Pneumocystis Carinii Pneumonia Prophylaxis Research Articles

Pneumocystis Jirovecii: Quality Improvement of Prophylaxis in Hematopoietic Stem Cell Transplant Patients

Introduction Pneumocystis jirovecii is an uncommon life threatening infection with a predilection towards immune compromised individuals. The National Comprehensive Cancer Network guidelines recommend anti-Pneumocystis prophylaxis in all hematopoietic stem cell transplant (HCT) patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is a category 1 recommendation due to its significant reduction in Pneumocystis pneumonia (PCP) occurrence and related mortality, as well as its activity against other infectious agents, such as Nocardia. Objectives A retrospective chart review was performed to assess if our medical center's practice aligned with the standard guidelines for PCP prophylaxis in HCT patients. We aimed to identify factors contributing to deviation from guidelines as potential targets for process interventions. Methods Chart review was performed on all patients who received a stem cell transplant from 2011 to 2017. Information collected included: type of PCP prophylaxis, factors contributing to use of alternative therapy, breakthrough cases of Pneumocystis jirovecci or other infections. Results Of 204 charts reviewed, 11 were excluded due to early death. Most patients 85% (n=165) received TMP-SMX, 14.5% (n=27) received alternative therapy and 0.5% (n=1) received no prophylaxis. Reasons for alternative therapy included: allergy/intolerance, pancytopenia, renal insufficiency and elevated liver enzymes. There were no breakthrough cases of PCP. There were two breakthrough cases of Nocardia in patients not receiving TMP-SMX and a single case where a patient did not receive PCP prophylaxis due to miscommunication between the transplant physician and the primary oncologist. Conclusion Over the past several years there has been a trend towards choosing alternative agents, especially in the allogenic population, without impacting the incidence of PCP. However, there were two cases of breakthrough Nocardia when alternative agents were used. Development of a checklist, which outlines antibiotic prophylaxis and duration of treatment, may enhance communication between the transplant physician, primary oncologist and medical team.

Pneumocystis pneumonia prophylaxis with low-dose trimethoprim/sulfamethoxazole during rituximab-containing chemotherapy

Although Pneumocystis pneumonia (PCP), a life-threatening infection, has been reported in patients with non-Hodgkin B-cell lymphoma (BNHL) who were treated with rituximab-containing chemotherapies (R-CTX), the PCP prophylaxis regimen awaits establishment to date. This study reports a retrospective analysis of the efficacy and safety of a low-dose trimethoprim/sulfamethoxazole (TMP/SMX) in patients with BNHL receiving R-CTX. We retrospectively analyzed 156 patients newly diagnosed with BNHL who received R-CTX at our institute from 2010 to 2015. We collected patients' clinical and laboratory data, including lymphocytes count, IgG level, PCP prophylaxis regimens, and adverse events (AEs). Patients were categorized into the following two groups based on the TMP/SMX regimen: group A (33 patients; 80 mg/400 mg×3/week) or group B (65 patients; 160 mg/800 mg×2/week). Both lymphocytes count and IgG level declined during R-CTX. No patient developed PCP. Patients in group B exhibited a significantly higher incidence of AEs (18.2% vs. 63.1%; p<0.05) and increased AST (6.1% vs. 26.6%; p<0.05), compared with those in group A. Thus, TMP/SMX (80 mg/400 mg×3/week) effectively prevents PCP and is preferable because of the lower rates of AEs.

Prophylaxis of Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia in Diffuse Large B-Cell Lymphoma Treated with R-CHOP Therapy: A Single Center Experience

