Bacterial culture and sensitivities, what do they really mean? (Proceedings)

Antimicrobials

Treatment of bacterial infections can be difficult and frustrating. There are many different opinions for empiric antimicrobial therapy. Empiric therapeutic decisions should be based on the most likely causative organism, expected susceptibility of the bacteria, location of suspected infection, antimicrobial adverse effects, owner compliance, and pharmacokinetic properties of the drug. For example, bacterial prostatitis is often caused by gram-negative aerobic bacteria such as E. coli or Klebsiella spp. The culture may grow an E. coli susceptible to amoxicillin / clavulanate. However a therapeutic cure is unlikely due to the location of the infection. The prostate in considered a "protected" area for which many drugs, including most beta lactams, cannot achieve sufficient concentrations to clear the infection. Likewise an E. coli may be grown from a suspected urinary tract infection susceptible to enrofloxacin, but a cure is not achieved due to presence of uroliths. Therefore empiric choices which may superficially seem appropriate may be ineffective when all factors are considered.

Interpretation of a culture and sensitivity (C&S) result can be frustrating due to different methods of determination. Laboratories which follow CLSI (Clinical Laboratory Standards Institute) standards should be used for C&S as they perform the testing following specific criteria. Results from laboratories not using CLSI validated breakpoints and methods may not accurately predict clinical outcome from the susceptibility testing. The two most commonly used methods for determining antimicrobial sensitivity are disk diffusion (aka Kirby-Bauer) and broth microdilution. Kirby-Bauer susceptibility testing usually reports results just as an S, I, or R. Broth microdilution provides additional information on the susceptibility of the organism. In addition to an S, I, or R, a minimum inhibitory concentration (MIC) is also given. The MIC is the lowest antibiotic concentration that inhibited the growth of the bacteria in the culture. For example an E. coli culture may grow in cephalexin concentrations up through 4 mcg/mL, but not in cultures containing 8 mcg/mL of cephalexin and above. Therefore an MIC of 8 mcg/mL will be assigned, the minimum concentration which inhibited growth of the organism, and would also be labeled as resistant (R). The MIC's can be useful when multi-drug resistant bacteria are present as sometimes a clinical cure can still be achieved with an "R" by altering dose or route of administration.

It is important to realize that the breakpoints (concentrations that receive an S, I, R) are dependent on the species (dog, cat, horse, etc.), the disease (UTI, respiratory, skin, etc.), the organism (E coli, Staphylococcuspseudintermedias, Pseudomonasaeruginosa, etc.), the drug (cephalexin, cefazolin, cefpodoxime, cefocevin), and dosage regimen: dose (22 mg/kg, 30 mg/kg, etc.), route (IV, IM, PO), duration (7, 10, 14 days, etc.) and frequency. When any of these parameters are changed, the breakpoint may no longer be valid and success may be changed. Unfortunately there are few approved breakpoints in veterinary medicine for companion animals (see table 1). Therefore a result of S, I, R for drugs and indications other than those in table 1 are often extrapolated from breakpoints from other indications, veterinary species, or humans which may or may not be applicable to our veterinary patients. For example, the breakpoint of cefpodoxime for susceptible bacteria causing canine soft tissue infections is ≤ 2 mcg/mL. If the urine from a dog with prostatitis is cultured and a Staphylococcus is isolated with an MIC of 1 mcg/mL, most labs will assign an "S" for the isolate. However a clinical cure will not occur, because the breakpoint was for dermal infection, the infection is in the prostate, and cefpodoxime does not penetrate the prostate. However, if the dog only had a UTI and the prostate was not involved, than the outcome of treatment would likely be a clinical cure.

Urinary Tract Infections

Bacterial urinary tract infections (not involving the prostate) are relatively common in dogs with up to 14% of dogs having an episode during its lifetime. Female dogs are 2-4x as likely as male dogs to develop UTIs, probably because of the shorter urinary tract. UTI's are infections of the urinary tract epithelium, not urine infections, although many of the infections are confined to the epithelial surface.

