Mycobacterium abscessus infection in solid organ transplant recipients: report of three cases and review of the literature.

Mycobacterium abscessus is an ubiquitous organism found in the environment. This rapidly growing mycobacterium infrequently causes disease in humans; however, in immunocompromised hosts, disease can range from localized cutaneous lesions to disseminated infection. The organism is resistant to most antimycobacterial drugs and therapy can be limited by drug interactions. The exact incidence of M. abscessus infection among solid organ transplant (SOT) recipients is unknown; data are only available from previously reported cases in the literature. We describe 3 cases of M. abscessus infection in SOT recipients diagnosed within a 5-month period. One of the cases followed multi-visceral transplantation, the first such case to be reported in the literature. An epidemiological investigation did not reveal significant commonalities among the cases, and pulsed-field gel electrophoresis of genomic DNA of the case isolates confirmed their non-identity. All cases improved with antibiotic therapy, most notably with the new glycylcycline, tigecycline, along with surgical intervention in 2 of the cases. In addition, we review features and characteristics of M. abscessus infections in recipients of SOT reported in the literature from 1992 to 2008 and summarize some selected therapeutic concerns and issues related to treatment.

A case of subcutaneous Mycoleptodiscus indicus infection in a liver transplant recipient successfully treated with antifungal therapy.

Mycoleptodiscus indicus, a dematiaceous mold, occurs on the leaves of a number of different host plants and has been only recently described as a cause of human infection. Immunosuppressed individuals are at risk for developing infections with opportunistic fungal pathogens, which are a major cause of morbidity and mortality in this population. In addition, the treatment of infections caused by these fungi is frequently challenging. We report a case of M. indicus subcutaneous infection in a 51-year-old man with human immunodeficiency virus and hepatitis C co-infection, who had a liver transplant. He developed skin nodules with a sporotrichoid lymphangitic distribution. Histopathology demonstrated unusual fungal elements with angioinvasion. Mycology cultures isolated a dematiaceous mold with the characteristic curved hyaline conidia of M. indicus. Initial treatment involved a combination of amphotericin B lipid complex and voriconazole, followed by monotherapy with voriconazole. The subcutaneous lesions resolved completely after 4 months of antifungal therapy.

Antimicrobial activity of UMFix tissue fixative.

AIMS: The aim of this study was to determine the antimicrobial effects of UMFix, an alcohol based tissue fixative, on various microorganisms. The UMFix solution was compared with 10% neutral buffered formalin. METHODS: Standard methods to determine microorganism colony counts were performed after exposure of the microorganisms to UMFix and 10% neutral buffered formalin. RESULTS: After a short exposure, UMFix rapidly killed vegetative bacteria, yeasts, moulds, and viruses. Bacterial spores were resistant to killing by UMFix. All organisms were killed by the 10% neutral buffered formalin preparation. CONCLUSIONS: UMFix was microbicidal for vegetative bacteria, yeasts, and aspergillus species after a short exposure, although it was not active against spore forming bacillus species. The methanol content of the fixative was responsible for the killing effect of this fixative. No killing was seen when polyethylene glycol was used alone.

Steady state hemodynamic and energetic characterization of the Penn State/3M Health Care Total Artificial Heart.

Total Artificial Heart (TAH) development at Penn State University and 3M Health Care has progressed from design improvements and manufacturing documentation to in vitro and in vivo testing to characterize the system's hemodynamic response and energetic performance. The TAH system is completely implantable and intended for use as an alternative to transplantation. It includes a dual pusher plate pump and rollerscrew actuator, welded electronics and battery assembly, transcutaneous energy transmission system, telemetry, and a compliance chamber. In vitro testing was conducted on a Penn State mock circulatory loop with glycerol/water solution at body temperature. Tests were performed to characterize the preload and afterload response, left atrial pressure control, and power consumption. A sensitive preload response was demonstrated with left atrial pressure safely maintained at less than 15 mm Hg for flow rates up to 7.5 L/min. Variations in aortic pressure and pulmonary vascular resistance were found to have minimal effects on the preload sensitivity and left atrial pressure control. In vivo testing of the completely implanted system in its final configuration was carried out in two acute studies using implanted temperature sensors mounted on the electronics, motor, and energy transmission coil in contact with adjacent tissue. The mean temperature at the device-tissue interface was less than 4 degrees C above core temperature.

