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

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Lit Review Feb #3

February 15, 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 :).

Spread of Meropenem-Resistant Streptococcus pneumoniae Serotype 15A-ST63 Clone in Japan, 2012–2014

https://wwwnc.cdc.gov/eid/article/24/2/17-1268_article

  • 7-, 10-, and 13-valent pneumococcal conjugate vaccines (PCVs): decreased the total number of cases of invasive pneumococcal disease, but also a shift in serotype not covered by PCV

  • During 2012-2014 in Japan: emergence of strains of multidrug (penicillin, macrolide, and meropenem)–resistant pneumococcal serotype 15A and sequence type (ST) 63 (serotype 15A-ST63)

  • Resistance most likely due to recombination in pbp1a, which was identical to that in multidrug (including meropenem)–resistant serotype 19A-ST320 pneumococci, which have spread in the United States

The Clinical Utility of Methicillin Resistant Staphylococcus aureus (MRSA) Nasal Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis with Antimicrobial Stewardship Implications

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy024/4798927

  • Current IDSA/ATS guidelines for treatment of HCAP/CAP pneumonia recommend empiric MRSA coverage in patients at risk (exposure to healthcare, previous antibiotic use, septic shock, etc) but prevalence of MRSA pneumonia is not high

  • Metaanalysis looking at 5,163 patients: MRSA nares screen had sens 70.9% and spec 90.3% for MRSA pneumonia of all types (CAP, HCAP, HAP, VAP)

    • When using prevalence of MRSA pneumonia of 10%: PPV 44.8%,NPV 96.5%

  • When looking only at CAP and HCAP: sens 85% spec 92.1%, respectively

    • PPV 56.8% and NPV 98.1%, respectively

  • When looking at VAP: sensitivity and PPV were low but specificity and NPV were still high (93.7% and 94.8%)

  • Nares screening for MRSA may be a good rule out test to predict MRSA pneumonia so people don’t have to get empirical treatment when they don’t need it

Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis

https://www.ncbi.nlm.nih.gov/pubmed/29116995

  • Time over MIC is important for action of beta lactams

  • Metaanalysis in >3000 patients: prolonged infusion associated with 1.46-fold lower odds of mortality, 1.77-fold higher odds of clinical cure, 1.22-fold higher odds of microbiological cure

Strongyloidiasis Outside Endemic Areas: Long-term Parasitological and Clinical Follow-up After Ivermectin Treatment

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/cix1069/4817467

  • Rx is ivermectin but no strong evidence showing actual cure (absence of larvae by parasitological methods 1 year after treatment)

  • Study in Argentina in 71 patients with confirmed diagnosis, F/U for 4 years after treatment, looked at stool exam and PCR

  • PCR remained positive even at 4 years, most common manifestation is asymptomatic eosinophilia

Outbreak of Fluoroquinolone-Resistant Campylobacter jejuni Infections Associated with Raw Milk Consumption from a Herdshare Dairy — Colorado, 2016

https://www.cdc.gov/mmwr/volumes/67/wr/mm6705a2.htm?s_cid=mm6705a2_e

  • Selling of raw milk is illegal in CO but…..

  • Herdsharing: members can purchase a share of a herd of cows or goats, and are entitled to a portion of raw milk – technically no “redistribution”

  • Identified 12 confirmed and five probable cases of Campylobacter jejuni infection among people in 171 households that drank raw milk from same herdshare

  • All isolates R to ciprofloxacin, tetracycline, and nalidixic acid

  • Dairy not closed since pasteurization (which is the only way to ensure safety) was not an option on site (if closed, there would be no way to re-openand retain safety)

    • Technically, dairy did not sell or redistribute raw milk

    • People are entitled to take their “share” of milk in its original form

    • They are encouraged to discard potentially affected milk and reminded that redistribution is illegal

Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin

https://www.cdc.gov/mmwr/volumes/67/wr/mm6705a3.htm?s_cid=mm6705a3_e

  • Basically, this article is a reminder that unvaccinated individuals who have received IVIG may test positive for rabies antibody without actually having rabies

Notes from the Field: Assessment of Rabies Exposure Risk Among Residents of a University Sorority House — Indiana, February 2017

https://www.cdc.gov/mmwr/volumes/67/wr/mm6705a4.htm?s_cid=mm6705a4_e

  • Report of bat exposures at university sorority house

    • Bats had been routinely sighted in shared living areas and hallways, later learned that bats had been in at least one of the walls for 30 years

    • Risk assessment with abundance of caution identified and interviewed 140 students and 8 employees who resided or worked in the sorority house during the preceding 12 months

      • Based on longest report of incubation period from bat exposure (270 days)

    • A LOT of interviews: finally identified 4 people with highest risk (a bite, scratch, or direct skin contact), offered postexposure prophylaxis (PEP), which consists of human rabies immune globulin and a series of 4 doses of rabies vaccine

      • Two persons completed the PEP series

      • Two declined PEP because of a perceived lack of risk

Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance

http://mbio.asm.org/content/9/1/e02011-17.full

  • 2-year environmental surveillance at NIH Clinical Center: WGS of 108 isolates

  • All samples from ICU pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs) harboring blaKPC/blaNDM, suggesting a vast, resilient reservoir (the actual rate of infection with CPOs was still low and surveillance of HCWs did not show CPO. Phew!)

