Australian and New Zealand practice in intensive care (ANZPIC II): Predictors of physician confidence to diagnose pneumonia and determine illness severity in ventilated patients

The manner in which elements of clinical history, physical examination and investigations influence subjectively assessed illness severity and outcome prediction is poorly understood. This study investigates the relationship between clinician and objectively assessed illness severity and the factors influencing clinician's diagnostic confidence and illness severity rating for ventilated patients with suspected pneumonia in the intensive care unit (ICU). A prospective study of fourteen ICUs included all ventilated admissions with a clinical diagnosis of pneumonia. Data collection included pneumonia type - community-acquired (CAP), hospital-acquired (HAP) and ventilator-associated (VAP), clinician determined illness severity (CDIS), diagnostic methods, clinical diagnostic confidence (CDC), microbiological isolates and antibiotic use. For 476 episodes of pneumonia (48% CAP, 24% HAP, 28% VAP), CDC was greatest for CAP (64% CAP, 50% HAP and 49% VAP, P < 0.01) or when pneumonia was considered life-threatening (84% high CDC, 13% medium CDC and 3% low CDC, P < 0.001). Life-threatening pneumonia was predicted by worsening gas exchange (OR 4.8, CI 95% 2.3-10.2, P < 0.001), clinical signs of consolidation (OR 2.0, CI 95% 1.2-3.2, P < 0.01) and the Sepsis-Related Organ Failure Assessment (SOFA) Score (OR 1.1, CI 95% 1.1-1.2, P < 0.001). Diagnostic confidence increased with CDIS (OR 163, CI 95% 8.4-31.4, P < 0.001), definite pathogen isolation (OR 3.3, CI 95% 2.0-5.6) and clinical signs of consolidation (OR 2.1, CI 95% 1.3-3.3, P = 0.001). Although the CDIS, SOFA Score and the Simplified Acute Physiologic Score (SAPS II) were all associated with mortality, the SAPS II Score was the best predictor of mortality (P = 0.02). Diagnostic confidence for pneumonia is moderate but increases with more classical presentations. A small set of clinical parameters influence subjective assessment. Objective assessment using SAPS II Scoring is a better predictor of mortality.

Elevated inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-acquired pneumonia in children.

BACKGROUND: Our objective was to evaluate procalcitonin (PCT) and C-reactive protein (CRP) as predictors of a pneumococcal etiology in community-acquired pneumonia (CAP) in hospitalized children. METHODS: Children requiring hospitalization for CAP were prospectively enrolled. The following indices were determined: antibodies against pneumococcal surface proteins (anti-PLY, pneumococcal histidine triad D, pneumococcal histidine triad E, LytB and pneumococcal choline-binding protein A), viral serology, nasopharyngeal cultures and polymerase chain reaction for 13 respiratory viruses, blood pneumococcal polymerase chain reaction, pneumococcal urinary antigen, PCT and CRP. Presumed pneumococcal CAP (P-CAP) was defined as a positive blood culture or polymerase chain reaction for Streptococcus pneumoniae or as a pneumococcal surface protein seroresponse (≥2-fold increase). RESULTS: Seventy-five patients were included from which 37 (49%) met the criteria of P-CAP. Elevated PCT and CRP values were strongly associated with P-CAP with odds ratios of 23 (95% confidence interval: 5-117) for PCT and 19 (95% confidence interval: 5-75) for CRP in multivariate analysis. The sensitivity was 94.4% for PCT (cutoff: 1.5 ng/mL) and 91.9% for CRP (cutoff: 100 mg/L). A value≤0.5 ng/mL of PCT ruled out P-CAP in >90% of cases (negative likelihood ratio: 0.08). Conversely, a PCT value≥1.5 ng/mL associated with a positive pneumococcal urinary antigen had a diagnostic probability for P-CAP of almost 80% (positive likelihood ratio: 4.59). CONCLUSIONS: PCT and CRP are reliable predictors of P-CAP. Low cutoff values of PCT allow identification of children at low risk of P-CAP. The association of elevated PCT or CRP with a positive pneumococcal urinary antigen is a strong predictor of P-CAP.

Low C-reactive protein values at admission predict mortality in patients with severe community-acquired pneumonia caused by Streptococcus pneumoniae that require intensive care management.

