lymphocytes count: 220 cells x mm(-3) versus 100 cells x mm(-3), and 109 cells x mm(-3), respectively). No significant differences in clinical presentation of tuberculosis according to antiretroviral therapy status were recorded. Failure of tuberculosis control interventions (e.g. noncompletion of treatment) and of HIV care (delayed diagnosis of HIV infection and suboptimal uptake of therapy) may contribute to continuing occurrence of HIV-associated tuberculosis in a country where highly active antiretroviral therapy is largely available. However, a significant proportion of cases occur in patients who are on antiretroviral treatment.     

Respiratory infection complicating HIV infection

PURPOSE OF REVIEW: Respiratory infections remain a major cause of morbidity among HIV-infected persons. Thus, knowledge of recent advances regarding HIV-associated opportunistic pneumonias is crucial for optimal care of HIV-infected persons. RECENT FINDINGS: Bacterial pneumonia is the most common HIV-associated opportunistic pneumonia in the USA and its incidence remains appreciable. Worldwide, tuberculosis dominates the clinical picture. The absence of rapid, affordable diagnostics for active and latent tuberculosis remains a major obstacle that must be overcome if the global epidemic is to be slowed. The specter of extensively drug resistant tuberculosis and its overlap with HIV infection highlight the importance of rapid diagnostics and the need for accessible drug susceptibility testing. Pneumocystis (carinii) jirovecii pneumonia appears to be a more common pneumonia among HIV-infected persons residing in developing countries than was previously appreciated. Similar to tuberculosis, the absence of available diagnostics in developing areas is a major obstacle to clinical care and epidemiologic studies. The critical care of HIV-infected persons is challenging. SUMMARY: Although tremendous advances have been made in our understanding of the management, treatment, and prevention of HIV and its associated respiratory infections, significant gaps remain. Thus, continued epidemiologic, clinical, and bench research is needed.     

HIV and pneumococcal disease

PURPOSE OF REVIEW: To describe the impact of highly active antiretroviral therapy on the burden of pneumococcal disease and advances in our understanding of the impact of HIV on this disease. RECENT FINDINGS: Although highly active antiretroviral therapy has reduced the burden of pneumococcal disease among HIV-infected adults, these infections remain far more common than in HIV uninfected adults. HIV-infected adults who smoke or have comorbidities are at particular risk. In the absence of highly active antiretroviral therapy, pneumococcal meningitis has emerged in Africa as a major disease burden with a high mortality among HIV-infected children and adults. Conjugate pneumococcal vaccine protects HIV-infected infants from pneumococcal pneumonia. In the United States, where conjugate vaccine is given to children, herd immunity has reduced the burden of invasive pneumococcal disease among HIV-infected adults. SUMMARY: The pneumococcus remains a significant cause of morbidity and mortality among HIV-infected children and adults, both in developed and in developing countries.     

Pulmonary infections in the HIV-infected patient in the era of highly active antiretroviral therapy: An update

The highly active antiretroviral therapy (HAART) era began in 1996 when the combination of multiple antiretroviral agents was found to improve outcomes in HIV-infected patients. HAART has made a tremendous impact on the progression of HIV and on the morbidity and mortality associated with its opportunistic infections. HIV-positive patients who respond to HAART have a decreased incidence of opportunistic infections. Studies have documented close to a 50% decline in the incidence of pneumocystis pneumonia and bacterial pneumonia with the use of antiretroviral therapy. Primary and secondary prophylaxis for pneumocystis pneumonia can be discontinued in patients who show a sustained response to antiretroviral therapy. Unique to the HAART era, immune reconstitution syndrome is characterized by a paradoxical deterioration of a preexisting infection that is temporally related to the recovery of the immune system. Recently, more and more patients are being admitted for non-AIDS related illnesses in the HAART era.     

艾滋病抗病毒治疗后机会感染的变化和分布状况

目的探讨艾滋病(AIDS)抗病毒治疗后机会感染疾病谱的变化及分布状况。方法采用回顾性分析的方法,对2006年9月-2008年12月期间,在郑州市第六人民医院接受门诊及住院治疗的128例HIV/AIDS病人,抗病毒治疗前后机会感染发生情况进行总结分析。结果 (1)128例HIV/AIDS病人中,高效抗反转录病毒疗法(HAART)治疗3-12月期间共发生100例次机会感染,主要为呼吸系统(46.09%)和消化系统(11.72%)感染,其中前4位机会感染是细菌性肺炎(29.69%)、肺结核(9.38%)、口腔念珠菌感染(7.81%)、带状疱疹(3.91%);与HAART治疗前相比,治疗后机会感染中细菌性肺炎、肺结核占绝大多数(86.46%),存在一定比例的口腔念珠菌感染和带状疱疹,AIDS晚期常见的机会感染如肺孢子菌肺炎、感染性腹泻及消耗综合征、中枢神经系统病变发病明显减少。(2)128例HIV/AIDS病人HAART治疗前机会感染发病率为80.47%,治疗后3-6月时下降至28.13%,治疗6-12月时为25.89%,3组相比差异有统计学意义(P<0.05)。HAART治疗后同时合并多种机会感染的病例减少。结论 HAART治疗后的机会感染发病率明显下降,机会感染疾病谱较治疗前有所不同,同时合并多种机会感染的几率减少。     

