Staphylococcus aureus versus Staphylococcus epidermidis in periprosthetic joint infection-Outcome analysis of methicillin-resistant versus methicillin-susceptible strains.

Periprosthetic joint infections (PJIs) are a major complication in total joint arthroplasty. Staphylococcus aureus and coagulase-negative staphylococci are known to cause the majority of all PJIs. This study aimed to analyze the eradication rates of S. aureus and S. epidermidis with methicillin susceptibility and methicillin resistance in a 2-stage therapy algorithm. Seventy-four patients with PJI caused by methicillin-resistant S. aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRSE), methicillin-susceptible S. aureus (MSSA), and methicillin-susceptible coagulase-negative staphylococci (MSSE) were included, and the outcome was analyzed retrospectively. After a minimal follow-up of 2 years, n = 56 patients (75.7%) were definitively free of infection. The analysis revealed significant differences between the groups, with eradication rates as follows: MSSA (92.6%), MSSE (95.2%), MRSA (80%), and MRSE (54.2%). MRSE showed a significantly lower rate of patients graded as "definitively free of infection" as compared to patients with infections caused by MSSA, MSSE, and MRSA.

Rapid monitoring of vancomycin-resistant Enterococcus faecium in hospital departments by repetitive element palindromic polymerase chain reaction.

BACKGROUND: The current increase in nosocomial infections caused by vancomycin-resistant enterococci (VRE) warrants improvement of detection methods and hygiene measures. Knowledge of the local epidemiology is important for monitoring compliance of medical personnel with hygiene measures. AIM: To evaluate semi-automated repetitive element palindromic polymerase chain reaction (rep-PCR) for rapid molecular typing of VRE. METHODS: Primary VRE isolates were collected during an observation period of one year and retrospectively typed by rep-PCR. Molecular typing was performed on isolates from two departments with elevated VRE rates and patients with increased risk for systemic VRE infections. Typing results were correlated with temporal and spatial information on patient moves, VRE laboratory results and multi-locus sequence typing (MLST). FINDINGS: Approximately 70% of VRE isolates within a department could be assigned to similarity clusters. Spread of VRE was limited to the individual departments. There was no evidence for spread of endemic VRE strains within the geographical catchment area of the hospital. Our results demonstrate the utility of rep-PCR typing on a department level. However, a Diversilab® threshold of ≥98% had to be applied to claim similarity, and suspected transmissions needed to be confirmed by vanA/B genotyping and compiled information on spatial and temporal patient contact. MLST verified the findings. CONCLUSION: Spread of predominantly detected vancomycin-resistant Enterococcus faecium was limited to the department level with no evidence for wider dissemination within the hospital. Well-standardized and validated (semi-)automated rep-PCR systems are useful for rapid detection of possible VRE transmission. However, suspected transmissions need to be confirmed by clinical and microbiological parameters.

Multidrug resistant Acinetobacter baumannii reaches a new frontier: prosthetic hip joint infection.

Acinetobacter baumannii is an emerging nosocomial pathogen primarily in countries with a high prevalence of multidrug resistance. Here we report the detection of a bla OXA23 carbapenemase-producing A. baumannii strain in a German patient with prosthetic hip joint infection following several hip joint surgeries but no history of foreign travel.

False positivity of the Aspergillus galactomannan Platelia ELISA because of piperacillin/tazobactam treatment: does it represent a clinical problem?

OBJECTIVES: False-positive results of the galactomannan (GM) ELISA caused by concurrent administration of piperacillin/tazobactam have been reported in patients with febrile neutropenia. PATIENTS AND METHODS: This prospective study investigated different sampling times in 30 patients receiving piperacillin/tazobactam for febrile neutropenia. RESULTS: Prior to the first piperacillin/tazobactam infusion, a median GM index of 0.2 [interquartile range (IQR) 0.1-0.3] was noted; in two patients (7%) the index was 0.5. Immediately after piperacillin/tazobactam infusion, the median index increased to 0.3 (IQR 0.2-0.4, P = 0.002) leading to 21% (7/30) false-positive results, if > or = 0.5 is assumed as the cut-off level. GM indices before the next piperacillin/tazobactam infusion were not increased (median 0.2, IQR 0.2-0.35, P > 0.05), but 10% (3/30) were still > or = 0.5. With a cut-off level of > 0.7, no false-positive results were noted at any sampling time point. CONCLUSIONS: We conclude that the clinical relevance of false-positive GM results during piperacillin/tazobactam treatment is small if samples are collected prior to infusion and if a cut-off level of > 0.7 is used.

