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.

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.

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.

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.

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.

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.

Effects of inducible beta-lactamase and antimicrobial resistance upon the activity of newer beta-lactam antibiotics against Pseudomonas aeruginosa.

The activity of carbenicillin, ticarcillin, piperacillin, cefotaxime, moxalactam, and N-formimidoyl thienamycin was evaluated against 262 clinical isolates of Pseudomonas aeruginosa. There were 242 (92%) of the isolates that were susceptible to carbenicillin or ticarcillin by an agar dilution method. Against this population of susceptible isolates, the median MICs were 1.56 microgram/ml of N-formimidoyl thienamycin, 3.13 microgram/ml of piperacillin, 25 microgram/ml of ticarcillin, 25 microgram/ml of cefotaxime, 50 microgram/ml of carbenicillin and 50 microgram/ml of moxalactam. N-Formimidoyl thienamycin was the only beta-lactam antibiotic not affected by an inducible beta-lactamase detected in 24 randomly selected susceptible isolates by a disk approximation assay, while cefotaxime was inactivated to a greater extent than any of the other beta-lactam antibiotics. Resistance to carbenicillin and ticarcillin was noted in 20 isolates (8%); these were susceptible to N-formimidoyl thienamycin, but cross-resistance with piperacillin, cefotaxime, and moxalactam was frequent. Only four of these resistant isolates were found to have a constitutive beta-lactamase. Gentamicin resistance occurred in 51 isolates (19%) and was an independent variable of resistance to the beta-lactam drugs.

Disseminated Mycobacterium avium-intracellulare infection appearing as a panniculitis.

A 34-year-old woman had wide-spread panniculitis due to a disseminated infection with Mycobacteria avium-intracellulare. The patient had previously received treatment with high dosages of corticosteroids. Suppurative lesions teeming with acid-fast bacilli and without formation of granulomas were found in many organs, including the skin, mediastinum, spleen, liver, and gastrointestinal tract. Both the appearance of disseminated M avium-intracellular infection resembling panniculitis and the involvement of mediastinum have not previously been reported, to our knowledge.

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.

Modifying cerebral candidiasis by altering the infectious entry route.

Diffuse leptomeningitis did not occur in healthy adult male Wistar rats with transient candidemia produced by the injection of organisms into the internal carotid artery, even though intraparenchymal microabscesses with yeasts and pseudohyphae were seen throughout the brain. Candida albicans was culturally identified in the brain and kidney. Injecting the organisms into the cisterna magna caused an infection characterized by lymphocytes and histiocytes and was confined to the leptomeninges. In this meningeal model, fungi were recovered only from the CNS. The overwhelming prevalence at autopsy of cerebral candidal microabscesses without diffuse leptomeningitis is apparently due to transient candidemia. Meningitis due to candidemia is rare and seems to require a microabscess that is accessible to the circulating CSF. This latter event is a late and overwhelming feature of cerebral candidiasis.

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.

The effects of transient candidemia on the brain: preliminary observations on a rodent model for experimental deep candidosis.

Deep candidosis was established in healthy uncompromised Wistar rats by injecting Candida albicans into the right internal carotid artery. Death of these animals could be produced within seven days by injecting 10(7) yeasts. The kidneys were most severely infected, and the entire brain was involved. No animal demonstrated leptomeningitis. Within one to two days microabscesses developed, subsiding into a histiocytic response in five to seven days. By seven days, chronic inflammation with noncaseating granulomas was seen. Throughout the study, cerebrospinal fluid and blood cultures failed to demonstrate the fungus. This rodent model is similar to human cerebral candidosis.

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.

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.

Fungal cerebritis from intravenous drug abuse.

Three intravenous drug abusers (predominantly cocaine) developed a fulminant fungal cerebritis without any other identifiable predisposing factor. Two died and one survived with a severe neurologic deficit. Zygomycetes (nonseptated fungi) were identified in the brain tissue of two victims and Acremonium alabamensis was cultured from the brain tissue of the third. Fulminant fungal cerebritis in intravenous drug abusers (in the absence of any predisposing illness) may represent a unique variant of the acquired immunodeficiency syndrome (AIDS). Future surviving patients should be evaluated for the possibility of a cellular immune deficiency state in order to confirm this impression.

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.

Bacterial agents causing gastroenteritis in various patient populations from South Florida.

A respective review was done on all stool specimens submitted for culture during an 18 month period at 5 hospitals in South Florida. The patient population seen at these hospitals was heterogeneous. All laboratories used a similar methodology for the isolation of enteric pathogens. The number of isolates from all institutions were as follows: (table; see text) The majority of Salmonella und Shigella isolates were from pediatric patients whereas Campylobacter was the major bacterial isolate in the adult population. Yersinia enterocolitica was an infrequent bacterial isolate and was only isolated from pediatric patients. No major outbreak of infection was detected. The distribution of Salmonella serotypes was in agreement with the serotype distribution reported in the United States. Approximately 58% of the isolates were serogroup B, 19% were serogroup C and 13% were serogroup D. Over two-thirds of the Shigella isolates were Shigella sonnei followed by S. flexneri, S. dysenteriae and S. boydii accounted for less than 3% of the isolates. Antibiotic resistance among Salmonella for ampicillin, tetracycline and chloramphenicol was 13%, 19% and 5%, respectively. Most resistant isolates were serogroup B. Overall, 40% of Shigella isolates were resistant to ampicillin, 15% resistant to tetracycline and 4% resistant to chloramphenicol.