Background: Recent studies reported increased risk of Pneumocystis pneumonia (PCP) in patients treated with rituximab-containing chemotherapy and its incidence ranged from 2% up to 13%. However, there are no standard guidelines for PCP prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL). Herein, we investigated the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis for PCP in patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).Method: We retrospectively review the patients with DLBCL who received R-CHOP every 21 days (R-CHOP-21) and received PCP prophylaxis with daily single-strength TMP/SMX (80mg/400mg) in Asan Medical Cencer, Seoul, Korea. We included patients only who completed at least 4 cycles of R-CHOP-21 and PCP prophylaxis. At first, we searched for patients with a positive test result for an immunofluorescence assay for PCP using bronchoalveolar lavage (BAL) samples. As a confirmative test of PCP, a direct immunofluorescence assay to detect P.jirovecii was performed with a commercially available kit (Light Diagnostics TM Pneumocystisjirovecii DFA Kit, Millipore, Billerica, MA, USA). Secondly, we searched for patients who received therapeutic doses of TMP/SMX for following clinical conditions; 1) symptoms such as fever, cough, or dyspnea, 2) radiologic findings compatible to PCP on chest X-ray or chest computed tomography, 3) no other definite cause of pneumonia.Result: We identified 176 patients with DLBCL who received at least 4 cycles of R-CHOP-21 and concurrent PCP prophylaxis between June 2016 and December 2017. The median age was 59 (range, 22-84), 79 patients (44.8%) had advanced stage (stage III/IV) and 163 patients (92.6%) received 6 or 8 cycles of R-CHOP. The median follow-up duration of 13.6 months (range, 4.4 - 24), and TMP/SMX prophylaxis median cycles was 6 (range, 4-8). Among 176 patient, we identified 2 patients who had undergone bronchoscopy and the immunofluorescence assay for PCP using BAL samples in suspicious of PCP but no patients revealed positivity for the test. We also found that no patients received therapeutic doses of TMP/SMX during the chemotherapy. Grade 3/4 neutropenia and thrombocytopenia occurred in 30.6% and 8.1% of patients, respectively.Conclusion: There was no PCP event in patients with DLBCL treated with R-CHOP-21 and TMP/SMX prophylaxis with daily single-strength TMP/SMX (80mg/400mg). Side effect profiles seems to be comparable with R-CHOP-21 alone. DisclosuresNo relevant conflicts of interest to declare.

Therapy and Management of Pneumocystis jirovecii Infection.

The rates of Pneumocystis pneumonia (PcP) are increasing in the HIV-negative susceptible population. Guidance for the prophylaxis and treatment of PcP in HIV, haematology, and solid-organ transplant (SOT) recipients is available, although for many other populations (e.g., auto-immune disorders) there remains an urgent need for recommendations. The main drug for both prophylaxis and treatment of PcP is trimethoprim/sulfamethoxazole, but resistance to this therapy is emerging, placing further emphasis on the need to make a mycological diagnosis using molecular based methods. Outbreaks in SOT recipients, particularly renal transplants, are increasingly described, and likely caused by human-to-human spread, highlighting the need for efficient infection control policies and sensitive diagnostic assays. Widespread prophylaxis is the best measure to gain control of outbreak situations. This review will summarize diagnostic options, cover prophylactic and therapeutic management in the main at risk populations, while also covering aspects of managing resistant disease, outbreak situations, and paediatric PcP.

Optimizing the use of trimethoprim-sulfamethoxazole for prevention of PCP and opportunistic infections in allogeneic hematopoietic cell transplant recipients.

138 Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is preferred for prevention of Pneumocystis pneumonia (PCP), toxoplasmosis and other opportunistic infections after allogeneic hematopoietic cell transplantation (HCT), but it is often withheld due to potential adverse events (AE). From July 2016-June 2017 we observed that 31% of allogeneic HCT recipients at our hospital were prescribed TMP-SMX throughout the high risk period (day +30-180). Therefore, we developed an intervention to explore reasons for such a low prescription rate and to optimize TMP-SMX use. Methods: Our institution’s HCT practice guidelines were revised to include indications for TMP-SMX and alternative agents for PCP and Toxoplasma prophylaxis and specific clinical and laboratory criteria for withholding TMP-SMX. Education on the guidelines was provided to transplant clinicians. Outpatient encounters were prospectively audited from January to April 2018. Providers received real-time feedback with recommendations in accordance with our guidelines prior to patients’ visits. Results: We reviewed 321 outpatient encounters among 112 patients. Seventy-six (68%) patients were on TMP-SMX prophylaxis at the first reviewed encounter. Cytopenias were the most common reason for withholding TMP-SMX, occurring in 50 (57%) encounters, followed by elevated liver function tests (LFTs) (13.6%), hyperkalemia (3.4%), elevated creatinine (3.4%), rash or hypersensitivity (3.4%), and unknown/other (22%) . In 73 encounters in which patients received alternative or no PCP prophylaxis, we recommended changing to TMP-SMX. This intervention was accepted in 15 patients, 11(73%) of whom tolerated TMP-SMX well. In the remaining four patients, TMP-SMX was subsequently discontinued due to unrelated AE (N = 3) and possible TMP-SMX-associated elevated LFTs (N = 1). Conclusions: Provider education and real-time feedback led to increased utilization of TMP-SMX for prevention of PCP and other opportunistic infections in HCT recipients without an increase in TMP-SMX-related adverse effects. Further study is needed to understand the low clinician acceptance rate of the intervention.

