Interpreting culture and sensitivity data What the %@&$ does ...

INTERPRETING CULTURE AND SENSITIVITY DATA WHAT THE %@&$ DOES THIS MIC MEAN??? Jennifer Garcia, DVM, DACVIM WHY SHOULD WE CULTURE? Is there a bacterial infection there to begin with? What bacteria is it and what should I use to treat it? Have I successfully treated the infection? To recognize and address antimicrobial resistance CLINICAL AND LABORATORY STANDARDS INSTITUTE (CLSI) Provides standardized guidelines for lab quality

Quality control procedures, culture methods Publishes guidelines for the methods of susceptibility testing and the interpretive criteria for each drug Drug manufacturers must submit the appropriate data to CLSI for determination of interpretive data, so not all drugs will have MIC info. If the drug company has not pursued validation, then the drug will not be available for microbiological testing. TYPES OF BACTERIAL CULTURES Disk diffusion method (Kirby Bauer) Agar streaked with known amount of cultured organism Disks impregnated with known amount of drug that diffuses into the agar at a known rate.

Size of the zone around the disk determines if sensitive or resistant based on CSLI standards. Drawbacks: Semiquantitative only Only good for rapidly growing, aerobic organisms TYPES OF BACTERIAL CULTURES Tube dilution method Provides quantitative data regarding the amount of drug needed to inhibit bacterial growth Tubes of liquid media with increasing concentration of drug are inoculated with a known amount of infecting organism Tubes are observed for growth over a standard

period of time (24-48hours) Tube with the lowest concentration of drug at which there is no visible bacterial growth = minimum inhibitory concentration (MIC) MIC = lowest concentration of antibiotic that inhibits bacterial growth MIC In order to be effective, the drug you choose needs to reach this Minimum Inhibitory Concentration at the site of the infection. Pharmacokinetics of the drug Toxicity Host factors breakpoint MIC takes into account the clinical pharmacology of the drug as well as the susceptibility of the organism = approximation of drug concentration that can be safely achieved using std dose and route.

BREAKPOINT MIC This is established by the CSLI susceptible breakpoint = below this level the organism is considered susceptible to that drug resistant breakpoint = above this level the organism is considered resistant to this drug. The grey zone in between may be considered intermediate This may be overcome depending on site of infection and drug in question. Breakpoints will be different for different bacteria SOURCE: URINE CFU E.COL >100,000 Drug

MIC MIC breakpoints Interpretation Amikacin <=8 8-64 ug/ml S Clavamox <=4 4-32 ug/ml S Ampicillin/amox 2 0.25-32 ug/ml

S Cefpodoxime <=2 2-8 ug/ml S Cephalexin/cefadroxil <=4 4-32 ug/ml S Enrofloxacin <=0.50 0.5 4 ug/ml S Marbofloxacin <=0.50

0.5 4 ug/ml S Nitrofurantoin <=16 16-128 ug/ml S Tetracycline <=2 2-16 ug/ml S Ticarcillin <=16 16-128 ugml S Trimethoprim/sulfa

<=0.50 0.5-4 ug/ml S URINE E. COLI >100,000 CFU Drug MIC MIC breakpoints Interpretation Amikacin <=8 8-64 ug/ml R Clavamox >=32 4-32 ug/ml R

Ampicilin/ Amoxicilin >=8 0.25-32 ug/ml R Cefpodoxime >=8 2-8 ug/ml R Cephalexin/Cefadroxil >=32 4-32 ug/ml R Enrofloxacin >4 0.5-4 ug/ml

R Marbofloxacin >4 0.5-4 ug/ml R Nitrofurantoin 32 16-128 ug/ml S Tetracycline >16 2-16 ug/ml R Ticarcilin >=128

16-128 ug/ml R Trimethoprim/ Sulfa >2 0.5-4 ug/ml R EXTENDED SENSITIVITY PANEL CefiximeR (Suprax-3rd gen, PO) Cefotaxime R (Claforan-3rd gen, IV) Cefoperazone R (Cefobid,3rd gen, IV) Ceftiofur R (Naxcel, 3rd gen IV)

CefoxitinR (2nd gen, IV) Ceftazidime R (Fortaz, 3rd gen, IV) Ciprofloxacin S (PO) Imipenem S (IV) Meropenum S (IV, SC) Ticarcillin R (IV, IM) Timentin R (IV, IM) URINE: PSEUDOMONAS >100,000 CFU Drug MIC MIC breakpoints Interpretation Amikacin <=8 8-64 ug/ml S Clavamox N/A

