Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs... more Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs poses treatment challenges. Decisions regarding the need for operation are affected by concern for relapse of IE from ongoing injection drug use (IDU). The purpose of this study was to evaluate the effect of active IDU on outcomes after operation for IE. All patients with IE surgically treated at Cleveland Clinic from July 1, 2007 to July 1, 2012 were identified from the Cleveland Clinic Infective Endocarditis Registry and the Cardiovascular Information Registry. Of 536 patients operated on for IE during the study period, 41 (8%) actively injected drugs. The primary outcome of the study was death or reoperation for IE. Patients who injected drugs had poorer survival free of reoperation, and the risk of events varied with time. In a multivariable Cox proportional hazards model, using time-dependent covariates, IDU was associated with a higher hazard of death or reoperation between 90 and...
ABSTRACT Background: In devising a treatment plan for patients with infective endocarditis (IE), ... more ABSTRACT Background: In devising a treatment plan for patients with infective endocarditis (IE), risk of mortality and complications with medical therapy alone have to be balanced against those with surgery. Decision-making can be improved by knowledge of outcomes in patients undergoing surgery for IE in experienced cardiac centers. Objective: To report contemporary outcomes in patients undergoing cardiac surgery for infectious endocarditis (IE) at Cleveland Clinic. Methods: From 1/2003 to 1/2008, 509 patients underwent surgical treatment of native valve (NVE) or prosthetic valve (PVE) IE. Data abstracted from prospective registries and medical records included demographics, microbiology, operative procedure, and surgical outcomes (Society for Thoracic Surgery National Database definitions). Results: 308 (61%) had NVE, and 201 (39%) had PVE, with or without other NVE. Mean age was 56 yrs and 70% were men. Isolated aortic valve (39%), isolated mitral valve (21%), and combined aortic and mitral (19%) procedures were most common. 21% had concomitant coronary artery bypass grafting. Most common pathogens were CN staphylococci (24%); S. aureus (23%), Streptococcus sp. (18%), and Enterococci (15%). Time from admission to cardiac surgery was 7.6 days. Postoperative stay was 15.3 days. Overall hospital mortality was 9.2%. Complications included reoperation for bleeding (7.5%), respiratory insufficiency (17%), renal failure (6.5%), and stroke (3.1%). Patients undergoing surgery for PVE vs. NVE were likely to have more preoperative heart failure (60% vs. 48%, P<.01), more postoperative renal failure (13% vs. 4.2%, P=.03), and higher hospital mortality (15% vs. 6.5%, P=.02). Conclusions: Approximately 100 patients undergo surgical treatment of IE at our institution annually. Patients with PVE have a significantly higher risk for post operative renal failure and hospital death when compared to patients with native valve IE.
The use of humanized antibody against tumor necrosis factor alpha (TNF-␣) may increase the risk o... more The use of humanized antibody against tumor necrosis factor alpha (TNF-␣) may increase the risk of various opportunistic infections, including tuberculosis and fungal infections. We report a case of cryptococcal pneumonia in a patient who was taking infliximab for rheumatoid arthritis. A temporally related exposure history raised the possibility that our patient acquired the infection from his pet cockatiel. It seems prudent to advise patients receiving infliximab to avoid exposure to pet avian excreta.
Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs... more Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs poses treatment challenges. Decisions regarding the need for operation are affected by concern for relapse of IE from ongoing injection drug use (IDU). The purpose of this study was to evaluate the effect of active IDU on outcomes after operation for IE. All patients with IE surgically treated at Cleveland Clinic from July 1, 2007 to July 1, 2012 were identified from the Cleveland Clinic Infective Endocarditis Registry and the Cardiovascular Information Registry. Of 536 patients operated on for IE during the study period, 41 (8%) actively injected drugs. The primary outcome of the study was death or reoperation for IE. Patients who injected drugs had poorer survival free of reoperation, and the risk of events varied with time. In a multivariable Cox proportional hazards model, using time-dependent covariates, IDU was associated with a higher hazard of death or reoperation between 90 and...