Efficacy of selective digestive decontamination in patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell transplantation

Selective digestive decontamination (SDD) with the oral, non-absorbable antimicrobial substances gentamicin, vancomycin and amphotericin B was optionally used at our institution to reduce the risk of gastrointestinal tract derived infections in multiple myeloma (MM) patients undergoing high-dose chemotherapy with subsequent autologous stem cell transplantation (HDCT/ASCT). The majority of patients received sulfamethoxazole-trimethoprim as pneumocystis pneumonia prophylaxis. From 203 patients receiving their first HDCT/ASCT between 2009 and 2015, we compared retrospectively 90 patients receiving SDD to 113 patients not receiving SDD. The administration of SDD was associated with a reduction of bacterial infections after HDCT/ASCT (overall: 8% versus 24%, p = .002; gram-negative pathogens: 1% versus 11%, p = .006) and less use of systemic antibiotics (62% versus 77%, p = .022). Omission of SDD was an independent risk factor for developing neutropenic fever and bloodstream infections. SDD could be an option to reduce bacterial infections in patients undergoing HDCT/ASCT that needs to be tested in prospective trials.

A Multicenter Case-control Study of the Effect of Acute Rejection and Cytomegalovirus Infection on Pneumocystis Pneumonia in Solid Organ Transplant Recipients.

Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between posttransplant PCP and 3 variables: cytomegalovirus (CMV) infection, allograft rejection, and prophylaxis. Eight transplant centers participated. For each case (SOT recipient with PCP), 3-5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft, and date of transplantation (±6 months). We enrolled 53 cases and 209 controls. Transplant types included kidney (n = 198), heart (n = 30), liver (n = 15), kidney-pancreas (n = 14), and lung (n = 5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to the intensive care unit, and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases, and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (P = .009), kidney dysfunction (P = .001), cardiac diseases (P = .005), diabetes mellitus (P = .03), allograft rejection (P = .001), CMV infection (P = .001), and severe lymphopenia (P = .001) were significantly higher in cases. In the logistic regression model, CMV infection (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 2.0-10.5]) and allograft rejection (aOR, 3.0 [95% CI, 1.5-6.1]) significantly increased the likelihood of PCP. PCP was mostly a late-onset disease occurring after complete course of prophylaxis, particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP.

An outbreak of Pneumocytis jirovecii pneumonia among liver transplant recipients.

An outbreak of Pneumocystis pneumonia (PCP) in liver transplant recipients occurred between 2009 and 2011 at the Beaujon University Hospital just after immediate-release tacrolimus was replaced by extended-release tacrolimus. We conducted a retrospective study to analyze the transmission mode of Pneumocystis, the role of the change in the immunosuppressive regimen, and the factors associated with PCP. To analyze transmission, we built a transmission map. Two control groups were built. First, to assess the role of the change from tacIR to tacER, cases were matched to controls transplanted before 2009 (tacIR control group). Tacrolimus trough concentrations were compared between the 2 groups. Then, to assess factors associated with PCP, each PCP case was matched to 2 control patients: the one transplanted just before and the one just after (PCPAsFact control group). No PCP prophylaxis was given to any patient. Fifteen cases of PCP were recorded. A contact between a case and a patient who developed PCP afterward was identified in 4 occasions. The comparison of tacrolimus trough concentrations did not conclude to a difference in the exposure to the drug. Lymphopenia was the only factor independently associated with the occurrence of PCP (odds ratio 0.78, 95% confidence interval 0.61-0.99, P=.04). Our results suggest that patient-to-patient transmission was not the main mode of transmission of PCP. We found no evidence that the switch from tacIR to tacER led to an overexposure to tacrolimus. Our results suggest the possibility of targeted prophylaxis in immunosuppressed liver transplant recipients.

