Serious complications of vascular catheter-relatedStaphylococcus aureus bacteremia in cancer patients

Over the period 1986 to 1989, 53 cancer patients were identified with catheter-relatedStaphylococcus aureus bacteremia at the University of Texas M.D. Anderson Cancer Center. Septic thrombosis was diagnosed in 12 (23 %) patients and was suspected in another 3 (6 %). Of the 12 patients, five developed deep-seated infections (septic emboli, endocarditis, meningitis, abscess), compared with 2 of the 38 other patients with no septic thrombosis (p<0.01). Fever persisted for more than three days after antibiotic initiation in 52 % of the patients with complications (septic thrombosis and/or deep-seated infections), compared with 19 % of those without complications (p<0.02). Of the three patients with complications who were treated for 14 days with intravenous antistaphylococcal antibiotics, two relapsed; in contrast, all of the nine patients with complications who were treated for more than 14 days (mean 4 weeks) were cured, and none relapsed (p<0.05). Of the nine patients with complications who were treated with a long course of therapy, only one required surgery. The possibility of septic thrombosis and/or deep-seated infections should be considered in all cancer patients with catheter-relatedStaphylococcus aureus bacteremia, and if present, the condition should be treated with appropriate intravenous antibiotics for at least four weeks.     

Phase 3 evaluation of HP802‐247 in the treatment of chronic venous leg ulcers

In 2012 we reported promising results from a phase 2 clinical trial of HP802‐247, a novel spray‐applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802‐247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802‐247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty‐one patients were enrolled in the North American (HP802‐247, 211; Vehicle 210) and 252 in the European (HP802‐247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802‐247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802‐247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802‐247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.     

Treatment of typhoid fever with cefamandole

Cefamandole therapy was evaluated in nine patients with typhoid fever. Six patients, including all five who received the antibiotic by continuous intravenous drip (8.0 g daily), were cured. Dosage schedules resulting in maintenance of antibiotic concentrations in serum high above the MIC seemed to correlate well with treatment success.     

Child Care in Outpatient Substance Abuse Treatment Facilities for Women: Findings from the 2008 National Survey of Substance Abuse Treatment Services

Mothers with substance use disorders who lack access to child care are often unable to enter or remain in substance abuse treatment. This study examined the availability of child care in outpatient substance abuse treatment facilities and whether or not certain facility characteristics were associated with the availability of child care. Using data from the 2008 National Survey of Substance Abuse Treatment Services, 6.5% of outpatient substance abuse treatment facilities that served women provided child care. The results of multivariate logistic regression found that child care was more common among facilities that were located in metropolitan areas, were operated by non-profit or government agencies, received public funding, or provided free services or other ancillary services including case management, domestic violence counseling, and transportation assistance. Facilities that served only women had more than three times higher odds of providing child care compared with mixed-gender facilities. Further research is needed to identify strategies for expanding child care in outpatient substance abuse treatment facilities.     

A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy.

The in vitro susceptibilities of 130 Xanthomonas maltophilia isolates to 12 antibiotics--trimethoprim-sulfamethoxazole, minocycline, ticarcillin-clavulanate, ceftazidime, cefoperazone, cefoperazone-sulbactam, imipenem, ciprofloxacin, and the investigational quinolones PD 117558, PD 117596, PD 127391, and sparfloxacin--were determined by a microtiter broth dilution technique. Other than the investigational quinolones, the most active antibiotics were minocycline, trimethoprim-sulfamethoxazole, and ticarcillin-clavulanate, in order. However, the first two were not bactericidal, while about half of the isolates exhibited intermediate susceptibility to ticarcillin-clavulanate. Patterns of susceptibility to trimethoprim-sulfamethoxazole and ciprofloxacin relative to the years of isolation of these strains reflected the development of resistance to the antibiotic prophylaxis practices in the hospital. We recommend that a combination of antibiotics, such as trimethoprim-sulfamethoxazole, minocycline, and ticarcillin-clavulanate, at or close to the maximum tolerated doses be in the treatment of serious X. maltophilia infections.     

