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Lit Review April #1

April 6, 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 :).

 

Leading Photo by CDC (https://www.cdc.gov/salmonella/index.html)

Distinct fermentation and antibiotic sensitivity profiles exist in salmonellae of canine and human origin

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828451/

 

  • S. enterica is pathogenic in both humans and dogs, but no evidence showing possibility of transfer between dog and owner

  • Looked at 88 human and 86 dog isolates (clinical)

  • Carbon utilization profiles between two groups was different (determined using a phenotypic array ala API

  • Canine isolates seemed to have higher AMP, AMX, CHL MICs compared to human isolates

  • Suggested separated reservoirs for disease

  • WGS would have given a better resolution

Salmonella enterica Serotype 4,[5],12:i:- in Swine in the United States Midwest: An Emerging Multidrug-Resistant Clade

 

https://www.ncbi.nlm.nih.gov/pubmed/29069323

  • Examples of Kauffmann-White-Le Minor scheme (from WHO document)

  • "4,[5],12" = somatic O antigen

  • ":i:-" = H antigen phase 1 is "i"

  • "-" = no phase 2 H antigen

 

  • Emerging globally, including in pork in the US, lacks the second-phase flagellar antigen

  • Compared WGS data from hundreds of 4,[5],12:i:- and Typhimurium from US and Europe, with a focus on isolates from pork in the US Midwest

  • 4,[5],12:i:- regardless of source could be divided into two clades – B I and B II

    • 85% of US isolates from 2014-15 in clade B II, which is emerging globally

  • R to AMP, STR, sulfonamides, TET

  • Subset of isolates R to enrofloxacin or ceftiofur associated with presence of plasmid-mediated resistance genes (qnrB19/qnrB2/qnrS1 for FQ and blaCMY-2/blaSHV-12 for ceph), with FQ resistance probably acquired in the US

 

Epidemiology, Microbiological Diagnosis, and Clinical Outcomes in Pyogenic Vertebral Osteomyelitis: A 10-year Retrospective Cohort Study

 

https://academic.oup.com/ofid/article/5/3/ofy037/4925997

 

  • PVO: difficult to treat, sometimes culture-negative, pt on broad-spectrum treatment for a long time with little benefit compared to a shorter course, besides reduction of relapse in some studies

  • A study from Australia looking at 129 patients over 10 years

    • Most patients had blood culture, 44% had vertebral samples (open Bx better yield than core or FNA)

    • 78% organism identified, MSSA or gram positive most prevalent, these patients were more likely to be febrile and had elevated CRP on admission – makes sense

    • 22% - only 5 patients had histology results, with varying evidence of inflammation, 16s PCR in these patients was not conclusive

  • Overall clinical outcomes poor regardless of organism ID (only 15% complete recovery upon D/C)

  • However, not having org ID associated with more risk of adverse outcomes (mortality during index admission or attributable readmission within 2 years due to stuff like pain, disability, or need for more investigation)

  • It may be reasonable to go above and beyond to get a microbiological diagnosis to guide treatment instead of empirical

 

Systemic Antibiotics for the Treatment of Skin and Soft Tissue Abscesses: A Systematic Review and Meta-Analysis

 

http://www.annemergmed.com/article/S0196-0644(18)30142-2/fulltext

 

  • To use or not to use antibiotics after I&D? Classical way of thinking is that antibiotics wouldn’t add much

  • Meta-analysis looking at 2400 patients

    • About half had MRSA

    • Treated with SXT or CLI

    • Treatment failure in antibiotic group (7.7%) less than placebo (16.1%)

    • Antibiotic also reduced risk of developing more lesions, while increase in adverse effects was minimal and mild (GI, rash, etc)

  • Mark Crislip on his podcast: DOX and LZD result in less chance of developing C. diff

 

Management of an Outbreak of Exophiala dermatitidis Bloodstream Infections at an Outpatient Oncology Clinic

 

https://academic.oup.com/cid/article/66/6/959/4602217

  • Dematiaceous, may cause CNS infection in IC hosts, resp pathogen in CF patients

     

     