The Authors' Reply.

Our recent study showed that the contagious nature of Pneumocystis jirovecii allows development of outbreaks of Pneumocystis pneumonia (PCP) in immunosuppressed kidney transplant recipients without prophylaxis. Although short-term prophylaxis at developing of PCP is effective in controlling transient outbreak, recurrence of PCP outbreak may arise under free anti-Pneumocystis regimens. We asserted that implementation of lifelong prophylaxis is required for prevention of repeated PCP outbreak in kidney transplant recipients.1 A recent Letter to the Editor by Momoko Kono, MD, et al: “A case of a Pneumocystis pneumonia twenty-four years after living kidney transplantation due to withdrawal of Sulfamethoxazole/Trimethoprim prophylaxis” supports our study.2 Guidelines for kidney transplant recipients recommend anti-Pneumocystis prophylaxis for all recipients for at least 6 to 12 months posttransplant. However, this is only directed to protect individuals against PCP infection soon after transplantation, but not for long-term prevention of PCP outbreak. Because kidney transplant recipients account for the largest proportion of organ transplant recipients, they are at high risk of exposing each other through their contact in the outpatient clinic. Once a patient developed PCP in these populations, who are taking standard immunosuppression, an outbreak of PCP may easily occur. Although a 3-month prophylaxis provided to all recipients (universal short-term prophylaxis) is sufficient to control the outbreak, intermittent new PCP outbreaks caused by different genotypes are not prevented in our experience.1 There are 3 ways of acquiring PCP: (1) via direct transmission from patients with active PCP, (2) from asymptomatic carriers, or from (3) environmental exposure. P. jirovecii is currently classified as a fungus, not a protozoan. Because a culture system for P. jirovecii in vitro has not yet been established, the life cycle of P. jirovecii remains poorly defined. Pneumocystis organisms differ depending on mammalian species, so that strains from one host mammal do not transmit to a different one. Reports of evidence for the cysts as the agent of transmission of P. jirovecii have also been shown by aerial route from host to host in mice.3,4 Accordingly, the reasons for emergence of PCP among immunocompromised host can be explained by the reactivation developing from de novo infection or reinfection with different genotypes. In PCP lungs, trophic forms are the most abundant, whereas cysts which are detected in the bronchial lumen may be the major form through colonization. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first drug of choice for PCP prophylaxis, as well as for treatment. The TMP-SMX is an antiprotozoal agent, not meant to target fungus, but is highly effective for PCP (trophic forms) treatment. Unlike trophic forms, as cysts are not sensitive to TMP-SMX, colonies of P. jirovecii in the bronchial lumen cannot be eliminated. Macrophages which are phagocytic immune cells have a function for clearance of activated P. jirovecii, but those in kidney transplant recipients are basically suppressed. Thus, susceptible kidney transplant patients are ready to import any genotypes of P. jirovecii that they are exposed to in the outpatient clinic. Although short-term administration of TMP-SMX effectively blocks the onset of PCP which changes from cysts to trophic forms, it is impossible to eradicate the nest of P. jirovecii. Therefore, lifelong administration could be approved to protect recipients from PCP outbreaks by different genotypes in a transplant facility where many immunosuppressed patients visit. Previously, we experienced repeated outbreaks of PCP in the past decade, but no PCP outbreaks have been observed over a 40-month period after a lifelong prophylaxis strategy was adopted in our kidney transplant center.

Pneumonia Prophylaxis Benefits Patients with Rheumatic Diseases

Pneumocystis pneumonia (PCP) prophylaxis is effective in HIV-positive patients and other immunosuppressed groups, but consensus is lacking on PCP

Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids

ObjectivesTo investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.MethodsThe study included 1522 treatment episodes with...

Taking the challenge: A protocolized approach to optimize Pneumocystis pneumonia prophylaxis in renal transplant recipients.

