Pneumocystis jiroveci pneumonia in giant cell arteritis: A case series

Objective

To describe the clinical presentation, laboratory findings, and outcome of patients with Pneumocystis jiroveci pneumonia (PCP) and biopsy‐proven giant cell arteritis (GCA) seen at a tertiary referral center.

Methods

Using International Classification of Diseases, Ninth Revision codes, all patients with GCA and PCP between January 1, 1976 and December 31, 2008 were identified. Medical records were reviewed. PCP was defined by the identification of Pneumocystis jiroveci organisms in the clinical setting of pneumonia.

Results

We identified 7 patients with GCA (5 women and 2 men) who developed PCP (the mean ± SD age at diagnosis was 71.6 ± 6.1 years). The median time from GCA diagnosis to PCP diagnosis was 3 months (range 1–18 months). All patients were taking prednisone (the median dosage 50 mg/day [range 30–80]) when diagnosed as having PCP. No patients were receiving PCP prophylaxis. PCP was diagnosed by positive smear on bronchoalveolar lavage fluid in 6 patients (86%) and by positive sputum polymerase chain reaction in 1 patient. All the patients were hospitalized (median duration 17 days [range 12–39 days]). Four patients (57%) were admitted to the intensive care unit. Three patients (43%) required mechanical ventilation. Two patients (29%) died; both were on mechanical ventilation.

Conclusion

Although PCP is rare among patients with GCA, this preventable infection is associated with significant morbidity and mortality.     

Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case–control study of 21 patients

Objective

To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.

Methods

Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case–control study to compare patients with and without PCP were performed.

Results

The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground‐glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.

Conclusion

PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.     

Outcome of HIV-associated <Emphasis Type="Italic">Pneumocystis</Emphasis> pneumonia in hospitalized patients from 2000 through 2003

Background  

Pneumocystis pneumonia (PCP) remains a leading cause of morbidity and mortality in HIV-infected persons. Epidemiology of PCP in the recent era of highly active antiretroviral therapy (HAART) is not well known and the impact of HAART on outcome of PCP has been debated.     

Low prevalence of DHFR and DHPS mutations in <Emphasis Type="Italic">Pneumocystis jirovecii</Emphasis> strains obtained from a German cohort

Background

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.

Methods

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.

Results

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.

Conclusion

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.

     

Detection of <Emphasis Type="Italic">Pneumocystis</Emphasis>DNA in samples from patients suspected of bacterial pneumonia- a case-control study

Background  

Pneumocystis jiroveci (formerly known as P. carinii f.sp. hominis) is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised individuals. Pneumocystis jiroveci can be detected by polymerase chain reaction (PCR). To investigate the clinical importance of a positive Pneumocystis-PCR among HIV-uninfected patients suspected of bacterial pneumonia, a retrospective matched case-control study was conducted.     

Autoimmune inflammatory disorders,systemic corticosteroids and pneumocystis pneumonia: A strategy for prevention

Background  

Pneumocystis pneumonia (PCP) is an increasing problem amongst patients on immunosuppression with autoimmune inflammatory disorders (AID). The disease presents acutely and its diagnosis requires bronchoalveolar lavage in most cases. Despite treatment with intravenous antibiotics, PCP carries a worse prognosis in AID patients than HIV positive patients. The overall incidence of PCP in patients with AID remains low, although patients with Wegener's granulomatosis are at particular risk.     

Hygienic safety of reusable tap water filters (Germlyser<Superscript>®</Superscript>) with an operating time of 4 or 8 weeks in a haematological oncology transplantation unit

Background  

Microbial safe tap water is crucial for the safety of immunosuppressed patients.     

Non-HIV <Emphasis Type="Italic">Pneumocystis</Emphasis> pneumonia: do conventional community-acquired pneumonia guidelines under estimate its severity?

Background

Non-HIV Pneumocystis pneumonia (PCP) can occur in immunosuppressed patients having malignancy or on immunosuppressive agents. To classify severity, the A-DROP scale proposed by the Japanese Respiratory Society (JRS), the CURB-65 score of the British Respiratory Society (BTS) and the Pneumonia Severity Index (PSI) of the Infectious Diseases Society of America (IDSA) are widely used in patients with community-acquired pneumonia (CAP) in Japan. To evaluate how correctly these conventional prognostic guidelines for CAP reflect the severity of non-HIV PCP, we retrospectively analyzed 21 patients with non-HIV PCP.