  • Photo: Mycology Online: https://mycology.adelaide.edu.au/descriptions/hyphomycetes/exophiala/

  • May 2016 NY: 4 cases of E. dermatitidis in oncology patients receiving infusion through port-a-cath at a clinic

  • Identified a total of 15 cases of fungemia with E. dermatitidis and 2 with Rhodotorula mucilaginosa, some positive in all cultures (peripheral, CVC-drawn blood, CVC device), most are asymptomatic

  • Source of contamination: IV flush solution containing saline, VAN, CAZ, heparin

    • Compounded in the clinic in substandard conditions, in 1 L bags, kept for 4-8 weeks with multiple access per day until bag was depleted

    • 38 patients exposed to potentially contaminated fluids

  • Isolates confirmed by WGS to be the same

  • Pts with positive blood culture had CVC removed, treated with mainly voriconazole, 3 died

 

mcr-3 and mcr-4 Variants in Carbapenemase-Producing Clinical Enterobacteriaceae Do Not Confer Phenotypic Polymyxin Resistance

 

http://jcm.asm.org/content/56/3/e01562-17.full

  • Fact: mcr-1 isolates don’t always have NWT CST MICs (>=4): choosing isolates to screen is challenging

  • Singapore: sequenced a bunch of Enterobacteriaceae

    • Found mcr-3-like element in E. coli

      • Initial assembly showed a 9kb contig with this element

      • Claimed to not be plasmid-associated: mapping reads onto closest reference genome and re-assemble reads that did not match, found no plasmid-associated gene on the 9kb contig containing this element

      • Seems to be associated with transposable elements

      • I have a problem with this approach

        • Plasmid are notoriously difficult to assemble, lots of repeated sequences

        • One cannot make this assumption without long read sequencing

        • Transposable elements can be on a plasmid too

        • Was PlasmidFinder used on assembled contigs? Any origin of replication?

    • Found mcr-4-like elements in E. cloacae

      • 7.7kb contig with this element matched existing mcr-4 harboring plasmid

    • Both isolates S to CST, cloned genetic elements in E. coli did not confer resistance either

    • Why is this exciting?

 

Two Cases of Meningococcal Disease in One Family Separated by an Extended Period — Colorado, 2015–2016

 

https://www.cdc.gov/mmwr/volumes/67/wr/mm6712a4.htm?s_cid=mm6712a4_e

 

  • Transmitted through large respiratory droplets

  • April 2015 in CO: 75 yo F came down with sepsis, GS CFF positive for GNDP but culture neg, BCB positive, treated and survived

  • 7 family members were prescribed PEP, but compliance unknown

    • Adults CIP PO single dose

    • Children RIF q12 for 2 days or CRO IM one dose

  • 15 mo later, a 3 mo grandbaby of patient came down also with meningococcemia

    • WGS: same bug

  • Treatment in patients usually eradicate organisms

  • Where did the bug come from?

    • Baby shared close unknown contact with index patient

    • Circulating strain

    • Incomplete eradication during PEP

 

Notes from the Field: Fatalities Associated with Human Adenovirus Type 7 at a Substance Abuse Rehabilitation Facility — New Jersey, 2017

 

https://www.cdc.gov/mmwr/volumes/67/wr/mm6712a6.htm?s_cid=mm6712a6_e

 

  • HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7): reported to be associated with outbreaks in communal facilities and the military

  • Feb 2017 in NJ: potential outbreak reported in substance abuse treatment facility

  • During Jan-Mar: 79 people defined as probable (respiratory illness)

    • 4 hospitalized, 3 died

      • For the 3 - HAdV-7, all alcoholic with cirrhosis and/or DM

 

Vital Signs: Containment of Novel Multidrug-Resistant Organisms and Resistance Mechanisms — United States, 2006–2017

 

https://www.cdc.gov/mmwr/volumes/67/wr/mm6713e1.htm?s_cid=mm6713e1_e

 

  • National Healthcare Safety Network: keep data for CLABSIs, CAUTIs

    • Facilities are required by CMS to report

    • Looked at percentage of EC and KP that were ESBLs or CREs

  • Antibiotic Resistance Laboratory Network (ARLN): provide testing for CRE, CRPA in PHLs

 

  • Decreased may be due to early aggressive responses: IP, reporting, testing, etc.

