Ernst Molitor

Clostridium difficile infection in patients with neutropenia.

Clostridium difficile is the most important cause of nosocomial infectious diarrhea. The importance of C. difficile-associated diarrhea (CDAD) has been poorly investigated in patients with neutropenia who have hematologic malignancies. A retrospective chart review of all patients treated in the leukemia ward of a university medical center during 1991-2000 determined that 875 courses of myelosuppressive chemotherapy were administered. CDAD occurred in 7.0% of all cycles. In 8.2% of the patients, severe enterocolitis developed. Two patients died while they had diarrhea. However, in no patient was C. difficile infection clinically considered to be the primary cause of death. The response rate to oral metronidazole was 90.9%. These data indicate that C. difficile infection is not rare and should be suspected whenever a hospitalized patient with neutropenia develops diarrhea. Oral metronidazole can be recommended as initial drug of choice for treatment of patients with neutropenia who have hematologic malignancies and CDAD.

Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole

This study analyses invasive fungal infections in neutropenic patients with haematological malignancies during antifungal prophylaxis with itraconazole. From September 1994 to December 1998 20 patients developed fungal infections. Two patients suffered from disseminated infections by yeasts and 18 patients suffered from pulmonary infections by moulds (eight proven, 10 highly probable in high‐resolution CT scans). In these patients the itraconazole trough concentrations exceeded 500 ng ml−1 (measured by high performance liquid chromatography) significantly less often (median 48%, interquartile range 0–100%) than in another group of 150 leukaemia patients without invasive fungal infections who received 287 courses of prophylaxis with itraconazole at our institution (median 100%, interquartile range 38–100%, P=0.039). Twelve patients died, six of these had refractory disease. Patients with fatal invasive fungal infections had lower median itraconazole concentrations immediately before occurrence of the infection than patients with non‐fatal infections: 120 (0–478) ng ml−1 versus 690 (305–1908) ng ml−1 (P=0.039). In conclusion, this analysis of breakthrough invasive fungal infections during prophylaxis with itraconazole demonstrates that patients with itraconazole trough concentrations below 500 ng ml−1 were significantly more likely to develop fungal infections and that the last itraconazole trough concentration before occurrence of the infection was significantly lower in patients with fatal invasive fungal infections.

Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-β-cyclodextrin oral solution or coated-pellet capsules

We have previously shown that a trough concentration of at least 500 ng ml−1 itraconazole is necessary for an effective antifungal prophylaxis in neutropenic patients. Since the bioavailability of itraconazole is reduced in these patients, a satisfactory dosing regimen remains to be defined. In this study, six dosing regimens with itraconazole capsules 400, 600 or 800 mg day−1, itraconazole solution 400 mg day−1 (additional loading dose: 400 mg day−1 solution for 2 days), 800 mg day−1 or 400 mg day−1 (additional loading dose: 800 mg day−1 capsules for 7 days, s/c1200) were compared during 160 courses of myelosuppressive chemotherapy in 123 patients with acute leukaemia. After the first week, patients taking 800 mg day−1 or 400 mg day−1 (s/c1200) itraconazole solution achieved significantly higher trough concentrations (high‐performance liquid chromatography) than patients in other groups (P<0.05) and 87 and 100%, respectively, of these had concentrations >500 ng ml−1. Contrary to a dose of 400 mg day−1, a dose of 800 mg day−1 itraconazole solution induced severe nausea and vomiting in 46% of the patients. We conclude that 400 mg day−1 itraconazole solution with a loading dose of 800 mg day−1 capsules for 7 days resulted in sufficient trough concentrations from the first week onwards and appears to be suitable for antifungal prophylaxis in neutropenic patients.

Epidemiology, Prevention and Management of Ventriculoperitoneal Shunt Infections in Children

The advent of ventriculoperitoneal shunts (VPS) represented a substantial progress in the neurosurgical management of hydrocephalus in children. VPS infection is the most frequently observed complication. VPS infection is related to substantial morbidity and mortality, and exerts a negative impact on the quality of life of patients. Considerable personnel and financial resources have been devoted to its diagnosis and treatment. This article reviews the current literature and includes suggestions for the prevention, diagnosis and management of VPS infections.

Pseudomembranous and obstructive Aspergillus tracheobronchitis - optimal diagnostic strategy and outcome

Pseudomembranous and obstructive Aspergillus tracheobronchitis (PMATB/OATB) are still considered to be refractory to therapy and to have a fatal outcome. To evaluate the optimal diagnostic strategy and to describe factors affecting the outcome of PMATB and OATB. Retrospective analysis of four new cases of PMATB and OATB combined with 16 previously reported cases over a 10‐year period (1995–2004). Among the four new cases reported and the 16 published cases, four patients survived their infection. The mortality rate was significantly higher in the group of ventilated patients [94% (15 of 16 patients)] than in the group of non‐ventilated patients [25% (1 of 4 patients), P < 0.05, Fishers exact test]. In all 20 patients, diagnosis was established by bronchoscopy. Culture examination of mucous plugs was positive in 8 of 10, culture of the tracheobronchial aspirate was positive in 8 of 12, and bronchoalveolar lavage was diagnostic in 7 of 13 patients. All bronchoscopic techniques were complementary in improving the yield of bronchoscopy. However, microscopy of mucous plugs and/or necrotic material was the best diagnostic modality [positive in 94% (17 of 18 patients)]. Prognosis of PMATB and OATB remains poor. Microscopy of respiratory specimens is the most sensitive tool to confirm the diagnosis. The characteristic appearance of the disease makes it possible to start antifungal therapy immediately.