Hepatitis A can cause decompensation and death in patients with previous liver injury. The hepati... more Hepatitis A can cause decompensation and death in patients with previous liver injury. The hepatitis A vaccine is recommended for patients with chronic liver disease. The aim of this study was to screen, immunize, and measure the safety and antibody response of the hepatitis A vaccine in liver failure and liver transplant patients. This was a prospective immunization trial at a referral center for liver disease and liver transplantation. A total of 193 patients with severe chronic liver disease were screened and 24 patients were vaccinated. Sixteen end stage liver disease patients were compared with eight liver transplant patients. Hepatitis A vaccinations using 1440 ELISA units were given at 0 and 2 months. Serum hepatitis A antibody titers were measured after each vaccine dose. An antibody response > or = 33 mIU/ml was considered protective. Screening seropositive rate was 70 of 193 (36%) and 24 patients were available for vaccination. The median antibody titer was markedly low...
Alice Kim, MD, Marion J. Tuohy, MT(ASCP), Steve M. Gordon, MD, Gerri S. Hall, PhD, and Gary W. Pr... more Alice Kim, MD, Marion J. Tuohy, MT(ASCP), Steve M. Gordon, MD, Gerri S. Hall, PhD, and Gary W. Procop, MD, MS ... Mycobacteria cause a variety of human diseases that ... We present 3 scenarios of patients seen at The Cleve-land Clinic Foundation, in which molecular ...
To describe the investigation and interventions necessary to contain an outbreak of methicillin-r... more To describe the investigation and interventions necessary to contain an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in a neonatal intensive care unit (NICU). Retrospective case finding that involved prospective performance of surveillance cultures for detection of MRSA and molecular typing of MRSA by repetitive-sequence polymerase chain reaction (rep-PCR). Level III NICU in a tertiary care center. Three neonates in a NICU were identified with MRSA bloodstream infection on April 16, 2004. A point prevalence survey identified 6 additional colonized neonates (attack rate, 75% [9 of 12 neonates]). The outbreak strain was phenotypically unusual. Cohorting and mupirocin therapy were initiated for neonates who had acquired MRSA during the outbreak. Contact precautions were introduced in the NICU, and healthcare workers (HCWs) were retrained in cleaning and disinfection procedures and hand hygiene. Noncolonized neonates and newly admitted patien...
The Journal of Thoracic and Cardiovascular Surgery, 2014
Objective: Despite increasing efforts to prevent infection, the prevalence of hospital-associated... more Objective: Despite increasing efforts to prevent infection, the prevalence of hospital-associated Clostridium difficile infections (CDI) is increasing. Heightened awareness prompted this study of the prevalence and morbidity associated with CDI after cardiac surgery.
Testing excised valves in surgically treated infective endocarditis (IE) patients provides an opp... more Testing excised valves in surgically treated infective endocarditis (IE) patients provides an opportunity to identify the microbial etiology of IE. Microbial sequencing (universal bacterial, mycobacterial, or fungal polymerase chain reaction followed by DNA sequencing) of valves can identify microorganisms accurately, but the value it adds beyond information provided by blood and valve cultures has not been adequately explored. Three hundred fifty-six patients who underwent surgery for active IE from January 1, 2010, to January 1, 2013, were identified from our cardiovascular information registry and outpatient parenteral antibiotic therapy registry. Their records were reviewed to identify 174 patients whose valves were sent for sequencing. The microbial etiology of IE was defined using comprehensive clinical, pathologic, and microbiological criteria. Blood culture, valve culture, and valve sequencing were examined to determine how frequently they identified the definitive cause of IE. Of the 174 patients, 162 (93%) had acute inflammation on histopathologic examination of their valves. Valve sequencing was significantly more sensitive than valve culture in identifying the causative pathogen (90% versus 31%, p < 0.001), and yielded fewer false positive results (3% versus 33%, p <0.001). The pathogen would not have been identified in 25 patients (15%) had it not been for valve sequencing. All the value provided by sequencing was attributable to bacterial DNA sequencing; mycobacterial and fungal sequencing provided no additional information beyond that provided by blood culture, histopathology, and valve culture. Valve sequencing, not valve culture, should be considered the primary test for identifying bacteria in excised cardiac valves.
Background. Infectious complications continue to represent a significant source of morbidity and ... more Background. Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels.
Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in... more Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate 1.6%) for an incidence of 4.8 cases per 1000 patient-years (33 cases/6813 pt-years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000-pt year vs. heart 0.4% (3/686) or 1.4 per 1000-pt year vs. liver 0.7% (3/439) or 2.1 per 1000-pt year vs. renal 0.4% (3/733) or 1.2 per 1000-pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.
A fatal case of hepatitis C seroconversion following living related kidney transplantation: anoth... more A fatal case of hepatitis C seroconversion following living related kidney transplantation: another argument for nucleic acid amplification testing of transplant recipients and donors To the Editor False-negative test results for hepatitis C virus (HCV) antibodies are not uncommon in patients with end-stage renal disease. In the past few years, new assays based on the molecular detection of HCV RNA have been introduced (1). The main benefit of nucleic acid amplification testing (NAT) is its ability to directly detect the presence of viral nucleic acid, rather than just measure the body's immune response to infection, which is the basis for most standard pretransplant screening tests. We report a patient with end-stage renal disease, without evidence of antibodies to HCV, who underwent a kidney transplant with subsequent hepatitis and death associated with high levels of HCV RNA viremia. A 53-year-old Kuwaiti woman with end-stage renal disease (hypertensive nephrosclerosis) underwent an uncomplicated living related kidney transplant from her daughter. Both recipient and donor had preoperative negative serologic test results for hepatitis B virus (HBV), including HBV core antibody, HBV surface antigen, HBV surface antibody, and a negative HCV antibody enzyme immunoassay (EIA). On postoperative day 60 the patient developed pruritus and painless jaundice (peak serum bilirubin 29.1 mg/dL, AST 210 I/U, ALT 106 I/U). She had a serum HCV RNA of 4,980,000 IU/mL (genotype 1-a), negative serum HBV DNA, and negative serologies for HBV and HCV. Testing of stored (preoperative) sera showed no HCV RNA in the donor, but detectable HCV RNA (1,460,000 IU/mL) in the recipient. A liver biopsy on postoperative day 74 showed fibrosing cholestatic hepatitis consistent with acute HCV. Despite reduction in immunosuppression and treatment with interferon (3 million units thrice weekly) and ribavirin (600 mg daily), she died 8 months after transplantation. This case underscores the benefit of molecular testing methods for HCV in screening potential renal transplant recipients. The US Food and Drug Administration has licensed a nucleic acid test that is intended for screening plasma donors for HIV and HCV infection. We have started 113
Epidemic hypotension in a dialysis center caused by sodium azide The water used for dialysate (di... more Epidemic hypotension in a dialysis center caused by sodium azide The water used for dialysate (dialysis fluid) in hemodialysis centers is produced by water treatment systems (WTS), which require careful and frequent monitoring. On November 3, 1988, nine patients receiving hemodialysis treatments at a single dialysis center suddenly developed hypotension within 30 minutes of onset of dialysis. Eight patients exhibited symptoms and two experienced syncopal episodes; there were no deaths. The incidence of dialysis-associated hypotension occurring within 30 minutes after dialysis onset for these patients was significantly higher during outbreak treatments than during preoutbreak (September 1 through November 2, 1988) treatments, (9 of 9 vs. 0 of 238, P < 0.00001, Fisher's t-test). Sodium azide, a potent hypotensive agent, was identified as the probable contaminant within the WTS of the dialysis center at the time of the outbreak because: I) it was mixed with glycerine as the preservative solution of each of the four ultrafilters that were put on-line in the WTS without rinsing, 12 hours before the outbreak; and 2) high levels of total organic carbons were detected from dialysis water collected at point-of-use sites at the time of the outbreak, suggesting contamination of the WTS with the sodium azide-glycerine preservative solution. To prevent similar occurrences, we recommend that ultrafilters (and other components of the WTS) be rinsed free of potentially toxic chemicals prior to use. Dialysis center personnel need to be aware of the potential affects that each modification or disinfection of the WTS may have upon the product water used to prepare dialysate for patient treatments.
