Overall survival and fungal infection-related mortality in patients with invasive fungal infection and neutropenia after myelosuppressive chemotherapy in a tertiary care centre from 1995 to 2006.

OBJECTIVES: Invasive fungal infections (IFIs) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for haematological malignancies. The present study investigates the overall survival (OS), infection-related mortality and changes in treatment of IFIs in our department from 1995 until 2006. METHODS: Outcomes of all chemotherapy courses were retrospectively evaluated using a standard questionnaire. Modified EORTC/MSG criteria for IFIs were applied: a positive PCR result for Aspergillus spp. in bronchoalveolar lavage was also defined as probable IFI. RESULTS: In total, 1693 chemotherapy courses in 592 patients were evaluated. Sixty-three percent of chemotherapy courses were given to treat acute myeloid leukaemia, with the rest for acute lymphoblastic leukaemia or aggressive lymphoma. IFIs were observed in 139/592 patients [23.5%, 95% confidence interval (CI) 20%-27%] and in 149/1693 courses (8.8%, 95% CI 8%-10%). IFI-related mortality was 56.9% in 1995-2001 and 28.6% in 2002-06, P < 0.001. Accordingly, median OS in patients with IFI increased: 54 days (95% CI 26-82 days) in 1995-2001 versus 229 days (95% CI 35-423 days) in 2002-06, P = 0.001. By multivariate analysis, factors predictive for better OS were controlled disease after chemotherapy [hazard ratio (HR) 0.228, P < 0.001], possible IFI (in contrast to proven/probable IFI, HR 0.537, P = 0.005), age <60 years (HR 0.583, P = 0.008), time period 2002-06 (HR 0.612, P = 0.021) and use of novel antifungals (HR 0.589, P = 0.033). CONCLUSIONS: Compared with 1995-2001, IFI-related mortality decreased and OS in patients with IFI increased significantly in recent years. Improved OS was associated with controlled haematological disease, certainty of IFI diagnosis (possible), younger age, time period 2002-06 and the use of novel antifungals.

Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia.

Infection is the main treatment-related cause of mortality in cancer patients. Rapid and accurate diagnosis to facilitate specific therapy of febrile neutropenia is therefore urgently warranted. Here, we evaluated a commercial PCR-based kit to detect the DNA of 20 different pathogens (SeptiFast) in the setting of febrile neutropenia after chemotherapy. Seven hundred eighty-four serum samples of 119 febrile neutropenic episodes (FNEs) in 70 patients with hematological malignancies were analyzed and compared with clinical, microbiological, and biochemical findings. In the antibiotic-naïve setting, bacteremia was diagnosed in 34 FNEs and 11 of them yielded the same result in the PCR. Seventy-three FNEs were negative in both systems, leading to an overall agreement in 84 of 119 FNEs (71%). During antibiotic therapy, positivity in blood culture occurred only in 3% of cases, but the PCR yielded a positive result in 15% of cases. In six cases the PCR during antibiotic treatment detected a new pathogen repetitively; this was accompanied by a significant rise in procalcitonin levels, suggestive of a true detection of infection. All patients with probable invasive fungal infection (IFI; n = 3) according to the standards of the European Organization for Research and Treatment of Cancer had a positive PCR result for Aspergillus fumigatus; in contrast there was only one positive result for Aspergillus fumigatus in an episode without signs and symptoms of IFI. Our results demonstrate that the SeptiFast kit cannot replace blood cultures in the diagnostic workup of FNEs. However, it might be helpful in situations where blood cultures remain negative (e.g., during antimicrobial therapy or in IFI).

Hospital-acquired legionellosis originating from a cooling tower during a period of thermal inversion.

A case of hospital-acquired legionellosis occurred in a 75-year-old male patient who underwent surgery due to malignant melanoma. Legionellosis was proven by culture of Legionella pneumophila serogroup 1 from bronchoalveolar lavage (BAL) fluid. Being a chronic smoker the patient used to visit the sickroom balcony that was located about 90 m to the west of a hospital cooling tower. Routine cooling tower water samples drawn during the presumed incubation period revealed 1.0x10(4) CFU/100 ml (L. pneumophila serogroup 1). One of three isolates from the cooling tower water matched the patient's isolate by monoclonal antibody (mab)- and genotyping (sequence-based typing). Horizontal transport of cooling tower aerosols probably was favoured by meteorological conditions with thermal inversion. The case report stresses the importance of routine maintenance and microbiological control of hospital cooling towers.

Successful treatment of methicillin-resistant Staphylococcus aureus meningitis using linezolid without removal of intrathecal infusion pump. Case report.

Infection of an intrathecal pump system is a rare but serious complication and usually leads to the removal of the pump. The authors report the first case of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a patient with such a pump successfully treated with linezolid without the need for removal of the intrathecal pump. A 77-year-old woman with cervical myelopathy underwent implantation of an intrathecal pump system for baclofen administration. Two weeks after the procedure she developed meningitis caused by MRSA as isolated in cerebrospinal fluid (CSF) cultures, blood samples, and serum obtained from the pump pouch. Clinically she presented with meningism, somnolence, and signs of sepsis. When a combined intravenous antibiotic treatment regimen of vancomycin and rifampicin resulted in no clinical improvement, that regimen was discontinued and linezolid was administered intravenously as monotherapy. Within 3 days clinical and laboratory findings showed significant improvement. After 1 week of linezolid treatment, blood and CSF cultures were sterile. Intravenous treatment was administered for a total of 3 weeks, after which the patient was treated with oral linezolid for 3 months. During 18 months of follow-up, no new clinical or laboratory signs of infection were observed. These results confirm previous reports of the efficacy of linezolid for the treatment of severe infections of the central nervous system caused by multidrug-resistant Gram-positive bacteria, especially postneurosurgical infections.