The clinical spectrum of stenotrophomonas (xanthomonas) maltophilia respiratory infection

During a 15-month retrospective clinical study in an academic referral-based cancer center, 26 patients with S. maltophilia respiratory tract infections were identified (which were associated with bacteremia in 13 patients). Five of these 26 patients had previously undescribed sinopulmonary involvement. The infections were typically nosocomial. Nine patients with solid tumors had malignant involvement of the respiratory tract (five with obstruction). In two patients, the infection co-existed with pulmonary aspergillosis. Fifteen patients (58%) died of the infection. The factors that correlated with a poor outcome included bacteremic pneumonia, persistent neutropenia, presence of obstruction, development of septic shock or multiple organ dysfunction, and delay in institution of appropriate antibiotic therapy. In multivariate analysis, only septic shock and delayed therapy remained significant. Trimethoprim-sulfamethoxazole and/or ticarcillin-clavulanate were most commonly associated with a favorable outcome.     

New spectrum of fungal infections in patients with cancer

We report on 44 cancer patients who had serious infections with unusual fungal pathogens and who were cared for at our cancer center between 1974 and 1986. Twelve different fungal species accounted for these infections, including Trichosporon beigelii, Fusarium species, Geotrichum candidum, Curvularia species, Drechslera species, Penicillium species (but not Penicillium marneffei), Rhodotorula rubra, Pseudallescheria boydii, Pichia farinosa, Torulopsis pintolopesii, Saccharomyces cerevisiae, and Cunninghamella bertholletiae. Skin lesions were noted in seven patients, and sinusitis occurred in four. Twenty-four patients had disseminated infection, 12 had involvement of a single organ, and eight had fungemia alone. Features that correlated with a poor prognosis were persistent neutropenia and disseminated visceral infection but not fungemia alone. We suggest that unusual fungi have now emerged as significant pathogens in this patient population. Fungal sinusitis, previously caused by Aspergillus species and the phycomycetes, also occurs as a result of some of these newly recognized fungi. A high level of suspicion should be maintained when any of these unusual fungi are cultured from clinical specimens from immunocompromised patients.     

On weighting the rates in non-response weights

A basic estimation strategy in sample surveys is to weight units inversely proportional to the probability of selection and response. Response weights in this method are usually estimated by the inverse of the sample-weighted response rate in an adjustment cell, that is, the ratio of the sum of the sampling weights of respondents in a cell to the sum of the sampling weights for respondents and non-respondents in that cell. We show by simulations that weighting the response rates by the sampling weights to adjust for design variables is either incorrect or unnecessary. It is incorrect, in the sense of yielding biased estimates of population quantities, if the design variables are related to survey non-response; it is unnecessary if the design variables are unrelated to survey non-response. The correct approach is to model non-response as a function of the adjustment cell and design variables, and to estimate the response weight as the inverse of the estimated response probability from this model. This approach can be implemented by creating adjustment cells that include design variables in the cross-classification, if the number of cells created in this way is not too large. Otherwise, response propensity weighting can be applied.     

Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon-gamma and granulocyte-colony-stimulating factor

BACKGROUND: Fungal infections represent a difficult challenge to clinicians caring for neutropenic patients with hematologic malignancies, as antifungal therapy often has limited success in that setting. One promising yet problematic alternative approach is leukocyte transfusion. The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosis and functional deterioration, and irradiation to prevent transfusion-associated graft-versus-host disease causes further functional deterioration. STUDY DESIGN AND METHODS: The ability of interferon-gamma and granulocyte-colony-stimulating factor (G-CSF), used both alone and in combination, to protect PMNs after 0 or 20 hours' storage in cell culture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied. RESULTS: Without cytokine treatment, 20-hour-old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans. In contrast, cytokine treatment significantly reduced apoptosis and protected chemotaxis, C. albicans killing, and surface-receptor expression from both storage and irradiation. Although the majority of the benefit appeared to be due to G-CSF, consistent trends suggested better function of PMNs after combined treatment with interferon-gamma and G-CSF. CONCLUSION: Judicious use of cytokines may preserve PMN function. These findings have important implications for the transfusion of PMNs to cytopenic patients.