PubMed Health⌕ Search

Biomedical subjects

W V Kern

Publications and source records attributed to W V Kern.

At least 19 recordsLinked to original sources
PubMed2003

Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Adolescent↗
PubMed2002

Glycopeptide use at four university hospitals in southern Germany.

BACKGROUND: Excessive use of glycopeptide antibiotics may enhance the risk of glycopeptide resistance among enterococci and staphylococi, but there is little data on the use of these antibiotics in German hospitals. METHODS: Hospital pharmacy records for the years 1992 to 1994 were evaluated. The number of defined daily doses (DDD) per 100 patient days was calculated to compare glycopeptide use between four state university hospitals. At one of the hospitals with comparatively low glycopeptide usage but an active antimicrobial management program, data were prospectively evaluated for 1995 to 2000 to assess the variation of glycopeptide use over time. RESULTS: The 3-year averages in glycopeptide use for the four hospitals ranged between 1.03 and 3.14 DDD/100 patient days. In all four hospitals, glycopeptide use was higher in the medical service (range, 1.59-7.26) than in the surgical service (range, 0.66-4.39). Active antimicrobial management in one of the hospitals was associated with containment of glycopeptide consumption in the medical and surgical service at < 1.5 DDD/100 patient days in the last 3 years. CONCLUSION: Glycopeptide use differs considerably at tertiary care hospitals in southern Germany, but use of < 1.5 DDD/100 patient days in both surgical as well as medical tertiary care hospital departments appears achievable.

Anti-Bacterial Agents↗
PubMed2001

Prediction of gram-negative bacteremia in patients with cancer and febrile neutropenia by means of interleukin-8 levels in serum: targeting empirical monotherapy versus combination therapy.

In a prospective observational study of 133 neutropenic episodes, interleukin (IL)-8 serum levels > 2000 pg/mL at the onset of fever had a sensitivity of 53% and a specificity of 97% as a predictor of gram-negative bacteremia (GNB; positive predictive value, 73%; negative predictive value, 94%). The rates of early death differed significantly between patients with high and those with low IL-8 levels (3/11 vs. 1/122; P< .01). Serum IL-8 levels at the onset of fever define a low-risk subgroup of patients who can safely be treated with monotherapy.

Adolescent↗
PubMed2001

Practices of infectious disease prevention and management during hematopoietic stem cell transplantation: a survey from the European group for blood and marrow transplantation.

Protocols for the prevention of infections after allogeneic or autologous hemopoietic stem cell transplantations are usual. A questionnaire was sent out to the members of the European Group for Bone and Marrow Transplantation (EBMT) in the spring of 1999. A total of 308 questionnaires from 180 centers were returned. Both allogeneic and autologous transplantation was reported from 128 centers, and allogeneic or autologous transplantation alone from four and 48 centers, respectively. Hemopoietic stem cell transplantation is still a domain of university hospitals. Intensive measures of isolation are usual. Allotransplantation is commonly performed in single rooms with HEPA-filtered air on special wards. However, even in the autologous setting, extensive measures of isolation are commonly used. This observation could be explained by historical developments and by the fact that nearly all centers for allogeneic transplantation perform both allogeneic and autologous transplantations, and thus similar measures are used in both settings. Other measures are usual but heterogeneous due to lack of clinical trials in this field. Drug prophylaxis during transplantation is mostly carried out with quinolones, TMP/SMZ, fluconazole, acyclovir, and pentamidine. Differences in drug prophylaxis after engraftment and in the use of different venous accesses do reflect the requirements after engraftment and discharge of patients from the transplant unit. The intensity of measures in autologous stem cell reinfusion does not reflect the development during the last decade. For cost effectiveness and convenience, it is necessary to abolish senseless measures. It is necessary to investigate anti-infectious strategies separately for allogeneic transplantation and other modalities of anti-cancer treatment in future.

Anti-Infective Agents↗
PubMed2001

Risk assessment and risk-based therapeutic strategies in febrile neutropenia.