Dynamic in vitro and in vivo performance of a permanent total artificial heart.

In vivo characterization studies were performed to compare the dynamic in vivo performance of the Penn State/3M Health Care electric total artificial heart to existing in vitro data. Fully implanted systems were utilized including the artificial heart, controller, backup batteries, compliance chamber, and transcutaneous energy transmission. Catheters were implanted to measure central venous pressure (CVP), left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure (PAP), and aortic pressure (AoP). Cardiac output (CO) was determined from the implanted controller, and systemic vascular resistance (SVR) was calculated. Steady state data were collected for each animal along with data regarding the transient responses to changes in preload and afterload. Preload was manipulated through volume changes. Afterload changes were accomplished through vasoactive agents. Increased preload caused little change in cardiac output because the pump output was nearly maximum at baseline. LAP, AoP, and SVR increased with increasing RAP. Decreased preload caused a reduction in CO, LAP, and SVR. Afterload increase resulted in a slight decrease in flow and an increase in system power and SVR. Afterload reduction was accompanied by a decrease in preload and a concomitant reduction in flow. Overall, the system response was similar to the response observed in vitro.

The effect of diet on the bearing mucosa during adjustment to new complete dentures: a pilot study.

PURPOSE: This pilot study investigated the reliability of the conventional prosthodontic wisdom that a modified diet ameliorates soreness during the adjustment to new complete dentures. Tissue ulceration of the bearing mucosa served as the indicator of patient soreness as a function of diet. MATERIAL AND METHODS: Fourteen men were randomly assigned to two equal treatment groups. One group consumed a consistency-gradated diet and the other (control) ate as they wished. New complete dentures were fabricated for both groups by the same provider, technician, materials, and method; the study was double-blinded. Tissue ulceration was assessed and totaled for the 10 days after denture placement, constituting a soreness score. RESULTS: Data analysis identified a significant difference in soreness scores between dietary groups (p < 0.05). Wearing time had a significant inverse relation to soreness (p < 0.05) in this study. A host of potential explanatory variables of clinical interest failed to relate significantly to the outcome of soreness. CONCLUSIONS: The results of this study indicated that a consistency-gradated diet had a significant effect in diminishing tissue ulceration during the immediate postplacement period for this group of men. Potentially, these findings could contribute to enhanced quality of care and to the more efficient allocation of provider-based resources.

An assessment of the association between functional edentulism, obesity, and NIDDM.

OBJECTIVE: To assess the association between a measure of extensive tooth loss (functional edentulism) and obesity with non-insulin-dependent diabetes mellitus (NIDDM) in a racially heterogeneous sample. RESEARCH DESIGN AND METHODS: A cross-sectional survey (370 subjects) was performed by reviewing the medical and dental records of dependently or independently living individuals who were treated as inpatients and/or outpatients at a Department of Veterans Affairs facility. Frequencies and descriptive measures were derived; univariate and multiple logistic regression analyses were conducted to test for associations, confounding, effect modification, and interaction using functional edentulism and obesity as the independent variables and NIDDM as the dependent measure. RESULTS: Functionally edentulous individuals were at significantly greater risk for NIDDM (estimated odds ratio [OR] = 4.06), than the obese (OR = 3.29). These relationships were not confounded by age or race in this sample. Obesity did confound functional edentulism in the multivariable model, suggesting that they act independently on the outcome variable (NIDDM). CONCLUSIONS: Dentist-assessed functional edentulism and physician-diagnosed obesity were significantly associated with NIDDM in this sample of predominantly older men. This finding ought to be considered by primary care providers in formulating dietary strategies in order to facilitate the realization of their therapeutic goals.