--- --- Ampicillin/ Amox N/A --- --- Cefpodoxime >=8 2-8 ug/ml R Cephalexin N/A --- --- Enrofloxacin

>=4 0.5-4 ug/ml R Marbofloxacin 1 0.5-4 ug/ml S Nitrofurantoin >128 16-128 ug/ml R Tetracycline >=16 2-16 ug/ml R

Ticarcillin 32 16-128 ug/ml S TMS N/A --- --- CAVEATS In vitro in vivo Susceptibility to a drug within a class does not always correspond to susceptibility to all drugs in that class Sensitivity tests are assessed based on plasma levels and may not predict tissue concentrations

i.e. may be able to overcome resistance via topical application Do not take into account local factors such as pus, necrosis, poor perfusion, etc For human drugs, MIC data is based on human pharmacokinetics SO HOW DO I CHOOSE A DRUG BASED ON THE MIC? Consider the body system you are treating Renally excreted drugs best for kidney infections Drugs that concentrate in WBCs for pneumonia Pick one that is the farthest from the lowest

end of the breakpoint range. If similar susceptibility, consider breadth of spectrum, toxicity and ease of administration RENAL ELIMINATION = INCREASE URINE CONCENTRATION: Penicillins Cephalosporins Tetracyclines (NOT doxy) Fluorquinolones Aminoglycosides TMS URINE CONCENTRATION OF COMMON DRUGS Drug Dose Route [urine] (mg/kg) Amikacin 5 SC 342 (143) Amoxicillin 11 Oral 202 (93) Ampicillin 26 Oral 309 (55) Cephalexin 18 Oral 500 Chloramph 33 Oral 123.8 (39.7)

Enrofloxacin 5 Oral 40 (10) Gentamicin 2 SC 107.4 (33.0) Nitrofurantoin 4.4 Oral 100 Tetracycline 18 Oral 137.9 (64.6) TMS 13 Oral 55.0 (19.2) METHICILLIN RESISTANCE Not all staph with methicillin resistance are cause for panic Our biggest worry is with MRS-aureus (MRSA) MRS-pseudintermedius Pseudintermedius normal canine flora but CAN be an opportunistic pathogen in dogs Transmittable to humans but low incidence Scary thing is the rise in resistance we are beginning to see with pseud. (15% of skin cultures!) MRSA

S. aureus is a common commensal in people so dogs can get it from people and become colonized Resistance usually seen in cases where there has been previous abx use Carry it in the nose and GIT Limit nose to mouth contact (no licking!) 3.8 x more likely to have MRSA if abx used within the last 90 days 4.6 x more likely if that abx was a fluorquinilone ** Colonization is usually transient so once people are tx, dog will usually self-clear within 2-4 weeks unless re-infected. There is no data that we can successfully decolonize these dogs with antibiotic therapy so tx of aysmptomatic dogs is not indicated and may just lead to increased resistance.

**Methicillin-Resistant and -Susceptible Staphylococcus aureus Infections in Dogs Meredith C. Faires, Michelle Traverse, Kathy C. Tater, David L Pearl, and J. Scott Weese Emerging Infectious Diseases Vol. 16, No. 1, January 2010 CONCERNS ABOUT MRSA Is My Pet The Source Of My MRSA Infection? Pets can be carriers of MRSA, especially in households where people are repeatedly found to have MRSA infections, but this does not mean they are the source. Pets are often innocent bystanders that acquire the MRSA from their owners. If household infection control measures fail to control transmission of MRSA between people, AND there is evidence that a pet may be a source of MRSA, temporarily removing the pet from the household can be considered (but is rarely necessary). This should allow the pet to naturally eliminate MRSA colonization while the human members of the household undergo decolonization. Permanent removal of pets is not indicated.

TREATMENT OPTIONS Prevention is best strategy Minimize contact with open wounds, draining pustules Wear gloves! Keep wounds covered Keep toys and bedding clean (daily) Hand washing between patients Culture all dermal infections if expect protracted treatment TREATMENT OPTIONS Antibiotics

Chloramphenicol and amikacin are the only drugs that have retained sensitivity Maybe TMS and doxy No good options on the horizon Good news is that systemic infections in dog with MRSA are rare RESOURCE FOR MRSA INFO promo/services/

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