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PloS One 2011HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with antiretroviral therapy may allow for discontinuation of PCP prophylaxis even with CD4 count <200 cells/µL.
METHODS
A systematic review was performed to determine the incidence of PCP in HIV-infected individuals with CD4 count <200 cells/µL and fully suppressed VL on antiretroviral therapy but not receiving PCP prophylaxis.
RESULTS
Four articles examined individuals who discontinued PCP prophylaxis with CD4 count <200 cells/µL in the context of fully suppressed VL on antiretroviral therapy. The overall incidence of PCP was 0.48 cases per 100 person-years (PY) (95% confidence interval (CI) (0.06-0.89). This was lower than the incidence of PCP in untreated HIV infection (5.30 cases/100 PY, 95% CI 4.1-6.8) and lower than the incidence in persons with CD4 count <200 cells/µL, before the availability of highly active antiretroviral therapy (HAART), who continued prophylaxis (4.85/100 PY, 95% CI 0.92-8.78). In one study in which individuals were stratified according to CD4 count <200 cells/µL, there was a greater risk of PCP with CD4 count ≤100 cells/µL compared to 101-200 cells/µL.
CONCLUSION
Primary PCP prophylaxis may be safely discontinued in HIV-infected individuals with CD4 count between 101-200 cells/µL provided the VL is fully suppressed on antiretroviral therapy. However, there are inadequate data available to make this recommendation when the CD4 count is ≤100 cells/µL. A revision of guidelines on primary PCP prophylaxis to include consideration of the VL is merited.
Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; HIV Infections; Humans; Incidence; Pneumocystis carinii; Pneumonia, Pneumocystis; Viral Load
PubMed: 22194853
DOI: 10.1371/journal.pone.0028570 -
The Pediatric Infectious Disease Journal Oct 2011Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected children. (Review)
Review
BACKGROUND
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected children.
OBJECTIVES AND METHODS
A systematic review of studies that were published between January 1990 and February 2009 on the etiology and antimicrobial or adjunctive systemic management of CAP in HIV-infected children.
RESULTS
Pneumocystis jirovecii had the strongest association with HIV infection, with a summary odds ratio of 10.1 (95% confidence interval [CI], 17.7-62.1) and 9.1 (95% CI, 2.5-33.1) in antemortem and postmortem studies, respectively. Cytomegalovirus was strongly associated with HIV positivity among fatal cases of pneumonia (summary odds ratio = 14.4 [95% CI, 6.7-30.8]). There was a trend toward a greater prevalence of Staphylococcus aureus (odds ratio, 2.5; 95% CI, 0.95-6.4) in HIV-infected children. Major limitations identified included substantial methodological heterogeneity across studies, limited sensitivity of assays for diagnosing bacterial pneumonia, and studies primarily being undertaken in the absence of antiretroviral treatment or cotrimoxazole prophylaxis. No a priori-planned randomized controlled trials on antimicrobial management of CAP in HIV-infected children were identified.
CONCLUSIONS
A World Health Organization panel used this review as well as analysis of risks and benefits to revise recommendations for antimicrobial treatment of CAP. Ampicillin plus gentamicin or ceftriaxone is now recommended as first-line empiric regimens for treating severe and very severe CAP in HIV-infected children. In addition, treatment with cloxacillin or vancomycin is recommended in settings with a high incidence of methicillin-resistant S. aureus, and particularly if clinical or microbiological evidence of S. aureus pneumonia exist. Further studies in HIV-infected children on CAP etiology and antibiotic treatment are required in the era of antiretroviral treatment.
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Community-Acquired Infections; Cytomegalovirus; HIV Infections; Humans; Infant; Infant, Newborn; Pneumocystis carinii; Pneumonia; Prevalence; Staphylococcus aureus
PubMed: 21857264
DOI: 10.1097/INF.0b013e31822d989c -
Revista Iberoamericana de Micologia Mar 2009Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Although several new antifungal agents have been... (Review)
Review
BACKGROUND
Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Although several new antifungal agents have been developed in the past few years, the management of serious fungal infections continues to be problematic.
AIMS
To review the pharmacodynamics and pharmacokinetics of a new antifungal agent: micafungin.
METHODS
A systematic review of biomedic databases (EBSCO Open Journals, Ovid Online, Proquest Medical Library, PubMed/Medline, Science Direct, Springer Links and Wiley Interscience) has been performed. Search was conducted from 2000 to 2008. Supplementary sources included abstracts from the Interscience Conference on Antimicrobial Agents (ICAAC) and Chemotherapy and the Infectious Diseases Society of America (IDSA) from 1998 to 2008.
RESULTS
Micafungin has a potent mechanism of action: inhibits beta-1,3-D-glucan synthase interfering with fungal cell wall synthesis. This agent shares with caspofungin an identical spectrum of in vitro activity against Candida albicans, non-albicans Candida species, and Aspergillus. Due to the limited oral availability, micafungin is available for parenteral administration only. Micafungin is characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. Micafungin is a poor substrate for the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions have been described. No dose reduction is required in renal impairment or in mild to moderate liver failure.