Use of the lactose-[13C]ureide breath test for diagnosis of small bowel bacterial overgrowth: comparison to the glucose hydrogen breath test.

PURPOSE: The glucose hydrogen breath test (GHBT) is commonly used as a noninvasive test to diagnose small bowel bacterial overgrowth (SBBO) but its validity has been questioned. Our aim was to evaluate the lactose-[(13)C]ureide breath test (LUBT) to diagnose SBBO and to compare it with the GHBT, using cultures of intestinal aspirates as a gold standard. METHODS: In 22 patients with suspected SBBO (14 male, age range 18-73 years) aspirates were taken from the region of the ligament of Treitz under sterile conditions and cultured for bacterial growth. More than 10(6) colony-forming units/mL fluid or the presence of colonic flora was defined as culture positive (c+). After oral intake of 50 g glucose and 2 g of lactose-[(13)C]ureide, end-expiratory breath samples were obtained up to 120 min. The (13)C/(12)C ratio in breath CO(2) was determined by isotope ratio-mass spectrometry and hydrogen concentration in breath was analyzed electrochemically. RESULTS: After analyzing receiver operating characteristic curves of the LUBT results, total label recovery of >0.88% at 120 min was considered positive. The test had a sensitivity of 66.7% and a specificity of 100% to predict c+. In the GHBT, an increase of the signal of > or =12 ppm from baseline was considered positive. The sensitivity and specificity of the test were 41.7 and 44.4%, respectively. CONCLUSIONS: The new stable isotope-labeled LUBT has excellent specificity but suboptimal sensitivity. In contrast, the standard GHBT lacks both high sensitivity and specificity. The LUBT is superior to the GHBT for detecting SBBO.

Regulatory mechanisms underlying agmatine homeostasis in humans.

Regulation of agmatine homeostasis has so far only been poorly defined. In the present study, three mechanisms regulating human agmatine homeostasis were investigated. 1) Enzymatic regulation: expression of arginine decarboxylase, diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively, than in the adjacent normal tissue; expression of agmatinase was unchanged. 2) Bacteria-derived agmatine: ten representative bacteria strains of the human intestinal microbiota considerably differed in agmatine production and its efflux into their surrounding fluid, suggesting that the composition of the intestinal microbiota influences the agmatine availability in the gut lumen for absorption. 3) Regulation of blood plasma agmatine concentration by the human liver: at low concentrations in portal venous blood plasma, agmatine either slightly increased or further decreased in blood plasma through liver passage. Above a threshold of 14 ng/ml agmatine in the portal venous blood plasma, substantial hepatic agmatine removal from blood occurred. Taken together, a perturbation of agmatine homeostasis has been proven to be involved in the regulation of malignant cell proliferation. The amount of agmatine available for absorption, which is an important physiological source of agmatine in the human organism, should differ considerably depending on the composition of the bacterial flora in the chyme since the various species of intestinal bacteria largely differ in their ability to form agmatine. Finally, evidence has been presented that the liver plays a crucial physiological role in the maintenance of agmatine homeostasis in the human organism.

Abdominal infections in patients with acute leukaemia: a prospective study applying ultrasonography and microbiology.

A prospective study of 62 chemotherapy-induced neutropenic episodes in patients with acute leukaemia was conducted to determine the incidence and causes of abdominal infections, and to assess the diagnostic value of the combined use of ultrasonography (US) and microbiology. Each patient underwent US of liver, gallbladder and complete bowel before chemotherapy, on days 2-4 after the end of chemotherapy and in cases of fever, diarrhoea or abdominal pain. US was combined with a standardized clinical examination and a broad spectrum of microbiological investigations. From January to August 2001, 243 US examinations were performed. The overall incidence of abdominal infectious diseases was 17.7% (11 out of 62, 95% confidence interval (CI): 9-29%). Four patients (6.5%) developed neutropenic enterocolitis; two of them died, two survived. Bowel wall thickening (BWT) > 4 mm in these four patients ranged from 5.8 to 23.6 mm and was detected only in one patient with mucositis. In three other patients (4.8%) Clostridium difficile, and in one patient (1.6%) Campylobacter jejuni, caused enterocolitis without BWT. Cholecystitis was diagnosed in three patients (4.8%) and hepatic candidiasis was strongly suspected in one patient. Abdominal infections caused by gastroenteritis viruses, cytomegalovirus (CMV) or Cryptosporidium were not observed. We conclude that in neutropenic patients with acute leukaemia receiving chemotherapy: (i) BWT is not a feature of chemotherapy-induced mucositis and should therefore be considered as sign of infectious enterocolitis; (ii) viruses, classic bacterial enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas, Vibrio subsp., enterohaemorrhagic Escherichia coli) and Cryptosporidium have a very low incidence; and (iii) abdominal infections may be underestimated when US is not used in every patient with abdominal pain.