Journal of Infection - Articles in Press

Impact of inappropriate antimicrobial therapy on outcome in patients with hospital-acquired pneumonia caused by Acinetobacter baumannii - Corrected Proof

2010-07-21

Summary: Objectives: The purpose of this study was to evaluate the impact of inappropriate antimicrobial therapy on the outcome of patients with hospital-acquired pneumonia (HAP) caused by Acinetobacter baumannii.Methods: All cases of HAP caused by A. baumannii from January 2000 to March 2006 at the Samsung Medical Center (Seoul, Korea) were analyzed retrospectively.Results: A total of 116 patients with clinically significant Acinetobacter HAP were enrolled. Among the A. baumannii isolates, 60.3% showed multi-drug resistance (MDR), 16.4% were found to have imipenem resistance, and 15.5% had pan-drug resistance (PDR). The mean APACHE II score of the patients was 22.3 ± 7.9. The overall in-hospital and pneumonia-related mortality rates were 47.4% and 37.9%, respectively. The univariate analysis showed that the factors associated with pneumonia-related mortality were: MDR, PDR, high APACHE II score, inappropriate empirical antimicrobial therapy, and inappropriate definitive antimicrobial treatment (All p < 0.05). Among these, a high APACHE II score and inappropriate definitive antimicrobial therapy were found to be independent factors associated with a high mortality, after adjustment for other variables.Conclusions: The appropriate definitive antimicrobial therapy should be provided in patients with HAP caused by A. baumannii.

Diagnostic usefulness of a T-cell-based assay for osteoarticular tuberculosis - Corrected Proof

2010-07-21

Summary: Background: Although diagnosing osteoarticular tuberculosis (TB) remains a challenge, a recently developed Mycobacterium tuberculosis-specific ELISPOT assay for diagnosing TB infection has shown promising results. We performed a prospective, blinded, observational study to compare its diagnostic usefulness with those of conventional tests in patients with suspected osteoarticular TB.Methods: All patients presenting at a tertiary hospital between April 2008 and September 2009 with suspected osteoarticular TB were enrolled. In addition to conventional tests for TB, we used ELISPOT assays to measure the IFN-γ response to ESAT-6 and CFP-10 in T-cells in samples of peripheral blood mononuclear cells (PBMC). Patients with suspected osteoarticular TB were classified by diagnostic category.Results: Of the 65 patients with suspected osteoarticular TB, 5 (8%) were excluded due to inconclusive diagnoses. Of the remaining 60 patients, 23 (38%) were classified as having confirmed TB, 3 (5%) as having probable TB, 2 (3%) as having possible TB, and 32 (53%) as not having active TB. Five (8%) patients with probable or possible TB were excluded from the final analysis. Of the 23 patients with confirmed osteoarticular TB, 15 (65%) had TB spondylitis, 4 (17%) had TB arthritis, 2 (9%) had prosthetic joint infection, and 2 (9%) had extra-spinal TB. The sensitivities of the tuberculin skin test (≥10 mm) and the ELISPOT assay for active osteoarticular TB were 80% (95% confidence interval [CI], 58%–92%) and 100% (95% CI, 85%–100%) (P = 0.04), respectively and their specificities were 68% (95% CI, 51%–81%) and 58% (95% CI, 41%–74%) (P = 0.60), respectively.Conclusion: A negative ELISPOT assay using PBMC may be a useful test for excluding a diagnosis of active osteoarticular TB.

Tropheryma whipplei in the skin of patients with classic Whipple’s disease - Corrected Proof

2010-07-16

Summary: Positive Tropheryma whipplei PCR results in skin biopsies were frequent in patients with classic Whipple’s disease without skin manifestations. The bacterium was alive, as a strain was successfully cultured. The skin may be a reservoir for T. whipplei and may be helpful in the non-invasive diagnosis of the disease.

Humoral immunity following chickenpox is influenced by geography and ethnicity - Corrected Proof

Karen L. Ayres, Yamima Talukder, Judith Breuer — 2010-07-15

Summary: Objectives: To investigate the contribution of ethnicity and geographical location to varicella-zoster virus (VZV) serostatus and antibody concentrations.Methods: The presence and concentrations of antibodies to VZV were measured in 639 Bangladeshi women born in Bangladesh (BBB), 94 Bangladeshi women born in the UK (BUK) and 262 White women born in the UK (WUK). The results were anaylsed in relation to demographic and social data.Results: BBB women were significantly less likely to be VZV seropositive at all ages than both BUK and WUK women. However, the odds of a Bangladeshi-born woman being seropositive increased by 1.04 for each year under the age of 15 spent in the UK. In contrast, antibody concentrations were significantly lower in ethnic Bangladeshi women, irrespective of country of birth. White, but not Bangladeshi women, showed evidence of antibody boosting over time despite the latter having more exposure to children.Conclusion: Geographical location during childhood is the major influence on age of primary infection with VZV while the level of antibody is related to ethnicity. Since the risk of re-infection with VZV following both natural infection and vaccination is increased as antibody concentrations fall, these results have implications for VZV vaccination programmes particularly in non-White populations.

Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R - Corrected Proof

2010-07-09

Summary: Objectives: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine.Methods: We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from previously collected frozen plasma. The patients were followed for clinical and resistance outcome after treatment intensification with only zidovudine.Results: Five patients had experienced antiretroviral treatment failure on various nucleoside analogue combinations, containing abacavir, didanosine, lamivudine, nevirapine, reverset and/or tenofovir. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. The patients’ median viral load prior to zidovudine intensification was 3.551 Log10 (range 3.053–4.681) and despite evidence for resistance to the failing drug regimen, all responded within 4 weeks to undetectable levels (<1.699 Log10 or <50 copies/mL) and remained virologically suppressed during follow-up (20 months through 6.5 years).Conclusions: In virologically failing patients due to K65R- and other non-thymidine-mutations, simple regimen intensification with zidovudine resulted in sustained HIV-1 suppression. The finding of re-sensitized HIV-1 in patients may be clinically relevant.

