En este número:

1. Portada. Nuevas guías

de PPE: el RAL gana pro-

tagonismo

2. Impactos (y enlaces) a

artículos de interés en

aspectos generales, bac-

terias, virus, hongos y

parásitos

Que el Boletín de la

SEICV sea de utilidad

Boletín de la Sociedad de Enfermedades Infecciosas de la Comunidad Valenciana

VOLUMEN 2 NÚMERO 4 SEPTIEMBRE 2013

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GENERAL

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)

Ellen Jo Baron et al. Clin Infect Dis. (2013) doi: 10.1093/cid/cit278

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiolo-gists who provide enormous value to the health care team. This document, devel-oped by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diag-nostic decisions. Sections are divided into anatomic systems (enlace)

Review of Infectious Diseases Applications for iPhone/iPad and Android: from Pocket to Patient Amaran Moodley, et al. Clin Infect Dis (published 9 July 2013), (enlace)

The explosion of medical apps creates challenges amongst providers trying to find reliable trustworthy infectious disease apps. This has opened the door for regulation by the FDA. We reviewed over 900 apps to find eleven new useful ID apps.

Physical exercise is associated with less neurocognitive impairment among HIV-infected adults Catherine A. Dufour et al. J. Neurovirol. June 2013

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"In summary, NCI still affects nearly half of the HIV+ population. Our results suggest that exercise is associated with less NCI among HIV-infected persons and may have specific impact on working memory and speed of information processing. Fu-ture intervention studies would help better determine whether exercise is an effec-tive tool to address the neurocognitive deficits associated with this disease."

Medical Students’ Perceptions and Knowledge About Antimicrobial Stewardship: How Are We Educating Our Future Prescribers? Lilian M. Abbo et al. Clin Infect Dis published 31 May 2013, doi 10.1093/cid/cit370 (enlace)

This study highlights an important education gap among US medical schools, sug-gesting that more attention should be given to instruction of medical students about the principles of antimicrobial stewardship. Medical schools should be partners in global efforts to reduce antimicrobial resistance.

BACTERIAS

Is Fidaxomicin Worth the Cost? An Economic Analysis Sarah M. Bartsch, et al. Clin Infect Dis (published 23 May 2013), doi 10.1093/cid/cit346 (enlace)

Our model suggests that when approximately 50% of isolates are NAP1/BI/027, fi-daxomicin use for Clostridium difficile infection is not cost-effective at its current cost. However, typing and treatment with fidaxomicin based on strain may be more promising depending on its costs.

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Colistin and Rifampicin Compared With Colistin Alone for the Treatment of Serious Infections Due to Extensively Drug-Resistant Acinetobacter baumannii: A Multi-center, Randomized Clinical Trial Emanuele Durante-Mangoni, et al Clin Infect Dis 2013 57: 349-358 (enlace)

In this randomized trial including patients with serious extremely drug-resistant Aci-netobacter baumannii infections, the combination of rifampicin with colistin did not reduce 30-day mortality, infection-related death, or hospitalization length. It did in-crease the eradication rate from the primary infectious source.

U.S. Hospitalizations for Pneumonia after a Decade of Pneumococcal Vaccination

Marie R. Griffin, et al

N Engl J Med 2013; 369:155-163

Declines in hospitalizations for childhood pneumonia were sustained during the dec-ade after the introduction of PCV7. Substantial reductions in hospitalizations for pneumonia among adults were also observed.

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Treatment Trials for Post-Lyme Disease Symptoms Revisited Mark S. Klempner, e al. American Journal of Medicine 2013; 126: 665-669.

Some patients given recommended antibiotic therapy for Lyme disease have non-specific symptoms, believed—but not proven—to be caused by a persistent Borrelia infection. Four clinical trials report that extended antibiotic therapy is of little or no benefit; however, others claim that these trials are flawed. The present analysis of all 4 trials reaffirms that extended antibiotic therapy pro-vides no meaningful benefit.

VIRUS

Interhuman transmissibility of Middle East respiratory syndrome coronavirus: es-timation of pandemic risk Romulus Breban et al Lancet 2013; 382: 694 – 699 (enlace)

Our analysis suggests that MERS-CoV does not yet have pandemic potential. We recommend enhanced surveillance, active contact tracing, and vigorous searches for the MERS-CoV animal hosts and transmission routes to human beings.

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Marijuana Smoking Does Not Accelerate Progression of Liver Disease in HIV–Hepatitis C Coinfection: A Longitudinal Cohort Analysis Laurence Brunet, et al. Clin Infect Dis published 28 June 2013, doi: 10.1093/cid/cit378 (enlace)

In a large HIV-HCV coinfection cohort, we found no evidence that marijuana smok-ing accelerated progression to significant liver fibrosis, cirrhosis, or end-stage liver disease. Previous studies reporting an association may have been biased by reverse causation due to self-medication.

