Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus.

Norovirus is a major cause of self-limited gastroenteritis worldwide. Prevention and treatment are thwarted by rapid viral evolution, and thus supportive care remains the mainstay of therapy. Chronic infection in immunocompromised hosts is increasingly described. We report a case of norovirus infection lasting 2543 days in a pancreas transplant recipient. Serial fecal specimens were obtained, from which a map of genetic relatedness was derived. The clinical course was complicated by renal failure that progressed to end-stage renal disease. Minimization of immunosuppression was associated with resolution of the infection. Subsequently, the patient experienced a suspected allograft rejection that did not compromise pancreas function. The patient later underwent living-related renal transplantation without recurrence of enteritis.

Carbapenem-resistant Acinetobacter baumannii infections after organ transplantation.

Multi-drug resistant (MDR) gram-negative infections among solid organ transplant (SOT) recipients have long been associated with high morbidity and mortality. Acinetobacter baumannii has emerged as a potent nosocomial pathogen with the recent acquisition of resistance to broad-spectrum beta-lactams, aminoglycosides, fluoroquinolones, and most notably, carbapenems. Despite a national rise in carbapenem-resistant A. baumannii (CRAB) infections, outcomes among SOT recipients with this emerging MDR pathogen are largely unknown. This single-center cohort is the first to describe the characteristics, complications, and outcomes among abdominal organ transplant recipients with CRAB. The current study suggests that SOT patients with CRAB suffer from prolonged hospitalization, infection with other MDR organisms, allograft dysfunction and loss, and high overall infection-related mortality.

Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae among high-risk patients and rates of subsequent bacteremia.

BACKGROUND: Bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have been associated with increased hospital costs, length of stay, and patient mortality. However, the role of routine inpatient surveillance for ESBL colonization in predicting related infection is unclear. METHODS: From 2000 through 2005, we screened 17,872 patients hospitalized in designated high-risk units for rectal colonization with vancomycin-resistant enterococci and ESBL-producing Enterobacteriaceae using a selective culture medium. In patients with a bloodstream infection due to ESBL-producing Enterobacteriaceae (ESBL-BI) during the study period, surveillance results were evaluated for evidence of antecedent ESBL-producing Enterobacteriaceae colonization. RESULTS: The rate of ESBL-producing Enterobacteriaceae colonization doubled during the 6-year study period, increasing from 1.33% of high-risk patients in 2000 to 3.21% in 2005. Among patients with ESBL-producing Enterobacteriaceae colonization, 49.6% also carried vancomycin-resistant enterococci. The number of ESBL-BIs increased >4-fold in 5 years, from 9 cases in 2001 to 40 cases in 2005. Of 413 patients colonized with ESBL-producing Enterobacteriaceae, 35 (8.5%) developed a subsequent ESBL-BI. Of concern, more than one-half of all ESBL-BIs occurred in patients who were not screened. These 56 patients received a diagnosis of ESBL-BI in the emergency department, when hospitalized in low-risk medical units, or at transfer from an acute or long-term health care facility. CONCLUSIONS: Colonization with ESBL-producing Enterobacteriaceae is increasing at a rapid rate, and routine rectal surveillance for ESBL-producing Enterobacteriaceae may have clinical implications. However, in our experience, over one-half of patients with an ESBL-BI did not undergo screening through our current surveillance measures. As a result, targeted screening for ESBL-producing Enterobacteriaceae among additional patient populations may be integral to future ESBL-BI prevention and management efforts.

Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients.

Voriconazole, a new antifungal agent, is increasingly being used after HSCT. The hepatic cytochrome P450 isoenzyme 2C19 plays a significant role in voriconazole metabolism. As CYP2C19 exhibits significant genetic polymorphism, some patients metabolize voriconazole poorly resulting in increased plasma drug levels. The clinical significance of this is unknown, and the utility of monitoring voriconazole levels is unclear. Steady-state trough plasma voriconazole levels were obtained in 25 allogeneic HSCT recipients using an HPLC assay. Patients had drug levels checked once (n=13), twice (n=10), or > or =3 times (n=2) 5-18 days (median 10) after starting voriconazole or dose modification. The 41 voriconazole levels were 0.2-6.8 microg/ml (median 1.6); 6 (15%) were <0.5 (possibly below the in vitro MIC90 for Aspergillus spp.). Voriconazole concentrations correlated with aspartate aminotranferase (AST) (r=0.5; P=0.0009) and alkaline phosphatase (r=0.34; P=0.03), but not with creatinine, bilirubin and alanine aminotransferase (ALT). Since liver dysfunction is common after HSCT, it was not possible to determine if elevated AST and alkaline phosphatase levels were the cause or the consequence of higher voriconazole levels. We conclude that trough voriconazole levels vary considerably between patients, and suggest monitoring levels in patients receiving voriconazole for confirmed fungal infections, and in those with elevated AST or alkaline phosphatase levels.