Methods

A total of 21 patients were diagnosed by conventional staining and polymerase chain reaction (PCR) for respiratory samples with chest x-ray and computed tomography (CT) findings. We compared the severity of 21 patients with PCP classified by A-DROP, CURB-65, and PSI. Also, patients’ characteristics, clinical pictures, laboratory results at first visit or admission and intervals from diagnosis to start of specific-PCP therapy were evaluated in both survivor and non-survivor groups.

Results

Based on A-DROP, 18 patients were classified as mild or moderate; respiratory failure developed in 15 of these 18 (83.3%), and 7/15 (46.7%) died. Based on CURB-65, 19 patients were classified as mild or moderate; respiratory failure developed in 16/19 (84.2%), and 8 of the 16 (50%) died. In contrast, PSI classified 14 as severe or extremely severe; all of the 14 (100%) developed respiratory failure and 8/14 (57.1%) died. There were no significant differences in laboratory results in these groups. The time between the initial visit and diagnosis, and the time between the initial visit and starting of specific-PCP therapy were statistically shorter in the survivor group than in the non-survivor group.

Conclusions

Conventional prognostic guidelines for CAP could underestimate the severity of non-HIV PCP, resulting in a therapeutic delay resulting in high mortality. The most important factor to improve the mortality of non-HIV PCP is early diagnosis and starting of specific-PCP therapy as soon as possible.

     

Pneumocystis jiroveci pneumonia following rituximab treatment in Wegener's granulomatosis

Objective

Wegener's granulomatosis (WG) is a devastating small‐vessel vasculitis in children. Standard treatment consists of immunosuppressive medications with cyclophosphamide potentially associated with significant infectious side effects, including Pneumocystis jiroveci pneumonia (PCP). Recently, rituximab, a monoclonal antibody against B cells, has successfully been used in refractory disease.

Methods

We describe the first pediatric patient with refractory WG with sinus and lung disease who developed PCP 6 months after treatment with rituximab, while being treated with methotrexate and prednisone. This 9‐year‐old child had no CD20+ B cells at time of infection, with normal lymphocyte and CD4 counts.

Results

This study provides a review of the published literature, including current protocols, which suggest chemoprophylaxis only in WG patients receiving T cell–targeted immunosuppression such as cyclophosphamide. However, clinical and laboratory evidence points toward a possible role of B cells in the defense against PCP.

Conclusion

Routine PCP chemoprophylaxis should be strongly considered in patients with WG treated with rituximab.     

JC Virus T-Antigen DNA in Gastrointestinal Mucosa of Immunosuppressed Patients: A Prospective,Controlled Study

Background  

JC virus (JCV), a polyoma virus, is the etiological agent of progressive multifocal leukoencephalopathy in immunosuppressed patients. JCV T-Ag has proven oncogenic potential and is expressed in colonic polyps and carcinomas. We proposed that the prevalence of JCV T-Ag DNA is higher in the normal gastrointestinal (GI) mucosa of immunosuppressed patients compared with their immunocompetent counterparts.     

Adjunctive corticosteroids for <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials

Background  

The objective of this study was to review the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with Pneumocystis jiroveci pneumonia (PCP) and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air).     

Faecal pharmacokinetics of orally administered vancomycin in patients with suspected <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Background  

Oral vancomycin (125 mg qid) is recommended as treatment of severe Clostridium difficile infection (CDI). Higher doses (250 or 500 mg qid) are sometimes recommended for patients with very severe CDI, without supporting clinical evidence. We wished to determine to what extent faecal levels of vancomycin vary according to diarrhoea severity and dosage, and whether it is rational to administer high-dose vancomycin to selected patients.     

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitis B virus infection in Caucasians

Aim

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population.

Method

A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitis B envelope antigen (HBeAg) negative chronic hepatitis B (n = 255), with HBeAg positive chronic hepatitis B (n = 99) and with HBeAg negative HBV infection (n = 228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n = 195) and in healthy controls (n = 160).

Results

In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR = 1.75, 95% CI 1.04–2.94, p = 0.034), with an increased likelihood of HBeAg negative chronic infection (OR = 1.93, 95% CI 1.05–3.54, p = 0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07–3.39, p = 0.029) in male patients.

Conclusion

The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.     

