Acute dento-alveolar infections: microbiology ...€¦ · Microbiology of acute dentoalveolar...
Transcript of Acute dento-alveolar infections: microbiology ...€¦ · Microbiology of acute dentoalveolar...
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)
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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