Interpretation of Culture & Susceptibility Reports

Antimicrobial stewardship programs typically recommend culture and susceptibility testing to guide clinicians in choosing optimal antimicrobial therapy; however, the majority of antimicrobial selections are made empirically,^1,2 rather than based on test results from individual patients. Antimicrobial selection guided by culture and susceptibility testing is conducted mostly for chronic or recurrent infections.<sup3,4 sup>

Culture and susceptibility reports are often underused by veterinary practitioners because of a number of limitations, including cost and the time delay between sampling and results<sup.4sup> Even after results are obtained, clinicians may lack the information necessary to interpret the reports in a meaningful way.

Culture & Susceptibility Reports

A culture and susceptibility report from a microbiology laboratory identifies the bacterial pathogen and lists antimicrobials labeled with an S, R, or I, designating Susceptible, Resistant, or Intermediate, respectively.⁵ These labels indicate the likelihood of a clinical response to antimicrobial treatment. Categories are determined by clinical breakpoints (ie, values that express whether specific bacterial pathogens will respond to certain antimicrobials), which are determined for specific antimicrobial/bacteria combinations based on the minimum inhibitory concentration (MIC) and the designation S, R, or I that corresponds to a specific MIC value (see Determining Breakpoints). MIC values are based on populations of the specific bacteria, the pharmacodynamic data for a specific species, and evidence from clinical use in patients treated with that antimicrobial.⁶ The clinical use is specific to the dose regimen (ie, dose, route of administration, frequency of administration) and disease. If any aspect of the regimen is altered (eg, the drug is administered orally instead of by injection), the predictive values of the breakpoints are no longer reliable.

Established Breakpoints

The Clinical Laboratory Standards Institute (CLSI) sets the standards for conducting and interpreting veterinary antimicrobial susceptibility tests.⁷ Breakpoints have been set only for a limited number of antimicrobial/bacteria combinations in veterinary species. If veterinary breakpoints are not available, breakpoints derived from human data are often provided on the report; this practice, however, is controversial, with some veterinary microbiologists stating that interpretation from nonveterinary breakpoints should not be performed or should only be performed with extreme caution.^8,9 The CLSI recommends that microbiology laboratories should inform clinicians of the breakpoint source (ie, human or veterinary), but such designations rarely appear on culture and susceptibility reports. Thus, the report must be used in conjunction with knowledge of the pharmacokinetics and pharmacodynamics of the antimicrobial and the pathophysiology of the disease to determine if a specific drug is a reasonable treatment option (see Table).¹⁰

Diagnostic laboratories independently choose which bacterial isolates and which antimicrobial susceptibilities to report. Although laboratories recommend reporting only isolates that are clinically relevant, as reporting clinically irrelevant isolates can lead to unnecessary antimicrobial use, this would require oversight by a veterinary microbiologist with an adequate clinical background¹; however, not all laboratories have the services of such specialists. It is also recommended that laboratories practice selective reporting (ie, all determined susceptibilities are not automatically reported), which helps prevent clinicians from choosing antimicrobials for cases in which they are not appropriate.¹ For example, the susceptibility of an Escherichia coli isolate to nitrofurantoin should only be reported for isolates from an uncomplicated UTI, as UTI is the only clinical situation in which nitrofurantoin is an effective treatment. Susceptibilities for last resort drugs important in human medicine (eg, vancomycin, imipenem) should not be routinely reported.

Resistance & Susceptibility

It is important to recognize intrinsic resistance when interpreting culture and susceptibility reports.¹¹ There are certain antimicrobial/bacteria combinations for which resistance should be assumed (eg, enterococci and cephalosporins). Some pathogens are intrinsically resistant to most major categories of antimicrobials. For example, Pseudomonas aeruginosa is a common secondary invader in cases of chronic otitis externa in dogs. Therefore, it is common to see resistance reported to all antimicrobials except aminoglycosides, fluoroquinolones, and antipseudomonal penicillins (eg, piperacillin). As another example, methicillin-resistant staphylococci should be reported as resistant to all penicillins and cephalosporins and imipenem; even if in vitro test results indicate susceptibility, the laboratory should report the result as resistant if there is a known intrinsic resistance. Results reported as susceptible should be questioned, as they are most likely the result of an identification or susceptibility testing error, indicating potential problems with the laboratory’s adherence to standard guidelines.

Unexpected resistance results (eg, penicillin-resistant streptococci) should also be identified and investigated (see Table). Although such results might be due to the emergence of antimicrobial resistance, it is more commonly the result of laboratory error.^8,12

Rather than listing drugs in alphabetical order, it is preferable for the reporting laboratory to list drugs in groups according to class and in order of appropriate first-line, second-line, and third-line treatment choices to support prudent antimicrobial use. Cross-resistance often occurs within classes of antimicrobials and may be more difficult for the clinician to visualize if drugs are listed in alphabetical order. This order may also prevent practitioners from simply choosing the first drug labeled “S” for therapy.