CONCLUSIONS
The pharmacodynamic and pharmacokinetic profiles of micafungin imply that this drug is a safe alternative for the treatment of fungal infections. Micafungin can be safely co-administered with most drugs without the need for dosage adaptation even in patients with renal o liver function impairment.
Topics: Adolescent; Adult; Aged; Animals; Antifungal Agents; Aspergillus; Biotransformation; Candida; Child; Child, Preschool; Drug Evaluation, Preclinical; Drug Interactions; Echinocandins; Fungal Proteins; Glucosyltransferases; Humans; Infant, Newborn; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Middle Aged; Molecular Structure; Mycoses; Pneumocystis carinii; Young Adult
PubMed: 19463274
DOI: 10.1016/S1130-1406(09)70005-1 -
Transplantation Proceedings May 2009The aim of this study was to clarify the potential advantages of a low-dose regimen of trimethoprim-sulfamethoxazole prophylaxis to prevent Pneumocystis jirovecii... (Comparative Study)
Comparative Study Review
A systematic review of two different trimetoprim-sulfamethoxazole regimens used to prevent Pneumocystis jirovecii and no prophylaxis at all in transplant recipients: appraising the evidence.
BACKGROUND
The aim of this study was to clarify the potential advantages of a low-dose regimen of trimethoprim-sulfamethoxazole prophylaxis to prevent Pneumocystis jirovecii pneumonia (PJP) in transplant recipients (80/400 mg/d every day or 160/800 mg/d every other day) with those obtained from the full-dose prophylaxis (160/800 mg/d every day) or no prophylaxis.
METHODS
Prospectively randomized and retrospectively case controlled studies were selected.
RESULTS
Four studies matched the inclusion criteria-2 randomized and 2 case controls-for a total of 570 patients. The pneumonia incidence was 0% after full-dose prophylaxis (0/181), 1% after the low-dose regimen (1/105), and 11% with no prophylaxis (31/284). Pneumonia occurrences were significant lower between the full-dose prophylaxis versus the no prophylaxis group (0% vs 11%; P < .001), and between the low-dose and no prophylaxis groups (1% vs 11%; P < .001). There was no difference between patients receiving the full-dose prophylaxis versus the low-dose regimen (0% vs 1%; P = NS).
CONCLUSIONS
The low-dose gives similar results as the full-dose regimen for the prevention of PJP and seems a feasible, safe option for transplanted patients.
Topics: Anti-Infective Agents; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 19460516
DOI: 10.1016/j.transproceed.2009.03.004 -
Journal of Acquired Immune Deficiency... May 2008Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). (Review)
Review
BACKGROUND
Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP).
METHODS
We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs).
RESULTS
Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82 individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3.2] and 2.7 [95% CI: 1.3 to 4.0], respectively) but were considerably lower for intravenous pentamidine (44%; OR = 0.8 [95% CI: 0.6 to 1.0]).
CONCLUSIONS
Clindamycin-primaquine is an alternative to intravenous pentamidine as second-line treatment for PCP in patients who fail treatment with TMP-SMX. TMP-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX.
Topics: AIDS-Related Opportunistic Infections; Clindamycin; Cohort Studies; Humans; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Primaquine; Salvage Therapy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 18360286
DOI: 10.1097/QAI.0b013e31816de84d -
Mayo Clinic Proceedings Sep 2007To assess the efficacy of prophylaxis for Pneumocystis pneumonia (PCP), caused by Pneumocystis jirovecii (formerly Pneumocystis carinii), for immunocompromised... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy of prophylaxis for Pneumocystis pneumonia (PCP), caused by Pneumocystis jirovecii (formerly Pneumocystis carinii), for immunocompromised non-HIV-infected patients by conducting a systematic review and meta-analysis.
METHODS
We searched for randomized controlled trials that compared prophylaxis using antibiotics effective against P jirovecii, given orally or intravenously, vs placebo, no intervention, or antibiotics with no activity against P jirovecii. In addition, we included trials that compared different PCP prophylactic regimens or administration schedules. The search included the Cochrane Central Register of Controlled Trials, PubMed, Latin American and Caribbean Health Sciences Literature, and conference proceedings. No language, year, or publication restrictions were applied. Two reviewers (H.G. and M.P.) independently searched, selected trials, extracted data, and performed methodological quality assessment. Relative risks (RRs) with 95% confidence intervals (CIs) are reported. Meta-analysis was performed using the random-effects model.
RESULTS
Twelve randomized trials were identified, including 1245 patients (50% children) who had undergone autologous bone marrow or solid organ transplant or who had hematologic cancer. When trimethoprim-sulfamethoxazole was administered, a 91% reduction was observed in the occurrence of PCP (RR, 0.09; 95% CI, 0.02-0.32); the number needed to treat was 15 (95% CI, 13-20) patients, with no heterogeneity. Pneumocystis pneumonia-related mortality was significantly reduced (RR, 0.17; 95% CI, 0.03-0.94), whereas all-cause mortality did not differ significantly (RR, 0.79; 95% CI, 0.18-3.46). Adverse events that required discontinuation occurred in 3.1% of adults and none of the children, and all were reversible. No differences between once-daily and thrice-weekly administration schedules were found.