While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty-two patients (35%) had 48 trimethoprim-sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non-immune-mediated and 17% were immune-mediated. Significantly more patients underwent trimethoprim-sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; P=.0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self-limiting with only 1 recurrence of an immune-mediated reaction. After protocol implementation, aerosolized pentamidine-associated costs were reduced. The introduction of a standard approach to trimethoprim-sulfamethoxazole rechallenge in the context of both prior immune and non-immune-mediated reactions was safe and successful in improving the uptake of first-line Pneumocystis pneumonia prophylaxis in renal transplant recipients.

The Effect of Ophthalmic Artery Chemosurgery on Immune Function in Retinoblastoma Patients: A Single Institution Retrospective Analysis.

Ophthalmic artery chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting Pneumocystis pneumonia prophylaxis. IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC. Twenty-three patients received ≥3 cycles of OAC and had immune function testing (absolute CD4 count) performed at a median of 34 days postcompletion of therapy (range, 15 to 63 d). Only 1 patient had a low absolute CD4 count of 189 cells/μL (normal, 359 to 1570 cells/μL) 2 and a half months after IV carboplatin and 28 days after their third dose of OAC. This patient was found to have coexisting hypogammaglobulinemia. Repeat immune function testing normalized through continued OAC treatment. Clinically significant immune suppression appears rare following OAC alone, but patients previously treated with IV chemotherapy may be immunosuppressed and may benefit from pneumocystis pneumonia prophylaxis until the CD4 count recovers.

A study on the colonization of Pneumocystis jirovecii among outpatients during cancer chemotherapy and among healthy smokers.

Pneumocystis Jirovecii (PJ) is regarded as an agent of fungal infection and in cases of pneumocystis pneumonia (PCP) in immune-compromised patients including cancer patients. It is not clear what kinds of cancer, treatments, and environment need prophylaxis for PCP. In this study, we have analyzed the detectability of PJ DNA from sputum, and discussed prophylaxis and risk factors regarding PCP. A total of forty-nine materials (twenty-four from outpatients during cancer chemotherapies and twenty-five from healthy control subjects) was collected. Their PJ DNAs were amplified using nested PCR with specific primers of the PJ gene (the mitochondrial small subunit rRNA gene). PJ DNA was detectable in 46% of specimens (sputum) from cancer patients during chemotherapies, and incidences of not significantly different among types of cancer and chemotherapy regimens. Prophylactic use of Sulfamethoxazole/Trimetoprim (ST) reduced the detection of PJ DNA. Detection of PJ DNA is not high among healthy non-smokers (20%) and high among healthy smokers (47%). Prophylactic use of ST may be necessary for cancer patients during chemotherapies. Also, smoking may be associated with PJ colonization in the airway and air vesicles, and may increase the mortality rate for PCP. All patients undergoing cancer chemotherapies should cease smoking.

Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis.

The number of patients with non-human immunodeficiency virus (HIV) related pneumocystis carinii pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We performed a meta-analysis to describe the clinical characteristics and factors associated with outcomes of PCP in HIV-negative patients. A total of 13 studies including 867 patients with non-HIV related PCP was included. The overall mortality for non-HIV patients with PCP was 30.6%. The most common underlying disorder for the development of PCP is hematological malignancies (29.1%), followed by autoimmune disease (20.1%), organ or bone marrow transplantation (14.0%), and solid tumors (6.0%). Risk factors associated with increased mortality rate including old age, female sex, longer time from onset of symptoms to diagnosis, respiratory failure, solid tumors, high lactate dehydrogenase, low serum albumin, bacterial, and aspergillus co-infection, etc (P < 0.05). Adjunctive corticosteroid and PCP prophylaxis was not shown to improve the outcome of PCP in non-HIV patients (P > 0.05). Our findings indicate that mortality in non-HIV patients with PCP is high. Improved knowledge about the prognostic factors may guide the early treatment.

Pneumocystis Pneumonia and the Rheumatologist: Which Patients Are At Risk and How Can PCP Be Prevented?