The Journal of Thoracic and Cardiovascular Surgery, 2010
and recurrent aortic insufficiency (>2þ) at 3 years was 100% in the plication-only group and 94% ... more and recurrent aortic insufficiency (>2þ) at 3 years was 100% in the plication-only group and 94% AE 6% and 89% AE 11% in the plication with resuspension group.
Mycobacteria cause a variety of illnesses that differ in severity and public health implications.... more Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. Despite advances in molecular diagnostics, the ability to rapidly diagnose M. tuberculosis infections by PCR is still inadequate, largely because of the possibility of false-negative reactions. We designed and validated a real-time PCR for mycobacteria by using the LightCycler system with 18 reference strains and 168 clinical mycobacterial isolates. All clinically significant mycobacteria were detected; the mean melting temperatures (with 99.9% confidence intervals [99.9% CI] in parentheses) for the different mycobacteria were as follows: M. tuberculosis, 64.35°C (63.27 to 65.42°C); M. kansasii, 59.20°C (58.07 to 60.33°C); M. avium, 57.82°C (57.05 to 58.60°C); M. intracellulare, 54.46°C (53.69 to 55.23°C); M. marinum, 58.91°C (58.28 to 59.55°C); rapidly growing mycobacteria, 53.09°C (50.97 to 55.20°C) or 43.19°C (42.19 to 44.49°C). This real-time PCR assay with melting curve analysis consistently accurately detected and differentiated M. tuberculosis from NTM. Detection of an NTM helps ensure that the negative result for M.
A real-time PCR assay for the mip gene of Legionella pneumophila was tested with 27 isolates of L... more A real-time PCR assay for the mip gene of Legionella pneumophila was tested with 27 isolates of L. pneumophila, 20 isolates of 14 other Legionella species, and 103 non-Legionella bacteria. Eight culture-positive and 40 culture-negative clinical specimens were tested. This assay was 100% sensitive and 100% specific for L. pneumophila.
end-organ disease should help with treatment management. We determined the CMV viral load by hybr... more end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.
Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs... more Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs poses treatment challenges. Decisions regarding the need for operation are affected by concern for relapse of IE from ongoing injection drug use (IDU). The purpose of this study was to evaluate the effect of active IDU on outcomes after operation for IE. All patients with IE surgically treated at Cleveland Clinic from July 1, 2007 to July 1, 2012 were identified from the Cleveland Clinic Infective Endocarditis Registry and the Cardiovascular Information Registry. Of 536 patients operated on for IE during the study period, 41 (8%) actively injected drugs. The primary outcome of the study was death or reoperation for IE. Patients who injected drugs had poorer survival free of reoperation, and the risk of events varied with time. In a multivariable Cox proportional hazards model, using time-dependent covariates, IDU was associated with a higher hazard of death or reoperation between 90 and...
ABSTRACT Background: In devising a treatment plan for patients with infective endocarditis (IE), ... more ABSTRACT Background: In devising a treatment plan for patients with infective endocarditis (IE), risk of mortality and complications with medical therapy alone have to be balanced against those with surgery. Decision-making can be improved by knowledge of outcomes in patients undergoing surgery for IE in experienced cardiac centers. Objective: To report contemporary outcomes in patients undergoing cardiac surgery for infectious endocarditis (IE) at Cleveland Clinic. Methods: From 1/2003 to 1/2008, 509 patients underwent surgical treatment of native valve (NVE) or prosthetic valve (PVE) IE. Data abstracted from prospective registries and medical records included demographics, microbiology, operative procedure, and surgical outcomes (Society for Thoracic Surgery National Database definitions). Results: 308 (61%) had NVE, and 201 (39%) had PVE, with or without other NVE. Mean age was 56 yrs and 70% were men. Isolated aortic valve (39%), isolated mitral valve (21%), and combined aortic and mitral (19%) procedures were most common. 21% had concomitant coronary artery bypass grafting. Most common pathogens were CN staphylococci (24%); S. aureus (23%), Streptococcus sp. (18%), and Enterococci (15%). Time from admission to cardiac surgery was 7.6 days. Postoperative stay was 15.3 days. Overall hospital mortality was 9.2%. Complications included reoperation for bleeding (7.5%), respiratory insufficiency (17%), renal failure (6.5%), and stroke (3.1%). Patients undergoing surgery for PVE vs. NVE were likely to have more preoperative heart failure (60% vs. 48%, P&lt;.01), more postoperative renal failure (13% vs. 4.2%, P=.03), and higher hospital mortality (15% vs. 6.5%, P=.02). Conclusions: Approximately 100 patients undergo surgical treatment of IE at our institution annually. Patients with PVE have a significantly higher risk for post operative renal failure and hospital death when compared to patients with native valve IE.
