PEERA HEMARAJATA, M.D., PH.D., D(ABMM)

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Lit Review Feb #4

February 28, 2018

Disclaimer: this compilation of synopses have been collected from multiple sources, including Mark Crislip's Puscast, Journal Watch Infectious Diseases, Medscape Infectious Diseases, CDC MMWR, AMA Morning Rounds, ProMED Mail, Journal of Clinical Microbiology, Antimicrobial Agents and Chemotherapy, Clinical Infectious Diseases, and more. I chose these articles based on their relevance to clinical microbiology and would be of interest to my fellows, and some other pieces that I found amusing to read. All credit goes to these original contributors. I'm just a messenger :).

Drugs that reduce transmission of falciparum malaria

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30070-7/fulltext

  • Current artemisinin-containing regimens and alternative  sulfadoxine-pyrimethamine /amodiaquine combination reduce gametocyte development, but do not have effect on existing mature PF gametocytes that are ready to infect mosquitoes at time of initiation of treatment

  • Primaquine and methylene blue have potent PF gametocidal effects, administered orally

    • High dose of primaquine can induce hemolysis I G6PD patients, but single low dose is ok

    • MB is pretty safe, administer in a 3-day course

    • Use of either, combined with standard regimens reduced transmission completely at day 2

    • The only side effect is with MB (blue pee)

New HBV vaccine Recommended by Advisory Committee on Immunization Practices

https://apnews.com/028195fb92054ea5b4370e5c800509de/US-panel-recommends-new-adult-vaccine-against-hepatitis-B

  • Heplisav-B: the first new hepatitis B vaccine in 25 years.

  • Given in two shots over a month, as opposed to regimen of three doses over six months

Notes from the Field: Increase in Acute Hepatitis B Infections — Pasco County, Florida, 2011–2016

https://www.cdc.gov/mmwr/volumes/67/wr/mm6707a6.htm?s_cid=mm6707a6_e

  • From 2011 to 2016: number of acute HBV-infected persons in Pasco County increased from 1.5 to 17.28 per 100,000 residents (p<0.001)

  • More than half reported injection drug use in the 6 months preceding symptom onset

  • HIV?

WHO Announces Recommended Components of 2018–19 Flu Vaccine

http://www.who.int/influenza/vaccines/virus/recommendations/2018_19_north/en/

  • For 2018–19 season in the northern hemisphere

    • An A/Michigan/45/2015 (H1N1)pdm09-like virus

    • An A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus

      • Switched from an A/Hong Kong/4801/2014 (H3N2)-like virus due to lack of efficacy

    • A B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage)

      • Switched from a B/Brisbane/60/2008-like (B/Victoria lineage) due to genetic changes in circulating viruses

    • A B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage)

      • Omitted in trivalent vaccines

Neonatal Immunization with a Novel Vaccine Against Rotavirus

http://www.nejm.org/doi/10.1056/NEJMoa1706804

  • Novel RV3-BB vaccine: strain RV3 (isolated from asymptomatic infants, natural infection with this virus is associated with prevention of GE for 3 years)

  • Study in >1500 infants in Indonesia

    • Four doses the followed for 18 months

    • Vaccine efficacy: 75% (neonatal schedule - 0 to 5 days, 8 weeks, and 14 weeks of age), 51% (infant schedule - 8 weeks, 14 weeks, and 18 weeks of age), and 63% (overall)

    • Time to first gastroenteritis significantly longer among vaccine recipients compared with placebo

    • No intussusception occurred during standard 21-day risk period

  • Rotavirus vaccination in neonates thought to be meh due to possibility of low vaccine strain binding in immature gut and immature immune system, but this proved otherwise

Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study

https://www.sciencedirect.com/science/article/pii/S1473309918300586?via%3Dihub

  • Case-control study in 349 women in sub-Saharan Africa with or without HIV

  • Vaginal samples collected and follow-up for HIV acquisition

    • 16S metagenomics, bacteria-specific PCR

    • 55 acquired HIV, compared with 55 control cases

  • Lower relative abundance of Lactobacillus iners associated with higher probability of HIV acquisition

  • Higher relative abundance of these organisms associated with higher probability of HIV acquisition

    • Parvimonas species type 1 and type 2

    • Gemella asaccharolytica

    • Mycoplasma hominis

    • Leptotrichia/Sneathia

    • Eggerthella species type 1

    • Megasphaera

  • Nugent score of 7-10 associated with twice risk of HIV acquisition compared to lower scores

  • Probiotics to prevent transmission?