Different approaches have developed over time regarding the empirical antimicrobial therapy of fever in neutropenic patients. The use of intravenous antibiotics remains the standard approach. Clinical criteria and 'low-risk' prediction rules have been developed that help select patients in whom oral therapy is well tolerated and who may be eligible for outpatient management. Comorbidity and clinical status at presentation remain important criteria in the risk-assessment process. Outpatient management requires additional assessment of non-medical criteria. Patients without documented infection and who have responded to initial therapy may benefit from simplified therapy such as a switch to oral drugs and/or outpatient management. Discontinuation of therapy may be considered in selected cases. Risk assessment in neutropenic patients with persistent unexplained fever is challenging. Available data suggest that broadening of the antibacterial coverage is of limited value. Instead, definition of the risk of fungal infection by using clinical criteria, imaging and laboratory studies, as well as the identification of those patients likely to benefit from antifungal therapy, appear to be of critical importance.

Administration, Oral↗
PubMed2001

Enhanced expression of the multidrug efflux pumps AcrAB and AcrEF associated with insertion element transposition in Escherichia coli mutants Selected with a fluoroquinolone.

The development of fluoroquinolone resistance in Escherichia coli may be associated with mutations in regulatory gene loci such as marRAB that lead to increased multidrug efflux, presumably through activation of expression of the AcrAB multidrug efflux pump. We found that multidrug-resistant (MDR) phenotypes with enhanced efflux can also be selected by fluoroquinolones from marRAB- or acrAB-inactivated E. coli K-12 strains having a single mutation in the quinolone-resistance-determining region of gyrA. Mutant 3-AG100MKX, obtained from a mar knockout strain after two selection steps, showed enhanced expression of acrB in a reverse transcriptase PCR associated with insertion of IS186 into the AcrAB repressor gene acrR. In vitro selection experiments with acrAB knockout strains yielded MDR mutants after a single step. Enhanced efflux in these mutants was due to increased expression of acrEF and associated with insertion of IS2 into the upstream region of acrEF, presumably creating a hybrid promoter. These observations confirm the importance of efflux-associated nontarget gene mutations and indicate that transposition of genetic elements may have a role in the development of fluoroquinolone resistance in E. coli.

Anti-Infective Agents↗
PubMed2000

Early detection of aspergillus infection after allogeneic stem cell transplantation by polymerase chain reaction screening.

Invasive aspergillosis (IA) has become a major cause of mortality in patients after allogeneic stem cell transplantation. To assess the potential of prospective polymerase chain reaction (PCR) screening for early diagnosis of IA, 84 recipients of an allogeneic stem cell transplant were analyzed with the investigators blinded to clinical and microbiologic data. Of 1193 blood samples analyzed, 169 (14.2%) were positive by PCR. In patients with newly diagnosed IA (n=7), PCR positivity preceded the first clinical signs by a median of 2 days (range, 1-23 days) and preceded clinical diagnosis of IA by a median of 9 days (range, 2-34 days). Pretransplantation IA (relative risk [RR], 2.37), acute graft-versus-host disease (RR, 2.75), and corticosteroid treatment (RR, 6.5) were associated with PCR positivity. The PCR assay revealed a sensitivity of 100% (95% confidence interval [CI], 48%-100%) and a specificity of 65% (95% CI, 53%-75%). None of the PCR-negative patients developed IA during the study period. Thus, prospective PCR screening allows for identification of patients at high risk for subsequent onset of IA.

Adolescent↗
PubMed2000

Modifications of therapy.

Rates of response to empirical therapy in the neutropenic patient with fever, range between 40 and 90%. Modifications of therapy are needed in patients who do not respond but may also be considered in patients who respond. In patients with unexplained fever and rapid defervescence, switch to oral therapy is an acceptable option and there is no need to continue the regimen until neutrophil recovery. Neutropenic patients with persistent undefined fever and those with progressive pneumonia benefit from the addition of antifungals while the empiric addition of a glycopeptide is unlikely to be effective. In patients with gram-negative bacterial infection initially treated with monotherapy, response may be increased after the addition of an aminoglycoside. In cases of a defined etiology, the institution of narrow-spectrum antimicrobials in a persistent neutropenic patient carries a substantial risk for superinfection and is not generally recommended. Improved diagnostic tools and sensitive clinical risk-assessment methods will allow selecting and targeting therapy modifications better.

