William F. Marshall

Xanthomonas maltophilia: an emerging nosocomial pathogen.

Xanthomonas maltophilia is a potentially pathogenic organism with a broad clinical spectrum. Nosocomial colonization and infection are the most common manifestations. The incidence of clinical isolation of X. maltophilia is on the rise, possibly in part because of the selective pressure from the new antimicrobial agents to which it is resistant. The organism is usually resistant to commonly used antimicrobial agents, including most cephalosporins, aztreonam, antipseudomonal penicillins, imipenem, and the quinolones.

Prophylaxis of cytomegalovirus infection in liver transplantation: A randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir

BACKGROUND The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Successful Treatment of Cerebral Blastomycosis with Voriconazole

Blastomycosis can occasionally involve the central nervous system (CNS). Amphotericin B deoxycholate is considered the drug of choice for the treatment of CNS blastomycosis. Significant toxicity may be associated with its use. We describe a case of cerebral blastomycoma that was successfully treated with voriconazole.

The impact of invasive fungal diseases on survival after lung transplantation.

Arthurs SK, Eid AJ, Deziel PJ, Marshall WF, Cassivi SD, Walker RC, Razonable RR. The impact of invasive fungal diseases on survival after lung transplantation.
Clin Transplant 2010: 24: 341–348.

Results of a 6-Month Survey of Stool Cultures for Escherichia coli O157:H7

Escherichia coli O157:H7 is a recently recognized enteric pathogen that causes acute hemorrhagic colitis. Although the infection is usually self-limited, it may be complicated by hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. At our institution, stool specimens are now routinely cultured for this organism. To determine the prevalence of E. coli O157:H7-associated diarrhea in our patient population, we surveyed all submitted stool cultures for 6 months for this organism. Specimens were screened for non-sorbitol fermenting E. coli and confirmed by slide-agglutination and immobilization testing. Of 2,164 specimens, 10 yielded E. coli O157:H7. It was the fourth most common bacterial stool pathogen found. Bloody diarrhea and abdominal pain were the most common symptoms of the infected patients. E. coli O157:H7 causes sporadic infections in our patient population and should be considered in the differential diagnosis of acute hemorrhagic colitis.

Detecting Delayed Microbiology Results After Hospital Discharge: Improving Patient Safety Through an Automated Medical Informatics Tool

We developed a computerized medical informatics tool to identify patients who had a culture performed on a sterile body site specimen during their hospitalization that subsequently turned positive after hospital dismissal. During a 13-month period, 533 patients had a positive culture identified by our Computer-Based Antimicrobial Monitoring (CBAM) program after hospital dismissal, and 112 (21%) of these culture results necessitated an intervention and communication with the primary health care professional. Thirty-two (29%) of positive cultures were from the blood. Thirty-eight (34%) of the CBAM interventions with available outcome data resulted in initiation of, change in, or prolongation of outpatient antimicrobial therapy. The CBAM program serves an important role in optimizing patient care and communication with the health care professional during the transition from inpatient to outpatient management.

Voriconazole, but not Posaconazole, Exposures Are Significantly Decreased by Letermovir (MK-8228) Coadministration in Healthy Subjects

Introduction: Letermovir (MK-8228) is a potent inhibitor of the cytomegalovirus (CMV) terminase complex that is being developed for the prophylaxis of CMV infection in transplant patients, who often also receive antifungal prophylaxis. The pharmacokinetics (PK) of the azole antifungals voriconazole or posaconazole were evaluated along with their tolerability when coadministered with letermovir. Materials and Methods: In the open-label, fixed-sequence trial designed to evaluate the potential effect of letermovir on the PK of voriconazole in 14 healthy female subjects, voriconazole was administered for 4 days to achieve steady state followed by 24 hours of PK sampling after the last 200 mg dose of voriconazole. The following day letermovir was dosed for 4 days alone at 480 mg daily, then, letermovir was coadministered with voriconazole for 4 days, followed again by voriconazole PK sampling. In the openlabel, fixed-sequence, 2-period, drug-drug interaction study between letermovir and posaconazole, in Period 1 an oral single dose of 300 mg of posaconazole was given to 16 healthy female subjects. In Period 2, 480 mg of letermovir was given once daily for 14 days and 300 mg of posaconazole was coadministered on Day 14. Each period was followed by PK sampling for posaconazole. Safety was monitored throughout both studies by repeated clinical and laboratory evaluations. Results: The geometric mean ratios (GMRs) for voriconazole+ letermovir/voriconazole for AUC0-12 and Cmax were 0.56 and 0.61, respectively, with corresponding 90% confidence intervals (CIs) of [0.51, 0.62] and [0.53, 0.71]. The GMRs (90% CI) for AUC0-∞ and Cmax of posaconazole when coadministered with multiple doses of letermovir were similar to that after administration of posaconazole alone with GMRs 0.98 (0.82, 1.16) and 1.11 (0.95, 1.29), respectively. When given with either voriconazole or posaconazole, letermovir was well tolerated with no severe adverse events (AEs) or discontinuations due to AEs. Conclusions: The decrease in voriconazole exposures when coadministered with letermovir may be clinically meaningful, whereas the exposures of posaconazole are unaffected by letermovir coadministration. Letermovir was well tolerated when coadministered with either posaconazole or voriconazole. 1228