Steven D. Burdette

Histoplasmosis After Solid Organ Transplant

BACKGROUND To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.

Histoplasmosis Complicating Tumor Necrosis Factor–α Blocker Therapy: A Retrospective Analysis of 98 Cases

BACKGROUND Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Tedizolid: the first once daily oxazolidinone class antibiotic

Tedizolid phosphate is the second commercially available oxazolidinone antibiotic, although the first one in class that is dosed once daily. It is a prodrug that is rapidly converted to the active compound tedizolid. Tedizolid has activity against a wide range of gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. It is approved to treat acute bacterial skin and skin structure infections (ABSSSIs). In 2 randomized controlled phase 3 trials, 6 days of tedizolid (200 mg once daily) has been proven to be noninferior to 10 days of linezolid (600 mg twice daily). These 2 ABSSSI studies have positioned tedizolid among the growing armamentarium of newer, novel, anti-gram-positive agents. Tedizolid appears to differ from linezolid in the incidence of gastrointestinal and hematologic side effects and appears to lack drug interactions with selective serotonin reuptake inhibitors. Conditions other than ABSSSI are currently being evaluated in clinical studies.

Leukemoid reactions complicating colitis due to Clostridium difficile.

Background: We sought to describe the characteristics of patients who had Clostridium difficile colitis complicated by leukemoid reactions (total leukocyte count greater than 35 × 109/L) and to determine whether this complication is associated with higher morbidity or mortality than C difficile colitis without leukemoid reactions. Methods: We performed a retrospective case series analysis of patients with a positive fecal assay for C difficile toxin and a peak leukocyte count greater than 35 × 109/L during 1998 and 1999. Twenty cases that met these criteria were compared with 65 randomly selected control patients (patients with a positive C difficile toxin and a peak leukocyte count less than 35 × 109/L). Results: The mean peak leukocyte count was 52 ± 18.2 × 109/L (± SD) in the case group and 14.9 ± 6.5 × 109/L in the control group. Patients with a leukemoid reaction had a lower temperature, a lower serum albumin level, and a higher hematocrit value. Multivariable logistic regression showed respiratory tract infection and lower temperature to be independent predictors of a leukemoid reaction. There were 10 deaths (50%) in the leukemoid reaction group and 5 deaths (7.7%) in the control group. All seven patients with a peak leukocyte count greater than 50 × 109/L died, compared with eight deaths (10.3%) among the remaining 78 patients whose peak leukocyte count was less than 50 × 109/L. Conclusion: Patients with C difficile colitis and a leukocyte count greater than 35 × 109/L have a poor prognosis with a much higher mortality rate than patients who have C difficile colitis without a leukemoid reaction.

Intestinal invasion and disseminated disease associated with Penicillium chrysogenum

BackgroundPenicillium sp., other than P. marneffei, is an unusual cause of invasive disease. These organisms are often identified in immunosuppressed patients, either due to human immunodeficiency virus or from immunosuppressant medications post-transplantation. They are a rarely identified cause of infection in immunocompetent hosts.Case presentationA 51 year old African-American female presented with an acute abdomen and underwent an exploratory laparotomy which revealed an incarcerated peristomal hernia. Her postoperative course was complicated by severe sepsis syndrome with respiratory failure, hypotension, leukocytosis, and DIC. On postoperative day 9 she was found to have an anastamotic breakdown. Pathology from the second surgery showed transmural ischemic necrosis with angioinvasion of a fungal organism. Fungal blood cultures were positive for Penicillium chrysogenum and the patient completed a 6 week course of amphotericin B lipid complex, followed by an extended course oral intraconazole. She was discharged to a nursing home without evidence of recurrent infection.DiscussionPenicillium chrysogenum is a rare cause of infection in immunocompetent patients. Diagnosis can be difficult, but Penicillium sp. grows rapidly on routine fungal cultures. Prognosis remains very poor, but aggressive treatment is essential, including surgical debridement and the removal of foci of infection along with the use of amphotericin B. The clinical utility of newer antifungal agents remains to be determined.

Ceftaroline-induced eosinophilic pneumonia.

