BK Virus: Opportunity Makes a Pathogen

More than 70% of the general population worldwide has serological evidence of exposure to Polyomavirus hominis type 1, better known as BK virus (BKV). BKV infection typically occurs during childhood, without specific symptoms, followed by a state of nonreplicative infection in various tissues, with the urogenital tract as the principal site. Asymptomatic reactivation and low-level replication with viruria is observed in 5% of healthy individuals. Persistent high-level BKV replication is the hallmark of polyomavirus-associated nephropathy in renal transplantation and of hemorrhagic cystitis in bone marrow transplantation. Since these manifestations are rare in other types of immunocompromised patients, the presence of specific cofactors is postulated. The role of BKV in autoimmune disease and cancer is a controversial topic and is difficult to determine, because the pathology no longer depends on BKV replication. This article discusses current views of pathogenesis, diagnosis, and treatmen

Severe Sepsis: Variation in Resource and Therapeutic Modality use Among Academic Centers

Background: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. Methods: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. Results: The adjusted mean total hospital charges varied from $69 429 to US$237 898 across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72). Conclusion: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level

Severe sepsis: variation in resource and therapeutic modality use among academic centers

BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. RESULTS: The adjusted mean total hospital charges varied from $69 429 to US$237 898 across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r(2 )= 0.72). CONCLUSION: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level

Human Cytomegalovirus Fcγ Binding Proteins gp34 and gp68 Antagonize Fcγ Receptors I, II and III

Human cytomegalovirus (HCMV) establishes lifelong infection with recurrent episodes of virus production and shedding despite the presence of adaptive immunological memory responses including HCMV immune immunoglobulin G (IgG). Very little is known how HCMV evades from humoral and cellular IgG-dependent immune responses, the latter being executed by cells expressing surface receptors for the Fc domain of IgG (FcγRs). Remarkably, HCMV expresses the RL11-encoded gp34 and UL119-118-encoded gp68 type I transmembrane glycoproteins which bind Fcγ with nanomolar affinity. Using a newly developed FcγR activation assay, we tested if the HCMV-encoded Fcγ binding proteins (HCMV FcγRs) interfere with individual host FcγRs. In absence of gp34 or/and gp68, HCMV elicited a much stronger activation of FcγRIIIA/CD16, FcγRIIA/CD32A and FcγRI/CD64 by polyclonal HCMV-immune IgG as compared to wildtype HCMV. gp34 and gp68 co-expression culminates in the late phase of HCMV replication coinciding with the emergence of surface HCMV antigens triggering FcγRIII/CD16 responses by polyclonal HCMV-immune IgG. The gp34- and gp68-dependent inhibition of HCMV immune IgG was fully reproduced when testing the activation of primary human NK cells. Their broad antagonistic function towards FcγRIIIA, FcγRIIA and FcγRI activation was also recapitulated in a gain-of-function approach based on humanized monoclonal antibodies (trastuzumab, rituximab) and isotypes of different IgG subclasses. Surface immune-precipitation showed that both HCMV-encoded Fcγ binding proteins have the capacity to bind trastuzumab antibody-HER2 antigen complexes demonstrating simultaneous linkage of immune IgG with antigen and the HCMV inhibitors on the plasma membrane. Our studies reveal a novel strategy by which viral FcγRs can compete for immune complexes against various Fc receptors on immune cells, dampening their activation and antiviral immunity.DFG grant He 2526/6-2.European Commission grants QLRT-2001-01112 and MRTN-CT-2005-019248.Helmholtz Association through VISTRIE VH-VI-242.UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Capnocytophaga species: Infections in nonimmunocompromised and immunocompromised hosts

Retrospective review of isolates of Capnocytophaga, a genus of capnophilic gramnegative bacilli, referred to the Massachusetts State Laboratory Institute in Boston revealed 31 patients with infection due to Capnocytophaga, 16 in nonimmunocompromised hosts. These infections included empyema (three patients), lung abscess (one), sinusitis (one), conjunctivitis (three), subphrenic abscess (one), wound (three), osteomyelitis (one), and bacteremia (three). Two of the wound infections were closed-fist injuries involving bone or soft tissue. Capnocytophaga was frequently isolated as part of a polymicrobial infection with other oral flora. There was only one death in the nonimmunocompromised group. In contrast, of 15 mmunocompromised patients with 16 pisodes of bacteremia due to Capnocytophaga, 87% had leukopenia and 73% had significant oral pathology such as gingivitis, mucositis, or ulceration. Five immunocompromised patients died. Thus, Capnocytophaga species may cause disease in both nonimmunocompromised and immunocompromised hosts. Isolation of this organism should suggest an oral source for infection. © 1985 The University of Chicago. All Rights Reserved

