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.
CONCLUSIONS
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.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Mayo Clinic ProceedingsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
REFERENCES
- Cotrimoxazole prophylaxis for opportunistic infections in adults with HIV.Cochrane Database Syst Rev. 2003; (CD003108)
- Pneumocystis pneumonia.N Engl J Med. 2004; 350: 2487-2498
- Pneumocystis species.in: Mandell GL Bennett JE Dolin R Principles and Practice of Infectious Diseases. 6th ed. Churchill Livingstone, Philadelphia, PA2005: 3080-3094
- An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital.Br J Cancer. 2005; 92: 867-872
- Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy.Mayo Clin Proc. 1996; 71: 5-13
- Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome.Clin Infect Dis. 2002 Apr 15; 34 (Epub 2002 Mar 21.): 1098-1107
- Prevention of infectious complications in rheumatic disease patients: immunization, Pneumocystis carinii prophylaxis, and screening for latent infections.Curr Opin Rheumatol. 1999; 11: 173-178
- Infections in solid-organ transplant recipients.Clin Microbiol Rev. 1997; 10: 86-124
- Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients.Clin Microbiol Rev. 2004; 17: 770-782
- Infections and anti-tumor necrosis factor alpha therapy.Arthritis Rheum. 2003; 48: 3013-3022
- Safety update on TNF-alfa antagonists: infliximab and etanercept.(Accessed July 18, 2007.)
- Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.MMWR Recomm Rep. 2004; 53: 1-112
- A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection.N Engl J Med. 1995; 332: 693-699
- Meta-analysis of prophylactic treatments against Pneumocystis carinii pneumonia and toxoplasma encephalitis in HIV-infected patients.J Acquir Immune Defic Syndr Hum Retrovirol. 1997; 15: 104-114
- Higgins JPT Green S Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]. John Wiley & Sons, Chichester, UK2005 (The Cochrane Library, Issue 3, 2005.)
- Infection prophylaxis in neutropenic patients with acute leukaemia—a randomized, comparative study with ofloxacin, ciprofloxacin and co-trimoxazole/colistin.J Antimicrob Chemother. November 1990; 26: 137-142
- A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation.Bone Marrow Transplant. 1999; 24: 897-902
- A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis.Am J Med. 1990; 89: 255-274
- Use of trimethoprim-sulfamethoxazole to prevent bacterial infections in children with acute lymphoblastic leukemia.Pediatr Infect Dis. 1985; 4: 265-269
- Trimethoprim-sulfamethoxazole compared with ciprofloxacin for the prevention of urinary tract infection in renal transplant recipients: a double-blind, randomized controlled trial.Online J Curr Clin Trials. 1992; (Doc No. 15)
- Successful chemoprophylaxis for Pneumocystis carinii pneumonitis.N Engl J Med. 1977; 297: 1419-1426
- Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis.N Engl J Med. 1987; 316: 1627-1632
- Ofloxacin versus co-trimoxazole for prevention of infection in neutropenic patients following cytotoxic chemotherapy.Antimicrob Agents Chemother. 1990; 34: 215-218
- Prevention of Pneumocystis carinii pneumonia in cardiac transplant recipients by trimethoprim sulfamethoxazole.Transplantation. 1993; 56: 359-362
- Prospective randomized comparison of two prophylactic regimens with trimethoprim-sulfamethoxazole in leukemic children: a two year study.Eur J Cancer Clin Oncol. 1987; 23: 1679-1682
- Randomized trial of weekly sulfadoxine/pyrimethamine vs. daily low-dose trimethoprim-sulfamethoxazole for the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation.Clin Infect Dis. 1999; 29: 771-774
- Effect of trimethoprim/sulfamethoxazole prophylaxis on outcome of childhood lymphocytic leukemia: a Pediatric Oncology Group Study.Cancer. 1987; 59: 19-23
- Pneumocystis carinii infection in heart transplant recipients: efficacy of a weekend prophylaxis schedule.Medicine (Baltimore). 1997; 76: 415-422
- Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience.Rev Infect Dis. 1982; 4: 1119-1132
- Intensity of immunosuppressive therapy and the incidence of Pneumocystis carinii pneumonitis.Cancer. 1975; 36: 2004-2009
- Wegener granulomatosis: an analysis of 158 patients.Ann Intern Med. 1992; 116: 488-498
- Autoimmune inflammatory disorders, systemic corticosteroids and pneumocystis pneumonia: a strategy for prevention.BMC Infect Dis. 2004; 4 (doi 10.1186/1471-2334-4-42.): 42
- A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity.Pharmacotherapy. 1995; 15: 428-432
- Hospitalization for serious blood and skin disorders following co-trimoxazole.Br J Clin Pharmacol. 1997; 43: 649-651
- Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients.Ann Intern Med. 2005; 142: 979-995
- Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS.JAMA. 1988; 259: 1185-1189
- A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens.Arch Intern Med. 1996; 156: 177-188
- Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised states.Chest. 2000; 118: 704-711
- Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients [published correction appears in MMWR Recomm Rep. 2004;53(19):396].MMWR Recomm Rep. 2000; 49 (CE1-7.): 1-125
- Prediction of and prophylaxis against Pneumocystis pneumonia in patients with connective tissue diseases undergoing medium- or high-dose corticosteroid therapy.Mod Rheumatol. 2005; 15: 91-96
- Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients.Cochrane Database Syst Rev. 2007; (CD005590. doi: 10.1002/14651858.CD005590.pub2.)
Article Info
Footnotes
This article is based on a Cochrane Review published in The Cochrane Library 2007 (see end of article for more details).
Identification
Copyright
© 2007 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.