Phaeohyphomycosis fungal infections in solid organ transplant recipients: clinical presentation, pathology, and treatment.

BACKGROUND: Dematiaceous, or dark-pigmented, fungi are known to cause infections such as phaeohyphomycosis, chromoblastomycosis, and mycetoma. These fungi are becoming increasingly important opportunistic pathogens in solid organ transplant recipients (SOTR). We present a retrospective chart review of 27 SOTR who developed phaeohyphomycosis infections post transplant from 1988 to 2009. METHODS: Cases were reviewed for fungal species isolated, date and source of culture, immunosuppressive and fungal therapy used, and outcome. The majority of isolates obtained were from the skin and soft tissue, with 3 pulmonary and brain abscesses. RESULTS: The time from transplantation to onset of infection ranged from 2 months to 11 years. The species isolated were Exophiala (11), Ochroconis (3), Alternaria (2), Phoma (2), Wangiella (1), Cladosporium (1), Aureobasidium (1), Chaetomium (1), Coniothyrium (1), and non-sporulating fungi (2). An additional 4 patients had infections confirmed by pathology, but no cultures were done. Most of the affected skin lesions were surgically debrided and treated with itraconazole; 2 patients were treated with voriconazole and 2 with amphotericin D. Death from fungal disease occurred only in patients with pulmonary and brain abscesses. CONCLUSIONS: As the number of SOTR increases, so does the incidence of fungal infections in that population. Surgery, along with antifungal therapy and a reduction in immunosuppression, are the cornerstones of treatment.

Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease.

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.

Kaposi's sarcoma with a non-Hodgkin's lymphoma. Its association in a male homosexual with human T-cell lymphotropic virus type III infection.

Combined tumor syndromes, specifically reticuloendothelial malignancies and Kaposi's sarcoma, have long been recognized. With the recognition of the acquired immunodeficiency syndrome (AIDS), several patients with concurrent non-Hodgkin's lymphoma and Kaposi's sarcoma have been reported at high risk for developing AIDS. The present Centers for Disease Control definition of AIDS excludes these patients on the assumption that one tumor is affecting the cellular immunity, allowing for the development of the second malignancy. In evaluating such a patient who had serologic evidence of human T-cell lymphotropic virus type III infection, the probable cause of AIDS, we have reviewed reports of patients with similar concurrent malignancies before and since the onset of the AIDS epidemic. We conclude that patients in high-risk groups for AIDS who develop similar combined tumor syndromes should be classified as having AIDS.

Studies in homosexual patients with and without lymphadenopathy. Relationships to the acquired immune deficiency syndrome.

We studied the immunologic function of 19 sexually active homosexual men, ten of whom had persistent lymphadenopathy. Analysis of mononuclear cell populations distinguished homosexuals from heterosexual controls since, as a group, homosexuals had increased percentages of natural killer cells (Leu 7+), decreased helper-inducer T lymphocytes (OKT-4+), increased suppressor/cytotoxic (OKT-8+) T lymphocytes, low OKT-4:OKT-8 ratios, and depressed mitogenic responses. Homosexuals without lymphadenopathy were distinguishable from controls by increased percentages of Ia+ cells, decreased OKT-4+ cells, and decreased OKT-4:OKT-8 ratios. Four had positive findings simultaneously for hepatitis B surface antigen (HBsAg) and surface antibody, and five had positive findings for HBsAg alone. Homosexuals with lymphadenopathy were distinguishable from controls by increased percentages of Leu 7+ cells, increased total lymphocyte numbers per cubic millimeter, decreased percentages of both OKT-4+ and OKT-8+ cells, abnormal OKT-4:OKT-8 ratios, and depressed mitogenic responses. Only histories of larger numbers of sexually acquired diseases, higher numbers of OKT-8+ cells per cubic millimeter, and lower mitogenic responses in homosexuals with lymphadenopathy distinguished this group from homosexuals without lymphadenopathy. Furthermore, none of the nine patients tested in this group was HBsAg positive. We conclude that homosexuals without lymphadenopathy are distinguishable from those with lymphadenopathy by both immunologic and serologic abnormalities.

Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections.

The distinction between bactericidal and bacteriostatic agents appears to be clear according to the in vitro definition, but this only applies under strict laboratory conditions and is inconsistent for a particular agent against all bacteria. The distinction is more arbitrary when agents are categorized in clinical situations. The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems. Bacteriostatic agents (e.g., chloramphenicol, clindamycin, and linezolid) have been effectively used for treatment of endocarditis, meningitis, and osteomyelitis--indications that are often considered to require bactericidal activity. Although bacteriostatic/bactericidal data may provide valuable information on the potential action of antibacterial agents in vitro, it is necessary to combine this information with pharmacokinetic and pharmacodynamic data to provide more meaningful prediction of efficacy in vivo. The ultimate guide to treatment of any infection must be clinical outcome.

Temafloxacin: an overview.

Temafloxacin (6-fluoro-7-piperazino-4-quinolone) is a new fluoroquinolone with a 7-8 hour half-life and rapid gastrointestinal absorption. These characteristics make it an ideal antimicrobial for once- or twice-daily oral dosing. With the exception of the central nervous system (CNS), temafloxacin has excellent tissue and body fluid penetration and concentration. Temafloxacin has broad antimicrobial activity against gram-positive and gram-negative bacteria, including improved in vitro activity against Streptococcus pneumoniae, Mycoplasma hominis, and anaerobic bacteria, including Bacteroides fragilis. Temafloxacin is as effective as beta-lactam therapy and superior to ciprofloxacin in the treatment of S. pneumoniae lower respiratory infections. It has been clinically effective when given in a short 3-day regimen for the treatment of uncomplicated urinary tract infections. Multiple clinical trials indicate that temafloxacin is also clinically effective, well tolerated, and safe for use in adult patients for the treatment of other lower respiratory tract, genitourinary tract, and skin and skin-structure infections.

Safety and efficacy of intravenous ciprofloxacin in the treatment of selected infections.

A prospective study of the efficacy and safety of intravenous ciprofloxacin in the treatment of selected infections was conducted at the Ochsner Medical Institutions from October 1986 through March 1987. Thirty-three patients were treated with intravenous ciprofloxacin at dosages of either 200 mg or 300 mg every 12 hours. The mean duration of therapy was 12 days. Various infection sites were treated and included urinary tract, respiratory tract, skin and skin structure, bone, intra-abdominal, blood, and heart. Clinical improvement was noted in 20 of the 26 evaluable patients (77 percent). Fifty-two bacterial pathogens were isolated with eradication of 37 (71 percent). There was bacteriologic persistence in seven patients (13 percent). Superinfection occurred in one patient; however, no recurring or reinfecting organisms were isolated. Adverse events related to ciprofloxacin occurred in six patients and were primarily mild. Overall, ciprofloxacin was useful in the treatment of a variety of infections, and adverse events were minimal.

Overview of bacterial infections of the skin and soft tissue and clinical experience with ticarcillin plus clavulanate potassium in their treatment.

The etiology, diagnosis, and treatment of skin and soft tissue infections are discussed, and the results of clinical experience with ticarcillin plus clavulanate potassium in these diseases at one clinic are reported. In a randomized and controlled clinical trial, the safety and effectiveness of ticarcillin plus clavulanate potassium and cefazolin were compared in the treatment of soft tissue infections in 20 patients. The 12 patients in the group treated with ticarcillin plus clavulanate potassium included 10 men and two women, with a mean age of 61 years; the eight patients in the group treated with cefazolin were five men and three women, with a mean age of 63.8 years. Ticarcillin plus clavulanate potassium was administered for four to 26 days (mean 12.5 days), and cefazolin for four to 20 days (mean 12 days). There were 29 evaluable pathogens in the group receiving ticarcillin plus clavulanate potassium and 22 in the group receiving cefazolin. Of the 29 pathogens in the former group, 22 were eradicated; three reinfections or superinfections occurred but were ultimately eradicated, and four pathogens persisted. Eighteen of the 22 pathogens in the cefazolin-treated group were eliminated and the other four persisted. Clinically, six of the 12 patients in the ticarcillin plus clavulanate potassium-treated group had cures, four showed improvement, and two failed to show a response. In the cefazolin-treated group, five of the eight patients had cures, one showed improvement, and two failed to show a response.