The use of humanized antibody against tumor necrosis factor alpha (TNF-␣) may increase the risk o... more The use of humanized antibody against tumor necrosis factor alpha (TNF-␣) may increase the risk of various opportunistic infections, including tuberculosis and fungal infections. We report a case of cryptococcal pneumonia in a patient who was taking infliximab for rheumatoid arthritis. A temporally related exposure history raised the possibility that our patient acquired the infection from his pet cockatiel. It seems prudent to advise patients receiving infliximab to avoid exposure to pet avian excreta.
Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs... more Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs poses treatment challenges. Decisions regarding the need for operation are affected by concern for relapse of IE from ongoing injection drug use (IDU). The purpose of this study was to evaluate the effect of active IDU on outcomes after operation for IE. All patients with IE surgically treated at Cleveland Clinic from July 1, 2007 to July 1, 2012 were identified from the Cleveland Clinic Infective Endocarditis Registry and the Cardiovascular Information Registry. Of 536 patients operated on for IE during the study period, 41 (8%) actively injected drugs. The primary outcome of the study was death or reoperation for IE. Patients who injected drugs had poorer survival free of reoperation, and the risk of events varied with time. In a multivariable Cox proportional hazards model, using time-dependent covariates, IDU was associated with a higher hazard of death or reoperation between 90 and...
Hepatitis A can cause decompensation and death in patients with previous liver injury. The hepati... more Hepatitis A can cause decompensation and death in patients with previous liver injury. The hepatitis A vaccine is recommended for patients with chronic liver disease. The aim of this study was to screen, immunize, and measure the safety and antibody response of the hepatitis A vaccine in liver failure and liver transplant patients. This was a prospective immunization trial at a referral center for liver disease and liver transplantation. A total of 193 patients with severe chronic liver disease were screened and 24 patients were vaccinated. Sixteen end stage liver disease patients were compared with eight liver transplant patients. Hepatitis A vaccinations using 1440 ELISA units were given at 0 and 2 months. Serum hepatitis A antibody titers were measured after each vaccine dose. An antibody response > or = 33 mIU/ml was considered protective. Screening seropositive rate was 70 of 193 (36%) and 24 patients were available for vaccination. The median antibody titer was markedly low...
Alice Kim, MD, Marion J. Tuohy, MT(ASCP), Steve M. Gordon, MD, Gerri S. Hall, PhD, and Gary W. Pr... more Alice Kim, MD, Marion J. Tuohy, MT(ASCP), Steve M. Gordon, MD, Gerri S. Hall, PhD, and Gary W. Procop, MD, MS ... Mycobacteria cause a variety of human diseases that ... We present 3 scenarios of patients seen at The Cleve-land Clinic Foundation, in which molecular ...
To describe the investigation and interventions necessary to contain an outbreak of methicillin-r... more To describe the investigation and interventions necessary to contain an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in a neonatal intensive care unit (NICU). Retrospective case finding that involved prospective performance of surveillance cultures for detection of MRSA and molecular typing of MRSA by repetitive-sequence polymerase chain reaction (rep-PCR). Level III NICU in a tertiary care center. Three neonates in a NICU were identified with MRSA bloodstream infection on April 16, 2004. A point prevalence survey identified 6 additional colonized neonates (attack rate, 75% [9 of 12 neonates]). The outbreak strain was phenotypically unusual. Cohorting and mupirocin therapy were initiated for neonates who had acquired MRSA during the outbreak. Contact precautions were introduced in the NICU, and healthcare workers (HCWs) were retrained in cleaning and disinfection procedures and hand hygiene. Noncolonized neonates and newly admitted patien...