ARDS in an HIV-positive patient associated to respiratory syncytial virus.

We describe a clinical case of ARDS in an HIV infected patient. ARDS was associated to a respiratory syncytial virus infection that triggered a suspected Pneumocystis infection that despite missing etiologic proofs was treated with antimycotics. As rather limited information on RSV associated ARDS in HIV patients is available in the current literature, this case is of significant interest.

Piperacillin-tazobactam in pediatric cancer patients younger than 25 months: a retrospective multicenter survey.

Piperacillin-Tazobactam (Pip-Taz) is an evidence-based empirical treatment of febrile neutropenia in adolescents and adults. No data are available in pediatric cancer patients <25 months of age. In this retrospective, multicenter data survey, the analysis focuses on safety, tolerance, and efficacy. The daily dose administered was 240 mg/kg given in three equally divided doses. Data on 156 Pip-Taz treatment courses in 69 children <25 months from five pediatric cancer treatment centers (2001-2005) were analyzed. The median duration of treatment with Pip-Taz was 5 days (range, 1-23 days; 1-12 Pip-Taz courses per patient). Pip-Taz was started on the first day of fever in 90% of all courses, in 6% in the first 72 h, and in 4% as second- or third-line agent. Forty-five percent of all patients were neutropenic. In all patients, the outcome was favorable independent whether Pip-Taz was given as monotherapy (42 courses; 27%) or in combination. Overall, Pip-Taz was well tolerated and discontinued due to adverse events in only two patients who experienced non-life-threatening allergic reactions (skin rash and wheezing). The results of this study are preliminary due to the methodological limitations of a retrospective survey. Taking this bias into consideration, Pip-Taz appears to be a safe, and feasible alternative in pediatric cancer patients with febrile neutropenia <25 months of age suggesting that the inclusion of children of all age groups in future prospective controlled studies evaluating Pip-Taz is justified.

Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison.

GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues. Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside. Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined. PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response. RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047). If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added. All patients still febrile then received meropenem, teicoplanin and amphotericin B. With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005). The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010). CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies.

Low frequency of enteric infections by Salmonella, Shigella, Yersinia and Campylobacter in patients with acute leukemia.

BACKGROUND: Several authors found that isolation of Salmonella, Shigella, Yersinia and Campylobacter spp. (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 classic 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.

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.

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 (< or = 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.

Developmentally regulated patterns of expression directed by poplar PAL promoters in transgenic tobacco and poplar.

Phenylalanine ammonia-lyase (PAL) catalyzes the first step in phenylpropanoid metabolism and plays a central role in the biosynthesis of phenylpropanoid compounds. We have previously cloned two PAL genes, PALI and PAL2, from a Populus trichocarpa x P. deltoides F1 hybrid. Here, we describe the properties of PALI and PAL2 promoters and their expression patterns in transgenic tobacco and poplar. The promoters were 75% identical in the regions sequenced, and each contained two copies of AC-rich putative cis-acting elements that matched a consensus plant myb transcription factor binding site sequence. In transgenic tobacco, PALI-GUS and PAL2-GUS fusions directed similar patterns of expression in developing primary xylem of leaves, stems, and other organs, and in secondary xylem of stems. Contrary to previously documented patterns of PAL1/2 expression in poplar, no expression of either fusion was detected in epidermal or subepidermal cell layers of young tobacco leaves or stems. In poplar, the PAL2-GUS fusion directed the highest levels of expression in roots and young leaves and stems. In young leaves and stems, high GUS activity was detected in epidermal or subepidermal cells as well as in primary xylem and phloem fibers. GUS activity was low in woody stems, and was weak or absent in developing secondary xylem. The patterns of PAL2-GUS expression in poplar are very similar to those of PAL1/2 mRNA accumulation in poplar. However, the distinct patterns of expression directed by the PAL2 promoter in poplar and tobacco show that PAL2-GUS expression in tobacco does not accurately reflect all aspects of PAL2 expression in poplar.

Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-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.

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia.

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.

Geotrichum capitatum septicaemia in neutropenic patients: case report and review of the literature.

We report a case of systemic infection with Geotrichum capitatum in a patient with acute myeloid leukaemia. Three days before death, the patient developed acute renal failure, probably caused by occlusion of glomerula with hyphae of G. capitatum. Up until now, prophylaxis and treatment of infections caused by Geotrichum capitatum have not been established. However, the prophylactic administration of high-dose itraconazole and the therapeutic use of liposomal amphotericin B are subjects of discussion.

[The typical radiological findings and course of invasive pulmonary aspergillosis in the immunosuppressed patient]. / Typische radiologische Befunde und Verlauf der invasiven pulmonalen Aspergillose des immunsupprimierten Patienten.

PURPOSE: This retrospective study was designed to show whether invasive pulmonary aspergillosis, which is often difficult to diagnose by bronchoscopy or serology, can be diagnosed at an early stage by typical radiological findings on conventional radiographs or by CT, specially high resolution CT (HR-CT). PATIENTS AND METHODS: In 19 Patients with 20 disease episodes, 20 thorax radiographs and eight spiral CT examinations were performed and in four cases HR-CT was also available. The earliest pathological findings and the course of the disease were analysed and the results of the various examinations were compared. RESULTS: 90% of chest examinations, including CT and HR-CT, showed the following lesions as part of the earliest changes: round or wedge-shaped opacities or the so-called "halo" sign. CT or HR-CT always demonstrated more lesions than plain chest radiographs; 75% of lesions appeared typical and thereby contributed to the diagnosis. CONCLUSION: The typical radiological findings of round or wedge-shaped opacities and the so-called "halo" sign are additional criteria for the diagnosis of invasive pulmonary aspergillosis. The superiority of CT or HR-CT in the demonstration of pathological changes suggests that these should be used early in the investigation of patients who are specially at risk.

Effects of the lantibiotic mersacidin on the morphology of staphylococci.

Mersacidin is a lanthionine-containing peptide antibiotic (lantibiotic), able to inhibit the growth of a number of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) in a manner similar to, but distinct from, vancomycin. In order to further understand the mode of action of this lantibiotic, Staphylococcus simulans 22 cells were treated either with the antibiotics penicillin, tunicamycin or vancomycin or with mersacidin and then compared with untreated cells after electron microscopic examination. Mersacidin treatment brought about a time-dependent, generalised decrease in the thickness of the bacterial cell wall. In addition, mersacidin treatment caused a roughening of the cell wall surface layer and also reduced the thickness and frequency of formation of dividing cell septa. Reduction of cell wall thickness appears to result from inhibition of new wall biosynthesis combined with cell wall turnover. These features of mersacidin-induced effects on cell morphology confirm that it has a novel mode of action (Brötz, H., G. Bierbaum, A. Markus, E. Molitor, and H.-G. Sahl: Antimicrob. Agents Chemother. 39 [1995] 714-719), probably directed towards a membrane-bound biosynthetic step but not towards a specific penicillin-binding-protein.

Rapid chemotaxonomic diagnosis of human tuberculosis.

65 different clinical specimens from patients suspected of being infected with Mycobacterium tuberculosis were examined by three different diagnostic methods. Two of these methods were the conventional microscopic and cultural examinations. The third, a modern chemotaxonomical method is based upon the detection of tuberculostearic acid by GC-MS analysis using selected ion monitoring (GC-MS/SIM). Comparison of the results of the GC-MS analysis with those of the conventional methods has indicated that tuberculostearic acid analysis can be used for diagnosing tuberculosis under diagnostic routine conditions. The GC-MS method is rapid, usually providing results within 20 hours or less.