Chronic lung disease in human immunodeficiency virus (HIV) infected children

The development of chronic lung disease is common in HIV-infected children. The spectrum of chronic HIV-associated lung disease includes lymphocytic interstitial pneumonia (LIP), chronic infections, immune reconstitution inflammatory syndrome (IRIS), bronchiectasis, malignancies, and interstitial pneumonitis. Chronic lung disease may result from recurrent or persistent pneumonia due to bacterial, mycobacterial, viral, fungal or mixed infections. In high tuberculosis (TB) prevalence areas, M. tuberculosis is an important cause of chronic respiratory illness. With increasing availability of highly active antiretroviral therapy (HAART) for children in developing countries, a rise in the incidence of IRIS due to mycobacterial or other infections is being reported. Diagnosis of chronic lung disease is based on chronic symptoms and persistent chest X-ray changes but definitive diagnosis can be difficult as clinical and radiological findings may be non-specific. Distinguishing LIP from miliary TB remains a difficult challenge in HIV-infected children living in high TB prevalence areas. Treatment includes therapy for specific infections, pulmonary clearance techniques, corticosteroids for children with LIP who are hypoxic or who have airway compression from tuberculous nodes and HAART. Children who are taking TB therapy and HAART need adjustments in their drug regimes to minimize drug interactions and ensure efficacy. Preventative strategies include immunization, chemoprophylaxis, and micronutrient supplementation. Early use of HAART may prevent the development of chronic lung disease.     

Necropsy in HIV-infected patients

Human immunodeficiency virus (HIV)infection is usually followed by opportunistic infections, especially in the full-blown acquired immunodeficiency syndrome (AIDS). This study details the histopathological changes of different organs in relation to HIV infection, with particular emphasis on the opportunistic infections. Various organs from seventeen HIV-infected patients were collected by necropsy and analyzed for histopathological changes. The major histopathological changes included cytomegalovirus infection, cryptococcosis, penicilliosis, bacterial pneumonia, cryptosporidiosis, pneumocystosis, candidiasis, tuberculosis, granulomatosis of unknown etiology, early cirrhosis and chronic active hepatitis. General organ changes from seventeen cases of HIV-infected patients were described and discussed.     

Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection

We compared the occurrences of several types of infections in HIV-infected patients participating in a randomized clinical trial of three treatment strategies given for the primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis. In a phase III open label trial, 842 patients with HIV infection and fewer than 200 CD4+ cells/mm(3) received zidovudine (standard dose) plus one of three randomly assigned prophylactic agents: trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone (DAP), or aerosolized pentamidine (AP). Patients developing intolerance to treatment were crossed over to another predefined prophylactic therapy. Patients were monitored for infections every other week for 8 weeks and then monthly until the study was completed. Primary statistical models were proportional hazards models adapted to recurrent end points. In an intent-to-treat analysis, compared with AP and DAP, TMP-SMZ significantly reduced the risk of any bacterial infection (combining all distinct types) (p = 0.02 and p = 0.01, respectively). When considering distinct types separately, compared with AP, TMP-SMZ significantly reduced the risk of infectious diarrhea (p = 0.04); compared with DAP, AP and TMP-SMZ significantly reduced the risk of sinusitis/otitis media (p = 0.03 and p = 0.04, respectively); compared with AP and DAP, TMP-SMZ significantly reduced the risk of a second occurrence of pneumonia (p = 0.04 and 0.02, respectively). For any bacterial infection, infection rates per 100 patient-years of follow-up were 31, 39, and 38 for TMP-SMZ, DAP, and AP, respectively. In patients with advanced HIV infection not taking highly active antiretroviral therapy, the treatment strategy that initiates prophylaxis with TMP-SMZ is superior to those initiating with AP or DAP for preventing any bacterial infection, with most of the advantage manifested through infectious diarrhea, sinusitis/otitis media, and pneumonia.     