Invasive aspergillosis in liver transplant recipients in the 1990s.

Invasive aspergillosis occurred in 26 liver transplant recipients since 1990 at five liver transplant centers. The median time to onset was 17 days after transplantation. Twenty-seven percent of the patients had undergone retransplantation. Invasive aspergillosis occurred significantly earlier after transplantation in smokers than in nonsmokers (P=0.017). Patients with late-onset aspergillosis (occurring after posttransplant day 90) were more likely to have had prior cytomegalovirus infection than those with early-onset aspergillosis (occurring within 90 days of transplantation) (67% vs. 10%, respectively, P=0.013). Only 8% of the patients had received additional corticosteroids or OKT3, which suggests that augmented immunosuppression may not be a relevant risk factor for invasive aspergillosis in the 1990s due to less frequent use of these agents. The median serum bilirubin level of the patients was 21.8 mg/dl, 85% of the patients had renal insufficiency, and 54% were on dialysis before the onset of invasive aspergillosis, which suggest that overall severity of illness, including poorly functioning hepatic allograft and renal failure may be the major determinants of disease occurrence. Overall mortality was 92% (24/26). No difference in mortality could be shown for the patients who received amphotericin B versus liposomal amphotericin B preparations (100% vs. 89%); however, the mean time to death after the initiation of therapy was 20 days in patients who received amphotericin B and 43 days in those who received liposomal amphotericin B preparations.

Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management.

BACKGROUND: Precise diagnosis of central nervous system (CNS) lesions in liver transplant recipients remains problematic. Brain biopsies are often not feasible as a result of coagulopathy. We sought to determine whether selected clinical or radiologic characteristics can predict the likely etiology of CNS lesions in liver transplant recipients and thus obviate the need for diagnostic brain biopsies. METHODS: A 4-year prospective, observational, cohort study was conducted at liver transplant centers at four geographically diverse medical institutions. A total of 1730 consecutive liver transplant recipients were evaluated for CNS lesions; 60 patients with radiologically documented CNS lesions comprised the study sample. RESULTS: Vascular events (52%, 31/60), infections (181%, 11/60), immunosuppressive associated leukoencephalopathy (12%, 7/60), central pontine myelinolysis (8%, 5/60), and malignancy (3%, 2/60) were the predominant etiologies of CNS lesions. CNS lesions were most likely to occur within 30 days of transplantation (43%, 26/60); central pontine myelinolysis, subdural hematoma, acute infarcts, and Aspergillus brain abscesses were the predominant etiologies during this time. All brain abscesses were fungal; 73% (8/11) of these patients concurrently had documented extraneural (pulmonary) infection as a result of the same fungal pathogen. Thus, a diagnostic brain biopsy is not warranted in these patients. Patients on dialysis were more likely to have ischemic or infectious CNS lesions (P=0.03). Vascular events were more likely to occur in repeat transplant recipients (P=0.03). Twenty-five percent (15/60) of the CNS lesions occurred more than 1 year after transplantation; small vessel ischemic lesions, malignancy, or non-Aspergillus fungal brain abscesses accounted for all such lesions. CONCLUSIONS: A presumptive etiologic diagnosis can be established in a vast majority of CNS lesions in liver transplant recipients based on identifiable presentation that includes time of onset, unique risk factors, and neuroimaging characteristics. Empiric therapy of brain abscesses in liver transplant recipients should include antifungal and not antibacterial agents.