Anti-Infective Agents↗
PubMed2000

Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropenia.

Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5.75 d (range 0-14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections.

Acute Disease↗
PubMed2000

Severe Chlamydia pneumoniae infection in patients with neutropenia: case reports and literature review.

Three cases of life-threatening C. pneumoniae infection in patients with acute leukemia and treatment-induced neutropenia are described. Diagnosis was made on the basis of the detection of C. pneumoniae-DNA, complemented by serology. The role of the widely distributed respiratory tract pathogen C. pneumoniae in febrile neutropenia is poorly understood, and studies are needed to estimate the frequency of severe pulmonary infection caused by this agent in patients with neutropenia.

Adolescent↗
PubMed2000

Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump.

Fluoroquinolone-resistant mutants, selected from a wild-type Escherichia coli K-12 strain and its Mar mutant by exposure to increasing levels of ofloxacin on solid medium, were analyzed by Northern (RNA) blot analysis, sequencing, and radiolabelled ciprofloxacin accumulation studies. Mutations in the target gene gyrA (DNA gyrase), the regulatory gene marR, and additional, as yet unidentified genes (genes that probably affect efflux mediated by the multidrug efflux pump AcrAB) all contributed to fluoroquinolone resistance. Inactivation of the acrAB locus made all strains, including those with target gene mutations, hypersusceptible to fluoroquinolones and certain other unrelated drugs. These studies indicate that, in the absence of the AcrAB pump, gyrase mutations fail to produce clinically relevant levels of fluoroquinolone resistance.

Anti-Infective Agents↗
PubMed2000

Non-target gene mutations in the development of fluoroquinolone resistance in Escherichia coli.

Mutations in loci other than genes for the target topoisomerases of fluoroquinolones, gyrA and parC, may play a role in the development of fluoroquinolone resistance in Escherichia coli. A series of mutants with increasing resistance to ofloxacin was obtained from an E. coli K-12 strain and five clinical isolates. First-step mutants acquired a gyrA mutation. Second-step mutants reproducibly acquired a phenotype of multiple antibiotic resistance (Mar) and organic solvent tolerance and showed enhanced fluoroquinolone efflux. None of the second-step mutants showed additional topoisomerase mutations. All second-step mutants showed constitutive expression of marA and/or overexpressed soxS. In some third-step mutants, fluoroquinolone efflux was further enhanced compared to that for second-step mutants, even when the mutant had acquired additional topoisomerase mutations. Attempts to circumvent the second-step Mar mutation by induction of the mar locus with sodium salicylate and thus to select for pure topoisomerase mutants at the second step were not successful. At least in vitro, non-target gene mutations accumulate in second- and third-step mutants upon exposure to a fluoroquinolone and typically include, but do not appear to be limited to, mutations in the mar or sox regulons with consequent increased drug efflux.

Anti-Infective Agents↗
PubMed2000

Zinc serum level in human immunodeficiency virus-infected patients in relation to immunological status.

In human immunodeficiency virus (HIV) infection, serum level of zinc, an important micronutrient for immune function, is frequently diminished. The aim of this study was to determine the zinc status in relation to immunological parameters and disease stage in 79 HIV-1 seropositive patients. The median serum level of zinc was within normal limits (12.5 micromol/L) but in 23% of patients, zinc deficiency was seen. Decreased serum zinc was associated with a low CD4 cell count, high viral load, and increased neopterin and IgA levels. According to current treatment recommendations, the majority of patients received antiretroviral triple therapy. Zinc levels in treated and untreated patients were comparable. Referring to disease stage (CDC classification, 1993), the mean zinc level was highest in stage C and lowest in stage A. In conclusion, even under antiretroviral triple therapy, zinc deficiency is still of great importance in HIV infection, and zinc substitution in zinc deficient individuals should be taken into account to optimize therapeutical success.

Adult↗