Evaluation of Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test and PCR for direct detection of Mycobacterium tuberculosis in clinical specimens.

The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTD) is a direct specimen assay for the identification of Mycobacterium tuberculosis from respiratory samples. rRNA is amplified, and the product is detected with a specific chemiluminescent probe. We performed a retrospective evaluation of three separate respiratory specimens from each of 250 patients by using the AMTD and compared the results with those of microscopy, culturing, and a patient chart review. From the latter results, 198 patients (594 specimens) were found negative for M. tuberculosis by culturing and clinical criteria. The overall specificity of the AMTD after discrepancy resolution was 98.5% (585 of 594). There were 52 patients with culture-proven and/or clinically diagnosed tuberculosis. Of these 156 specimens, the organism was cultured from 142 (91%), and acid-fast microscopy was positive for 105 (67.3%). The AMTD was positive for 142 (91%) specimens from these patients. Tuberculosis patient samples were tested by a PCR assay which uses primers for amplification of the IS6110 insertion sequence of the M. tuberculosis complex. The PCR assay detected 144 of the 156 (92.3%) specimens. Overall, when three specimens per patient were examined, the AMTD found all 52 patients positive for tuberculosis, while the PCR assay found 51 patients positive by agarose gel analysis and all 52 patients positive by Southern blot hybridization.

An annular compliance chamber for the Pennsylvania State University electric total artificial heart.

To eliminate the need for a separate parapleural compliance chamber, we are currently investigating the feasibility of an annular compliance chamber. This chamber wraps around the energy converter and fits between the blood pumps of the Pennsylvania State University electric total artificial heart. For the 100 cc total artificial heart, the compliance chamber volume is 76 ml and the tissue contacting surface area is approximately 85 cm2. The chamber is made of Dacron velour covered segmented polyether polyurethane urea. The annular compliance chamber was evaluated in vitro by comparing pump balance control performance against that obtained with an open vent. In the CVP range of 5-12 mmHg, LAP was maintained within 1 mmHg of the values obtained with a vent. Studies continue to determine the range of volumes over which the chamber is effective, differences in rates of diffusion, and performance during changes in barometric pressure.

Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control.

Dramatic reductions in the incidence of diphtheria and high levels of childhood vaccination in recent decades have led the United States to establish the goal of diphtheria elimination among persons < or = 25 years of age by the year 2000. In 1990, an unimmunized 25-month-old child died of respiratory diphtheria in Dade County, Florida, before treatment with diphtheria antitoxin could be instituted. Twenty-three asymptomatic household contacts and other close contacts of the child were identified, cultured for Corynebacterium diphtheriae, given antimicrobial prophylaxis, and vaccinated with diphtheria toxoid when indicated. Three contacts (13%) had pharyngeal cultures positive for toxigenic C. diphtheriae of the same type as that causing infection in the deceased child, but no additional cases developed. Although the source of infection was not determined, three other close contacts had recently been to Haiti, where diphtheria is endemic. A serological survey of 396 children < 5 years of age who received care at a medical center in Dade County revealed that 22% lacked protective immunity to diphtheria. Attainment of the goal of diphtheria elimination among persons < or = 25 years of age--and ultimately among all persons--will depend on the maintenance of a high level of clinical awareness of the disease, the prompt institution of preventive measures among close contacts of patients with sporadic cases, and improved vaccination levels among infants, children, and adults.

An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection.

