Diagnosis of invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO).

Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

Leprosy in a pregnant woman.

Herein, we describe a case of leprosy in a 29-year-old pregnant southeast-asian woman who presented with joint pain and multiple disseminated erythematous macules, papules and plaques. Histological examination and stains for acid-fast bacilli from skin biopsies substantiated the clinical suspicion of a cutaneous mycobacterial disease and both should be performed in all patients with unidentified skin lesions. The definitive laboratory diagnosis of leprosy was achieved by the application of a species-specific real-time polymerase chain reaction from infected tissue.

Lymphadenitis cervicalis due to Mycobacterium interjectum in immunocompetent children.

UNLABELLED: This report presents two cases of cervical lymphadenitis due to Mycobacterium interjectum in healthy young children, identified by sequencing of the 16S rRNA gene. Surgical resection combined with chemotherapy resulted in cure. CONCLUSION: The attention of clinicians needs to be drawn to an emerging mycobacterial pathogen which might be overlooked or misidentified in routine laboratory testing.

Diagnosis of invasive fungal infections in hematology and oncology--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.

Disseminated cutaneous Mycobacterium marinum infection in a patient with non-Hodgkin's lymphoma.

A 60-year-old woman with non-Hodgkin's lymphoma was admitted to the hospital because of extensive subcutaneous abscesses developing on all limbs. The patient had an aquarium and kept tropical fish as pets. After repeated investigations, the diagnosis of Mycobacterium marinum was established from skin biopsy by PCR and culture. Long-term therapy with several drugs regimens had only a limited efficacy and was accompanied by severe adverse reactions. This report highlights the therapeutic problems posed by disseminated cutaneous M. marinum infection in the immunosuppressed host.

[Osteomyelitis of the tibial head caused by Mycobacterium haemophilium in a patient with AIDS]. / Tibiakopf-Osteomyelitis durch Mycobacterium haemophilum bei einem Patienten mit AIDS.

HISTORY AND ADMISSION FINDINGS: A 53-year-old man with known HIV infection and AIDS was admitted because of painful swelling at the right knee for 6 weeks. The cause was thought to be osteomyelitis and surgical treatment was planned. INVESTIGATIONS: No causative pathogen was found at curettage and lavage of an abscess at the right medical head of the tibia, but at a subsequent operative revision acid-fast rods were seen and identified as Mycobacterium haemophilum. TREATMENT AND COURSE: A systemic antibiotic, 1 g levofloxacin daily, had been started at the initial abscess operation. 2 weeks later, because swelling of the right knee had recurred with marked local and systemic signs of infection, a second surgical intervention was performed. Afterwards, in view of the histological finding of acid-fast bacteria suggesting tubercular osteomyelitis, the patient was put on combined treatment with 300 mg/d of isoniazid, 1600 mg/d of ethambutol, 2 g/d of pyrazinamide, and 1 g of streptomycin i.m. every other day. After molecular microbiological identification of M. haemophilum the antibiotic treatment was changed to 1600 mg/d of ethambutol, 300 mg/d of rifabutin and 1 g/d of clarithromycin. The operation wound healed well. CONCLUSION: M. haemophilum infection can be lethal in immunodeficient patients if untreated. Although there is no standard treatment, this rare infectious disease responds relatively well to a modified combined tuberculostatic regimen. Special laboratory techniques to identify the specific causative pathogen are therefore of great importance.

Mycobacterium malmoense infections in immunocompetent patients.

While Mycobacterium malmoense infections were originally restricted to northern Europe, there has been an increasing number of reports of cases of infection in other countries. Two cases of infections due to Mycobacterium malmoense in immunocompetent patients in Germany are presented. In both cases a presumptive diagnosis of tuberculosis was established initially. Mycobacterium malmoense was cultured after a long incubation period (6-8 weeks). The patients were successfully treated with a triple regimen consisting of rifampicin, ethambutol and clarithromycin. The epidemiology and difficulties in diagnosis of Mycobacterium malmoense infection are discussed.