Cavitary Legionella pneumonia in a liver transplant recipient.

This report describes the clinical course of a liver transplant recipient in whom cavitary pneumonia developed due to Legionella pneumophila. We review the experience with cavitary pulmonary processes caused by Legionella species in liver allograft recipients and describe the diagnostic microbiology of this organism. The clinical course of this patient demonstrates the importance of considering legionellosis in the differential diagnosis of lung abscesses after liver transplantation and the diagnostic difficulties encountered with this bacterium.

Yield of vancomycin-resistant enterococci and multidrug-resistant Enterobacteriaceae from stools submitted for Clostridium difficile testing compared to results from a focused surveillance program.

It has been suggested that a method of performing surveillance for vancomycin-resistant enterococci (VRE) is to screen specimens submitted for Clostridium difficile testing. We compared this approach to our focused surveillance program of high-risk units during October 1997 to compare the yield of VRE and multidrug-resistant Enterobacteriaceae (MDRE) with both methods. Of the stools submitted for C. difficile testing, 14% were positive for VRE or MDRE, whereas rectal swabs from routine surveillance yielded 11% VRE- or MDRE-positive results. Although stools submitted for C. difficile testing resulted in a higher percentage of positive cultures, 14 VRE- and 2 MDRE-positive patients from our high-risk population were missed because many patients had no stool submitted for C. difficile testing. Therefore, while screening stools submitted for C. difficile testing cannot replace our focused surveillance program, it appears advantageous to assess these stools at various intervals to detect new patient reservoirs of drug-resistant organisms that may benefit from routine surveillance cultures.

Outbreak of nosocomial infections due to extended-spectrum beta-lactamase-producing strains of enteric group 137, a new member of the family Enterobacteriaceae closely related to Citrobacter farmeri and Citrobacter amalonaticus.

A member of the Enterobacteriaceae initially identified as Kluyvera cryocrescens by the MicroScan Gram-Negative Combo 13 panel caused an outbreak of nosocomial infections in four patients (pneumonia, n = 2; urinary tract infection, n = 1; wound infection, n = 1) and urinary tract colonization in one patient. When the strains were tested by the Enteric Reference Laboratory of the Centers for Disease Control and Prevention, biochemical results were most compatible with Yersinia intermedia, Kluyvera cryocrescens, and Citrobacter farmeri but identification scores were low and test results were discrepant. However, when the biochemical test profile was placed in the computer database as a new organism, all strains were identified as the organism with high identification scores (0. 999968 to 0.999997) and no discrepant test results. By 16S rRNA sequence analysis the organism clustered most closely with, but was distinct from, Citrobacter farmeri and Citrobacter amalonaticus. Based on its unique biochemical profile and rRNA sequence, this organism is designated Enteric Group 137. Restriction endonuclease analysis and taxonomic antibiograms of strains causing the outbreak demonstrated a single clone of Enteric Group 137, and antibiotic susceptibility testing revealed the presence of extended-spectrum beta-lactamase (ESBL) resistance. Enteric Group 137 appears to be a new opportunistic pathogen that can serve as a source of ESBL resistance in the hospital.

The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance.