  • Evidence of common plasmid backbones in patients and environmental isolates, suggesting the presence of reservoir of mobile elements that may contribute to the spread of resistance genes

Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study

https://www.sciencedirect.com/science/article/pii/S1473309918300689

  • Standard Rx of P. falciparum in SEA: dihydroartemisinin–piperaquine

    • Combination of short and long acting drugs

    • Started to see Rx failures popping up, especially in western Cambodia

  • Analyzed genome sequence of 1492 P. falciparum from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013

  • The resistant strains had KEL1/PLA1 co-lineage (each conferring R to each drug), which emerged in western Cambodia the same year that dihydroartemisinin–piperaquine became standard of treatment

    • Spread throughout region within the next 5 years

U.S. FDA Approves Gilead's Biktarvy Triple HIV Drug

https://www.medscape.com/viewarticle/892429

  • New integrase inhibitor bictegravir with Descovy, an older medication that combines nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide

Olympics-IOC Discussing Norovirus Outbreak, More Cases Reported

https://www.medscape.com/viewarticle/892479

  • A rise from initial 32 cases to 128 in less than one week (Tue-Thu) mostly among security guards, just ahead of Friday's opening ceremony in Pyeongchang and led to some 1,200 security staff being quarantined

  • Athletes not yet affected

Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens

https://www.nature.com/articles/s41564-018-0110-1

  • Calcium-dependent antibiotics (including DAP) are a small family of N-acylated cyclic peptides that require calcium for antibacterial activity

  • Known members contain conserved Asp-X-Asp-Gly

  • Biosynthesized by non-ribosomal peptide synthetases (NRPS) – NPRS adenylation site, which is conserved among these peptides could be used as target for PCR to amplify all possible antimicrobial peptide genes in a metagenomics sample from soil, then clone to express then test with bacteria

  • Found malacidins, a distinctive class of antibiotics

    • Broadly active against Gram-positive bacteria including MRSA

    • Does not get inactivated by lung surfactant

    • Topical application in MRSA SSTI model in mice was effective

    • Attempts to induce resistance have not been successful

Baloxavir Marboxil Demonstrates Positive Phase 3 Influenza Results

http://www.mdmag.com/conference-coverage/idweek-2017/baloxavir-marboxil-demonstrates-positive-phase-3-influenza-results

  • A company in Japan invented a novel cap-dependent endonuclease inhibitor baloxavir marboxil

  • Potent anti-viral efficacy for influenza, demonstrated significant improvement in time to alleviation of symptoms (TTAS) and reduced virus levels in patients for both A and B viruses and is active against both H5N1 and H7N9 avian influenza viruses with a single 1-time oral dosing regimen

Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population

http://gut.bmj.com/content/gutjnl/early/2018/01/30/gutjnl-2017-315363.full.pdf

  • Helicobacter pylori is a risk factor for gastric cancer esp. non-cardia

  • Preneoplastic mucosal changes shown to improve with H. pylori eradication

  • A cohort of >95,000 patients in Sweden post-eradication therapy over 7.5 years (no comparison)

  • Only 75 patients developed gastric adenocarcinoma, 69 non-cardia

    • For both CA types (cardia and non-cardia), risk of developing cancer was high during 1-3 years post Rx compared to general population, but decreased to the point of lower risk compared to general population after 5 years

Acute HIV Discovered During Routine HIV Screening With HIV Antigen-Antibody Combination Tests in 9 US Emergency Departments

https://www.ncbi.nlm.nih.gov/labs/articles/29310870/

  • Fourth gen HIV tests include detection of p24 antigen, can be detected during acute HIV infection within the first few weeks post exposure

  • Recommended by the CDC as part of non-targeted screening (EVERYONE) in people coming to the ED, especially in places where undiagnosed HIV prevalence exceeds 0.1%

  • Study involved >200,000 people screened in 9 urban EDs in the US over 3 years

  • 839 (0.4%) received a new diagnosis of HIV

  • Among these new cases, 122 (14.5%) people had acute HIV infection that they did not know of – these cases would have been missed if using older tests or more selective screening

Figure: http://www.nejm.org/doi/full/10.1056/NEJMra1011874

  • That's all for now. Bug Hunters, may the odds be ever in your favor.