OBJECTIVE: To evaluate a nosocomial outbreak of tuberculosis caused by multiple-drug-resistant bacilli among patients with tuberculosis and HIV infection. DESIGN: A case-control study. PATIENTS: Patients with HIV infection and culture-proven tuberculosis. MEASUREMENTS: Patient characteristics, date of diagnoses of HIV infection and disease, date of diagnosis of tuberculosis, Mycobacterium tuberculosis susceptibility results, and medical center contact. RESULTS: Sixty-two patients who had tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients who had tuberculosis caused by susceptible or single-drug-resistant bacilli (controls) were identified. Controls were more likely to be black (odds ratio, 0.4; 95% CI, 0.2 to 0.9) or Haitian (odds ratio, 0.2; CI, 0.1 to 0.6) compared with cases, who were more likely to be homosexual men (odds ratio, 2.9; CI, 1.3 to 6.4). Forty-four cases (71%) had previous contact with an HIV clinic compared with 15 controls (27%) (P less than 0.0001). Cases were more likely to have had AIDS (odds ratio, 7.7; CI, 1.5 to 53.7), to have been hospitalized on an HIV ward (odds ratio, 8.3; CI, 2.3 to 29.7), to have been seen in an HIV clinic (odds ratio, 7.8; CI, 3.4 to 18.1), to have received intravenous therapy in an HIV clinic (odds ratio, 13.0; CI, 4.6 to 37.0), or to have received inhalation pentamidine in an HIV clinic before a diagnosis of tuberculosis was made. Multiple logistic regression analysis showed that a diagnosis of AIDS (odds ratio, 11.2; CI, 3.1 to 40.6) and HIV clinic visits (odds ratio, 13.0; CI, 2.7 to 63.7) before a diagnosis of tuberculosis were significantly associated with tuberculosis caused by multiple-drug-resistant bacilli. Using susceptibility patterns and appointment dates, we found that 22 cases had previous contact with a person who had tuberculosis caused by multiple-drug-resistant bacilli in the HIV clinic. CONCLUSIONS: Nosocomial transmission of M. tuberculosis from other HIV-infected patients with tuberculosis caused by multiple-drug-resistant bacilli can occur. These findings have serious public health implications and demand strict adherence to acid-fast bacilli isolation precautions.

Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli.

OBJECTIVE: To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug-resistant bacilli compared with those with single-drug-resistant or susceptible bacilli. DESIGN: Descriptive, case-control, and cohort studies. SETTING: A large urban teaching hospital. PATIENTS: Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls). MEASUREMENTS: Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course. RESULTS: Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test). CONCLUSIONS: Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality.

Antimicrobial susceptibility patterns of the Bacteroides fragilis group in the United States, 1989.

A national survey of Bacteroides fragilis group was continued in 1989 for the ninth consecutive year. Seven hundred thirty-nine isolates of B fragilis group from eight centers were tested for susceptibility to 14 antimicrobials. Sulbactam and clavulanic acid, beta-lactamase inhibitors, were tested at a constant concentration of 8 micrograms/ml and 2 micrograms/ml, respectively. Sulbactam was also tested in a fixed ratio of 1:2. Imipenem, ampicillin+sulbactam, and ticarcillin+clavulanic acid had resistance of less than 1% at breakpoints of 8 micrograms/ml, 16 micrograms/ml, and 64 micrograms/ml, respectively. At 32 micrograms/ml, resistance to cefoxitin, cefotetan, ceftizoxime, and ceftriaxone were 4%, 25%, 26%, and 46%, respectively. Clindamycin resistance was 10% at a breakpoint of 4 micrograms/ml. No isolates were resistant to chloramphenicol or metronidazole. Resistance for five B fragilis species to cefoxitin, ceftizoxime, and cefotetan varied greatly among both species and participating institutions. The addition of a beta-lactamase inhibitor increased the potency of the beta-lactam drugs tested as combinations. This finding suggests that beta-lactamase production is the major resistance factor in members of the B fragilis group.

Detection of herpesvirus DNA in vitreous and aqueous specimens by the polymerase chain reaction.