No indication of increased infection rates using low‐dose alemtuzumab instead of anti‐thymocyte globulin as graft‐versus‐host disease prophylaxis before allogeneic stem cell transplantation

Background

Alemtuzumab as part of the conditioning protocol is effective in reducing graft‐versus‐host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg).

Methods

We performed a retrospective, single‐center, case‐control study analyzing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein‐Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus‐6 (HHV6) infection using low‐dose alemtuzumab in comparison with anti‐thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation. Forty‐four patients transplanted from unrelated donors between 2001 and 2012 were matched by age, diagnosis, and conditioning regimen and treated either with alemtuzumab 10 mg at day ?2 (respectively, 20 mg in case of mismatch transplantation) or ATG. ATG Fresenius (10 mg/kg for 3 days) or Thymoglobulin (2 mg/kg for 3 days) were used.

Results

Rates of CMV reactivation, EBV reactivation, and clinical manifest HHV6 infection or toxoplasmosis did not differ significantly between both groups until 2 years after transplantation. No case of post‐transplant lymphoproliferative disorder was observed. Also, rates of neutropenic fever during inpatient treatment after transplantation did not differ significantly in both groups.

Conclusion

We saw no indication of increased infections rates when using low‐dose alemtuzumab as GvHD prophylaxis before allogeneic stem cell transplantation in this retrospective analysis.     

Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors

Objectives

The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy.

Methods

We conducted a multicenter, case–control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy.

Results

PCP developed within 26?weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65?years [hazard ratio (HR) 3.35, p?=?0.037], coexisting lung disease (HR 4.48, p?=?0.009), and concomitant methotrexate treatment (HR 4.68, p?=?0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p?<?0.001 for patients with two or more risk factors vs. those with no risk factor, and p?=?0.001 for patients with one risk factor vs. those with no risk factor).

Conclusion

Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.     

Clinical characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis receiving adalimumab: a retrospective review and case–control study of 17 patients

Objectives

To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab.

Methods

We conducted a multicenter, retrospective, case–control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected.

Results

For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p < 0.05) and had more structural changes (p < 0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died.

Conclusions

PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.     

Manifestations cliniques et biologiques de la primo-infection à parvovirus B19 chez l’adulte immunocompétent : étude rétrospective de 26 observations

Purpose

Parvovirus B19 causes erythema infectiosum in children, transient aplastic anemia in patients with hemoglobinopathies, pur red cell aplasia in immunocompromised persons and hydrops fetalis in pregnancy. The spectrum of clinical and biological manifestations in immunocompetent adult continues to grow up.

Methods

We report on a case series of 26 patients with primary parvovirus B19 infection in immunocompetent adults. This is a retrospective study over the period 2000 to 2010 in two departments of internal medecine. The diagnostic was clinical, serological or molecular.

Results

There was a female predominance (sex-ratio 3.33/1). Median patient age at diagnostic was 38.8 years (range: 18–68). The predominant symptoms were fever (65%), peripheral and symmetrical polyarthralgia (62%) and skin rash (58%). Two patients had neurological manifestations (sixth cranial nerve palsy, distal paresthesia) and one patient had myocarditis. Abnormal laboratory values included increased acute phase reactants (73%), thrombocytopenia (43%), lymphopenia (38%) and elevated liver enzymes (37%). Antinuclear (19%), anti-DNA (28%) and anti-phospholipids antibodies (14%), and hypocomplementemia (32%) were observed. False reaction with anti-CMV and anti-EBV IgM positivity was documented in 27% of cases. Two patients had persistent parvovirus B19 infection.

Conclusion

The diversity of the clinical manifestations of parvovirus B19 infection may be misleading for the clinician. However, the diagnosis should be suspected in immunocompetent adults to limit the risk of transmission to the patients who could develop a severe infection such as pregnant women or immunocompromised patients.     

Management of resistant mucocutaneous herpes simplex infections in AIDS patients: a clinical and virological challenge

Background

The use of highly active antiretroviral therapy (HAART) has been associated with a marked decrease in the prevalence of opportunistic infections in HIV‐infected patients. However, chronic mucocutaneous herpes simplex virus (HSV) infection remains a difficult clinical challenge.

Objective

The aim of the study was to optimize the diagnosis and follow‐up of chronic HSV‐2 infection in HIV‐infected patients and to correlate clinical data with CD4 cell count, in vitro HSV virological resistance and histology.

