Daniel R. Lucey

Infections in Patients with Immunodeficiency with Thymoma (good Syndrome): Report of 5 Cases and Review of the Literature

Immunodeficiency with thymoma (Good syndrome, GS) is a rare, adult-onset condition that is characterized by thymoma, hypogammaglobulinemia, and low numbers of peripheral B cells. CD4+ T lymphopenia and an inverted CD4:CD8+ T-cell ratio may be present. Here we report 5 patients with GS and infectious complications who were seen at 3 institutions between 1983 and 1999. Three patients had recurrent sinopulmonary infections, 3 had severe cytomegalovirus (CMV) disease, and 1 had Pneumocystis carinii pneumonia. Review of the literature identified 46 other reports of infections in GS patients. The infections reported in all 51 patients included recurrent sinopulmonary infection (19 cases with documented respiratory pathogens), generally with encapsulated bacteria, most often Haemophilus influenzae (11 cases); CMV disease (5 cases); bacteremia (7 cases); oral or esophageal candidiasis (6 cases); persistent mucocutaneous candidiasis (5 cases); chronic diarrhea (5 cases with documented stool pathogens); urinary tract infections (4 cases); P. carinii pneumonia (3 cases); tuberculosis (2 cases); Kaposi sarcoma (1 case); disseminated varicella (1 case); candidemia (1 case); wound infection with Clostridium perfringens (1 case); Mycoplasma arthritis (1 case); and other infections. Patients with GS present with a spectrum of sinopulmonary infections and pathogens similar to common variable immunodeficiency (CVID). Compared with patients with CVID, opportunistic infections, including severe CMV disease, P. carinii pneumonia, and mucocutaneous candidiasis, appear to be more common in patients with GS, and patients with GS may have a worse prognosis. GS should be ruled out in patients with thymoma or CVID who develop severe, especially opportunistic, infections. Treatment with intravenous immune globulin is recommended for all patients with GS.

Development and Evaluation of a Quantitative, Touch-Down, Real-Time PCR Assay for Diagnosing Pneumocystis carinii Pneumonia

ABSTRACT A rapid (time to completion, <4 h, including DNA extraction) and quantitative touch-down (QTD) real-time diagnostic Pneumocystis carinii PCR assay with an associated internal control was developed, using fluorescence resonance energy transfer (FRET) probes for detection. The touch-down procedure significantly increased the sensitivity of the assay compared to a non-touch-down procedure. Tenfold serial dilutions of a cloned target were used as standards for quantification. P. carinii DNA has been detected in respiratory specimens from patients with P. carinii pneumonia (PCP) and from patients without clinical evidence of PCP. The latter probably represents colonization or subclinical infection. It is logical to hypothesize that quantification might prove helpful in distinguishing between infected and colonized patients: the latter group would have lower copy numbers than PCP patients. A blinded retrospective study of 98 respiratory samples (49 lower respiratory tract specimens and 49 oral washes), from 51 patients with 24 episodes of PCP and 34 episodes of other respiratory disease, was conducted. PCR-positive samples from colonized patients contained a lower concentration of P. carinii DNA than samples from PCP patients: lower respiratory tract samples from PCP and non-PCP patients contained a median of 938 (range, 2.4 to 1,040,000) and 2.6 (range, 0.3 to 248) (P < 0.0004) copies per tube, respectively. Oral washes from PCP and non-PCP patients contained a median of 49 (range, 2.1 to 2,595) and 6.5 (range, 2.2 to 10) (P < 0.03) copies per tube, respectively. These data suggest that this QTD PCR assay can be used to determine if P. carinii is present in respiratory samples and to distinguish between colonization and infection.

The use of oral washes to diagnose Pneumocystis carinii pneumonia: A blinded prospective study using a polymerase chain reaction-based detection system

Pneumocystis carinii pneumonia (PCP) can be diagnosed by direct microscopic examination of induced sputum or by bronchoalveolar lavage (BAL). However, many institutions have little diagnostic success with induced sputum, and BAL is invasive and expensive. This prospective, blinded study assessed oral washes as a more convenient specimen than either sputum or BAL fluid and used a dissociation-enhanced lanthanide fluoroimmunoassay time-resolved fluorescent hybridization polymerase chain reaction (PCR) detection system that is feasible for clinical laboratories. The study assessed 175 oral washes, each paired with either an induced sputum that was positive for Pneumocystis or a BAL sample. The PCR test based on the Pneumocystis major surface glycoprotein primers had a sensitivity of 91% and a specificity of 94%, compared with a test based on mitochondrial large subunit rRNA primers, which had a sensitivity of 75% and a specificity of 96%. These results suggest that oral washes can provide a useful sample for diagnosis of PCP when a sensitive PCR detection system is used.

Endocarditis Caused by Penicillin-Resistant Viridans Streptococci: 2 Cases and Controversies in Therapy

Although penicillin-resistant viridans streptococci have been isolated from samples from the mouth, blood, and wounds in increasing numbers, viridans streptococci isolated from patients with endocarditis have remained sensitive to penicillin for the past 5 decades. We report the cases of 2 patients with penicillin-resistant viridans streptococcal endocarditis, review 6 other cases from the literature, and summarize 2 studies that used an animal model of penicillin-resistant viridans streptococcal endocarditis.