Review of tissue penetration and clinical efficacy of enoxacin in skin and skin structure infections and in osteomyelitis.

Enoxacin achieves a high penetration into skin tissue and blister fluid, reaching a maximum serum concentration (Cmax) of 3.7 mg/L at a time to reach maximum concentration (tmax) of 1.9 hours and a blister-fluid Cmax of 2.9 mg/L at a tmax of 3.7 hours after an oral dose of 600 mg. The half-life of enoxacin is 6.2 hours in serum and 7.2 hours in blister fluid. In a multicentre, open, non-comparative trial, clinical cure or improvement in skin or skin structure infections was achieved after oral administration of enoxacin 200 to 600 mg twice daily in 88% of 196 evaluable patients. Overall satisfactory bacteriological response was obtained in 76% of patients. In a multicentre, randomised, double-blind trial comparing oral enoxacin 400 mg twice daily with cephalexin 500 mg twice daily, satisfactory clinical outcome was achieved in 92% of 73 evaluable patients receiving enoxacin and in 99% of 72 evaluable patients receiving cephalexin. Furthermore, there was no statistically significant difference between the bacteriological efficacy of the 2 agents. In 3 single-centre trials, satisfactory clinical results were achieved in 75 to 100% of patients, and satisfactory bacteriological results occurred in 47 to 76% of patients after administration of oral enoxacin 400 mg twice daily for 7 to 14 days. In vitro uptake of enoxacin in bone leads to a concentration of 300 micrograms/g, with 83% being retained by bone after 3 washings with saline at pH 7.2. Clinical trials involving oral enoxacin in osteomyelitis are currently under way.

Optimum outpatient therapy of skin and skin structure infections.

Skin and skin structure infections appear in a variety of ways with multiple aetiologies. Optimum therapy is accomplished with a good understanding of both skin anatomy and common resident or transient bacterial flora present on the skin surface. Primary and secondary infections occur in both immunocompetent and immunocompromised patients, each of which require unique decision-making skills on the part of the prescriber. Deciding when culture and sensitivity should be performed or therapy should be begun empirically is often difficult and can be frustrating. This is complicated by the ever-increasing number of antimicrobial agents available today and their variable costs. Choosing the best antibiotic agent, based on evidence of which is the most effective agent for a particular lesion, the easiest dosage schedule and the most economical drug, is a goal that will best serve both the patient and the physician.

Pleural effusion and anicteric hepatitis associated with cat-scratch disease. Documentation by cat-scratch bacillus.

Prior to the discovery of the coccobacillus in the lymph nodes of patients with cat-scratch disease by Wear and associates, the diagnosis was based on clinical findings and a nonstandardized skin test. Atypical cases either remained an enigma or were questioned as to accuracy of diagnosis. We present here a case of cat-scratch disease associated with pleural effusion, anicteric hepatitis, and other systemic manifestations confirmed by identification of the coccobacillus. It is the first association with a pleural effusion. With the Warthin-Starry stain, we anticipate a redefinition of this disease. The confirmation of atypical cases will help broaden the clinical spectrum, as well as guide us to consider this diagnosis where its classic manifestations may be absent.

Diagnosis of disseminated cytomegalovirus infection and pneumonitis in a heart transplant recipient by skin biopsy: case report.

A pulmonary infection caused by both Toxoplasma gondii and cytomegalovirus (CMV) developed in a heart transplant recipient. A presumptive diagnosis of CMV pneumonitis was made on the basis of a skin biopsy finding demonstrating CMV inclusions. This diagnosis was later supported by a positive pleural fluid culture for CMV, a greater than fourfold increase in CMV IgG antibody, and a response to therapy with ganciclovir sodium. Biopsy of skin lesions in patients at risk for CMV infections may represent an important early diagnostic tool.

The histopathology of Mycobacterium marinum synovitis.

