Acute dento-alveolar infections: microbiology & susceptibility patterns. 1986-2015, Glasgow, Scotland, UK

AJ SmithProfessor & Hon Consultant Microbiologist

Plan

Defining antimicrobial resistance

Defining surveillance

Data interpretation

Surveillance of antimicrobial susceptibility in Glasgow

Acute Dento-alveolar infections

Resistance ?

Antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause ineffective.

http://www.who.int/features/qa/75/en/

Some commonly used terms……

Resistance ?Defined from a biological perspective

Resistance definitions usually based on in-vitro quantitative testing of bacterial suspensions to antibacterial agents

Minimum inhibitory concentration

Resistance ?

Sensitive Resistant

BreakpointA breakpoint = chosen

concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic.

Setting breakpoints ?By Breakpoint committees

http://www.eucast.org/clinical_breakpoints/eucast_setting_breakpoints/

Consider Dosages, pharmacokinetics, resistance mechanisms, MIC

distributions, zone diameter distributions, pharmacodynamics and epidemiological cutoff values (ECOFFs) .

Challenge with break points

EUCAST v8.0 (mg/L)Viridans Group StreptococciPen: S<=0.25 R> 2Ery/Clarithro: IE (Insufficient evidence)Tetra : no breakpoint- clinical evidence but not in vitroClinda: R>0.5AnaerobesBen Pen R>0.5Amoyxl (Gram Pos) R>8; (G neg) R>2 Clinda R> 4Ery/Cla: IE (Insufficient evidence)Tetra: clinical evidence but not in vitro

Defining resistance

Defined from a clinical perspective

• Clinical resistance: When infection is highly unlikely to respond even to maximum doses of antibiotic (EUCAST)

Resistance ?

LaboratoryInoculum size, growth phase, planktonic, pH, atmosphere…-Biofilm

ClinicalCo-morbidities, pus collections, foreign bodies, site of

infection ………..- BiofilmPharmacokineticsPharmacodynamics

Confounding variablesResistance ?

Microbiology of acute dentoalveolar infections

Ab resistance in acute oral infections: Lit. review: Roberston & Smith J Med Micro 2009�Data difficult to standardise

�Reports vary resistance between 9-54% of isolates

Microbiology & treatment of acute apical abscesses

How surveillance can improve health outcomes

With the ability of micro-organisms to change & adapt, surveillance for detecting biological

changes isvital

What is surveillance ?

Etymology =Early 19th century: from French,from sur- over + veiller watch

(from Latin vigilare keep watch). Oxford English Dictionary“Is the watch or guard kept over a person etc, esp over a suspected person, a prisoner, or the like; often, spying,supervision; less commonly supervision for the purpose of directionor control, superintendence.”

Purpose of surveillanceImpact of disease ?Detection of changes ?Monitoring of effectiveness of preventive measures ?Highlighting priorities ?Basis for costing studies ?Aetiological clues ?

Norman Noah “Controlling communicable disease”

Kuriyama et al BDJ 2005

In this study, penicillin-resistantbacteria were isolated from 42 (38%) pts.

UK based investigationN=112 patients

But Challenges in data interpretation ?

The observations made support surgical drainage as the first principle of management and question the value of prescribing penicillin as part of treatment.

But what does penicillin resistant bacteria mean?

(5) Disk diffusion testing in not reliable for testing penicillin and ampicillin

Antimicrobial susceptibility of Anginosus group

Challenges in data interpretation ?What does Penicillin resistance mean ?

Kuriyama et al Oral Micro Immunol 2005

CLSI M100-32 (2012) breakpoint Pen ≥4mg/L

EUCAST 2018 breakpoint breakpoint Pen >2mg/L

Antimicrobial susceptibility of Anginosus group

Kuriyama et al Oral Micro Immunol 2005

Challenges in data interpretation ?

& Small numbers …….

But EUCAST 2018 breakpoint breakpoint Pen >2mg/L

Metronidazole resistance !!EUCAST BP= 4ug

5- Nitro-imidazole ring

5

Imidazole ring

N

O-

O

Nitro group

Metronidazole (5-Nitro-imidazole)

Add anelectron

Metronidazole – mechanism of action

N-

O

O

✷

Reactive anion species

N

O-

ONitro group

OH &

Add twoelectrons &

hydrogen

Pyruvate

N+

OInactive

Metronidazole - Resistance

Nim gene

N

O-

ONitro group

Surveillance of microbiology of acute dentoalveolar infections

Glasgow data- 29 years worth of data summary- 1986 - 2015

Localised dento-alveolar infection

Baseline data

N= 50 specimens (collected 1986-1988)166 isolates43 facultatives & 123 strict anaerobes

Period 1986-88

Method : Disc diffusion (Stokes) n=166Pen G (2ug) 5/166 resistAmoxyl (10ug) 1/166 resistErythro (15ug) 1/166 resistClinda (2ug) 2/166 resist

Susceptibility Testing methods

Stokes Kirby-Bauer E-test

Broth & agar dilution MIC methods too

Glasgow 1998-2015

Isolates were identified using biochemical properties (API system), VITEK 2 and MALDI-TOF.

