Continuous function of 80 primary renal allografts for 30-47 years with maintenance prednisone and azathioprine/mycophenolate mofetil therapy: A clinical mosaic of long-term successes.

Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47 years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40-year success. At 35 years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.

Complex prosthetic joint infections due to carbapenemase-producing Klebsiella pneumoniae: a unique challenge in the era of untreatable infections.

OBJECTIVES: Limited clinical experience exists regarding the management of prosthetic joint infection (PJI) due to multidrug-resistant (MDR) Gram-negative organisms. We review three cases of carbapenem-resistant Klebsiella pneumoniae (CRKP) complicating PJI. METHODS: This was a retrospective study of all patients at a tertiary care institution with CRKP complicating PJI between January 2007 and December 2010. Demographic data, procedures, organisms involved, length of stay, antibiotic treatments, and outcomes were collected. Antimicrobial susceptibility testing was performed on CRKP isolates, and the mechanism of resistance was ascertained by PCR. RESULTS: This analysis demonstrated that: (1) the CRKP possessed blaKPC and were difficult to eradicate (persistent) in PJI; (2) multiple surgeries and antibiotic courses were undertaken and patients required a prolonged length of stay; (3) resistance to colistin and amikacin emerged on therapy; (4) the same strain of CRKP may be responsible for relapse of infection; (5) significant morbidity and mortality resulted. CONCLUSIONS: These cases highlight the opportunistic and chronic nature of CRKP in PJIs and the need for aggressive medical and surgical treatment. Further investigations of the management of CRKP PJI and new drug therapies for infections due to MDR Gram-negative organisms are urgently needed.

Challenges of interferon-γ release assay conversions in serial testing of health-care workers in a TB control program.

BACKGROUND: Clinical data with use of serial interferon-γ release assay (IGRA) testing in US health-care workers (HCWs) are limited. METHODS: A single-center, retrospective chart review was done from 2007 to 2010 of HCWs who underwent preemployment QuantiFERON-TB Gold In-Tube testing. Demographic data, bacille Calmette-Guérin history, prior tuberculin skin test result if done, and baseline and serial IGRA values were obtained. The number of IGRA converters and reverters and their subsequent management by infectious disease physicians were reviewed. Quantitative IGRA-negative values were not available. RESULTS: A total of 7,374 IGRAs were performed on newly hired HCWs. Of these tests, 486 (6.6%) were positive at baseline, 305 (4.1%) were indeterminate, and 6,583 (89.3%) were negative. From 2007 to 2010, 52 of 1,857 HCWs (2.8%) with serial IGRA tests were identified as converters, with a serial IGRA median value of 0.63 IU/mL. Seventy-one percent of HCWs with IGRA conversion had values ≤ 1 IU/mL. None of the converters had active TB or were part of an outbreak investigation. CONCLUSIONS: Clinical significance of most QuantiFERON-TB Gold In-Tube conversions in serial testing remains a challenging task for clinicians. The use of a single cutoff point criterion for IGRA may lead to overdiagnosis of new TB infections. Clinical assessment and evaluation may help to prevent unnecessary therapy in these cases. The criteria for defining conversions and reversions by establishing new cutoffs needs to be evaluated further, especially in HCWs.

Endovascular infections caused by Histoplasma capsulatum: a case series and review of the literature.

CONTEXT: Endovascular infection is an uncommon but devastating manifestation of histoplasmosis, which is often diagnosed late in disease. OBJECTIVES: To evaluate the clinical and pathologic characteristics of patients with endovascular infections caused by Histoplasma capsulatum. DESIGN: All cases of patients with documented endovascular histoplasmosis at a single tertiary care center in an endemic region during the period 1993-2010 were reviewed. RESULTS: Patients presented with a subacute febrile illness and a history of endovascular devices. All patients had positive Histoplasma serology. Routine bacterial culture results were negative for all patients. In addition to yeast forms typical of histoplasmosis, pathologic findings also revealed mycelial forms in 4 of 5 patients. Inflammation was scant. Urinary antigen detection was positive in 4 of 5 patients and Histoplasma blood culture results were positive for 3 of 5 patients. Four patients were treated with a combination of surgical and medical therapy, which consisted of amphotericin B followed by itraconazole; these 4 patients had complete resolution of symptoms and no documented relapse. One patient died before planned surgery. CONCLUSIONS: Histoplasma capsulatum endovascular infections are clinically characterized by a subacute febrile illness with negative bacterial cultures in patients with prosthetic endografts or valves. Noninvasive diagnostics are often the initial clue to the diagnosis. Combined medical and surgical treatment is associated with survival. On histopathologic examination both mycelial and yeast forms are often observed, with absent to minimal tissue inflammatory reaction.

Clinical presentation and management of histoplasmosis in older adults.

