Risk factors for fluoroquinolone resistance in Enterococcus urinary tract infections in hospitalized patients.

Past studies exploring risk factors for fluoroquinolone (FQ) resistance in urinary tract infections (UTIs) focused only on UTIs caused by Gram-negative pathogens. The epidemiology of FQ resistance in enterococcal UTIs has not been studied. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System in order to identify risk factors for FQ resistance in enterococcal UTIs. Subjects with positive urine cultures for enterococci and meeting CDC criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant enterococcal UTI. Controls were subjects with FQ-susceptible enterococcal UTI and were frequency matched to cases by month of isolation. A total of 136 cases and 139 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors [adjusted OR (95% CI)] for FQ resistance included cardiovascular diseases [2·24 (1·05-4·79), P=0·037], hospitalization within the past 2 weeks [2·08 (1·05-4·11), P=0·035], hospitalization on a medicine service [2·15 (1·08-4·30), P<0·030], recent exposure to ß-lactamase inhibitors (BLIs) [14·98 (2·92-76·99), P<0·001], extended spectrum cephalosporins [9·82 (3·37-28·60), P<0·001], FQs [5·36 (2·20-13·05), P<0·001] and clindamycin [13·90 (1·21-10·49), P=0·035]. Use of BLIs, extended spectrum cephalosporins, FQs and clindamycin was associated with FQ resistance in enterococcal uropathogens. Efforts to curb FQ resistance should focus on optimizing use of these agents.

Risk factors for fluoroquinolone resistance in Gram-negative bacilli causing healthcare-acquired urinary tract infections.

The prevalence of urinary tract infections caused by fluoroquinolone-resistant Gram-negative bacilli (FQ-resistant GNB-UTIs) has been increasing. Previous studies that explored risk factors for FQ resistance have focused only on UTIs caused by Escherichia coli and/or failed to distinguish colonisation from infection. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System to identify risk factors for FQ resistance among healthcare-acquired GNB-UTIs. Subjects with positive urine cultures for GNB and who met Centers for Disease Control and Prevention criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant GNB-UTI and controls were subjects with FQ-susceptible GNB-UTI matched to cases by month of isolation and species of infecting organism. In total, 251 cases and 263 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors (adjusted odds ratio; 95% confidence interval) for FQ resistance included male sex (2.03; 1.21-3.39; P=0.007), African-American race (1.80; 1.10-2.94; P=0.020), chronic respiratory disease (2.58; 1.18-5.62; P=0.017), residence in a long term care facility (4.41; 1.79-10.88; P=0.001), hospitalisation within the past two weeks (2.19; 1.31-3.64; P=0.003), hospitalisation under a medical service (2.72; 1.63-4.54; P<0.001), recent FQ exposure (15.73; 6.15-40.26; P<0.001), recent cotrimoxazole exposure (2.49; 1.07-5.79; P=0.033), and recent metronidazole exposure (2.89; 1.48-5.65; P=0.002).

Socioeconomic risk factors for bacteraemic pneumococcal pneumonia in adults.

Demographic and clinical risk factors are important in guiding vaccination policy for pneumococcal pneumonia. We present data on these variables from a population-based surveillance network covering adult bacteraemic pneumococcal pneumonia (BPP) in the Delaware Valley region from 2002 to 2004. Surveillance data were used with U.S. Census data and a community health survey to calculate stratified incidence rates. Missing data were handled using multiple imputation. Overall rates of adult BPP were 10.6 cases/100 000 person-years. Elevated rates were seen in the elderly (>65 years), Native Americans, African Americans, the less-educated (less than high-school education), the poor, smokers, and individuals with histories of asthma, cancer, or diabetes. Multivariable modelling suggested that income was more robustly associated with risk than African American race. Of methodological interest, this association was not apparent if census block-group median income was used as a proxy for self-reported income. Further research on socioeconomic risk factors for BPP is needed.

Recurrent catheter-related Rhodotorula rubra infection.