BACKGROUND: The development of antimicrobial guidelines is one way in which institutions attempt to control emerging resistance, but the real challenge falls on promoting and ensuring adherence to these guidelines. Investigating reasons for the prescribing of alternative antimicrobial agents outside of these guidelines is crucial for modifying practices that may adversely impact institutional antimicrobial goals. METHODS: Retrospective cross-referencing of computerized pharmacy printouts and concurrent manual medical record review. RESULTS: Approximately 25% (470/1893) of the patients requiring antimicrobial therapy reported an allergy to at least 1 antimicrobial agent. The most commonly reported antimicrobial allergy was penicillin (295/1893 [15.6%]). Eighty-five patients (18.1%) reported having an allergy to 2 or more antimicrobial agents. Only 4% (27/601) of the reported antimicrobial allergies contained documentation as to the nature of the specific allergic reactions, while a manual medical record review revealed that 32% (23/73) of the antimicrobial allergies contained documentation of the specific allergic reaction. Ninety-eight (39. 7%) of 247 patients reporting an allergy only to penicillin and/or cephalosporin received vancomycin in comparison with 247 (17.4%) of 1423 patients without any antimicrobial allergies (P<.001). Similarly, 53 (21.5%) of 247 patients with reported penicillin and/or cephalosporin allergies received levofloxacin compared with 114 (8.0%) of 1423 patients without any antimicrobial allergy (P<. 001). CONCLUSION: The incidence of penicillin allergy at our institution exceeds population averages. This finding, in combination with limited documentation of drug allergies, appears to lead to the prescribing of alternative antimicrobial agents that do not fit into institutional antimicrobial guidelines and, in some instances, may put the patient at risk for infection and/or colonization with resistant organisms. Use of these alternative agents may adversely impact the ability to manage emerging antimicrobial resistance.

Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin: a phenotypic assessment of NCCLS guidelines.

Between December 1, 1993, and December 1, 1996, we tested 4,411 isolates of Enterococcus sp. at gentamicin concentrations of 500 micrograms/mL and 2000 micrograms/mL using agar dilution to phenotypically categorize them into 3 groups: those with a MIC < or = 500 micrograms/mL (n = 3,132; 71%); a MIC > 500, but < or = 2000 micrograms/mL (n = 441; 10%); and those with a MIC > 2000 micrograms/mL (n = 838; 19%). Ten unique strains of each phenotype were tested to determine which gentamicin concentration was the best in vitro predictor of synergy with ampicillin. Testing was done by a time-kill method using clinically achievable levels of ampicillin and gentamicin. We found that for the gentamicin MIC < or = 500 micrograms/mL group, 7 of 10 isolates demonstrated synergy with ampicillin as manifested by a > or = 2 log10 increase in killing versus the effect of ampicillin alone (at 1/2 the MIC for ampicillin). In the group sensitive to a gentamicin MIC range between > 500 and < or = 2,000 micrograms/mL, none of the 10 isolates demonstrated synergy. Absence of synergy was also found in the group resistant to 2,000 micrograms/mL of gentamicin. Assessment of eight additional enterococcal isolates with reduced sensitivity to ampicillin (MIC from 32-256 micrograms/mL) found no correlation between gentamicin sensitivity at 500 micrograms/mL and any in vitro test for synergy, nor with clinical therapeutic outcome. Gentamicin at 2 micrograms/mL combined with ampicillin was as effective in enhancing killing as a higher level of 4 micrograms/mL. These findings validate the current NCCLS guideline for predicting synergistic activity against enterococci in strains with usual susceptibility to ampicillin, and suggest that a therapeutic level less than maximal recommended dosing is sufficient when using gentamicin in this setting.

Epidemiology of infectious complications in cancer patients.

Patients with underlying malignancies are at risk for a wide array of infectious diseases that cause significant morbidity and mortality. To develop a clear etiologic understanding of the infectious agents involved first requires a knowledge of the factors that predispose to infection. Neutropenia is clearly the single most important risk factor for infection in the cancer patient. However, a variety of both host and treatment-associated factors act together to predispose these patients to opportunistic infections. Approaching the individual malignancies with a knowledge of the underlying risk factors helps logically guide diagnosis and therapy. The astute clinician must also be aware of new and emerging infections in this patient population. As new pathogens are discovered and established pathogens become increasingly drug resistant, they will continue to present challenges for physicians caring for these patients in the years ahead.

The utility of aminoglycosides in an era of emerging drug resistance.

As the problem of global antibiotic resistance continues to worsen, aminoglycosides have assumed increasing importance in clinical practice. Their broad antimicrobial spectrum, rapid bactericidal action, and ability to act synergistically with other drugs have made them especially useful in the treatment of serious nosocomial infections. However, as with other drugs, their overuse and misuse leads to the development of resistance in important microbial pathogens. The appropriate use of the aminoglycosides is essential to assure their continued efficacy. Therefore, physicians must familiarize themselves with both the clinical indications and the limitations of these drugs if they are to remain efficacious in the years to come.