HCV reinfection incidence and treatment outcome among HIV-positive MSM in London Martin, Thomas C.S et al AIDS 2013 June 3 Epub (enlace) "Combining first, second and third reinfections, there were 54 reinfections in total"

"Our results demonstrate a high risk of HCV reinfection among HIV-positive MSM who are either treated for or who spontaneously clear their initial HCV infection. As many as 25% of individuals treated for HCV will become reinfected within 2 years. These results emphasize the need for effective sexual education for HIV-positive MSM presenting with primary HCV infection and the implementation of preventative interventions to reduce the risk of reinfection. Given their high risk, we recommend enhanced surveillance of previously infected individuals to enable the early detec-tion and treatment of any reinfections. New UK guidelines have been updated to re-flect this by recommending HCV PCR testing every 3-6 months among individuals who remain at risk following incident infection clearance [30]."

HIV/AIDS: Is Intrapartum Intravenous Zidovudine for Prevention of Mother-to-Child HIV-1 Transmission Still Useful in the Combination Antiretroviral Therapy Era? Nelly Briand, et al Clin Infect Dis published 31 May 2013, doi: 10.1093/cid/cit374 (enlace)

Intrapartum intravenous zidovudine in antiretroviral therapy–treated women mays not be necessary when maternal viral load is low at delivery, but it remains an effec-tive tool to reduce mother-to-child HIV transmission in cases of virological failure.

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Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS Iart Luca Shytaj et al Retrovirology 2013, 10:71 doi:10.1186/1742-4690-10-71 (Enlace)

Our data suggest that a combined H-iART/auranofin/BSO treatment was followed by aradical change in disease progression after therapy suspension. This change was as-sociated with enhanced specific immune responses following viral rebound after therapy suspension, thus suggesting the establishment of an “immune state” [7]. Similar effects had previously been observed only in the period immediately after acute infection but not in a pre-AIDS stage [21,39-41]. Although fully controlled stud-ies involving larger numbers of macaques will be necessary in order to obtain further mechanistic insight, it is becoming increasingly evident that dramatic changes in dis-ease progression cannot be evaluated only in terms of sheer numbers of study sub-jects [38,43]. Whether these results may pave the way to a significant improvement of current “ART-for-life” therapies will need to be assessed in human clinical trials.

Antiretroviral Therapy Initiated within Six Months of HIV Infection is Associated with Lower T-cell Activation and Smaller HIV Reservoir Size Vivek Jain et al J Infect Dis published 12 July 2013, 10.1093/infdis/jit311 (enlace)

ART initiation <6 months following infection is associated with lower T-cell activation and smaller HIV DNA and RNA reservoir size during long-term therapy

Figure 2. HIV DNA and cell-associated RNA levels in participants initiating early ver-sus later ART.

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(A) Box plots showing median log10(HIV DNA level), IQR (box), and adjacent values (1.5x IQR; whiskers) in patients starting early ART (green boxes) or later ART (orange boxes) assessed one year following ART initiation (“1Y ART”) and at particpants’ last available timepoint (“Max ART”). (B) Analogous box plots depicting cell-associated HIV RNA levels (S/Co units) in same subject groups and timepoints.

High incidence of serious adverse events in HIV-infected patients treated with a

telaprevir-based hepatitis C virus treatment regimen

Cachay, E.R.et al. AIDS. 2013 Jul 9. doi: 10.1097/01.aids.0000432466.15885.14 (enlace)

Of the 24 consecutive patients treated for HCV using telaprevir/pegylated interferon /ribavirin, 50% (12/24) developed serious adverse events and 29% (7/24) discontin-ued HCV treatment due to adverse events, despite an intensive multidisciplinary monitoring approach.

Response to Rituximab-Based Therapy and Risk Factor Analysis in Epstein Barr Vi-rus–Related Lymphoproliferative Disorder After Hematopoietic Stem Cell Trans-plant in Children and Adults: A Study From the Infectious Diseases Working Group of the European Group for Blood and Marrow Transplantation Jan Styczynski, et al Clin Infect Dis published 13 June 2013, 10.1093/cid/cit391 (enlace)

More than two-thirds of patients with Epstein-Barr virus–related posttransplant lymphoproliferative disorder after hematopoietic stem cell transplant can be cured with rituximab-based treatment. Reduction of immunosuppression is associated with improved outcome; older age, extranodal disease, and acute graft-vs-host dis-ease predict poor outcome.

Figure 2. Posttransplant lymphoproliferative disease (PTLD)–related mortality (PRM), overall survival (OS), and prognostic survival model.

A, Cumulative incidence of PRM in 144 patients with PTLD treated with rituximab. B, Probability of OS (estimate and confidence interval at 3 years) in the same cohort. C, Cumulative incidence of PRM of the 51 patients who could reduce immunosup-pression therapy upon PTLD diagnosis (RI) compared with the 93 patients who could not reduce immunosuppression (no RI). D, Probability of OS in patients with RI com-pared with patients with no RI. Combined approach with rituximab and RI was asso-ciated with significantly reduced PRM (P = .006) and improved OS (P = .024). E, Cu-mulative incidence of PRM according to the number of the following risk factors for each patient: age ≥ 30 years at transplant, extranodal involvement, acute graft-vs-host disease (GVHD) ≥ grade II at PTLD diagnosis, and no RI. The higher the number of risk factors, the worse the outcome: PRM with 0–1, 2, or 3 factors were 7%, 37%, and 72%, respectively (P < .0001), and the number of events was 4 of 58, 22 of 59, and 13 of 18, respectively. No patient presented with 4 factors simultaneously. F,