The Journal of Thoracic and Cardiovascular Surgery, 2014
Objective: Despite increasing efforts to prevent infection, the prevalence of hospital-associated... more Objective: Despite increasing efforts to prevent infection, the prevalence of hospital-associated Clostridium difficile infections (CDI) is increasing. Heightened awareness prompted this study of the prevalence and morbidity associated with CDI after cardiac surgery.
Testing excised valves in surgically treated infective endocarditis (IE) patients provides an opp... more Testing excised valves in surgically treated infective endocarditis (IE) patients provides an opportunity to identify the microbial etiology of IE. Microbial sequencing (universal bacterial, mycobacterial, or fungal polymerase chain reaction followed by DNA sequencing) of valves can identify microorganisms accurately, but the value it adds beyond information provided by blood and valve cultures has not been adequately explored. Three hundred fifty-six patients who underwent surgery for active IE from January 1, 2010, to January 1, 2013, were identified from our cardiovascular information registry and outpatient parenteral antibiotic therapy registry. Their records were reviewed to identify 174 patients whose valves were sent for sequencing. The microbial etiology of IE was defined using comprehensive clinical, pathologic, and microbiological criteria. Blood culture, valve culture, and valve sequencing were examined to determine how frequently they identified the definitive cause of IE. Of the 174 patients, 162 (93%) had acute inflammation on histopathologic examination of their valves. Valve sequencing was significantly more sensitive than valve culture in identifying the causative pathogen (90% versus 31%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and yielded fewer false positive results (3% versus 33%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The pathogen would not have been identified in 25 patients (15%) had it not been for valve sequencing. All the value provided by sequencing was attributable to bacterial DNA sequencing; mycobacterial and fungal sequencing provided no additional information beyond that provided by blood culture, histopathology, and valve culture. Valve sequencing, not valve culture, should be considered the primary test for identifying bacteria in excised cardiac valves.
Background. Infectious complications continue to represent a significant source of morbidity and ... more Background. Infectious complications continue to represent a significant source of morbidity and mortality in lung transplant recipients. Identifying specific, remediable immune defects is of potential value. After one lung transplant patient with recurrent infections was noted to be severely hypogammaglobulinemic, a screening program for humoral immune defects was instituted. The objectives were to define the prevalence of hypogammaglobulinemia in lung transplant recipients, assess levels of antibody to specific pathogens, and correlate infectious disease outcomes and survival with immunoglobulin levels.
Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in... more Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate 1.6%) for an incidence of 4.8 cases per 1000 patient-years (33 cases/6813 pt-years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000-pt year vs. heart 0.4% (3/686) or 1.4 per 1000-pt year vs. liver 0.7% (3/439) or 2.1 per 1000-pt year vs. renal 0.4% (3/733) or 1.2 per 1000-pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.
A fatal case of hepatitis C seroconversion following living related kidney transplantation: anoth... more A fatal case of hepatitis C seroconversion following living related kidney transplantation: another argument for nucleic acid amplification testing of transplant recipients and donors To the Editor False-negative test results for hepatitis C virus (HCV) antibodies are not uncommon in patients with end-stage renal disease. In the past few years, new assays based on the molecular detection of HCV RNA have been introduced (1). The main benefit of nucleic acid amplification testing (NAT) is its ability to directly detect the presence of viral nucleic acid, rather than just measure the body's immune response to infection, which is the basis for most standard pretransplant screening tests. We report a patient with end-stage renal disease, without evidence of antibodies to HCV, who underwent a kidney transplant with subsequent hepatitis and death associated with high levels of HCV RNA viremia. A 53-year-old Kuwaiti woman with end-stage renal disease (hypertensive nephrosclerosis) underwent an uncomplicated living related kidney transplant from her daughter. Both recipient and donor had preoperative negative serologic test results for hepatitis B virus (HBV), including HBV core antibody, HBV surface antigen, HBV surface antibody, and a negative HCV antibody enzyme immunoassay (EIA). On