CONCLUSION
Balanced against severe adverse events, PCP prophylaxis is warranted when the risk for PCP is higher than 3.5% for adults. Adverse events are less frequent in children, for whom prophylaxis might be warranted at lower PCP incidence rates.
Topics: Anti-Infective Agents; Antibiotic Prophylaxis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 17803871
DOI: 10.4065/82.9.1052 -
Clinical Rheumatology May 2007Patients suffering from connective tissue diseases (CTDs) constitute an important subgroup of immunosuppressed patients at risk for developing serious infections.... (Review)
Review
Patients suffering from connective tissue diseases (CTDs) constitute an important subgroup of immunosuppressed patients at risk for developing serious infections. Prophylactic antibiotic administration may decrease infection-related morbidity and mortality burden in patients with CTD, though one needs first to evaluate the overall effect of infection on morbidity and mortality in such patients and the presence of adequate prognostic/risk factors for infection development. Studies focusing on infection-related morbidity and mortality in patients with CTD were reviewed. Data on disease type, therapeutic regimens used, including corticosteroid dose and method of administration as well as other immunosuppressive agents, and outcome were extracted to evaluate the existence of specific treatment patterns predisposing to infection as well as infectious disease-related morbidity and mortality in patients with CTD. Thirty-nine studies focusing on infection incidence and/or outcome in patients with CTD were identified and analyzed; the majority of the reviewed studies (20) included patients with systemic lupus erythematosus (SLE). The mortality attributed to infection was 5.2%, while the overall mortality was 20%. There were no adequate data on the specific effect patterns of corticosteroid and immunosuppressant treatment on infection risk. Pneumocystis jiroveci (carinii) pneumonia, evaluated independently, exhibited significant mortality in patients with Wegener's granulomatosis, polymyositis/dermatomyositis, and SLE. In conclusion, infectious diseases are a major cause of mortality in patients with CTD. However, treatment-related factors predisposing to serious infections have not been adequately outlined. In addition, there are no data regarding the effect of prophylactic practices involving antibiotic administration in morbidity and mortality.
Topics: Connective Tissue Diseases; Humans; Immunocompromised Host; Infection Control; Infections; Risk Factors
PubMed: 17186117
DOI: 10.1007/s10067-006-0441-9 -
The Cochrane Database of Systematic... Jul 2006Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Chemotherapy, Adjuvant; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 16856118
DOI: 10.1002/14651858.CD006150 -
Emerging Infectious Diseases Oct 2004A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and... (Review)
Review
A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are too heterogeneous (p < 0.001) to warrant a single summary effect estimate. Estimated effects are weaker after 1996 and stronger in studies that included multiple isolates per patient. Five studies examined treatment outcome. The effect of DHPS mutations on treatment outcome has not been well studied, and the few studies that have been conducted are inconsistent even as to the presence or absence of an association.
Topics: Anti-Infective Agents; Dihydropteroate Synthase; Drug Resistance, Fungal; Humans; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Sulfonamides
PubMed: 15504261
DOI: 10.3201/eid1010.040362 -
The Cochrane Database of Systematic... 2003The prevention and early treatment of infections are the mainstay of the medical management of the majority of children with HIV infection, who live in low income... (Review)
Review
BACKGROUND
The prevention and early treatment of infections are the mainstay of the medical management of the majority of children with HIV infection, who live in low income countries without access to antiretroviral drugs. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis carinii pneumonia (PCP) which is an important cause of death and illness in the first year of life. It is safe with relatively few side-effects. Diagnosis of HIV in children is complicated by the presence of maternal antibodies in early life and providing prophylaxis based initially on maternal status is one possible solution. However routine prophylactic treatment is difficult to deliver in low-resource settings, and could also lead to increased resistance to the drug.
OBJECTIVES
To assess the effects of routinely administered cotrimoxazole on death and illness episodes in children with HIV infection, and in infants of HIV infected mothers.
SEARCH STRATEGY
We searched the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB conferences (search date July 2001). We checked reference lists of pertinent articles, and contacted pharmaceutical companies and experts in the field.
SELECTION CRITERIA
Randomised or quasi randomised trials comparing routinely administered cotrimoxazole versus placebo or no treatment in children (age less than 13 years) with HIV infection, or children less than 18 months with HIV infected mothers.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial eligibility and quality.
MAIN RESULTS
No studies were found that fulfilled the selection criteria.
REVIEWER'S CONCLUSIONS
No evidence from controlled trials was found of the effect of cotrimoxazole prophylaxis in HIV-infected children.
Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Humans; Infant; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 12804472
DOI: 10.1002/14651858.CD003508