A 34-year-old male receiving chronic parenteral nutrition for treatment of short bowel syndrome and intermittent immunosuppressive agents for juvenile rheumatoid arthritis developed recurrent, catheter-associated Rhodotorula rubra fungemia over a one-year period. Infection with this yeast is associated with insertion of central venous catheters. Recurrence of R. rubra infection is an unusual event that presumably occurred because of chronic skin colonization by the organism.

Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.

Impact of a hospital-based antimicrobial management program on clinical and economic outcomes.

Inappropriate use of antimicrobial agents results in unnecessary exposure to medication, persistent or progressive infection, emergence of resistance, and increased costs. We implemented a program to control use of restricted agents while improving care. This study compared 2 major mechanisms for improving use of antimicrobial agents: (1) recommendations made by the Antimicrobial Management Team (AMT), which included a clinical pharmacist backed up by a physician from the Division of Infectious Diseases (ID), and (2) recommendations made by ID fellows. Outcome measures included appropriateness of recommendations, cure rate, number of treatment failures, and cost of care, which were assessed for 180 patients. The AMT outperformed the ID fellows in all outcomes examined by the study (including appropriateness [87% vs. 47%; P<.001], cure rate [64% vs. 42%; P=.007], and treatment failures [15% vs. 28%; P=.03]), although the differences in economic outcomes between cases managed by the AMT and those managed by the ID fellows were not statistically significant. In an academic setting with a restricted formulary, the AMT demonstrated better antimicrobial prescribing than ID fellows.

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes.

The prevalence of antibiotic resistance among extended-spectrum beta-lactamase (ESBL)--producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03--1.18; P=.006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P<.001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P=.01 and P<.001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.

Impact of a vancomycin restriction policy on use and cost of vancomycin and incidence of vancomycin-resistant Enterococcus.

OBJECTIVE: To review the appropriateness of vancomycin therapy, changes in vancomycin use, and the incidence of vancomycin-resistant Enterococcus (VRE) after implementation of a limited restriction policy requiring approval from the Infectious Diseases Approval service to continue vancomycin therapy beyond 72 hours. DESIGN: A prospective chart review was conducted in April 1995. Pharmacy billing data and infection control data were compared before and after policy implementation. SETTING: A 725-bed university teaching institution. PATIENTS: All patients receiving vancomycin during April 1995. MAIN OUTCOME MEASURES: Appropriateness of use was based on the Centers for Disease Control and Prevention (CDC) recommendations for prudent vancomycin use. RESULTS: A total of 333 courses of vancomycin therapy were reviewed. Vancomycin use was appropriate in 219 (66%) courses. Of the 114 courses that did not meet the CDC guidelines, 76 (67%) were for empiric use, 35 (31%) were for prophylactic use, and 3 (3%) were for therapeutic use. Overall, the total number of grams used decreased 9%, grams per 1000 patient-days decreased by 10, and the total number of patients exposed to vancomycin decreased 0.5%. Several services had large decreases in vancomycin use. Vancomycin expenditures decreased by $15788 for the 7-month time period. The incidence of VRE remained unchanged, at 30% of all enterococcal isolates 2 years after policy implementation. CONCLUSIONS: The limited restriction policy was effective in decreasing the total grams of vancomycin used. However, one-third of vancomycin therapy was inappropriate and the incidence of VRE was unchanged. A more stringent restriction policy could potentially increase appropriate use, further decrease the amount of vancomycin used, and decrease the incidence of VRE.

Programmatic role of the infectious diseases physician in controlling antimicrobial costs in the hospital.

Controlling antimicrobial costs has preoccupied infectious diseases physicians (IDPs). IDPs have controlled antimicrobial costs by the use of eight strategies: education, formulary restriction, pharmacy justification, formulary substitution, computer surveillance, laboratory item cost listing, purchase plans, and multidisciplinary approaches. Most strategies had input from IDPs and resulted in cost savings (up to $500,000 annually), particularly during the initiation periods. Educational efforts were successful in reducing costs but needed continual intervention. Formulary restriction was the most straightforward cost-control mechanism. Restriction of "target antimicrobials" has given way to "switch" therapy between expensive and less costly agents or between parenteral and oral regimens. Switch therapy is facilitated through the use of innovative order forms and on-line computer interaction. Computer surveillance has a capacity for interactive controls. Purchase plans may give way to centralized pharmacy monitoring, a strategy that is attractive to managed care organizations. Multidisciplinary antimicrobial management programs (AMPs) offer the best potential for sustaining savings in antimicrobial costs. Ten recommendations lay a groundwork for IDPs to translate their expertise into leadership of AMPs.