postoperative day 60 the patient developed pruritus and painless jaundice (peak serum bilirubin 29.1 mg/dL, AST 210 I/U, ALT 106 I/U). She had a serum HCV RNA of 4,980,000 IU/mL (genotype 1-a), negative serum HBV DNA, and negative serologies for HBV and HCV. Testing of stored (preoperative) sera showed no HCV RNA in the donor, but detectable HCV RNA (1,460,000 IU/mL) in the recipient. A liver biopsy on postoperative day 74 showed fibrosing cholestatic hepatitis consistent with acute HCV. Despite reduction in immunosuppression and treatment with interferon (3 million units thrice weekly) and ribavirin (600 mg daily), she died 8 months after transplantation. This case underscores the benefit of molecular testing methods for HCV in screening potential renal transplant recipients. The US Food and Drug Administration has licensed a nucleic acid test that is intended for screening plasma donors for HIV and HCV infection. We have started 113
Epidemic hypotension in a dialysis center caused by sodium azide The water used for dialysate (di... more Epidemic hypotension in a dialysis center caused by sodium azide The water used for dialysate (dialysis fluid) in hemodialysis centers is produced by water treatment systems (WTS), which require careful and frequent monitoring. On November 3, 1988, nine patients receiving hemodialysis treatments at a single dialysis center suddenly developed hypotension within 30 minutes of onset of dialysis. Eight patients exhibited symptoms and two experienced syncopal episodes; there were no deaths. The incidence of dialysis-associated hypotension occurring within 30 minutes after dialysis onset for these patients was significantly higher during outbreak treatments than during preoutbreak (September 1 through November 2, 1988) treatments, (9 of 9 vs. 0 of 238, P < 0.00001, Fisher's t-test). Sodium azide, a potent hypotensive agent, was identified as the probable contaminant within the WTS of the dialysis center at the time of the outbreak because: I) it was mixed with glycerine as the preservative solution of each of the four ultrafilters that were put on-line in the WTS without rinsing, 12 hours before the outbreak; and 2) high levels of total organic carbons were detected from dialysis water collected at point-of-use sites at the time of the outbreak, suggesting contamination of the WTS with the sodium azide-glycerine preservative solution. To prevent similar occurrences, we recommend that ultrafilters (and other components of the WTS) be rinsed free of potentially toxic chemicals prior to use. Dialysis center personnel need to be aware of the potential affects that each modification or disinfection of the WTS may have upon the product water used to prepare dialysate for patient treatments.
The Journal of Thoracic and Cardiovascular Surgery, 2010
and recurrent aortic insufficiency (>2þ) at 3 years was 100% in the plication-only group and 94% ... more and recurrent aortic insufficiency (>2þ) at 3 years was 100% in the plication-only group and 94% AE 6% and 89% AE 11% in the plication with resuspension group.
Mycobacteria cause a variety of illnesses that differ in severity and public health implications.... more Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. Despite advances in molecular diagnostics, the ability to rapidly diagnose M. tuberculosis infections by PCR is still inadequate, largely because of the possibility of false-negative reactions. We designed and validated a real-time PCR for mycobacteria by using the LightCycler system with 18 reference strains and 168 clinical mycobacterial isolates. All clinically significant mycobacteria were detected; the mean melting temperatures (with 99.9% confidence intervals [99.9% CI] in parentheses) for the different mycobacteria were as follows: M. tuberculosis, 64.35°C (63.27 to 65.42°C); M. kansasii, 59.20°C (58.07 to 60.33°C); M. avium, 57.82°C (57.05 to 58.60°C); M. intracellulare, 54.46°C (53.69 to 55.23°C); M. marinum, 58.91°C (58.28 to 59.55°C); rapidly growing mycobacteria, 53.09°C (50.97 to 55.20°C) or 43.19°C (42.19 to 44.49°C). This real-time PCR assay with melting curve analysis consistently accurately detected and differentiated M. tuberculosis from NTM. Detection of an NTM helps ensure that the negative result for M.
A real-time PCR assay for the mip gene of Legionella pneumophila was tested with 27 isolates of L... more A real-time PCR assay for the mip gene of Legionella pneumophila was tested with 27 isolates of L. pneumophila, 20 isolates of 14 other Legionella species, and 103 non-Legionella bacteria. Eight culture-positive and 40 culture-negative clinical specimens were tested. This assay was 100% sensitive and 100% specific for L. pneumophila.
end-organ disease should help with treatment management. We determined the CMV viral load by hybr... more end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.
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Papers by Steven Gordon