Shellee A. Grim

Rapid development of Acinetobacter baumannii resistance to tigecycline

A 53‐year‐old woman experienced a multidrug‐resistant (MDR) Acinetobacter baumannii urinary tract infection 5 months after undergoing kidney and liver transplantation. The tigecycline minimum inhibitory concentration (MIC) for her A. baumannii isolate was 1.5 μg/ml; the patient received 2 weeks of therapy with intravenous tigecycline as a 100‐mg loading dose followed by 50 mg every 12 hours, with no lapses in treatment and with resolution of the infection. Three weeks later, MDR A. baumannii was isolated from her sputum in the setting of clinical evidence of pneumonia, and tigecycline was restarted; the tigecycline MIC for the A. baumannii isolate was 2 μg/ml. At approximately the same time, the patient was found to have a paraspinal abscess and spinal osteomyelitis. Cultures of the abscess fluid grew A. baumannii with a tigecycline MIC of 24 μg/ml. A follow‐up sputum culture again yielded A. baumannii, but with a tigecycline MIC of 24 μg/ml. Urine culture at that time also grew A. baumannii with a tigecycline MIC of 24 μg/ml. Clinicians should be aware that tigecycline MICs for A. baumannii isolates may increase during therapy with tigecycline after only brief exposure to the drug. Patients receiving tigecycline for Acinetobacter should be monitored for the development of clinical resistance, and isolates should be monitored for evidence of microbiologic resistance.

Trimethoprim‐Sulfamethoxazole as a Viable Treatment Option for Infections Caused by Methicillin‐Resistant Staphylococcus aureus

Objective. To review available data regarding the efficacy of trimethoprim‐sulfamethoxazole (TMP‐SMX) for the treatment of infections caused by methicillin‐resistant Staphylococcus aureus (MRSA).

Infectious complications associated with the use of rituximab for ABO-incompatible and positive cross-match renal transplant recipients

Abstract:  Immunosuppressive protocols for ABO‐incompatible (ABOI) and positive cross‐match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients.

A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation

S.A. Grim, L. Proia, R. Miller, M. Alhyraba, A. Costas‐Chavarri, J. Oberholzer, N.M. Clark. A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation.
Transpl Infect Dis 2011. All rights reserved

Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes

OBJECTIVES We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival. METHODS Patients ≥16 years of age with first episodes of candidaemia during 2001-09 were included. Clinical data were collected retrospectively, including time to appropriate antifungal therapy and patient survival. RESULTS The study population included 446 patients [243 (54%) female, mean age 53 years] with candidaemia, 380 (85%) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50%) followed by Candida glabrata (99, 22%), Candida parapsilosis (59, 13%), Candida tropicalis (48, 11%) and Candida krusei (6, 1%). Appropriate antifungal therapy consisted of fluconazole (177, 40%), an echinocandin (125, 28%), amphotericin B (41, 9%) and voriconazole (6, 1%); 97 (22%) failed to receive appropriate antifungal therapy. The 30 day mortality was 34% (151/446) and there was no clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30 day survival. On multivariable Cox regression, increased APACHE II score [hazard ratio (HR) 1.11, 95% CI 1.09-1.13, P<0.001], cirrhosis (HR 2.15, 95% CI 1.48-3.13, P<0.001) and HIV infection (HR 2.03, 95% CI 1.11-3.72, P=0.02) were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received ≥24 h of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 h of a positive blood culture being drawn (30 day mortality for early treatment: 27% versus 40%, P=0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95% CI 1.01-1.98, P=0.045). CONCLUSIONS Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.

Tenofovir Disoproxil Fumarate

OBJECTIVE: To review the pharmacology, virology, pharmacokinetics, efficacy, safety, resistance profile, and clinical use of tenofovir disoproxil fumarate. DATA SOURCES: A MEDLINE search was performed (1966–August 2002) using the following terms: tenofovir, tenofovir disoproxil fumarate, PMPA (9-(R)-[2-(phosphonomethoxy)propyl]adenine), and Viread. Abstracts from HIV-related meetings were reviewed. DATA EXTRACTION AND STUDY SELECTION: Publications and meeting abstracts regarding tenofovir were reviewed. The most recent and pertinent items were included. DATA SYNTHESIS: Tenofovir disoproxil fumarate is a nucleotide prodrug that is diphosphorylated to its active moiety, tenofovir diphosphate. In this form, tenofovir acts as a reverse transcriptase inhibitor to inhibit HIV-1 replication. In clinical trials, tenofovir was effective at suppressing HIV-1 RNA and boosting CD4+ cell counts. Tenofovir has a long intracellular half-life, which permits once-daily dosing. Since tenofovir does not interact with the cytochrome P450 pathway, it exhibits minimal drug interactions, with the exception of didanosine. Compared with other reverse transcriptase inhibitors, tenofovir may have advantages in terms of toxicity and medication adherence profiles. Ongoing studies are also analyzing tenofovirs activity against hepatitis B virus. CONCLUSIONS: Tenofovir has been shown to be active against HIV-1 in combination with other antiretrovirals. The drugs benefit as a single-agent intensifier of highly active antiretroviral therapy in treatment-experienced patients has been established, and preliminary data for treatment-naïve patients are encouraging.