Spectrum of opportunistic infections in hospitalized HIV-infected patients in Phnom Penh,Cambodia

The aim of the study was to provide more comprehensive data on the clinical characteristics of hospitalized AIDS patients in Cambodia. Chart review of 381 HIV-infected patients admitted to a public hospital in Phnom Penh, Cambodia between December 1999 and May 2000 was performed. The in-hospital mortality rate was 43.6%. Approximately 50% of patients had two or more concurrent illnesses. Very advanced HIV disease was common, with CD4 cell counts below 10 cells/mm(3) in 43.2%. Only 28.3% of the patients had documentation of their HIV infection prior to hospitalization. Chronic diarrhoea was the most frequent opportunistic illness (41.2%), followed by tuberculosis (26%), cryptococcal meningitis (12.6%), Pneumocystis carinii pneumonia (8.4%), and encephalitis (4.7%). Chronic diarrhoea and tuberculosis were the most important opportunistic infections observed in HIV-infected hospitalized patients in Cambodia. These findings illustrate the need for early diagnosis of HIV-infection, effective prophylaxis for opportunistic infections and improved access to antiretroviral therapy in Cambodia.     

Pyogenic bacterial pneumonia in the acquired immunodeficiency syndrome

Individuals with human immunodeficiency virus (HIV) infection are more susceptible to bacterial infections because of defects in both cellular and humoral immunity. The most common causes of community-acquired pyogenic bacterial pneumonia in HIV-infected patients are Streptococcus pneumoniae and Haemophilus influenzae. The clinical presentation of HIV-infected patients with pyogenic pneumonia does not seem to differ significantly from that of patients without HIV infection. Response to therapy is generally good, and complications relatively few. Prevention of bacterial pneumonia is very important in the care of HIV-infected persons. The pneumococcal vaccine is currently recommended for all HIV-seropositive individuals, although its efficacy is unknown is this setting. Other forms of prevention require further investigation but may prove to be helpful.     

Current issues in the diagnosis and management of tuberculosis and HIV coinfection in the United States

Approximately 10% of new cases of tuberculosis (TB) in the United States occur in HIV-infected persons. HIV infection dramatically increases the risk of TB, and this increased risk is present throughout the course of HIV infection. TB and HIV coinfection complicates the course and treatment of both diseases. Isoniazid preventive therapy and antiretroviral therapy both substantially reduce the risk of developing active disease in persons with latent TB infection. Antiretroviral therapy should be given during treatment for active TB, as mortality was reduced by 56% with initiation of antiretroviral therapy before the completion of TB therapy. In addition, for patients with low CD4+ cell counts (less than 200/microm3), starting antiretroviral therapy during the intensive phase of TB treatment reduced mortality by 34% compared with delaying antiretroviral therapy until 8 weeks after TB treatment initiation.     

Imaging features of bacterial respiratory infections in AIDS

PURPOSE OF REVIEW: Although an emphasis has historically been placed on nonbacterial, opportunistic respiratory infections in HIV-infected individuals, it is increasingly important for clinicians to be familiar with the spectrum of bacterial respiratory infections that may occur in this population. RECENT FINDINGS: Bacterial pneumonia and acute bronchitis are currently the most common causes of respiratory disease in HIV-infected individuals in developed countries. Moreover, these infections are frequently the first clinical manifestation of HIV infection. Among patients with sustained CD4 cell count >200 cells/microL, the discontinuation of Pneumocystis carinii pneumonia prophylaxis is not associated with an increased risk of bacterial pneumonia. The most common radiographic pattern of bacterial pneumonia is focal consolidation, which typically presents in either a segmental or lobar distribution. In cases in which the chest radiograph is inconclusive, high-resolution chest CT has a very high accuracy for detecting pyogenic small airways disease and for distinguishing between P. carinii pneumonia and other lung infections including bacterial infection. SUMMARY: Knowledge of the characteristic imaging and clinical features of bacterial respiratory infections can enhance their timely diagnosis and treatment.     

Changing trends in bacterial infections: Staphylococcus aureus, bacterial pneumonia, Clostridium difficile

Changing bacterial diseases in the general population of which HIV practitioners should be aware include: new staphylococcal syndromes caused by community-acquired methicillin-resistant Staphylococcus aureus USA300 strains (eg, necrotizing skin infections, pneumonia, fasciitis); continued high rates of community-acquired pneumonia in the potent antiretroviral therapy era; increase rates and severity of Clostridium difficile-associated disease due to the fluoroquinolone-resistant NAP1 strain, and the new scare from extensively drug-resistant tuberculosis, primarily as a potential threat to health care in Africa. This article summarizes a presentation on important bacterial infections made by John G. Bartlett, MD, at the International AIDS Society-USA course in New York in March 2007.