We present a case of eosinophilic pneumonia due to ceftaroline used for the treatment of methicillin‐resistant Staphylococcus aureus bacteremia associated with a postoperative spinal infection. Our patient developed shortness of breath and hypoxemia on the fifth week of ceftaroline therapy. Chest imaging disclosed diffuse bilateral infiltrates. Laboratory abnormalities included peripheral eosinophilia and eosinophilic predominant bronchoalveolar lavage fluid. The combination of ceftaroline discontinuation plus initiation of steroid treatment resulted in complete resolution of signs, symptoms, and radiologic abnormalities. We speculate about possible mechanisms underlying this adverse event and diagnostic criteria for drug‐induced eosinophilic pneumonia.

Staphylococcus aureus pyomyositis compared with non-Staphylococcus aureus pyomyositis

OBJECTIVES Pyomyositis is an acute bacterial infection of skeletal muscle not arising from contiguous infection. It is often hematogenous in origin and typically associated with abscess formation. Our objective was to determine if there were any differences in the clinical presentation of disease between Staphylococcus aureus (SA) and non-Staphylococcus aureus pyomyositis. We also sought to determine if methicillin-resistant SA (MRSA) occurred more frequently during the final years of the study period. METHODS A retrospective chart review study at three institutions in two cities. RESULTS Sixty cases of pyomyositis were identified between 1990 and 2010. Twenty-nine patients were infected with SA while 31 had other bacterial etiologies or were culture negative. Those with a traumatic event prior to the onset of infection were more likely to have a SA infection while SA infected patients were younger. Our first documented case of MRSA occurred in 2005, but the frequency of MRSA infection remained static over the following five years. CONCLUSIONS Pyomyositis is an emerging infection that is underappreciated by many physicians. While MRSA has emerged as the foremost cause of SA infections in a majority of clinical conditions, in this series most patients still had methicillin-sensitive SA as their cause of pyomyositis. In light of the severity of pyomyositis and the potential for bacteremia (either as a source or complication of the infection), empiric SA therapy should be initiated in all patients until the culture results are available.

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) infection is increasingly common. Treatment with vancomycin-based therapy is often unsuccessful. Daptomycin is a relatively new lipopeptide antibiotic with potent activity against MRSA. PURPOSE To describe the successful management of MRSA infection involving the spine. STUDY DESIGN Two case reports of MRSA infection, one involving epidural and lumbar subdural abscesses, the other with osteomyelitis and discitis. METHODS Two cases are described, one with lumbar epidural and subdural abscesses and the other with osteomyelitis and discitis of the spine. Switching from vancomycin to daptomycin plus rifampin-based therapy resulted in patient improvement that allowed discharge from the hospital. RESULTS Both patients recovered fully from their infection. CONCLUSIONS Daptomycin is a safe and effective option for the treatment of MRSA infection involving the spine.

Killing Bugs at the Bedside: A prospective hospital survey of how frequently personal digital assistants provide expert recommendations in the treatment of infectious diseases

BackgroundPersonal Digital Assistants (PDAS) are rapidly becoming popular tools in the assistance of managing hospitalized patients, but little is known about how often expert recommendations are available for the treatment of infectious diseases in hospitalized patients.ObjectiveTo determine how often PDAs could provide expert recommendations for the management of infectious diseases in patients admitted to a general medicine teaching service.DesignProspective observational cohort studySettingInternal medicine resident teaching service at an urban hospital in Dayton, OhioPatients212 patients (out of 883 patients screened) were identified with possible infectious etiologies as the cause for admission to the hospital.MeasurementsPatients were screened prospectively from July 2002 until October 2002 for infectious conditions as the cause of their admissions. 5 PDA programs were assessed in October 2002 to see if treatment recommendations were available for managing these patients. The programs were then reassessed in January 2004 to evaluate how the latest editions of the software would perform under the same context as the previous year.ResultsPDAs provided treatment recommendations in at least one of the programs for 100% of the patients admitted over the 4 month period in the 2004 evaluation. Each of the programs reviewed improved from 2002 to 2004, with five of the six programs offering treatment recommendations for over 90% of patients in the study.ConclusionCurrent PDA software provides expert recommendations for a great majority of general internal medicine patients presenting to the hospital with infectious conditions.

Pneumonia presenting as singultus

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