Early Intra-Abdominal Infections Associated With Orthotopic Liver Transplantation

Background. Postoperative infections remain a significant problem among liver transplant recipients (LTRs). An early cause of morbidity after liver transplantation is intra-abdominal infection (IAI) about which there are limited data. Methods. We report a retrospective review of 169 adult LTRs from January 1, 2002 to June 9, 2006, comparing those who developed early postoperative IAI (peritonitis, biliary tract infection, abdominal abscess, or enteritis) with those who did not to identify clinical features and risk factors, analyze epidemiology, and assess graft and patient survival. Results. Sixty-eight patients (40%) had 104 infections, with 148 pathogens isolated. Leukocytosis (53%) and fever (34%) were the most common clinical features, and peritonitis (43%) was the most common manifestation. Enterococcus spp., the most frequent single pathogens, comprised 26% of organisms cultured. There were significant associations of IAI with pretransplant ascites (P=0.002), posttransplant dialysis (P=0.015), and non-IAI surgical complications (P<0.001). There was a trend toward graft failure in patients with IAI (P=0.051) but increased mortality was not associated with IAI. Use of pretransplant antibiotics was significantly associated with development of multiple drug–resistant organisms in IAI (P=0.032). Conclusion. IAI occurred at a relatively high rate in the early postoperative period, and fever was not a major indicator. In patients receiving antibiotics within 2 weeks before transplantation, multiple drug–resistant organisms often caused IAI. In addition, the presence of pretransplant ascites, posttransplant dialysis, and wound infection or reoperation after transplant should alert one to the increased risk of IAI in LTRs.

Topiramate concentration in saliva: an alternative to serum monitoring.

This study examines the relationship between serum and saliva topiramate concentrations, and attempts to determine if saliva may be a useful alternative to serum for therapeutic monitoring. Saliva and blood specimens were collected from 31 epilepsy patients (mean age 10.5 +/- 6.0 years; range 2.5 years to 24.8 years), and topiramate concentrations were determined by fluorescence polarization immunoassay. One patients results were omitted because the saliva concentration was below the limit of quantitation of the assay. A strong correlation exists between serum and saliva topiramate concentrations (adjusted r(2) = 0.97, n = 30, P < 0.0001). The mean fraction of saliva to serum concentration is 89.8% +/- 12.1% (range 62.9% to 112.7%). The results of this study support the use of saliva as a viable alternative to serum for monitoring topiramate therapy. Topiramate concentration in saliva: an alternative to serum monitoring.

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD).

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were collected in the clinic and frozen until analysis. Blood samples were obtained by phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD concentrations were determined by high-performance liquid chromatography in the Clinical Laboratory at the Cincinnati Childrens Hospital Medical Center. Linear regression analysis was used to evaluate correlations. Saliva and blood specimens were collected from 28 epilepsy patients, but usable samples were obtained from only 23. The mean serum MHD concentration was 23.9 ± 10.0 μg/mL, and the mean saliva concentration was 23.1 ± 10.1 μg/mL. There was a significant positive correlation between the serum and saliva concentrations: saliva (y) = 0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD concentration ratio was 0.96 ± 0.15. The results of the current study indicate that the relationship between freely flowing (unstimulated) saliva and serum concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation of saliva MHD monitoring is that individuals who have difficulty producing small quantities of saliva or who have viscous saliva should generally be avoided for this type of monitoring. It is also recommended to avoid saliva collection within 8 hours after OXC dosing to allow complete absorption and transformation of the parent drug.

Correlation of Lamotrigine Concentrations between Serum and Saliva

Study Objective. To compare the relationship between serum and salivary concentrations of lamotrigine in pediatric and adult epilepsy populations.