Dataset Information

Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids-clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole.

ABSTRACT:

Objectives

To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis.

Methods

This study included 28,292 treatment episodes with prolonged (??4?weeks), non-high-dose steroids (low dose [?0.1/100 person-years. Cox regression with LASSO was used for analysis.

Results

One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001-0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2-1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n?=?173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1-8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR?=?0.2 (0.001-2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3-71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17-226)) was lower than the number needed to harm by serious ADR (45 (15-?)).

Conclusion

Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.

SUBMITTER: Park JW

PROVIDER: S-EPMC6744623 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids-clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole.

Park Jun Won JW Curtis Jeffrey R JR Kim Min Jung MJ Lee Hajeong H Song Yeong Wook YW Lee Eun Bong EB

Arthritis research & therapy 20190914 1

<h4>Objectives</h4>To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis.<h4>Methods</h4>This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and p ...[more]

PMID: 31521185

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Project description:The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.

Project description:ObjectivesTo characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.DesignPopulation based nested case-control study.SettingOntario, Canada, from 1 April 1992 to 1 March 2010.ParticipantsCases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date.Main outcome measuresOdds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia.ResultsDuring the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4)ConclusionsAmong older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.

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Project description:BackgroundAntimicrobial prophylaxis is indicated to prevent Pneumocystis jirovecii pneumonia (PJP) in profoundly immunosuppressed children. The incidence of PJP infection in children with chronic glucocorticoid exposure is unknown, and PJP prophylaxis has been associated with adverse events. We hypothesized that PJP infection is rare in children without human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), cancer, or a transplant history who are using chronic glucocorticoids and that those exposed to PJP prophylaxis are more likely to experience a cutaneous hypersensitivity reaction or myelosuppression than unexposed patients.MethodsThis study involved a retrospective cohort from the Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). We identified patients ?18 years of age who received at least 2 prescriptions for a systemic glucocorticoid within a 60-day period and excluded patients with a history of PJP infection, an oncologic diagnosis, transplant, or HIV/AIDS. PJP prophylaxis exposure was identified by using national drug codes. Cutaneous hypersensitivity reaction or myelosuppression was identified by using International Classification of Diseases, 9th Revision (ICD-9), codes. We used a discrete time-failure model to examine the association between exposure and outcome.ResultsWe identified 119399 children on glucocorticoids, 10% of whom received PJP prophylaxis. The incidences of PJP were 0.61 and 0.53 per 10000 patient-years in children exposed and those unexposed to PJP prophylaxis, respectively. In a multivariable model, trimethoprim-sulfamethoxazole was associated with cutaneous hypersensitivity reaction (odds ratio, 3.20; 95% confidence interval, 2.62-3.92) and myelosuppression (odds ratio, 1.85; 95% confidence interval, 1.56-2.20).ConclusionsPJP infection was rare in children using glucocorticoids chronically, and PJP prophylaxis-associated cutaneous hypersensitivity reactions and myelosuppression are more common. The use of PJP chemoprophylaxis in children without HIV/AIDS, cancer, or a transplant history who are taking glucocorticoids chronically should be considered carefully.

Project description:BACKGROUND:Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality. OBJECTIVES:To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis. SEARCH METHODS:Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials. SELECTION CRITERIA:Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model. MAIN RESULTS:Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP-related mortality was also significantly reduced, RR of 0.17 (95% CI 0.03 to 0.94; nine trials, 886 patients) (low quality of evidence due to possible risk of bias and imprecision), but in trials comparing PCP prophylaxis against placebo or no treatment there was no significant effect on all-cause mortality (low quality of evidence due to imprecision). Occurrence of leukopenia or neutropenia and their duration were not reported consistently. No significant differences in overall adverse events or events requiring discontinuation were seen comparing trimethoprim/sulfamethoxazole to no treatment or placebo (four trials, 470 patients, moderate quality evidence). No differences between once daily versus thrice weekly trimethoprim/sulfamethoxazole were seen (two trials, 207 patients). AUTHORS' CONCLUSIONS:Given an event rate of 6.2% in the control groups of the included trials, prophylaxis for PCP using trimethoprim/sulfamethoxazole is highly effective among non-HIV immunocompromised patients, with a number needed to treat to prevent PCP of 19 patients (95% CI 17 to 42). Prophylaxis should be considered for patients with a similar baseline risk of PCP.

Project description:Objectives: Pneumocystis jirovecii pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200 cells/?L. In other immunocompromised patients, the value of PCP prophylaxis is not always as well-established. This study aimed to describe the epidemiology of PCP in recent years and assess how many patients with PCP did or did not receive prophylaxis in the month preceding the infection. Material and Methods: A multicenter retrospective study was performed in 3 tertiary care hospital. A list of patients that underwent broncho-alveolar lavage sampling and Pneumocystis jirovecii (PJ) PCR testing was retrieved from the microbiology laboratories. An in-house PJ quantitative PCR (qPCR) was used in each center. A cycle threshold (Ct) value of ? 28.5-30 was considered a probable PCP. For patients with a positive PJ qPCR but above this threshold, a predefined case definition of possible PCP was defined as a qPCR Ct value ? 34-35 and both of the following criteria: 1. Clinical and radiological features compatible with PCP and 2. The patient died or received PCP therapy and survived. Patient files from those with a qPCR Ct value ? 35 were reviewed to determine whether the patient fulfilled the case definition and if PCP prophylaxis had been used in the weeks preceding the PCP. Disease-specific guidelines, as well as hospital-wide guidelines, were used to evaluate if prophylaxis could be considered indicated. Results: From 2012 to 2018, 482 BAL samples were tested. Two hundred and four had a qPCR Ct value ? 35 and were further evaluated: 90 fulfilled the definition of probable and 63 of possible PCP while the remaining 51 were considered colonized. Seventy-four percentages of the patients with PCP were HIV-negative. Only 11 (7%) of the 153 patients had received prophylaxis, despite that in 133 (87%) cases prophylaxis was indicated according to guidelines. Conclusion: In regions where HIV testing and treatment is available without restrictions, PCP is mainly diagnosed in non-HIV immunocompromised patients. More than four out of five patients with PCP had not received prophylaxis. Strategies to improve awareness of antimicrobial prophylaxis guidelines in immunocompromised patients are urgently needed.

Dataset Information

Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids-clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole.

Objectives

Methods

Results

Conclusion

Publications

Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids-clinical implication of primary prophylaxis using trimethoprim-sulfamethoxazole.

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