Eight patients with culture-proven Mycobacterium marinum synovitis had synovial specimens with a remarkably similar histologic appearance. There was considerable synovial hyperplasia, and the synovium was thickened by a moderately intense lymphohistiocytic infiltrate, notably devoid of plasma cells. Fibrin covered some synovial surfaces. Giant cells were both of the Langerhans' and foreign body types. Granulomas were noncaseating but varied in frequency and degree of definition. Knowledge of this morphologic picture has proved to be useful in patient care.

Histopathology of marine vibrio wound infections.

Although marine vibrio wound infections and septicemia are being reported with increasing frequency, description of the histopathologic changes has been scanty. The histologic alterations in three patients with primary marine vibrio wound infections are presented. The lesions are characterized by intense acute cellulitis of the subcutis with much tissue destruction and extension into the adjacent dermis. The superficial dermis is devitalized and lacks an inflammatory cellular infiltrate. Subepidermal noninflammatory bullae are formed. Many organisms are seen both within the areas of intense acute inflammation and in devitalized areas. Organisms and inflammation are especially oriented around vessels, with associated acute vasculitis. It is concluded that the morphologic picture in marine vibrio wound infections is nonspecific yet characteristic.

Dermatologic manifestations of nontuberculous mycobacterial diseases.

Various nontuberculous mycobacteria can cause infection of skin and soft tissues. These organisms are also known as atypical mycobacteria, anonymous mycobacteria, and mycobacteria other than tuberculosis. These organisms are much more common causes of cutaneous infection than Mycobacterium tuberculosis. Infections caused by nontuberculous mycobacteria are frequently misdiagnosed because clinicians fail to include them in the differential diagnosis of chronic skin infection.

Strongyloides hyperinfection in a renal transplant recipient receiving cyclosporine: possible Strongyloides stercoralis transmission by kidney transplant.

Strongyloides hyperinfection and dissemination are recognized complications in kidney allograft recipients; however, the development of strongyloidiasis in renal transplant recipients receiving cyclosporine A (CyA) has not been described, nor has the development of strongyloidiasis in other organ transplant recipients. The former observation has been attributed to the antiparasitic activity of CyA seen in animal studies; the latter has no explanation yet. We report the first case of Strongyloides hyperinfection in a renal transplant patient occurring immediately after CyA was discontinued. From the unique characteristics of this case, it appears that the anti-Strongyloides activity of CyA in animals may also be found in humans.

Wound infection and septic shock due to Vibrio vulnificus.

Vibrio vulnificus is an organism commonly found in the marine environment whose pathogenic potential for humans has been recently recognized. Two patients are described who developed rapidly progressing wound infections and bacteremia due to this halophilic, lactose-positive vibrio. The clinical manifestations of the resulting infection differed from patterns reported by other authors.

Hepatitis E seroconversion in United States travelers abroad.

Sporadic cases of symptomatic hepatitis E virus (HEV) infection have been reported in United States travelers to developing countries, including Mexico and Pakistan. To evaluate the risk of exposure in United States travelers, 356 patients seen in our Travel Clinics were tested for antibodies to HEV before and 6 weeks after traveling. Samples obtained 6 months after traveling were available for 211 travelers. IgG and IgM antibodies to HEV were assayed with HEV ELISA diagnostic kits containing 3 recombinant antigens expressed in Escherichia coli representing immunodominant epitopes within open reading frames 2 and 3 of HEV. Nine patients were IgG seropositive in specimens obtained before travel. Four individuals seroconverted. In all 4 patients, IgG seroconversion was demonstrated in samples obtained at least 6 months after return. Samples obtained 6 weeks after return were seronegative for HEV in all 3 patients for whom such samples were available. Travel destinations were diverse: Thailand, China, Russia, and Peru. These data are consistent with an infection acquired while traveling. None of the seropositive subjects reported any symptoms of hepatitis before or after travel. In the absence of overt disease, these results imply that exposure to HEV resulted in subclinical infections.