-
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 -
The Cochrane Database of Systematic... Jan 2006The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic... (Review)
Review
BACKGROUND
The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic infections are the mainstay of their medical management. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis jiroveci 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. 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 Feb 2005). 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 15 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. Where data were incomplete or unclear trial authors were contacted for further details.
MAIN RESULTS
One study was identified that fulfilled the inclusion criteria. It studied 534 children with HIV infection in Lusaka, Zambia. The study was conducted in an area of high bacterial resistance to cotrimoxazole (60-80%). A reduction in mortality of 33% was seen in the cotrimoxazole group as compared to placebo, relative risk 0.67 (95% CI 0.53 - 0.85). There was also a beneficial effect on hospitalisation, relative risk 0.77 (95% CI 0.62 - 0.96). There was no difference in adverse events between groups, and the beneficial effect was seen across all ages and CD4%.
AUTHORS' CONCLUSIONS
A single trial has shown a beneficial effect from the use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be decided whether this can be extrapolated to other resource-poor settings.
Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Humans; Infant; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 16437457
DOI: 10.1002/14651858.CD003508.pub2 -
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 -
The European Respiratory Journal Oct 2002Sputum induction is a simple and noninvasive procedure for Pneumocystis carinii pneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although... (Comparative Study)
Comparative Study Meta-Analysis Review
Sputum induction is a simple and noninvasive procedure for Pneumocystis carinii pneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although less sensitive than bronchoalveolar lavage (BAL). In order to obtain an overview of the diagnostic accuracy of sputum induction, a systematic review and meta-analysis of studies reporting the comparative sensitivity and specificity of BAL (the "gold standard") and sputum induction was performed. The odds ratio and related 95% confidence interval were calculated using summary receiving operating characteristic curves as well as fixed-effect and random-effect models. Based on pooled data, the negative and positive predictive values were calculated for a range of PCP prevalence using a Bayesian approach. Seven prospective studies assessed the comparative accuracy of BAL and sputum induction. On the whole, sputum induction demonstrated 55.5% sensitivity and 98.6% specificity. The sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%). In settings of 25-60% prevalence of PCP, the positive and negative predictive values ranged 86-96.7 and 66.2-89.8, respectively, with immunofluorescence, and 79-94.4 and 53-83.5% with cytochemical staining. In conclusion, in a setting of low prevalence of Pneumocystis carinii pneumonia, sputum induction, particularly with immunostaining, appears to be adequate for clinical decision-making.
Topics: AIDS-Related Opportunistic Infections; Adolescent; Adult; Bronchoalveolar Lavage Fluid; Confidence Intervals; Female; Humans; Male; Middle Aged; Odds Ratio; Pneumonia, Pneumocystis; ROC Curve; Sensitivity and Specificity; Sputum
PubMed: 12412693
DOI: 10.1183/09031936.02.01372002 -
Minerva Anestesiologica Apr 2002Corticosteroids were proposed to treat patients with severe sepsis as early as 1940. A summary of all available randomized controlled trials performed between 1966 and... (Review)
Review
Corticosteroids were proposed to treat patients with severe sepsis as early as 1940. A summary of all available randomized controlled trials performed between 1966 and 1993 was provided in two systematic review that recommended to abandon the use of high dose coricosteroids to treat patients with severe infection. Nonetheless, a doubt still persist regarding the efficacy of a strategy of replacement therapy in cathecolamines-dependent shock. This strategy relies mainly on the concept that septic shock may be complicated by 1) an occult adrenal insufficiency, 2) a glucocorticoid peripheral resistance syndrome. Some studies demonstrated the effect of replacement therapy with hydrocortisone on the sistemic inflammatory response and on the cardiovascular function during sepsis. The effect of this therapy on survival to septic shock is controversial both in recent and old studies. Finally a recently completed multicenter, placebo controlled, randomized, double-blind study has evaluated the efficacy and tolerance of a replacement therapy with a combination of hydrocortisone (50 mg intravenous bolus four times per day) and fludrocortisone (50 g orally once a day) given for 7 days. This study included 300 catecholamines- and ventilator-dependent septic shock. The authors found a significant reduction in 28-day mortality in patient with occult renal insufficiency. In sum, short course with high doses of corticosteroids should not be given in severe sepsis, except for specific entitles like severe typhoid fever, pneumocystis carinii pneumonia in AIDS or bacterial meningitis in children. The rational for a replacement therapy with hydrocortisone in catecholamines-dependent septic shock grows stronger.
Topics: Adrenal Cortex; Adrenal Cortex Hormones; Hormone Replacement Therapy; Humans; Resuscitation; Sepsis
PubMed: 12024069
DOI: No ID Found