  • CRE: 25% CPO

  • KPC, NDM most common in CRE

  • VIM most common is CRPA

  • 1,489 screening tests for asymptomatic individuals for carbapenemases performed during 70 surveys in 50 facilities in 7 large regional labs

  • Post-acute care facility tops the chart

 

Antibiotic Therapy Duration in US Adults With Sinusitis

 

https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2674867

 

  • Sinusitis: always been a problem – should or shouldn’t use antibiotic, if so, which one?

  • National Disease and Therapeutic Index (IQVIA): random sample of US office-based physicians in private practice, report on all patient contacts for 2 randomly selected consecutive workdays

    • Exclude chronic sinusitis

    • Findings are pretty sad

      • 69% of patients prescribed antibiotics for more than 10 days (IDSA guidelines say 5-7 days for acute bacterial sinusitis with low risk of developing resistance, 7-10 days saved for high risk or treatment failures

      • 20% prescribed 5 day course of AZT: NOT RECOMMENDED according to  IDSA over development of resistance

      • If remove AZT: >90% of patients prescribe for more than 10 days

 

Infectious Diseases Mortality in the United States Ongoing Investment Needed for Continued Progress

 

https://jamanetwork.com/journals/jama/fullarticle/2676088

 

  • National Center for Health Statistics: CDC initiative, collects data from birth and death records, medical records, interview surveys, and through direct physical exams and laboratory testing

  • 2014: death rate from infection = 34.10 per 100,000

  • 1980: 41.95 per 100 000 persons

    • 18.73% overall reduction

  • In 2014 LRTIs most common (78%), then diarrheal diseases (7% which is a >400% increase compared to 1980, most likely due to C. diff, which has been reported to cause almost half of death from GE associated diseases in the US)

  • Also looked at several aspects of the data (type of infection, geological, etc)

 

Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection

 

https://jamanetwork.com/journals/jama/fullarticle/2673552

 

  • Vaborbactam: cyclic boronic acid–based BLI, active against Ambler classes A (especially KPC) and C (AmpC)

  • Combination has trade name of Vabomere

  • Indicated for treatment of complicated UTI or acute pyelonephritis

  • Data from phase III: compared to TZP

    • When considering clinical improvement and microbiological: better than TZP (98.4% vs 94%)

    • When considering test of cure: non-inferior to TZP (66.7% vs 57.7%)

 

Carbapenem-Resistant Klebsiella pneumoniae Exhibiting Clinically Undetected Colistin Heteroresistance Leads to Treatment Failure in a Murine Model of Infection

 

http://mbio.asm.org/content/9/2/e02448-17

 

  • Resistance to CST is on the rise in CREs

  • 2 CRKP isolates harboring KPC, MIC by BMD = 0.5

    • Population analysis profile (PAP): plating serial dilutions on agar with various concentrations of

      • Presence of minor CST-R (actually, NWT) subpopulation (1:10^3-1:10^6) in both isolates with growth present in up 100 µg/ml CST. The colistin-resistant subpopulation was present at between 1 in 1,000 and 1 in 1,000,000 CFU at doses of colistin ranging from 2 to 100 µg/ml

      • Not seen in a control strain

    • After passaging in antibiotic-free media: MICs came down

    • WGS comparing between CST-WT and CST-NWT populations: genetically identical

    • Phenotypic changes, compatible with heteroresistance

  • Looked at expression of these genes

    • PhoPQ (two-component system pathway thought to regulate CST resistance in KP) increased in resistant cells

    • MgrB (negative regulator of PhoPQ) decreased in resistant cells

  • Peritonitis mouse model

    • Even in the absence of CST, enrichment in resistant population was seen: maybe due to cross-resistance with antimicrobial peptides

    • These strains resulted in 100% death, compared to control strain – this may also happen in vivo!