Two cases of chronic arthritis of the forearm due to Mycobacterium tuberculosis.

In the absence of coexisting active pulmonary disease, tuberculosis is frequently not considered in the differential diagnosis of chronic inflammation of the joints. The cases of two immigrant patients with tuberculous arthritis involving the forearm are reported. In both cases non-specific arthritis or trauma was suspected, resulting in a delay between the onset of symptoms and institution of specific therapy of 21 and 24 months, respectively. Diagnosis was achieved by histological and microbiological examination of synovial biopsy material. Polymerase chain reaction for Mycobacterium tuberculosis complex was positive in only one patient. Treatment consisted of antituberculosis chemotherapy, surgical synovectomy, and debridement of the affected joints. These cases serve as a reminder that, although rare, tuberculosis can cause chronic arthritis.

Impact of disseminated Mycobacterium avium-complex infection on survival of HIV-infected patients.

OBJECTIVE: To determine the frequency of disseminated Mycobacterium avium-complex infections (MAC) and the impact of MAC disease on overall survival in patients with HIV disease and AIDS. METHODS: Prospective study of HIV infected patients with a CD4 lymphocyte count < 150/microliter or patients with AIDS over a 7-year period. Blood cultures of all patients presenting symptoms and signs suggestive of disseminated MAC infection were grown. Only patients who deceased at our clinic (n = 427) were included in the final analysis in order to calculate MAC disease-free survival and overall survival after first CD4 lymphocyte count < 100/microliter. RESULTS: 101 out of 427 patients (24%) developed disseminated MAC disease: The median time between first CD4 lymphocyte count < 100/microliter and MAC disease was 441 days (range 16 to 1560). The actuarial risk of MAC disease for the entire patient population was 12%, 28%, and 42% after 1, 2, and 3 years, respectively. When comparing overall survival after first CD4 lymphocyte count < 100/microliter, there was no statistically significant difference between patients who subsequently developed disseminated MAC infection and those who did not. CONCLUSION: MAC disease is a very frequent opportunistic infection in advanced AIDS, mostly in patients with less than 50 CD4 cells/microliter. In contrast to reports from the US, only 24% of our patients developed MAC disease. Survival time between patients with and without MAC infection did not differ.

Epidemiology of penicillin-resistant Neisseria gonorrhoeae in Frankfurt, Germany.

In the present study 150 Neisseria gonorrhoeae strains from prostitutes in Frankfurt, Germany, were investigated for their in vitro susceptibility to eight antimicrobial agents by the agar dilution test. While 21.3% of gonococci were highly resistant to penicillin (MICs > or = 2 mg/l), 49.4% of the organisms were moderately sensitive (MICs = 0.125-0.5 mg/l) and only 29.3% of strains were fully susceptible to penicillin (MICs < or = 0.06 mg/l). No resistance to other antibiotics tested was observed, with the exception of doxycycline, to which overall resistance was 9.7%. Genotypic analysis of Neisseria gonorrhoeae by the restriction enzyme technique showed that most penicillin-resistant strains could be grouped into two main bacterial clones, whereas penicillin-susceptible isolates displayed a remarkable heterogeneity. This observation suggests that a restricted number of resistant Neisseria gonorrhoeae strains are likely to spread within the prostitute population of Frankfurt, Germany.

[Epidemiology of tuberculosis in patients with HIV infection of the Frankfurt University Clinic]. / Epidemiologie der Tuberkulose bei Patienten mit HIV-Infektion der Universitätsklinik Frankfurt.