The new microbiology lab technician

VITEK identification system

MALDI-TOF identification system

Matrix assisted

laserDesorption/Ionization

Time of flight

Mass spectroscopy

MALDI - TOF

Glasgow 1998 - 2015

Predominant facultative groups isolated during the study period comprised;

Mitis group Streptococci (n=448). Anginosis group Streptococci (n=196)

Strict anaerobes frequently isolated included Prevotella species (n=140). Anaerobic streptococci (n=116), Fusobacteria species (n=69)

Data available from 621 specimens.

Glasgow 1998-2015

Antimicrobial susceptibility tests were undertaken using combinations of Kirby-Bauer method and/or E-tests.

Kirby-Bauer method based on BSAC 2001 guidanceAlpha streps = Oxa (1ug), Ery (5ug), Clari

(2ug),Tetra (10ug) (Clinda: 2ug)

MIC breakpoints based initially on BSAC guidance

Anaerobes = difficult (BSAC Pen (2ug) & Clinda(2ug) for fast growers)

Glasgow 1986-2015

Anginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin Clindamycin

MIC breakpoints based initially on BSAC guidance

Pen R>=2ug/mlEry R>=1

Glasgow 1986-2015

Anginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin Clindamycin

Pen R>=2ug/mlEry R>=1

Glasgow 1986-2015

Anginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin Clindamycin

Glasgow 1986-2015

Anginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin Clindamycin

Glasgow 1986-2015

Anginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin ClindamycinAnginosus group Streptococci

1986-1988N= 25

2002-2015N=196

Penicillin Erythromycin Clindamycin

Summary

Relatively small numbers of annual specimens and isolates confounds data interpretation trends over time

Difficulties in defining breakpoints for microbes from oral infections

The majority of isolates remain susceptible to Penicillin, Macrolides and Clindamycin.

“Grandmother penicillin- not in vogue, but clinically still effective”

(Warnke et al JAC 2008)

Localised dental infections

Current diagnostic lab issuesGetting specimensSpecimen transportationSpecimen processing & reporting

Severe odontogenic infectionsAdmissions per 100,000 pop

Scotland

England

Dental sepsis cases and their management: OMFS Depart, Glasgow

12 months retrospective case note reviewEmma Ford DF2 NHS Lanarkshire, Mark Ansell SpR, Colin MacIver Consultant

Total of 108 patients required Incision and Drainage +/-dental extractions under GA at QEUH

4.31

10.13

0.00

2.00

4.00

6.00

8.00

10.00

12.00

All Cases Cases Returning to Theatre

Day

sAverage Hospital Stay

Shortest Stay: 1 DayLongest Stay: 20 Days

Shortest Stay: 4 DaysLongest Stay: 20 Days12 patients had ITU stays

Total ITU stay was 54 daysDoes it matter ? The cost….ITU: 54 days @ £2,260 pd = Ward: (mean 3 days): 324 days @ £1,874 =Theatre: 108 x £2,428 = Total approx = £1 million or (Euro 1.15 million)

34

5

5

11

3

1

1

1

0 5 10 15 20 25 30 35 40

S. millerii

S. aureus

Gram + Cocci

Mixed Anaerobes

Strep A

S. salivarius

K. oxytoca

E. Clocae

QEUH Microbiology - All Cases

17/108 cases had no micro samples sent,

Years = 1998 - 2007

N= 11,312 specimens

S. aureus & the diagnostic lab10yrs of dental aspirates

N of aspirates

Case 1: 44 yr old Female admitted with sepsis, facial swelling & cellulitis

Case 2: 32 yr old Female 3/7 history of submandibular swelling

Case 3: 13 year old male 4 day history toothache & trismus

Antimicrobial stewardship

• Diagnostic uncertainty is one of the principal drivers of excessive antimicrobial use

• Duncan RA, Lawrence KR. Improving the use of antimicrobial agents. In: SHEA Practical Healthcare Epidemiology, 2010.

“Successful chemotherapy must be rational and rational therapy demands a diagnosis.” LP Garrod

6 Consultant Clinical Oral Microbiologists in the UK

18 Dental Schools

39,894 Registered GDP's in UK

3.5 million antibiotic items by GDPs (England) in 2015

7: Improve the number, pay & recognition of people working in infectious disease