  • Strain with heteroresistance may result in treatment failure

  • Found that if incubated BMD to 48 hours: CST MIC in these strains increased to NWT level – but maybe not a great idea to do in a clinical lab

 

Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia

 

http://aac.asm.org/content/62/3/e01602-17

 

  • VAN: traditionally believed to have similar PD to BL (time over MIC)

  • More data suggested AUC/MIC: people like to target at 400 ug*hr/mL

    • Correlated with serum peak of 40 and trough of 15 ug/mL, with the assumption that MIC = 1 ug/mL

    • Data mostly for MRSA – not much for Enterococcus

  • Retrospectively looked at 57 patients bacteremic with Enterococcus spp.

    • AUC/MIC (by Etest) ≥389 achieved within 72 hours associated with reduced 30-day mortality (from 45.5 to 10.9%)

      • This was only safely achievable (nephrotoxicity) if MIC Etest <= 1.5

    • VAN trough not significantly different between treatment success and failure

      • Maybe we need to calculate AUC/MIC instead

UK case of Neisseria gonorrhoeae with high-level resistance to azithromycin and resistance to

ceftriaxone acquired abroad

 

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/694655/hpr1118_MDRGC.pdf

 

  • Public Health England reported an imported case of N. gonorrhoeae infection with treatment failure (CRO only, followed by SPT)

    • Not treated with double regimen (CRO+AZT)

    • Genital infection was cured, but throat was persistently positive

      • Not a surprise since throat infections are harder to get rid of, and ALL reported cases of CRO failure so far have exclusively been pharyngeal infections

  • Caused by a bug with:

    • CRO MIC > 0.125

      • EUCAST breakpoint for R: >0.125

      • CLSI breakpoint for R: >0.25

    • AZT MIC > 0.5

      • EUCAST breakpoint for R: >0.5

      • CLSI epidemiological cutoff (ECV) for NWT: >=2

    • End point MICs were not reported, so we don't know if this bug would be considered R/NWT for both drugs when using CLSI breakpoints/ECVs

  • Currently treated with ETP IV: based on MIC 0.032, but no breakpoint exists

  • Is this terrifying? Yes, but there are things to consider

    • Hawaii Department of Public Health has reported isolates with CRO MICs 0.125 by agar dilution and AZT MIC > 256, yet these infections were successfully treated with double regimen

      • Hawaii paper did not specify whether these include pharyngeal infections, and if so, whether treatment was successful

      • Would this UK case have been successfully treated with the double regimen? We'll never know

    • UK uses EUCAST BPs, which are lower than CLSIs

  • Let's wait and see how this turns out.......

 

UPDATE: they finally determined endpoint MICs

  • CRO = 0.5

  • AZT > 256

This is the real deal y'all.

 

Consensus Details H. pylori Testing, Treatment for US Patients

 

https://www.medscape.com/viewarticle/894578

 

  • A new consensus document from 11 US experts

    • http://www.cghjournal.org/article/S1542-3565(18)30268-4/pdf

  • Testing has been kind of a problem

    • Between 2010-2013: 100 million people got tested

      • 70% serology, 4.2% positive

        • US is a low prevalence country, and confirmatory testing (UBT, HpSAg) should be done

        • However, only about a third of all positive had these tests done within 14 days

  • Treatment is also a problem

    • Cure rate with standard triple regimen (AMX, CLR, a PPI) decreased below 80% since 2000, but only half of gastroenterologists reported eradication

  • Summary of statements that were accepted by panel and external reviewer

    • Everyone with H. pylori should be treated

    • Anybody with these following condition must be tested

      • Current or history of gastroduodenal ulcers

      • Uninvestigated dyspepsia (epigastric pain lasting longer than one month)

      • Gastric mucosal associated lymphoid tissue (MALT) lymphoma

      • Family history of gastric cancer

    • Some that did not reach unanimous opinion

      • Pt with reflux with high risk for infection

      • 1st gen immigrant from high-prevalence countries

      • Latino, African-American due to reported higher prevalence

 

Cervical Cancer to Double Across Middle East Without Vaccines

 

https://www.medscape.com/viewarticle/894318

 

  • Absence of public awareness of vaccines in conservative countries in ME and North Africa

  • Prevalence will double in 2035 without vaccination

 

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

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

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