Breakpoint Sources for & Resistance to Common Antimicrobials

This table provides antimicrobials commonly found on small animal culture and susceptibility reports and is organized according to antimicrobial classification and a general preference for order of use. Breakpoint information is derived from CLSI performance standards for veterinary isolates.⁷

Penicillins

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: Escherichia coli in dermal, soft tissue, and urinary tract infections; Staphylococcus pseudintermedius and Streptococcus canis in dermal and soft tissue infections

Human: Enterococcus spp

| Klebsiella spp, Proteus vulgaris, Serratia marcescens, Enterobacter spp, Pseudomonas aeruginosa |

• Susceptibility to ampicillin indicates susceptibility to amoxicillin.

• Aminopenicillins are inactivated by most β-lactamases, but sufficient concentrations are achieved in urine to overcome low-level resistance; therefore, amoxicillin is recommended as empiric treatment for UTIs even if reported as R.¹³

| | Amoxicillin–clavulanic acid | Canine and feline: E coli, Staphylococcus spp, and Streptococcus spp in dermal, soft tissue, and urinary tract infections | S marcescens, Enterobacter spp, P aeruginosa |

• Resistance indicates extended-spectrum β-lactamase–producing (ESBL) bacteria, which are typically susceptible to amoxicillin–clavulanic acid but resistant to third- and fourth-generation cephalosporins.¹⁴ 

• As a result of high urine concentrations of amoxicillin, amoxicillin alone is recommended as the first-line treatment of UTIs.

• The combination of amoxicillin with clavulanic acid is required for effective treatment of methicillin-susceptible staphylococcal superficial bacterial folliculitis/ pyoderma.¹⁵

| | Oxacillin | Human: Staphylococcus spp | Most gram-negative bacteria |

• Used solely to determine methicillin resistance in S pseudintermedius

• Disk-diffusion (ie, Kirby-Bauer) testing is not reliable for Staphylococcus aureus; cefoxitin disks should be used to determine methicillin resistance.⁷

| | Penicillin | Human: Enterococcus spp and Staphylococcus spp | Most gram-negative bacteria |

• All β-hemolytic streptococci are susceptible.

• Clinical use in small animals is limited due to available formulations.

| | Piperacillin | Human: P aeruginosa | N/A |

• An antipseudomonal penicillin

• Clinical use is limited due to available formulations.

|

Cephalosporins

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: E coli, Pasteurella multocida, S aureus, S pseudintermedius, and β-hemolytic

Streptococcus spp in dermal, respiratory, soft tissue, and urinary tract infections

Human: Enterobacteriaceae

| Enterococcus spp, P vulgaris, S marcescens, Enterobacter spp, P aeruginosa |

• Generally indicates susceptibility to cephalexin and cefadroxil

• Human breakpoints for cephalothin are used for other first-generation cephalosporins to treat Enterobacteriaceae infections, but cefazolin should be tested separately.

| | Cefoxitin | Human: Staphylococcus spp | Enterococcus spp, P aeruginosa |

• A second-generation human-approved cephalosporin with excellent activity against anaerobes

• Cefoxitin resistance is an indicator of methicillin-resistance in S aureus but is not reliable for S pseudintermedius; oxacillin resistance is the preferred indicator.¹⁶

• Indicates ESBL-producing bacteria, which are susceptible to cefoxitin but resistant to third-generation cephalosporins¹⁷

| | Cefpodoxime | Canine: E coli, Proteus mirabilis, P multocida, S aureus, S pseudintermedius, and S canis in wounds and abscesses | Enterococcus spp, P aeruginosa |

• Generally indicates susceptibility to third-generation cephalosporins, including cefovecin and ceftiofur

• Indicates ESBL-producing bacteria, which are often resistant to these cephalosporins but still susceptible to amoxicillin–clavulanic acid¹⁸

|

Tetracyclines

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: S pseudintermedius in dermal and soft tissue infections

Human: Enterococcus spp

| P aeruginosa |

• Frequently active against methicillin-resistant staphylococci⁹

| | Minocycline | Proposed Canine: S pseudintermedius in dermal and soft tissue infections | P aeruginosa |

• May be considered in the treatment of methicillin-resistant staphylococci when resistance to doxycycline has been documented

| | Tetracycline |

Canine: Staphylococcus spp in dermal and soft tissue infections

Human: Enterococcus spp

| Proteus spp, P aeruginosa |

• Susceptibility indicates susceptibility to oxytetracycline.

• Staphylococci with reduced susceptibility to tetracycline or oxytetracycline may be susceptible to doxycycline or minocycline.⁹

|

Sulfonamides

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Human: Enterobacteriaceae, Staphylococcus spp

| Enterococcus spp, P aeruginosa |

• Susceptibility indicates general susceptibility to all sulfonamides.<sup11​sup>​​​​​​

| | Trimethoprim– sulfamethoxazole | Human: Enterobacteriaceae, Staphylococcus spp | Enterococcus spp, P aeruginosa |

• Susceptibility indicates general susceptibility to sulfonamides in combination with trimethoprim.¹¹

|

Macrolides/Lincosamides

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: β-hemolytic Streptococcus spp in dermal and soft tissue infections

| Enterobacteriaceae¹¹ |

• Susceptibility indicates susceptibility to lincomycin.