OBJECTIVES: To describe the influence of age on clinical features of histoplasmosis. DESIGN: Retrospective single-center cohort study. SETTING: Large tertiary care center. PARTICIPANTS: All individuals who met criteria for probable or proven histoplasmosis between 1998 and 2008. MEASUREMENTS: Participants were divided into the following categories of histoplasmosis: acute pulmonary, chronic pulmonary, asymptomatic, disseminated, and other. Correcting for immune status, the influence of age at diagnosis on presentation, diagnosis, imaging, treatment, and all-cause mortality was evaluated. RESULTS: In 347 participants with histoplasmosis, a number of characteristics were associated with age when evaluating participants according to diagnostic category. An age-associated increase in asymptomatic histoplasmosis was observed (P < .001). In symptomatic pulmonary histoplasmosis, older adults were less likely to present with chest pain (P < .001) and less likely to have hilar lymphadenopathy on imaging (P = .04). Lower rates of seropositivity with older age were seen in asymptomatic (P = .04) but not other forms of histoplasmosis. Cavitary disease was associated with older age in chronic pulmonary histoplasmosis (P = .05). Treatment did not change with age. All-cause mortality at 6 months was 4% and was associated with older age (P = .02). CONCLUSION: Although most studied characteristics of histoplasmosis were similar, notable age-related differences were present. Chronic cavitary disease and asymptomatic histoplasmosis were more common with older age. In acute histoplasmosis, the lack of chest pain and hilar lymphadenopathy may hinder diagnosis in older adults.

Interferon-gamma-release assays: Better than tuberculin skin testing?

Although the tuberculin skin test has long been the standard for detecting latent tuberculosis infection, it has many limitations. Interferon-gamma-release assays are gaining acceptance as an alternative. In this paper we present cases to illustrate how these new tests can be used and how to interpret the results.

Nontuberculous mycobacterial blood stream and cardiac infections in patients without HIV infection.

Nontuberculous mycobacteria rarely cause bacteremia in HIV-negative patients. We describe 16 cases, including the first Mycobacterium neoaurum endocarditis. Nine cases were line related. Most patients were immunocompromised secondary to hematologic malignancy or other comorbid conditions. Amikacin had the most reliable in vitro activity. Combination therapy was frequently used. Mortality was 25%.

Reducing the rates of indeterminate results of the QuantiFERON-TB Gold In-Tube test during routine preemployment screening for latent tuberculosis infection among healthcare personnel.

We implemented the QuantiFERON-TB Gold (QFT-G) In-Tube test to identify latent tuberculosis infection among potential employees prior to employment. The rates of indeterminate QFT-G In-Tube test results were higher than expected and prompted an investigation that led to successful interventions (eg, manual vortexing before incubation and the use of a modified in-tube method). The tracking of indeterminate results is suggested as an important quality control measure.

Active tuberculosis in a healthcare worker: are you ready?

We describe a healthcare worker with a previously positive tuberculin skin test result who developed active tuberculosis. An investigation revealed 280 potential contacts, 3 of whom had positive tuberculin skin test results. Our experience demonstrates the potential benefits of therapy for latent tuberculosis infection as a component of a tuberculosis-control program.

Retroperitoneal cold abscess caused by mycobacteria chelonae abscessus after percutaneous nephrolithotomy in India: strategies for detection, management, and prevention in the United States.

Atypical, nontuberculous, mycobacteria (NTM) are emerging as significant pathogens in nosocomial infections. Historically, such outbreaks have been limited to developing countries, and clinicians in the United States have not been exposed to the nuances of diagnosing and treating such infections. With an increasing prevalence worldwide, all clinicians should be able to recognize and treat NTM infections. We report a case of a patient who developed a retroperitoneal cold abscess caused by NTM after percutaneous stone surgery in India. Through a comprehensive review of published reports, we offer strategies for the treatment and prevention of such outbreaks.

Rare Actinobacillus infection of the cavernous sinus causing painful ophthalmoplegia: case report.

OBJECTIVE AND IMPORTANCE: Actinobacillus actinomycetemcomitans is a gram-negative coccobacillus that is known to cause a wide array of clinical infections in debilitated patients, including periodontal disease, soft tissue abscess, pleural empyema, endocarditis, cerebral abscess, and meningitis. We report a rare A. actinomycetemcomitans cavernous sinus abscess that caused painful ophthalmoplegia in a healthy man. CLINICAL PRESENTATION: A 34-year-old man presented with a 3-month history of acute onset of left-sided retro-orbital pain that progressed to a complete left Cranial Nerve VI palsy and Cranial Nerve V1 and V2 hypesthesia. Magnetic resonance imaging revealed the presence of an enhancing lesion in the left cavernous sinus, which encased and narrowed the ipsilateral intracavernous segment of the internal carotid artery. Routine blood and cerebrospinal fluid analyses were normal. Tolosa-Hunt syndrome was suspected, and the patient was treated with high-dose corticosteroids. An open biopsy was performed after failed prolonged corticosteroid therapy. INTERVENTION: A left frontotemporal craniotomy and cavernous sinus exploration through an interdural approach were performed. A soft reddish mass was found in the cavernous sinus around Cranial Nerve V1 and V2. Multiple biopsies were obtained. Pathological analysis revealed a purulent infection containing multiple gram-negative coccobacilli. The patient's pain improved immediately, and cranial neuropathy resolved during the next several weeks. After cultures demonstrated growth of A. actinomycetemcomitans, a regimen of orally administered amoxicillin and metronidazole was initiated. Eight months after surgery, the patient was free of symptoms and a repeat magnetic resonance imaging scan was normal. CONCLUSION: We present a rare bacterial abscess of the cavernous sinus causing painful ophthalmoplegia. In patients who present with presumed Tolosa-Hunt syndrome and do not improve with prolonged high-dose corticosteroid therapy, an open biopsy is recommended to exclude a bacterial infection.