Primary Cutaneous Fungal Infections in Solid Organ Transplantation: A Case Series

Cutaneous fungal infections in solid‐organ transplant patients present in a variety of nonspecific ways, requiring a high index of suspicion to diagnose correctly. In the present series of four transplant recipients, subsequent primary cutaneous fungal infections presented as papules, plaques, ulcers and subcutaneous nodules. Transplantations included one cardiac, two renal and one renal–pancreatic transplant. Fungal infections were limited to the skin; there was no evidence of disseminated disease in any case. The pathogens isolated were Scedosporium apiospermum (Pseudallescheria boydii), Alternaria species, Aspergillus fumigatus, and a coelomycete in the Coniothyrium‐Microsphaeropsis complex of dark molds. Individuals were successfully treated with surgical debridement, antifungal agents, and reduction of immunosuppressive therapy. All patients and allografts survived. Accurate diagnosis, aggressive surgery and appropriate antifungal therapy, combined with close outpatient follow‐up, optimize the likelihood of a cure in a transplant population.

Pulmonary eosinophils express HLA-DR in chronic eosinophilic pneumonia

BACKGROUND Chronic eosinophilic pneumonia is a rare idiopathic disorder. role the eosinophil plays in the pathogenesis of this disease is unknown. The recent finding that nature eosinophils can express the class II major histocompatibility complex molecule HLA-DR suggests an immunologic role, perhaps through antigen presentation. The purpose of this research was to determine whether lung-derived eosinophils exhibit in vivo expression of HLA-DR. METHODS Eosinophils were obtained simultaneously from bronchoalveolar lavage and peripheral blood from a 59-year-old woman with asthma and chronic eosinophilic pneumonia. Eosinophil-enriched aliquots of peripheral blood were cocultured with human lung fibroblasts (with or without additional granulocyte-macrophage colony-stimulating factor). The percentage of cells expressing HLA-DR was quantitated by flow cytometric analysis. RESULTS Eosinophils derived from bronchoalveolar lavage displayed in vivo expression of HLA-DR (86%) in contrast to those from peripheral blood (7%), suggesting compartmentalization of eosinophil activation within the lung. Peripheral blood eosinophils retained the capacity for HLA-DR expression when coincubated with lung fibroblasts (83%) with augmentation by granulocyte-macrophage colony-stimulating factor (93%). CONCLUSION These data demonstrate that lung eosinophil HLA-DR expression occurs in vivo; it may contribute to the pathogenesis of inflammatory lung injury.

Multidrug-resistant Corynebacterium striatum pneumonia in a heart transplant recipient

Abstract: Corynebacterium striatum is a rare, but likely underreported, cause of serious infections in immunocompromised hosts and generally is susceptible to multiple classes of antimicrobial agents. Here we report the first case of C. striatum infection in a solid organ transplant recipient. Three years after heart transplantation, a 58‐year‐old man developed bilateral pneumonia and pulmonary embolism. He did not improve with levofloxacin, piperacillin/tazobactam, and heparin treatment. A homogeneous population of abundant gram‐positive rods was repeatedly demonstrated in sputum and bronchoalveolar lavage fluid, and C. striatum was grown in pure culture. The isolate was unusual for its multidrug‐resistant (MDR) antimicrobial susceptibility pattern. The pneumonia resolved with 4 weeks of vancomycin therapy, in combination with rifampin given only during the first 2 weeks of treatment. The isolation of coryneforms (“diphtheroids”) is often attributed to contamination. Their abundant presence on direct examination of specimens and/or their growth in pure culture suggest a pathogenic role, however, and indicate the need for accurate microbiological identification, particularly in immunocompromised hosts who have been hospitalized and previously treated with antibiotics. Combination therapy that includes vancomycin may be the most prudent treatment for MDR C. striatum infections.

Malakoplakia involving the abdominal wall, urinary bladder, vagina, and vulva: Case report and discussion of malakoplakia-associated bacteria

A 29-year-old woman presented with a 3-month history of multiple purulent discharging nodules involving her lower abdomen, vulva, and left thigh. Physical examination also disclosed vaginal nodules and a left pelvic mass. Cystoscopy revealed multiple mucosal nodules and a perforation of the left vesical wall that appeared to communicate with the pelvic mass. Biopsies of the vesical and vulvar nodules revealed malakoplakia. Surgery and antibiotic therapy resulted in regression of all the lesions.

Negative correlation between blood cell counts and serum neopterin concentration in patients with HIV-1 infection

Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) further enhances the effect of IFN gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN gamma and TNF alpha are involved inhibiting hematopoiesis.

Brevibacterium Endocarditis: A First Report

There are few case reports of infections caused by Brevibacterium species, and there have been no previously reported cases of endocarditis caused by any of the 6 known species of Brevibacterium. We report the first case of Brevibacterium endocarditis (caused by Brevibacterium otitidis) in a patient with prosthetic heart valves. The patient responded to 6 weeks of treatment with vancomycin and 2 weeks with gentamicin, and she has been receiving long-term maintenance therapy with oral azithromycin.