Christopher Ledtke

Cleveland Clinic, Cleveland, OH, United States

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Publications (5)7 Total impact

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    ABSTRACT: Endovascular infection is an uncommon but devastating manifestation of histoplasmosis, which is often diagnosed late in disease. To evaluate the clinical and pathologic characteristics of patients with endovascular infections caused by Histoplasma capsulatum. 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. 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. 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.
    Archives of pathology & laboratory medicine 06/2012; 136(6):640-5. · 2.78 Impact Factor
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    ABSTRACT: To describe the influence of age on clinical features of histoplasmosis. Retrospective single-center cohort study. Large tertiary care center. All individuals who met criteria for probable or proven histoplasmosis between 1998 and 2008. 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. 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). 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.
    Journal of the American Geriatrics Society 02/2012; 60(2):265-70. · 4.22 Impact Factor
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    ABSTRACT: Background: Infectious Endocarditis (IE) caused by candida species is increasing in incidence in recent years. Much of the data is derived from large case series including patients from multiple centers with a lack of follow up data. We present the largest case series to date from a single center with an active cardiac surgery service. Methods: Cases were ascertained using the Cardiovascular Information Registry and Diagnosis Related Group database searching for patients with a diagnosis of fungal or candidal infections and cross-matching with those diagnosed with endocarditis from 9/1996-3/2011. Case definition included those who met search criteria and were confirmed to have definite IE based on modified Duke’s criteria with candida species being the etiologic agent. Results: Thirty-five patients met case definition. Sixteen (46%) had a central venous catheter, 24 (69%) had a prosthetic valve, 8 (23%) had a pacemaker or defibrillator, 12 (34%) had a history of IE and 8 (23%) were IV drug abusers. Blood cultures were positive in 31 (89%), valve cultures in 83% and fungal smear in 63% of valves examined. Echocardiogram suggested IE in 22 (63%) and 29 (83%) patients on surface and transesophageal respectively. C. albicans was seen in 18 (51%) and C. parapsilosis in 11 (31%). Additional species included C. lusitaniae, C. tropicalis, C. dublinensis and C. krusei. Heart failure from IE occurred in 13 (37%), embolism in 18 (51%) and myocardial abscess in 13 (37%). Ten patients (29%) died prior to discharge and 13 (37%) within 6 months. Twenty-seven patients (77%) were treated surgically. There was no significant difference in in-hospital mortality or all-cause mortality at 6 months between surgically and non-surgically treated patients. Echinocandins were the predominant therapy in 8 (23%). There was no significant difference between those treated with echinocandins in in-hospital mortality or all-cause mortality at 6 months. Conclusion: Our data is consistent with prior reports of candida IE in regards to complications and outcomes. Echinocandin use is becoming an acceptable treatment alternative with similar outcomes compared to those without echinocandin use. Likewise, mortality data was similar between surgical and non-surgically treated patients.
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
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    ABSTRACT: Background: The microbial diagnosis of infective endocarditis (IE) requires the incorporation of routine blood and valve tissue cultures along with interpretation of tissue pathology in patients with a high clinical suspicion for disease. Molecular microbiological techniques are increasingly being utilized, particularly in patients with negative routine cultures. Methods: We evaluated all patients at our facility who had heart valve specimens tested by universal PCR (followed by sequencing) after valve surgery for suspected IE between January 1, 2010 and April 1, 2011. The electronic medical record for each patient was reviewed to examine specific aspects of their diagnostic process and to determine the contribution of blood culture, valve culture, and valve PCR to the etiologic diagnosis of IE. Results: Among the 61 patients who were included in the study, 52 were considered to have definite IE based on microbiology, histopathology and clinical picture. Histopathological examination found evidence of inflammation (either acute or chronic) in 37 (71%) patients, and microorganisms on special staining in 26 (50%) patients. Among those with definite IE, 40 (77%) had positive valve tissue PCR results, 27 (52%) had positive blood cultures and 20 (38%) had positive valve cultures. The relative contributions of valve PCR, valve culture and blood culture to the etiological diagnosis of IE are displayed in the Venn diagram (Figure). In 13 patients (25% of patients with definite IE), a positive valve PCR was the only clue to the microbiologic diagnosis. The pathogens identified solely by PCR included viridans streptococcus, Bartonella species, Propionibacterium acnes, Enterococcus faecalis and Streptococcus agalactiae. There were 2 patients with discrepant results wherein a different pathogen was isolated from blood or valve cultures than that found on PCR. Conclusion: Molecular techniques are a valuable addition to the diagnostic armamentarium for the diagnosis of IE. When used systematically this may be the only method that provides an etiologic diagnosis. Figure. Venn diagram showing the number of patients who had positive PCR, valve culture and blood culture results (all negative in 13 patients).
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
  • Christopher Ledtke, J. Walton Tomford
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    ABSTRACT: Background: Histoplasmosis is an important endemic mycosis. Here we describe the influence of age on the diagnosis of histoplasmosis in a large single center cohort. Methods: The electronic medical record was reviewed for patients diagnosed with histoplasmosis at the Cleveland Clinic from 1998 to 2008. Positive pathology specimens, serology, urine antigen, or cultures were required for inclusion. We compared patients younger than 50 years old (group I) with those 50 years old or older (group II) at the time of presentation. JMP software (SAS, Cary, NC) was used for statistical analysis. Results: A total of 361 patients were included in this study. Median age at presentation was 53 years (range 7-84, 7 patients <18 years old). In group I (n=152) vs. group II (n=209), 52% vs. 60% were male (NS), 87% vs. 96% were white (p<0.01), 26% vs. 20% were immunocompromised (NS). Older patients were more likely to have malignancy (13% vs. 30%, p<0.001), COPD (3% vs. 22%, p<0.001), or DM (7% vs. 15%, p=0.03). Significant differences were found in diagnostic category, serology in asymptomatic patients, the presence of non-necrotizing granulomas, mean SUV on PET scans, and hilar lymphadenopathy on CXR in acute pulmonary histoplasmosis (see table, *p value for distribution of categories). In acute pulmonary histoplasmosis a trend towards less necrotizing granulomas in older adults was seen (30/35 [86%] vs. 25/38 [66%] in I vs. II, p=0.06). No differences were seen in urinary antigen positivity (overall positive in 39/148 [26%]), CT (single or multiple nodules seen in 197/300 [66%]), and other CXR manifestations. n=361 Age<50 (n=152) Age≥50 (n=209) p Asymptomatic pulmonary 55 (36) 115 (55) <0.01* Serology positive/sent (%) 30/43 (70) 36/77 (47) 0.012 Non-necrotizing granuloma positive/sent (%) 9/32 (28) 11/93 (12) 0.048 Acute pulmonary, n (%) 51 (33) 53 (25) Non-necrotizing granuloma positive/sent (%) 5/35 (14) 14/38 (37) 0.035 SUV in PET positive, Mean (n, SD) 7.7 (10, 4.7) 4.8 (15, 3.1) 0.039 CXR hilar LAD positive/sent (%) 16/51 (31) 4/53 (8) <0.01 Chronic pulmonary, n (%) 10 (6) 21 (10) Disseminated or Other, n (%) 36 (24) 20 (10) Conclusions: In this large, single center cohort of patients with histoplasmosis, patients aged 50 years or older were more likely to present with asymptomatic or chronic histoplasmosis. Establishing the diagnosis in older patients may be more difficult, as asymptomatic older patients are less likely to have positive serology, and symptomatic older patients are less likely to have hilar LAD on CXR.
    Infectious Diseases Society of America 2009 Annual Meeting; 10/2009