Members of the herpesvirus family, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV), have been recognized as causal agents of chorioretinal inflammatory diseases. We investigated the use of the polymerase chain reaction for the detection of CMV, HSV, and EBV genomes in aqueous, subretinal fluid, and vitreous specimens in patients with clinically diagnosed CMV retinitis. Cytomegalovirus but not HSV or EBV genomic sequences were detected in all of these clinical specimens. We also investigated 18 normal aqueous and eight normal vitreous specimens obtained from patients undergoing cataract or vitrectomy surgery. Cytomegalovirus, HSV, and EBV DNA were not detected in any of the normal aqueous specimens. There was one weakly positive CMV normal vitreous, but none was HSV or EBV positive by the polymerase chain reaction. These results indicate that the polymerase chain reaction may be useful as a rapid and sensitive diagnostic technique to aid in the confirmation of clinical observations.

Permanent circulatory support systems at the Pennsylvania State University.

Permanent circulatory support systems are required for patients in whom myocardial damage is irreversible and cardiac transplantation is not possible. Two systems are described which provide long term circulatory support: the left ventricular assist system and the total artificial heart. These systems are based on the design of a pusher plate actuated blood pump, driven by a small brushless dc electric motor and rollerscrew driver. An implantable motor controller maintains suitable physiologic flow rates for both systems and controls left-right balance in the total artificial heart. Other parts of the system include an intra-thoracic compliance chamber, transcutaneous energy and data transmission system, and internal and external batteries.

Acquired immunodeficiency syndrome associated with Acanthamoeba infection and other opportunistic organisms.

A 29-year-old Haitian man with acquired immunodeficiency syndrome presented with nasal obstruction and epistaxis. A computed tomogram of the head showed thickened nasal and paranasal sinus mucosa. A biopsy specimen of the turbinate disclosed inflammatory tissue containing amoebic trophozoites. The patient was empirically treated with rifampin and ketoconazole. He died four months after biopsy of other complications of acquired immunodeficiency syndrome. At autopsy, the amoebic infection was found only in the paranasal sinuses, a calf nodule, and in an intradermal abscess in the left leg. Pneumocystitis carinii pneumonia, Mycobacterium avium-cellulare in the liver and retroperitoneal lymph nodes, cytomegalovirus infection of the adrenal glands, and Kaposi's sarcoma in the spleen were additionally present. The organism was cultured and studied by electron microscopy, dark-field microscopy, and immunofluorescence.

Immunohistologic identification of fungi in systemic and cutaneous mycoses.

Using specific antibodies and the peroxidase-antiperoxidase technique, we were able to demonstrate a variety of fungal organisms in smears and sections of formaldehyde-fixed, paraffin-embedded tissue. The procedure is simple, fast, and accurate and may be used as an alternative to, or in conjunction with, cultural methods to identify fungi specifically.

Salmonella bacteremia as manifestation of acquired immunodeficiency syndrome.

Multiple opportunistic infections are characteristic of the acquired immunodeficiency syndrome (AIDS). Although bacterial pathogens have presented few problems, we have noted an emerging problem with salmonellal infection among patients with AIDS. A review of all stool and blood cultures from adults between January 1982 and July 1984 showed that 80 stool cultures were positive for Salmonella species; serogroup B was the most common isolated. Eight (10%) were isolated from patients with AIDS. Nineteen blood cultures were positive for Salmonella species. Six (32%) were isolated from patients with AIDS: three were positive for Salmonella serogroup B; two yielded Salmonella choleraesuis; and one yielded Salmonella serogroup D. In three (50%), Salmonella bacteremia was a presenting manifestation of AIDS. Bacteremias were recurrent in five patients. Thus, it appears that AIDS not only predisposes patients to serious salmonellal infections but also compromises their ability to eradicate these bacteria.

Evaluation of the API latex conjugate reagent for serological typing of Salmonella and Shigella species.

The serological types of Salmonella and Shigella isolates were determined by using the SerImm Sure latex conjugates (Analytab Products, Plainview, N.Y.) and the standard slide agglutination test. The Salmonella latex conjugates correctly typed 114 of the 115 Salmonella isolates found in serogroups A through F; 50% these isolates were from serogroups B. The Shigella latex conjugates correctly typed 87 of the 92 Shigella isolates; 87% of these isolates were from serogroups B and D.