Immunosuppressive therapy for connective tissue diseases (CTDs) is steadily becoming more intense. The resultant impairment in cell-mediated immunity has been accompanied by an increasing risk for opportunistic infection (OI). Pneumocystis pneumonia (PCP) has been recognized as an OI in patients with CTDs, but specific risk factors and precise indications for PCP prophylaxis remain poorly defined. This review was undertaken to update information on the risk of PCP in patients with CTDs and to examine current guidelines for PCP prophylaxis in this population. Data on the occurrence of PCP and indications for prophylaxis in patients with CTDs is sparse. Large systematic reviews did not incorporate patients with CTD secondary to the lack of randomized control trials. Upon reviewing guidelines published since 2015, prophylaxis for PCP is recommended only for patients with ANCA-positive vasculitis, specifically granulomatosis with polyangiitis (GPA), who are undergoing intense induction therapy. Evidence-based recommendations for the prophylaxis of PCP in patients with CTDs cannot be provided. There is expert consensus that PCP prophylaxis is warranted in patients with GPA undergoing induction therapy. Prophylaxis should perhaps also be considered for other CTD patients who are receiving similar intense immunosuppressive therapy especially if they are lymphopenic or have a low CD4 count.

Low prevalence of Pneumocystis pneumonia in hospitalized patients with systemic lupus erythematosus: review of a clinical data warehouse.

Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearlydefined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm3. The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects to trimethoprim-sulfamethoxazole in systemic lupus erythematosus and the low prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, our data do not substantiate the need for Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus patients, except in those with concurrent HIV/AIDS.

Human immunodeficiency virus and fungal infections.

The discovery of HIV was largely due to the presence of Pneumocystis pneumonia (PCP) in young patients that did not have the usual known causes of immune deficiencies in the early 1980s. Currently, treatment with highly active anti-retroviral therapy (HAART) and the use of prophylaxis for PCP have lowered the frequency of fungal infections; however, these infections continue to cause morbidity and mortality in those patients that fall out or are not in care. The frequency of specific fungal diseases in HIV patients will depend on the prevalence of fungi in the particular geographic location. Nowadays, superficial and invasive Candida infections, PCP, and cryptococci are the most frequent fungal infections seen in HIV positive patients worldwide. The role of pathology in diagnosing fungal infections is crucial because a lesion may be biopsied without obtaining mycology cultures, certain organisms may take several weeks to grow, or the sample sent to the mycology laboratory may not have the organism. Following we will describe fungal infections that are particularly frequent in HIV infected patients and their key pathological features.

Low prevalence of DHFR and DHPS mutations in Pneumocystis jirovecii strains obtained from a German cohort.

Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of immunocompromised individuals. A combination of trimethoprim-sulfamethoxazole is widely used for prophylaxis and treatment of PCP. Polymorphisms in the drug targets, the dihydropteroate synthase (DHPS) or the dihydrofolate reductase (DHFR) are presumably a reason for treatment failure. We retrospectively examined the prevalence of DHPS and DHFR mutations in Pneumocystis jirovecii isolates obtained from HIV-infected and non-HIV-infected PCP patients. DHFR and DHPS genes were amplified using semi-nested PCR followed by sequencing. Obtained data were correlated with clinical findings. Sequencing of the DHPS gene was achieved in 81 out of 128 isolates (63%), the DHFR-gene was successfully sequenced in 96 isolates (75%). The vast majority of DHFR and DHPS sequences were either wild-type or showed synonymous single nucleotide polymorphisms. Only one sample contained a double mutation at DHPS codon 55 and codon 57 which was associated with treatment failure in some studies. No linkage of treatment failure to a DHFR or DHPS genotype was observed. In our cohort, 35 of 95 Patients (37%) were HIV-positive and 60 (63%) were HIV-negative. The overall mortality rate was 24% with a much higher rate among non-HIV patients. DHPS and DHFR mutations exist but are infrequent in our cohort. The contribution of gene polymorphisms to treatment failure needs further research. In immunocompromised HIV-negative patients PCP is associated with high mortality rates. Prophylactic treatment is warranted in this patient subset.

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

BackgroundSulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported.MethodsAdult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24.ResultsOf 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8–100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES.ConclusionsAlthough there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases.Trial registrationThe University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727, registered 10 April 2012.