Methods

A retrospective case series was collected from a specialist out‐patient clinic providing consultations to patients with infectious skin diseases. Clinical, biological, virological and histological data were analysed.

Results

Seven HIV‐infected patients with genital and perianal herpes simplex infection were followed over 10 years. Ulcerative and pseudo‐tumoral forms were observed. Lesions occurred at various stages of immune suppression (CD4 counts from 1 to 449 cells/μL). Clinical resistance to conventional anti‐herpetic drugs was correlated with the in vitro resistance of HSV in 70% of cases.

Conclusions

Chronic mucocutaneous HSV infection in AIDS patients remains a rare but regularly observed infection in very immunosuppressed patients or those with unstable immunity during HAART. Virological results obtained from mucocutaneous samples were in most cases found to be correlated with clinical evolution and should therefore be used in making decisions on treatment. Despite efficient antiviral therapy, mucocutaneous healing is slow in the majority of cases.     

Factors associated with recovery delay in a sample of patients diagnosed by MERS‐CoV rRT‐PCR: A Saudi Arabian multicenter retrospective study

Background

Research evidence exists that poor prognosis is common in Middle East respiratory syndrome coronavirus (MERS‐CoV) patients.

Objectives

This study estimates recovery delay intervals and identifies associated factors in a sample of Saudi Arabian patients admitted for suspected MERS‐CoV and diagnosed by rRT‐PCR assay.

Methods

A multicenter retrospective study was conducted on 829 patients admitted between September 2012 and June 2016 and diagnosed by rRT‐PCR procedures to have MERS‐CoV and non‐MERS‐CoV infection in which 396 achieved recovery. Detailed medical charts were reviewed for each patient who achieved recovery. Time intervals in days were calculated from presentation to the initial rRT‐PCR diagnosis (diagnosis delay) and from the initial rRT‐PCR diagnosis to recovery (recovery delay).

Results

The median recovery delay in our sample was 5 days. According to the multivariate negative binomial model, elderly (age ≥ 65), MERS‐CoV infection, ICU admission, and abnormal radiology findings were associated with longer recovery delay (adjusted relative risk (aRR): 1.741, 2.138, 2.048, and 1.473, respectively). Camel contact and the presence of respiratory symptoms at presentation were associated with a shorter recovery delay (expedited recovery) (aRR: 0.267 and 0.537, respectively). Diagnosis delay is a positive predictor for recovery delay (r = .421; P = .001).

Conclusions

The study evidence supports that longer recovery delay was seen in patients of older age, MERS‐CoV infection, ICU admission, and abnormal radiology findings. Shorter recovery delay was found in patients who had camel contact and respiratory symptoms at presentation. These findings may help us understand clinical decision making on directing hospital resources toward prompt screening, monitoring, and implementing clinical recovery and treatment strategies.     

The Role of Primary Care Physicians in Improving Colorectal Cancer Screening in Patients with HIV

BACKGROUND

As HIV positive patients live longer, they become susceptible to the development of non-AIDS defining malignancies. Little is known about routine cancer screening practices in that population and the factors associated with cancer screening.

OBJECTIVE

Evaluate 1) the proportion of patients with HIV who had any type of colorectal cancer (CRC) screening and 2) whether having a primary care physician (PCP) or seeking care in an integrated care practice is associated with higher CRC screening.

DESIGN

A cross-sectional chart abstraction study of patients with HIV enrolled in the Philadelphia Medical Monitoring Project (MMP).

PARTICIPANTS

MMP participants age 50 and older.

MAIN MEASURES

CRC screening defined as having a documented colonoscopy, sigmoidoscopy, barium enema, or fecal occult blood test after the age of 50.

KEY RESULTS

Out of 123 chart abstractions performed, 115 had a complete clinical record from MMP. The majority of the population was male (71.3%), Black/Hispanic (73.8%) and between the age of 50 and 59 (71.3%). 45.2% of patients did not have a PCP. The overall proportion of patients who received CRC screening was 46.9%. Having a documented PCP was the only factor strongly associated with CRC screening. Rates of screening were 66.7% among those with a PCP versus 28.5% among those without a PCP (??² p?p?CONCLUSIONS Having a PCP significantly increases the likelihood of receiving CRC screening in patients with HIV. Competency in addressing primary care needs in HIV clinics will only become more important as patients with HIV age.