Rhodococcus equi infection in foals: diagnosis and treatment (Proceedings)

Diagnosis:

The gold-standard for diagnosis of Rhodococcus equi pneumonia is isolation of the organism from fluid obtained by tracheobronchial aspiration (TBA) from a foal with clinical signs of pneumonia, preferably accompanied by cytologic evidence of sepsis, sonographic or radiographic evidence of pneumonia, or both. Performing a TBA transendoscopically may be less stressful for foals and technically easier to perform. MILA makes a double-guarded catheter that can be used for this purpose. Because microbiologic culture and TBA have limitations, alternatives for diagnosis of R. equi have been sought for each of these techniques.

A variety of polymerase chain reaction (PCR) tests have been developed as alternatives to culture. PCR is more rapid and usually more sensitive than microbiologic culture. Moreover, PCR can distinguish the virulent biotype of R. equi, whereas microbiologic culture cannot. A limitation of PCR is that it does not yield information regarding antimicrobial susceptibility testing. PCR tests are available commercially, including a test offered by IDEXX laboratories that was developed at the University of California, Davis.

Alternatives to TBA fluid for diagnostic testing include blood, feces, and other airway samples. A variety of serologic tests for R. equi have been developed. These tests are appealing because serum generally is faster and easier to collect than TBA fluid. However, THESE SEROLOGIC TESTS SHOULD NOT BE USED. Evidence from our laboratory and the laboratory of Dr. Steeve Giguère indicates that serologic testing is of no value for either diagnosis of or screening for R. equi pneumonia, even when paired samples are used. There are a number of reasons why serologic tests perform poorly for diagnostic purposes. They are a measure of exposure, and thus can't differentiate foals that are exposed from those that are infected. Given the widespread distribution of R. equi in the environment of foals (regardless of history of disease caused by this bacterium in foals), serologic evidence of exposure also will be widespread. The test cannot differentiate between antibodies that are maternally derived from those that are produced by the foal. Most mature horses and foals have been exposed to the organism and most mature horses and foals have serologic evidence of exposure to the organism, yet only a relatively small proportion of exposed foals develop disease. Paired titers may be of less value for an insidious disease like R. equi pneumonia than for more acute diseases because foals will have been infected for weeks or months before signs become apparent.

Blood culture has not been systematically evaluated as a sample for diagnosis of R. equi pneumonia in foals. In human medicine, the sensitivity of blood culture for detecting R. equi pulmonary disease has been reported to range from 50% to 100%, and the procedure is generally more sensitive than sputum culture, bronchial aspiration, or percutaneous aspiration. Evaluation of PCR of blood samples also should be considered because it might be more sensitive than culture.

There may be value in using fecal samples for detecting R. equi infection. A couple of studies have indicated reasonable sensitivity for the technique (around 75% - 80%); data regarding specificity, however, are too limited to recommend using feces at this time. Current evidence indicates that nasal or nasopharyngeal swabs are not useful sources of samples, regardless of whether one uses culture or PCR for detection of R. equi.

TREATMENT

Macrolides: The treatment of choice for R. equi remains a macrolide in combination with rifampin. Erythromycin, azithromycin, and clarithromycin are most commonly used. The latter 2 drugs have pharmacokinetic and pharmacodynamic characteristics that render them apparently superior to erythromycin. Clarithromycin is considered to be the superior treatment on the basis of a retrospective study and the pharmacokinetic and pharmacodynamic characteristics of the drug. Evidence to support the use of other macrolides, such as tulathromycin or tilmicosin, currently is inadequate. For tulathromycin, MIC data indicate that isolates of R. equi are not particularly susceptible to this drug (i.e., MIC values are high relative to concentrations that can be obtained following administration of the drug). In the case of tilmicosin, data regarding MICs, pharmacokinetics, and pulmonary disposition of the drug indicate that the available formulation will not achieve effective concentrations. Both drugs have been described to cause adverse effects at rates that are likely clinically unacceptable.

After decades of their use to treat R. equi pneumonia, it is not surprising that resistance to macrolides has been reported for isolates of R. equi obtained from foals that were resistant to macrolides. Resistance to macrolides is almost always class-specific. The report of macrolide-resistant isolates of R. equi revealed that some susceptible isolates were misclassified as resistant. Therefore, it is reasonable to request re-testing to validate resistance by either the original testing laboratory or another laboratory. Of greater importance, the odds of survival were significantly lower for foals infected with macrolide-resistant isolates relative to foals infected with macrolide-susceptible isolates. If true, this represents an ominous finding: we need to be mindful of principles for judicious and appropriate use of macrolides to minimize opportunities for the development of resistance.

Alternatives to Macrolides: Because of resistance and side-effects of diarrhea (in foals and occasionally their dams) and hyperthermia, alternatives to the macrolides have been sought. Although there are MIC data for R. equi isolates and pharmacokinetic and pulmonary disposition data that support the potential use of doxycycline, the author's clinical impression is that this antimicrobial is not particularly effective. Although chloramphenicol is commonly used as an alternative, pharmacokinetic data suggest the drug might not be expected to be therapeutic. In the report describing macrolide-resistant isolates of R. equi, the MICs of clarithromycin among the resistant isolates were generally below the intra-cellular concentrations attained by this antimicrobial.12 Although this finding suggests that clarithromycin might be effective in treatment of foals whose isolates were identified as resistant to macrolides, this should NOT be assumed because non-survivors in that study were treated with clarithromycin; further clinical data are needed. Many isolates of R. equi are susceptible to vancomycin, but this drug should not be used unless mo alternative exists and the foal's life is deemed to be in danger; even then, some would argue that vancomycin should NOT be used to treat horses or foals because of its importance for treating human infections with organisms resistant to important (e.g., methicillin-resistant staphylococcal infections) or multiple antimicrobials. Our laboratory has been exploring the use of gallium maltolate both for treatment and prevention of R. equi pneumonia. The value of gallium maltolate as monotherapy or as adjunctive treatment awaits sound clinical efficacy data in foals.

Because infections are often polymicrobic, it is important to consider including adding empiric treatment with antimicrobials to broaden the spectrum of treatment pending culture results (such as an aminoglycoside), or adding appropriate antimicrobials on the basis of results of susceptibility testing of isolates cultured from TBA fluid.

References:

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