Strains of bacterial species induce a greatly varied acute adaptive immune response: The contribution of the accessory genome

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006726

  • Why do clinical courses of infection vary between individuals?

    • Differences in bacteria vs host immune responses?

  • Study of acute adaptive T- and B-cell immune responses induced ex vivo by various Staphylococcus aureus (16) and Streptococcus pyogenes (3) strains using lymphocytes isolated from 11 healthy individuals

    • Evaluated acute adaptive immune responses (T- and B-cell mediated)

    • A lot of variability in strength of immune responses between strains, but strength of responses of same strain among individuals was pretty similar

      • The bacteria itself may have more effect on immune response (rather than host)

    • Knocking out accessory genomes (leaving “core” genome): blunted immune responses

      • Maybe it’s the accessory genome that matters

        • May contain unique combination of virulence determinants and superantigens

Culture-Negative Septic Shock Compared With Culture-Positive Septic Shock: A Retrospective Cohort Study

https://insights.ovid.com/crossref?an=00003246-900000000-96384

  • Studied clinical characteristics and outcomes of culture-negative septic shock (2651) in comparison with culture-positive septic shock (6019)

  • Survival and severity of disease (per Acute Physiology and Chronic Health Evaluation II - APACHE II scores) similar among groups

    • https://www.mdcalc.com/apache-ii-score

  • Delay in antimicrobial treatment negatively affected mortality in both groups

  • Moral of the story: the most important thing is to recognize clinical sepsis and initiate early appropriate antimicrobial therapy regardless of culture results

Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus

http://aac.asm.org/content/62/2/e02000-17

  • New Zealand: unrestricted use of mupirocin and fusidic acid (in the 90s) associated with increase in isolates with high levels of resistance (to 28%) in 2015 – among the highest in the world

  • ST5 MRSA, ST1 MRSA, ST1 MSSA seemed to predominate

  • This study looked at ST1 isolates

    • WGS

      • fusC on chromosome and mupA on plasmid, but both in mobile genetic element cassettes

      • BEAST timed phylogeny: expansion of strains harboring mupA occurred same time as initiation of clinical use of mupirocin in the early 90s, also co-selects for isolates harboring fusc, which experienced another expansion shortly after fusidic acid became available in the late 90s-early 2000s

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection

https://academic.oup.com/cid/article/66/3/355/4587924

  • Human monoclonal antibody directed against the toxin B (Bezlotoxumab) implicated in prevention of CDI recurrence in patients receiving antibiotic therapy for CDI

  • Cost-effectiveness study using data from 2 RCTs (comparing outcomes between SOC and giving Mab along with antibiotics to treat CDI) and computer models

    • Use of mab

      • Reduced first recurrence by 10.1%, total recurrences by 16.7%, and 180-day mortality by 1.1%

      • 0.12 quality-adjusted life-years (QALYs – 1 QALY equivalent of one year in perfect health) gained

      • Saved money! $2,444/pt, with incremental cost-effectiveness ratios (ICERs – cost of treatment to gain one QALY) $19824/QALY gained

        • Even better (save more money, less ICERs) in pt older than 65 or immunocompromised

Reduction in Rate of Nosocomial Respiratory Virus Infections in a Children’s Hospital Associated With Enhanced Isolation Precautions

https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/reduction-in-rate-of-nosocomial-respiratory-virus-infections-in-a-childrens-hospital-associated-with-enhanced-isolation-precautions/A1A9A96B004539DF8A4255B5B86F8D94

  • Current CDC recommendations for respiratory viral infections/viruses transmitted through respiratory tract