Immune evasion properties of herpes simplex virus type 1 glycoprotein gC.

Herpes simplex virus type I (HSV-1) glycoprotein gC binds complement component C3b, and purified gC inhibits complement activation. Two HSV strains carrying mutations in the gC gene which rendered them unable to bind C3b were compared with wild-type and marker-rescued viruses to evaluate the role of gC on the virion in protecting HSV-1 from complement-mediated neutralization. The gC mutant viruses were markedly susceptible to neutralization by nonimmune human serum, showing up to a 5,000-fold decline in titer after 1 h of incubation with serum. In contrast, wild-type or marker-rescued viruses showed a twofold reduction in titer. Studies with hypogammaglobulinemic and immunoglobulin G-depleted serum supported the observation that neutralization occurred in the absence of antibody. Neutralization of gC mutant strains by nonimmune serum was rapid; their half-life was 2 to 2.5 min, compared with 1 h for wild-type virus. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-treated human serum or C4-deficient guinea pig serum failed to neutralize gC mutant strains, indicating a role for components of the classical complement pathway. gC had little additional effect on neutralization by the combination of antibody plus complement compared with complement alone. The results indicate that the magnitude of the protection offered by gC-1 is larger than previously recognized; that in the absence of gC-1, complement neutralization is rapid and is mediated by components of the classical complement pathway; and that gC mainly protects against antibody-independent complement neutralization, suggesting a probable role for gC early in infection, before antibodies develop.

Acalculous candidal cholecystitis: a previously unrecognized complication after cardiac transplantation.

Acalculous cholecystitis is a life-threatening complication in critically ill surgical patients. Whereas Candida albicans and Torulopsis glabrata have been reported as the primary pathogens in 14 previous cases of acalculous cholecystitis, we report the first case of Candida parapsilosis as a biliary pathogen in a patient after cardiac transplantation. Although cardiac transplant recipients often have many of the risk factors for acalculous candidal cholecystitis, including major surgery, immunosuppression, antibiotic therapy, parenteral nutrition, and prolonged intensive care unit stay, this entity has not been previously reported in the cardiac transplant population. Although rare, acalculous candidal cholecystitis is associated with very high morbidity and a mortality rate of 40%. Early diagnosis necessitates an aggressive approach to the critically ill patient with abdominal complaints. Prompt drainage or cholecystectomy, if possible, represent the mainstays of therapy and offer the greatest chance for survival.

Coincident Kaposi sarcoma and T-cell lymphoma in a patient with the Wiskott-Aldrich syndrome.

A 24 year old male with a history of eczema, recurrent mild infections, and thrombocytopenia consistent with the Wiskott-Aldrich syndrome (WAS) presented with a mediastinal mass, generalized lymphadenopathy, splenomegaly, and severe thrombocytopenia. Studies of immune function including immunoglobulin levels and T-cell subsets were normal. Furthermore, his T lymphocytes proliferated normally in response to phytohemagglutinin, concanavalin A, and the combination of neuraminidase/galactose oxidase. However, their proliferative responses to anti-CD43 antibody and periodate were diminished, consistent with the clinical diagnosis of WAS. An initial inguinal lymph node biopsy surprisingly revealed Kaposi sarcoma. However, following splenectomy to increase the platelet count, biopsy of the mediastinal mass revealed T-cell large cell lymphoma. Studies of biopsied tissue for the presence of Epstein-Barr virus and cytomegalovirus were negative, as were studies of blood, including the polymerase chain reaction, for the presence of the human immunodeficiency virus (HIV). This is the first report of Kaposi sarcoma arising in a patient with a congenital immunodeficiency syndrome. Although Kaposi sarcoma can arise in the face of the severe immunosuppression that follows allograft transplantation and in patients infected with HIV, we postulate that longevity in the face of mild immunosuppression was the major factor in the development of Kaposi sarcoma in this patient.