PURPOSE: To identify risk factors associated with mortality in patients with severe community-acquired pneumonia (CAP) caused by S. pneumoniae who require intensive care unit (ICU) management, and to assess the prognostic values of these risk factors at the time of admission. METHODS: Retrospective analysis of all consecutive patients with CAP caused by S. pneumoniae who were admitted to the 32-bed medico-surgical ICU of a community and referral university hospital between 2002 and 2011. Univariate and multivariate analyses were performed on variables available at admission. RESULTS: Among the 77 adult patients with severe CAP caused by S. pneumoniae who required ICU management, 12 patients died (observed mortality rate 15.6 %). Univariate analysis indicated that septic shock and low C-reactive protein (CRP) values at admission were associated with an increased risk of death. In a multivariate model, after adjustment for age and gender, septic shock [odds ratio (OR), confidence interval 95 %; 4.96, 1.11-22.25; p = 0.036], and CRP (OR 0.99, 0.98-0.99 p = 0.034) remained significantly associated with death. Finally, we assessed the discriminative ability of CRP to predict mortality by computing its receiver operating characteristic curve. The CRP value cut-off for the best sensitivity and specificity was 169.5 mg/L to predict hospital mortality with an area under the curve of 0.72 (0.55-0.89). CONCLUSIONS: The mortality of patients with S. pneumoniae CAP requiring ICU management was much lower than predicted by severity scores. The presence of septic shock and a CRP value at admission <169.5 mg/L predicted a fatal outcome.

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

External Validation of the Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) Score for Predicting Stroke-Associated Pneumonia in the Athens Stroke Registry.

BACKGROUND AND PURPOSE: The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was developed recently for predicting stroke-associated pneumonia (SAP), one of the most common complications after stroke. The aim of the present study was to externally validate the ISAN score. METHODS: Data included in the Athens Stroke Registry between June 1992 and December 2011 were used for this analysis. Inclusion criteria were the availability of all ISAN score variables (prestroke independence, sex, age, National Institutes of Health Stroke Scale score). Receiver operating characteristic curves and linear regression analyses were used to determine the discriminatory power of the score and to assess the correlation between actual and predicted pneumonia in the study population. Separate analyses were performed for patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). RESULTS: The analysis included 3204 patients (AIS: 2732, ICH: 472). The ISAN score demonstrated excellent discrimination in patients with AIS (area under the curve [AUC]: .83 [95% confidence interval {CI}: .81-.85]). In the ICH group, the score was less effective (AUC: .69 [95% CI: .63-.74]). Higher-risk groups of ISAN score were associated with an increased relative risk of SAP; risk increase was more prominent in the AIS population. Predicted pneumonia correlated very well with actual pneumonia (AIS group: R(2) = .885; β-coefficient = .941, P < .001; ICH group: R(2) = .880, β-coefficient = .938, P < .001). CONCLUSIONS: In our external validation in the Athens Stroke Registry cohort, the ISAN score predicted SAP very accurately in AIS patients and demonstrated good discriminatory power in the ICH group. Further validation and assessment of clinical usefulness would strengthen the score's utility further.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was >= 2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT >= 2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

Risk factors for Hospital-Acquired Pneumonia in nonventilated adults

Although most recent publications focus on Ventilator-associated Pneumonia, Non-Ventilator-associated Hospital-acquired pneumonia (NVHAP) is still worrisome. We studied risk factors for NVHAP among patients admitted to a small teaching hospital. Sixty-six NVHAP case patients and 66 controls admitted to the hospital from November 2005 through November 2006 were enrolled in a case-control study. Variables under investigation included: demographic characteristics, comorbidities, procedures, invasive devices and use of medications (Sedatives, Antacids, Steroids and Antimicrobials). Univariate and multivariable analysis (hierarchical models of logistic regression) were performed. The incidence of NVHAP in our hospital was 0.68% (1.02 per 1,000 patients-day). Results from multivariable analysis identified risk factors for NVHAP: age (Odds Ratio[OR]=1.03, 95% Confidence Interval[CI]=1.01-1.05, p=0.002), use of Antacids (OR=5.29, 95%CI=1.89-4.79, p=0.001) and Central Nervous System disease (OR=3.13, 95%CI=1.24-7.93, p=0.02). Although our findings are coherent with previous reports, the association of Antacids with NVHAP recalls a controversial issue in the physiopathology of Hospital-Acquired Pneumonia, with possible implications for preventive strategies.