In Vitro Activity of Ceftaroline against a Broad Spectrum of Recent Clinical Anaerobic Isolates ▿

The in vitro activity of ceftaroline was compared with those of ceftriaxone, clindamycin, imipenem, metronidazole, moxifloxacin, tigecycline, and vancomycin against 514 clinical anaerobic isolates using Clinical and Laboratory Standards Institute (CLSI) standard methodology. Ceftaroline demonstrated good to excellent activity against Gram-positive anaerobic pathogens and limited activity against Gram-negative pathogens, particularly Bacteroides fragilis group isolates

In Vitro Activities of Doripenem, a New Broad-Spectrum Carbapenem, against Recently Collected Clinical Anaerobic Isolates, with Emphasis on the Bacteroides fragilis Group ▿

Doripenem was evaluated against 527 recent clinical isolates, i.e., 404 Bacteroides fragilis isolates and 123 gram-positive anaerobe isolates. Against B. fragilis, doripenem was as active as imipenem, meropenem, and piperacillin-tazobactam and more active than ertapenem or ampicillin-sulbactam. Doripenem was active against isolates resistant to ertapenem, ampicillin-sulbactam, cefoxitin, clindamycin, and moxifloxacin. All of the gram-positive isolates tested were susceptible to doripenem

Carbapenem-resistant enterobacteriaceae: analyzing knowledge and practice in healthcare providers

Background. Gram negative antibiotic resistance is increasing worldwide as both carbapenem-resistant enterobacteriaceae (CREs) and Enterobacteriaceae producing extended spectrum ß-lactamases (ESBLs) become more common.Objective. We analyzed clinicians’ knowledge regarding resistant gram-negative organisms with respect to infection control practices, prescribing practices and assessment of their patients’ risk for resistant infections.Design. Online survey.Participants. Target population included clinicians who prescribe antibiotics i.e., medical doctors and mid-level practitioners, at three Massachusetts hospitals.Methods. Questionnaires were sent to 3 Tufts-affiliated teaching hospitals to assess level of knowledge and elucidate perceptions about gram-negative resistance.Results. We received 434 responses from 3332 non-infectious disease clinicians (13%) surveyed at the three hospitals. 51.1% of clinicians correctly scored 50% or greater on the knowledge questions. Internal medicine clinicians had higher knowledge scores than non-internal medicine clinicians (62% vs 45%; OR = 1.67, p = 0.02). Clinicians within three years of training had higher scores than those with more than 10 years of training (64.3% vs 44%; OR = 2.3, p = 0.002). Clinicians with fewer years since training and those with higher knowledge scores were more likely to appropriately consider certain patients at risk for resistant infections (p < 0.05). 54.4% of clinicians were very concerned about gram-negative antibiotic resistance. 64.6% of clinicians felt comfortable de-escalating antibiotics as cultures are available.Conclusion. We found overall low knowledge scores and much variability in the way clinicians assess whether certain patient populations are at risk for antibiotic resistance. Internal medicine clinicians and those with fewer years since completion of their training scored higher and more appropriately considered patients at risk for resistance. The majority of clinicians are concerned about gram-negative resistance and indicated they would de-escalate antibiotic therapy if they had susceptibility information. These results will help focus and target our teaching and awareness-raising strategies

Infective endocarditis in solid organ transplant recipients

Infective endocarditis, defined as pathologically or clinically definite by the Duke criteria, was observed in 14 transplant recipients at our institutions. In addition, we reviewed 32 previously reported cases in solid organ transplant recipients. The spectrum of organisms causing infective endocarditis was clearly different in transplant recipients than in the general population; 50% of the infections were due to Aspergillus fumigatus or Staphylococcus aureus, but only 4% were due to viridans streptococci. Fungal infections predominated early (accounting for six of 10 cases of endocarditis within 30 days of transplantation), while bacterial infections caused most cases (80%) after this time. In 80% (37) of the 46 cases in transplant recipients, there was no underlying valvular disease. Seventy- four percent (34) of the 46 cases were associated with previous hospital- acquired infection, notably venous access device and wound infections. Three patients with S. aureus endocarditis had had an episode of S. aureus bacteremia >3 weeks prior to the diagnosis of endocarditis and had received treatment for the initial bacteremia o