Many drugs reach very high concentrations in the urine because they are primarily eliminated as unchanged drug in the urine. Beta lactams (amoxicillin, clavulanate, cephalexin, cefpodoxime, etc), most fluoroquinolones (enrofloxacin, marbofloxacin, orbifloxacin), many sulfonamides, and aminoglycosides (gentamicin, amikacin) reach much higher urine concentrations compared to plasma and tissue concentrations. Therefore administration of these drugs may result in an additional "topical" effect which can add to their antibacterial activity. Again, using cefpodoxime as an example, an E coli from a canine UTI with an MIC of 8 mcg/mL will be assigned an "R," but a clinical cure could be achieved if it is a uncomplicated UTI due to the high urine drug concentrations. However some bacteria create biofilms, which protect themselves and prevent drug penetration, or can deeply invade the epithelium in which cases the high drug concentrations in the urine are not beneficial, but the clinical cure will be dependent on the drug concentrations in the tissues of the urinary tract.

Conversely, some drugs do not reach very high concentrations in the urine such as clindamycin, in which ~7% of the total dose is eliminated in the urine as unchanged drug. However clindamycin still has clinical efficacy for many susceptible bacteria because it reaches the urinary tract epithelium through the vasculature in sufficient quantities to have antibacterial effects in addition to some of the drug being eliminated in the urine.

Infectious Arthritis

Similar to urinary tract infections, infectious arthritis / synovitis is an infection of the synovium, not synovial fluid. Therefore high concentrations of drug in the synovial fluid may be beneficial, but drug still has to reach to epithelial cells and interstitial spaces in order to elicit a cure. Despite its reference as a "protected" environment, most drugs penetrate the synovial membrane well.

Enterococcus spp.

Enterococcus spp. are gram positive bacteria that are normal inhabitants of the lower GI tract. Enterococcus spp. have been cultured from UTI's in dogs, but less commonly occur in wounds and respiratory infections. Despite the results of the C&S Enterococcus should be considered resistant to all cephalosporins, clindamycin, aminoglycosides, and trimethoprim / sulfonamide combinations as clinical cures rarely occur (even if an "S" is assigned). Combining an aminoglycoside with amoxicillin can result in synergy and increased efficacy when treating Enterococcus infections. Enterococcus spp. can display marked resistance to many of the antimicrobials commonly used in veterinary medicine with Enterococcus faecium often displaying more resistance than Enterococcus faecalis. Penicillin and ampicillin / amoxicillin are often good empirical choices if an Enterococcus spp. is suspected. Other antimicrobials which have variable activity include fluoroquinolones, doxycycline, rifampin (in combination with another antimicrobial), and nitrofurantoin. Erythromycin (but not clindamycin) may have activity against some infections not in the urinary tract, but is not a good routine choice. Clinical reports from humans indicated resistance to azithromycin is greater than erythromycin, therefore erythromycin would be a better choice than azithromycin for soft tissue infections. Although vancomycin is frequently listed on C&S, it must be administered by IV infusion 3-4 times daily to be effective. Oral vancomycin has very poor oral bioavailability and is only effective in treating enteric infections.

Enterococcus spp. may be an opportunistic pathogen in some polymicrobial infections. If the Enterococcus spp. is susceptible to commonly used drugs such as amoxicillin or a fluoroquinolone, than administering treatment targeted at both (all) organisms is anticipated to result in the best clinical outcome. However, Enterococcus is sometimes resistant to all of the available choices in a polymicrobial infection, in which case treating the other pathogens and clearing them may result in resolution of the Enterococcus as well.

Table 1. CLSI Approved Veterinary Breakpoints For Companion Animals.

Disclaimer: The information is accurate to the best of the author's knowledge. However recommendations change as new data become available and errors are possible. The author recommends double checking the accuracy of all information including dosages.