Is detection of bacterial DNA in ascitic fluid of clinical relevance

Background In patients with cirrhosis, bacterial DNA has been found in ascites reflecting bacterial translocation. However, the clinical relevance of this finding is ill-defined especially compared with the standard diagnostics for detection of spontaneous bacterial peritonitis (SBP). Furthermore, other DNA tests have not been sufficiently evaluated. Patients and methods We prospectively included 151 patients with cirrhosis and ascites admitted to our department. The patients were evaluated for diagnosis of SBP (polymorphonuclear count>250 cells/mm3) or finding of bacterascites, defined by positive bacterial culture from ascites. To detect bacterial species of bacterial DNA fragments in ascites, broad-range polymerase chain reaction and nucleotide sequencing analysis with the LightCycler SeptiFast Kit Mgrade were performed. Routine parameters were correlated with these findings. Results Eighteen of 151 patients (12%) had SBP according to the classic definition. Bacterial DNA was detected in five of these 18 patients (3%), whereas in 13 patients (9%), bacterial DNA was detected without standard SBP. Seven patients (5%) had culture-positive SBP, only in two of them bacterial DNA was detected. In multivariate analysis, C-reactive protein (P=0.000), white blood cell count (P=0.019), and lactic acid dehydrogenase in ascites (P=0.000) were independently associated with SBP. In the DNA-positive ascites group, none of the assessed parameters was significantly associated with the bacterial DNA positivity. Conclusion We found no correlation between detection of bacterial DNA in ascites and SBP (polymorphonuclear count>250/mm3). In contrast to the patients with bacterial DNA in ascites, patients with SBP showed clinical signs of infection. This study provides no evidence that detection of bacterial DNA in ascites of patients with liver cirrhosis is of clinical or diagnostic relevance when using the panel of LightCycler SeptiFast Kit Mgrade.

Antifungal prophylaxis with itraconazole in neutropenic patients: pharmacological, microbiological and clinical aspects.

Keywords: Fungal infections; aspergillosis; prophylaxis; itraconazole; antifungal activity; drug interactions

Fungal surveillance cultures during antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia.

Fungal colonization has been associated with an increased rate of invasive fungal infections in neutropenic patients. This study evaluates weekly fungal surveillance cultures from the oropharyngeal and perianal space as well as other suspected sites in 219 courses of myelosuppressive chemotherapy with itraconazole antifungal prophylaxis in 116 neutropenic patients with acute leukaemia. Itraconazole was given from the start of chemotherapy in one of six different dosing regimens. Fungal colonization occurred in 68 (31%) of courses, which was lower than in a historical control group without prophylaxis (53%, P=0.004). Twenty‐six per cent of these 116 isolates had a growth rate of more than 50 colony forming units (CFU) per culture. Candida glabrata (51%), Candida albicans (18%) and Candida krusei (4%) were the most frequently isolated species. Higher median itraconazole trough concentrations were associated with a lower growth rate in the cultures (≤50 CFU/culture versus>50 CFU/culture): 710 (430–1180) ng ml−1 versus 900 (560–1650) ng ml−1 (P=0.015). The use of itraconazole solution—compared with capsules—led to a reduced growth rate (P=0.035). In conclusion, compared with historical controls itraconazole antifungal prophylaxis reduces the incidence and the extent of fungal colonization during neutropenia in patients with acute leukaemia.

Low Frequency of Enteric Infections by Salmonella, Shigella, Yersinia and Campylobacter in Patients with Acute Leukemia

AbstractBackground: Several authors found that isolation of Salmonella, Shigella, Yersinia and Campylobacter ssp. (SSYC) from stool cultures after the 3rd day of hospitalization is a rare event. The significance of enteric infections caused by these pathogens has not been systematically investigated in severely immunosuppressed patients with acute leukemia. Patients and Methods: We screened all patients treated on the leukemia ward of a university medical center. A total of 1,185 stool cultures from 371 episodes of diarrhea, mostly following myelosuppressive chemotherapy, were examined for the complete range of classic bacterial enteric pathogens (i. e. SSYC). Results: Only three (0.25%) cultures from one patient were positive for Salmonella enteritidis. This patient suffered from cholangitis. S. enteritidis could also be detected by liver biopsy. Other infections by classic enteric pathogens were not observed. Conclusion: Symptomatic infections by classical bacterial enteric pathogens in hospitalized patients with acute leukemia are very rare. Stool cultures for these pathogens cannot be recommended as a routine test in uncomplicated diarrhea occurring after the 3rd hospital day.

Ein Fall von AIDS-assoziierter Histoplasmose in Deutschland

In a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection with Histoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication of H. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.SummaryIn a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection withHistoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication ofH. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.