    • Airborne + droplet + contact + standard: SARS

    • Airborne + contact + standard: VZV, Monkeypox , Smallpox

    • Airborne + standard: Measles

    • Droplet + contact + standard: Adenovirus

    • Droplet + standard: Influenza, Mumps, Parvovirus B19, Rhinovirus, Rubella (not congenital)

    • Contact + standard: RSV, Parainfluenza, HMPV, Enterovirus (children)

    • Standard: Enterovirus (adults), Hantavirus

    • Generally if not covered: children – contact + standard, adults – standard

    • https://www.cdc.gov/infectioncontrol/pdf/guidelines/isolation-guidelines.pdf

  • A study in a children’s hospital over 4 years in NY among RTI

    • 2 years of HICPAC recommendation, followed by 2 years of droplet + contact + standard for everybody

    • When using all 3, nosocomial viral RTI decreased 39% from 0.827/1,000 hospital days to 0.508/1,000 (P<.0013)

      • Excluding rhinovirus/entero: decreased 58% from 0.317 per 1,000 hospital days to 0.134 per 1,000 hospital days during enhanced precautions (P<.0014)

Nasal Flu Vaccine Back on CDC List of Recommended Vaccines

https://www.medscape.com/viewarticle/892970

  • Advisory Committee on Immunization Practices (ACIP) voted to bring back recommendation for nasal live attenuated influenza quadrivalent (different strains from inactivated) for the 2018-2019 influenza season, after rejecting it the last 2 years due to poor efficacy against circulating H1N1 strains

    • Found to be quite as effective as inactivated vaccine against flu B and H3N2

    • H1N1 strain was changed and found to be more effective

  • Give people options instead of not vaccinated at all

Association of Vegetation Size With Embolic Risk in Patients With Infective Endocarditis

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2672577

  • Meta-analysis involving 5116 vegetations with available dimensions

    • Patients with vegetation size > 10 mm had increased odds of embolic events (OR, 2.28; 95% CI, 1.71-3.05; P < .001) and mortality (OR, 1.63; 95% CI, 1.13-2.35; P = .009) compared with those with vegetation size < 10 mm

  • Helps with risk stratification: which patients should be promptly referred for higher level of care

Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins

http://mbio.asm.org/content/9/1/e00105-18.abstract

  • Multidrug-resistant (MDR) S. typhi are prevalent in parts of Asia and Africa, often associated with dominant H58 haplotype

    • Widespread FQ resistance, with sporatic 3rd gen ceph and macrolide (AZT) resistance

  • Identification of clonal expansion of a XDR strain (also H58, MDR – 1st line drugs: chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole PLUS fluoroquinolones, and third-generation cephalosporins) in Pakistan and a traveler in UK

    • WGS: some elements common to H58 – chromosomal cassette containing catA1, blaTEM-1, dfrA7, sul1, sul2, strA, strB, gyrA mutation (only I to FQ)

      • AND plasmid-mediated blaCTX-M-15 (3rd gen ceph) and qnrS (R to FQ)

      • On IncY plasmid, which was found in other enteric bacteria isolated from widely distributed geographic locations

Infrequent Testing of Women for Rectal Chlamydia and Gonorrhea in the United States

https://www.ncbi.nlm.nih.gov/pubmed/29028971

  • Anal sex: 35.9% of women aged 18–44 years reported to have had anal sex

  • CDC does not recommend testing at this time, but how many are positive?

    • Mucosal inflammation caused by NG/CT also increased risk of HIV transmission in women

  • A study with 7.9 million women tested for NG/CT by NAAT

    • Only 0.1% had rectal results, 0.5% had pharyngeal results

    • Among those that had rectal results (5499)

      • 8.0% CT+ only, 2.0% GC+ only, 0.8% both +

      • Rectal CT positivity significantly (P < .05) higher for women aged 15–24 years compared to older

      • +CT from rectal specimens was never repeated

      • 46.5% of rectal CT and GC infections would not have been identified with genital testing alone

  • Utility of testing for/treatment of rectal NG/CT in high-risk women?

Incidence, Etiology, and Outcomes of Community- Acquired Pneumonia: A Population-Based Study

https://acade