Imported Mayaro virus infection in the Netherlands - Corrected Proof

2010-07-08

Summary: A Dutch couple, presenting with persisting arthralgias, temporary fever and rash after a stay in Surinam were diagnosed with Mayaro virus infection. Mayaro virus is a relatively unknown South American Alphavirus responsible for dengue-like clinical features and persisting arthralgias. An important, but probably underappreciated cross-reactivity with other Alphaviruses like Chikungunya virus is present, which may become of clinical importance in the event the various Alphaviruses will have overlapping geographical distributions and in seroprevalence studies.

Chronic disseminated histoplasmosis with prolonged latency - Corrected Proof

Michael Addidle, Joanne Pynn, Philippa Skellern, Takao Kasuga, Kate Grimwade — 2010-07-08

It is well recognized that histoplasmosis may “reactivate” after many years of dormancy. We present a case of an ex-serviceman with chronic disseminated histoplasmosis. The clinical presentation, occupational and travel history indicate that the patient had Histoplasma capsulatum infection in its dormant state for a period of over sixty years.

A crackling priapism related to Fournier’s gangrene in a patient on chronic peritoneal dialysis - Corrected Proof

Hélène Charbonneau, Frédéric Pène — 2010-07-08

An 80-year-old man with a previous medical history of myocardial infarction and end-stage chronic renal failure treated with long-term peritoneal dialysis was referred to the intensive care unit for septic shock. Physical examination revealed a priapism associated with an extended perineal necrotizing cellulitis suggestive of Fournier gangrene involving the peri-anal area, the scrotum and the penis. Palpation of soft tissues and penis revealed diffuse and extensive subcutaneous crepitations. Pelvic and abdominal contrast-enhanced computed tomography displayed diffuse subcutaneous emphysema in the perineum and within abdominal walls, as well as gas within bladder and rectum walls (a). In addition, it showed penile subcutaneous emphysema and gas in corpora cavernosa and corpus spongiosum (b). A broad spectrum antibiotic treatment combining imipenem, amikacin, vancomycin and metronidazole was immediately initiated along with extensive life support including fluid resuscitation and norepinephrine, mechanical ventilation and hemodialysis because of profound lactic acidosis. However, the patient was declined for surgical treatment because of extensive and rapidly progressive tissue necrosis, and he died from uncontrolled multiple organ failure. Culture of peritoneal fluid was finally positive for the anaerobe Gram-positive Clostridium septicum.

Determinants of intention to get vaccinated against novel (pandemic) influenza A H1N1 among health-care workers in a nationwide survey - Corrected Proof

2010-07-05

Summary: A nationwide survey was conducted in October–November 2009 to investigate determinants of intention to get vaccinated against novel (pandemic) influenza A H1N1 among health-care workers (HCWs) in Greece. Out of 12,879 participating HCWs (response rate: 12.1%) working in 152 (40%) of 380 health-care facilities in Greece, 2814 (21.8%) reported that they intend to get vaccinated against novel influenza A N1H1. Intention rates to get vaccinated increased with age, male sex, being a physician, history of vaccination against seasonal influenza, training in use of personal protective equipment and hand hygiene, and training and involvement in the management of novel influenza cases. Main reasons for refusing vaccination were concerns about vaccine safety (43.1%), inadequate information about the vaccine (27.8%), and perception that they were not at risk for contracting novel influenza (10.7%). Given the low rates of acceptance of pandemic vaccination among HCWs, as found in this study, public health bodies should consider the implementation of a mandatory vaccination policy for HCWs for future pandemics, in order to prevent nosocomial transmission and to protect patients at high-risk for influenza-related complications and death, and to assure the continuity of the essential health-care infrastructure. New strategies should be explored to built safety perception towards influenza vaccines and enhance vaccination rates among HCWs.

Time to blood culture positivity in Staphylococcus aureus bacteremia: Association with 30-day mortality - Corrected Proof

Joseph Kim, Daniel B. Gregson, Terry Ross, Kevin B. Laupland — 2010-06-30

Summary: Objectives: Time to blood culture positivity (TTP) has been suggested as a prognostic factor for adverse clinical outcome. This study describes the relationship between TTP and clinical outcome in all patients with Staphylococcus aureus bacteremia (SAB) in a large Canadian health region.Methods: We performed a retrospective study of all first episodes of SAB occurring in the former Calgary Health Region (population ∼1.2 million) from July 1, 2006 to December 31, 2008.Results: Overall, 684 cases of SAB were evaluated. The median TTP was 16 h and 31/684 (5%) cases had TTP at >48 h. Time to positivity was shorter for methicillin-susceptible Staphylococcus aureus compared with methicillin-resistant S. aureus (MRSA) and for endovascular sources compared with other sources of infection. The overall 30-day case-fatality rate was 18% (124/684). Patients with delayed TTP (>48 h) suffered the highest case-fatality rate (39%) compared to those with earlier TTP (17%; P = 0.002). Multivariable logistic regression modeling showed that age, nosocomial acquisition, MRSA, focus of infection, liver disease, and TTP ≤12 and >48 h were associated with 30-day mortality.Conclusion: Although uncommon, delayed TTP may be associated with increased mortality. Empiric antimicrobial therapy should continue beyond 48 h in patients at high risk for SAB.

WITHDRAWN: JC Virus in the Irish Population: Significant Increase of Genotype 2 in Immunocompromised Individuals - Corrected Proof

K. Schaffer, N. Sheehy, S. Coughlan, C. Bergin, W.W. Hall — 2009-01-23