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Probability of OS according to the number of the following risk factors for each pa-tient: age ≥30 years at transplant, malignant disease, acute GVHD ≥grade II at PTLD diagnosis, and no RI. A higher number of risk factors was associated with an increas-ingly poor prognosis: 3-year OS rates with 0–1, 2, or 3 factors were 73%, 52%, and 26%, respectively (P < .0001), and the number of events was 12 of 49, 19 of 41, and 35 of 45, respectively. No patient presented with 4 factors simultaneously. Abbrevia-tions: CI, confidence interval; OS, overall survival; PTLD, posttransplant lymphopro-liferative disorder; RI, reduction of immunosuppression.

Clinical effects of viral relapse after interferon plus ribavirin inpatients co-infected with human immunodeficiency virus and hepatitis C virus

Berenguer J et al. J Hepatol. 2013;58(6):1104-12. doi: 10.1016/j.jhep.2013.01.042.

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Fig. 1.Proportion of patients free from events. (A)Overall mortality,(B)liver- related events (liver-related mortality, liver decompensation, hepatocellular carcinoma, liver transplantation) according to treatment respons e,(C) liver decompensation, and (D)hepatocellular carcinoma. ⁄p <0.05 with the NR group (Log-Rank test); _p <0.05 with the REL group (Log-Rank test). SVR, Sustained virologic response; REL, end-of-treatment response with subsequent relapse; NR, no response.

Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study.

SECOND-LINE Study Group Lancet. 2013;381:2091-9. doi: 10.1016/S0140-6736(13)61164-2. (enlace)

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NS5A inhibitors in the treatment of hepatitis C. Pawlotsky JM. J Hepatol. 2013; 59:375-82. doi: 10.1016/j.jhep.2013.03.030

Hepatitis C virus infection is a major health problem worldwide and no vaccine has yet been developed against this virus. In addition, currently approved pharma-cotherapies achieve suboptimal cure rates and have side effects that result in non-compliance and premature treatment discontinuation. Significant research has been devoted to developing direct-acting antiviral agents that inhibit key viral functions. In particular, several novel drug candidates that inhibit the viral non-structural pro-tein 5A (NS5A) have been demonstrated to possess high potency, pan-genotypic ac-tivity, and a high barrier to resistance. Clinical trials using combination therapies containing NS5A inhibitors have reported results that promise high cure rates and raise the possibility of developing interferon-free, all-oral regimens.

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Improvements of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C. Kraus MR, et al. Hepatology. 2013;58:497-504. doi: 10.1002/hep.26229.

Conclusion: Successful eradication of HCV eads to a significant improvement of rele-vant aspects of attentional and neurocognitive performance, indicating that the neu-rocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV.

Relationship Between Weight, Efavirenz Exposure, and Virologic Suppression in HIV-Infected Patients on Rifampin-Based Tuberculosis Treatment in the AIDS Clinical Trials Group A5221 STRIDE Study Anne F. Luetkemeyer, et al Clin Infect Dis 2013 57: 586-593 (enlace)

In human immunodeficiency virus (HIV)/tuberculosis–coinfected patients, coadmin-istration of efavirenz (EFV) and rifampin-based tuberculosis therapy was associated with a trend toward higher, not lower, EFV trough concentrations compared to EFV alone. Neither weight ≥50 kg nor ≥60 kg was associated with decreased HIV virologic suppression.

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Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study Pedro Cahn, et al. Lancet 2013; 382:700-708 (enlace)

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HONGOS

Antifungal Therapy and Management of Complications of Cryptococcosis due to Cryptococcus gattii Sharon C.-A. et al. Clin Infect Dis 2013 57: 543-551 (enlace)

Induction amphotericin plus 5-flucytosine is indicated for Cryptococcus gattii lung (2 weeks) and neurologic disease (6 weeks), followed by fluconazole (total course 6–12 and 18 months, respectively). Shunting for raised intracranial pressure is frequent. Immune reconstitution inflammatory syndrome occurs in 9% of cases.

Figure 1. Bar chart showing body sites of infection in 86 patients with Cryptococcus gattii infection. Abbreviations: CNS, central nervous system; lung–CNS, lung infection in the absence of CNS infection; CNS-lung, CNS infection in the absence of lung infec-tion; CNS + skin, both CNS and skininfection; blood + other, bloodstream infection plus at least 1 other siteof infection; lung, lung infection only.

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PARASITOS

Exchange Transfusion for Severe Malaria: Evidence Base and Literature Review Kathrine R. Tan, et al Clin Infect Dis published 24 June 2013, doi: 10.1093/cid/cit429 (enlace)

Despite biologic plausibility for using exchange transfusion (ET) as an adjunct to an-timalarial drugs for treatment of severe malaria, this matched study and a compre-hensive literature review provided no evidence for ET's efficacy on survival. Adjunct ET cannot be recommended.