Frequency and risk of tuberculosis were studied among a large group of HIV-infected patients (n = 2556), 869 of whom had AIDS, over a period of ten years (February 1982 through February 1992) at the University Hospital Frankfurt. A total of 148 (5.8%) out of 2.556 patients had tuberculosis. With increasing immunodeficiency, the frequency of tuberculosis rose. The rate of tuberculosis in post-mortem was even higher, i.e. 17.3%. I.v. drug-addict AIDS patients were inflicted with 18.5% considerably more often than homo-/bisexual patients with 12.3%. The same holds true with 25% of tuberculosis infections for AIDS patients from endemic areas as compared with 13% for patients from countries with lower tuberculosis incidence. 18% of patients contracted tuberculosis already at > 200 CD4-positive cells/microliters before AIDS manifestation. Coming from endemic areas, drug addiction and lower number of T-cells signify a high risk for HIV-infected patients to acquire a post-primary or primary tuberculosis, respectively. HIV-infected patients represent a relevant danger of infection for partners and health-care personnel. In contrast to the United States, no increase in the tuberculosis incidence, except for some areas like Frankfurt, has been noted. Preventive measures, which include the IHN prophylaxis for patients with T-cell counts < 150/microliters, should be discussed.

Multicenter evaluation of the novel ABN Western blot (immunoblot) system in comparison with an enzyme-linked immunosorbent assay and a different Western blot.

A new, modular Western blot (immunoblot) system for human immunodeficiency virus (HIV) antibodies (ABN WesPage; Wellcome) was compared with enzyme immunoassays (Wellcome, Behringwerke, and Abbott) and with a U.S. Food and Drug Administration (FDA)-licensed Western blot (DuPont) in a multicenter study. A total of 649 serum samples from HIV patients at different stages of the disease, as well as from high-risk patients, from patients with conditions unrelated to AIDS, and from healthy blood donors, were used in the evaluation along with nine seroconversion panels. For evaluation of Western blot reactivity, both Centers for Disease Control (CDC) and FDA criteria were used. With the DuPont Western blot as the reference assay, the overall sensitivity and specificity of the ABN WesPage were 100 and 99.1%, respectively, when indeterminate results were not taken into account and when both tests were interpreted in accordance with CDC criteria. The DuPont Western blot detected significantly more antibodies to pol and gag gene products than the ABN WesPage. The ABN WesPage showed a higher positive rate of detection of viral envelope band gp160. When both Western blots were interpreted in accordance with CDC criteria, the ABN WesPage and the DuPont Western blot yielded 9.3 and 10.4% indeterminate results, respectively. When the DuPont Western blot was interpreted in accordance with the manufacturer's instructions (FDA criteria), 25.7% of the samples tested were regarded as indeterminate. The choice of interpretation criteria is of paramount importance for the evaluation of HIV Western blot patterns.

Prevalence of antibodies to human herpesviruses and hepatitis B virus in patients at different stages of human immunodeficiency virus (HIV) infection.

The results of antibody assays for viruses of the herpes group (HSV, EBV, VZV and CMV) and for hepatitis B virus (HBV) were retrospectively evaluated in 439 HIV-seropositive patients classified into different stages of HIV infection. The prevalence of specific IgG, IgM and IgA antibodies in these groups was compared with that of a control group of HIV-negative unselected hospital patients. Antibodies to herpes viruses and HBV were more prevalent amongst HIV-seropositives, especially LAS and AIDS patients than in controls. However, marked differences were found only with CMV-IgG and anti-HBc-IgG, both with a comparatively low prevalence in HIV-negative persons (64.5% and 23.2%). Significantly more seropositives were found among asymptomatic HIV carriers (83.3% and 50%) and still more in patients with full-blown AIDS (95.4% and 82.5%). The increased frequency of CMV and HBV antibodies, already seen in asymptomatic HIV patients reflects their higher risk for sexually transmitted infections. Moreover, IgA antibodies to CMV were detected in 25.4% of LAS and 37.3% of AIDS patients, respectively, but only in 7.6% of the controls. Elevated CMV-IgA titres were found exclusively in HIV-infected persons. The differences in the antibody patterns found in this cross-sectional study may reflect the progression of the HIV disease. However, prospective follow-up studies are required to assess the value of these markers as indicators of prognosis in HIV-infected subjects.