Fatores de risco para pneumonia associada a ventilação mecânica: estudo de caso controle

A pneumonia associada a ventilação mecânica é a infecção hospitalar mais comum em pacientes de unidade de terapia intensiva. Estratégias de prevenção podem ser mais bem elaboradas com o conhecimento dos fatores de risco para esta infecção. Com o objetivo principal de identificar fatores associados com maior risco de desenvolvimento de pneumonia em pacientes que recebem ventilação mecânica, foi realizado estudo retrospectivo, caso controle, não pareado, em uma unidade de terapia intensiva, clínico-cirúrgica, de um hospital universitário na cidade de Belém do Pará, Brasil. O período de estudo foi de 19 meses (janeiro de 2003 a julho de 2004). Os critérios de definição foram adaptados a partir dos critérios dos Centers for Diseases Control and Prevention. Foram avaliadas características demográficas, procedimentos invasivos, morbidades associadas e variáveis dependentes de tempo (ventilação mecânica, nutrição, exposição a drogas), entre outros fatores, em 27 casos e 27 controles. A pneumonia associada à ventilação mecânica teve uma taxa bruta e incidência por 1000 ventiladores/dia de 10,6% e 12,3 episódios, respectivamente. O tempo médio de permanência na unidade de terapia intensiva dos pacientes foi de 34,2 ± 27,7 dias, enquanto dos controles foi de 15,4 ± 13,6 dias (p=0,003). O tempo médio para início da pneumonia foi de 14,29 ± 9,16 dias. A taxa global de mortalidade foi similar nos dois grupos (OR=1,60; p=0,576). A análise univariada demonstrou que medicamentos administrados em aerossóis (OR=4,75; p=0,01) e uso de curares (OR=8,61; p=0,003) estiveram associados a um maior risco de desenvolvimento da infecção. Conclui-se que a pneumonia associada a ventilação mecânica esteve associada ao uso de curares e aerossóis, sendo que medidas preventivas poderiam ser direcionadas a estes fatores por serem eles, potencialmente modificáveis.

Association between systemic corticosteroids and outcomes of intensive care unit-acquired pneumonia

Objective: The use of corticosteroids is frequent in critically-ill patients. However, little information is available on their effects in patients with intensive care unit acquired pneumonia. We assessed patients' characteristics, microbial etiology, inflammatory response, and outcomes of previous corticosteroid use in patients with intensive care unit acquired pneumonia. Design: Prospective observational study. Setting: Intensive care units of a university teaching hospital. Patients: Three hundred sixteen patients with intensive care unit acquired pneumonia. Patients were divided according to previous systemic steroid use at onset of pneumonia. Interventions: None. Measurements and Main Results: Survival at 28 days was analyzed using Cox regression, with adjustment for the propensity for receiving steroid therapy. One hundred twenty-five (40%) patients were receiving steroids at onset of pneumonia. Despite similar baseline clinical severity, steroid treatment was associated with decreased 28-day survival (adjusted hazard ratio for propensity score and mortality predictors 2.503; 95% confidence interval 1.176-5.330; p = .017) and decreased systemic inflammatory response. In post hoc analyses, steroid treatment had an impact on survival in patients with nonventilator intensive care unit acquired pneumonia, those with lower baseline severity and organ dysfunction, and those without etiologic diagnosis or bacteremia. The cumulative dosage of corticosteroids had no significant effect on the risk of death, but bacterial burden upon diagnosis was higher in patients receiving steroid therapy. Conclusions: In critically-ill patients, systemic corticosteroids should be used very cautiously because this treatment is strongly associated with increased risk of death in patients with intensive care unit acquired pneumonia, particularly in the absence of established indications and in patients with lower baseline severity. Decreased inflammatory response may result in delayed clinical suspicion of intensive care unit acquired pneumonia and higher bacterial count. (Crit Care Med 2012; 40:2552-2561)

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection

BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality. OBJECTIVES: To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air). SEARCH STRATEGY: We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles. SELECTION CRITERIA: Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days. DATA COLLECTION AND ANALYSIS: Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model. MAIN RESULTS: Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids. AUTHORS' CONCLUSIONS: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials

BACKGROUND: The objective of this study was to review the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with Pneumocystis jiroveci pneumonia (PCP) and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air). METHODS: We conducted a systematic search of the literature for randomised trials published up to December 2004. Selected trials compared adjunctive corticosteroids with placebo or usual care in HIV-infected patients with PCP and reported mortality data. Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. RESULTS: Six studies were included in the meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.54 (95% confidence interval [CI], 0.38-0.79) at 1 month and 0.67 (95% CI, 0.49-0.93) at 3-4 months of follow-up. Numbers needed to treat, to prevent 1 death, are 9 patients in a setting without highly active antiretroviral therapy (HAART) available and 22 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.37 (95% CI, 0.20-0.70) in favour of adjunctive corticosteroids. CONCLUSION: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but our results suggest a beneficial effect for patients with substantial hypoxemia.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection.

BACKGROUND Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients. OBJECTIVES To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air). SEARCH METHODS For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS. SELECTION CRITERIA Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days. DATA COLLECTION AND ANALYSIS Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality. MAIN RESULTS Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence). AUTHORS' CONCLUSIONS The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.