• Active against respiratory gram-negative pathogens but not gram-negative enteric bacteria

• If staphylococci are reported as susceptible to clindamycin but resistant to erythromycin, disk-diffusion test should be performed to check for inducible resistance that renders clindamycin ineffective.¹⁹

| | Erythromycin | Human: Staphylococcus spp | Enterobacteriaceae |

• Susceptibility indicates general susceptibility to azithromycin and clarithromycin.

• Active against respiratory gram-negative pathogens but not gram-negative enteric bacteria

|

Phenicols

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: P multocida in dermal and soft tissue infections

Human: Enterococcus spp

| P aeruginosa |

• Chloramphenicol is generally active against staphylococci (including methicillin-resistant isolates), enterococci, and E coli (including ESBL-producing isolates).^20,21

• Toxicity limits treatment to only a short duration in cats.

• Clinical use in small animals is limited due to human health concerns (eg, aplastic anemia).

|

Fluoroquinolones

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: Enterobacteriaceae, Staphylococcus spp, and Streptococcus spp in dermal, respiratory, soft tissue, and urinary tract infections

Feline: Enterobacteriaceae, P aeruginosa, and Streptococcus spp in dermal and soft tissue infections

| Anaerobes |

• Susceptibility indicates general susceptibility to veterinary fluoroquinolones, including marbofloxacin, difloxacin, and orbifloxacin.

• Ciprofloxacin (in humans) has the greatest activity of all the fluoroquinolones against Pseudomonas spp, but it has less ideal pharmacokinetics than veterinary fluoroquinolones.

| | Pradofloxacin |

Canine: Enterobacteriaceae, S pseudintermedius in dermal and urinary tract infections

Feline: Enterobacteriaceae, P multocida, S pseudintermedius, S aureus, Staphylococcus felis, and S canis in dermal, respiratory, and urinary tract infections

| N/A |

• Pradofloxacin is active against anaerobic bacteria.

• Many pathogens remain susceptible to pradofloxacin while testing resistant to other fluoroquinolones.²²

|

Aminoglycosides

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Canine: E coli, P aeruginosa, Staphylococcus spp, Streptococcus spp

| Enterococcus spp,¹¹ anaerobes |

• Amikacin is active against gram-negative enteric bacteria and staphylococci, including methicillin-resistant isolates.²³ It is less active against streptococci but more active against Pseudomonas spp than other aminoglycosides.

• Clinical use in small animals is limited by pharmacokinetic properties and toxicity.

| | Gentamicin | Canine: Enterobacteriaceae, P aeruginosa | Enterococcus spp,¹¹ anaerobes |

• Gentamicin is active against gram-negative enteric bacteria and staphylococci, including some methicillin-resistant isolates.²³

• Usually active against Pseudomonas spp but is more susceptible to enzymatic resistance than is amikacin.

• Clinical use in small animals is limited by pharmacokinetic properties and toxicity.

|

Limited-Use Antimicrobials

| Antimicrobial | Breakpoint Source

(Canine, Feline, Human)

Human: Enterococcus spp, Enterobacteriaceae

| P mirabilis¹¹ |

• Used exclusively to treat uncomplicated UTIs

• Usually active against E coli (including ESBL-producing isolates), enterococci, and staphylococci, including methicillin-resistant isolates²⁴

| | Mupirocin | There are no veterinary breakpoints for topical antimicrobial product; human breakpoints are questionable. | N/A |

• Topical product used for the treatment of methicillin-resistant staphylococci

• It is assumed that drug concentrations are high at the application site; however, for most topical agents, measured drug concentrations at the site are not known, nor is the length of time for which those concentrations are maintained. The decision to use is based on clinical experience of efficacy.

| | Fusidic acid | Human: Staphylococcus spp | N/A |

• Topical product used for the treatment of methicillin-resistant staphylococci²⁵

• See Mupirocin for limitations in susceptibility testing.

| | Rifampin | Human: Staphylococcus spp | N/A |

• Rifampin is generally active against methicillin-resistant staphylococci.

• Use is limited due to hepatotoxicity.

• Should not be used as monotherapy, as resistance rapidly emerges with this type of use

| | Imipenem | Human: Enterobacteriaceae, P aeruginosa | N/A |

• Susceptibility indicates susceptibility to carbapenems, including meropenem.

• Methicillin-resistant staphylococci are resistant to imipenem.

• Imipenem should be a last resort treatment in human medicine; use in veterinary medicine should be strictly limited.

| | Vancomycin | Human: Enterococcus spp, S aureus, coagulase-negative Staphylococcus spp | N/A |

• Vancomycin should be a last resort treatment for gram-positive infections (eg, enterococci, methicillin-resistant staphylococci) in humans; use in veterinary medicine should be strictly limited.

|

CLSI = Clinical Laboratory Standards Institute, ESBL bacteria = extended-spectrum β-lactamase–producing bacteria, MIC = minimum inhibitory concentration