Mycoplasmal Respiratory Infections in Small Animals: 17 Cases (1988–1999)

Introduction

The role of Mycoplasma spp. as a primary cause of respiratory disease in dogs and cats has been debated for several years. The genus was first described as a pleuropneumonia-like organism in 1932 when it was cultured from the nasal secretions, lung, and liver of dogs with distemper.¹ Since that time, Mycoplasma spp. have been thought to play a role, mostly secondarily, in disease processes.^1–7 A number of studies have shown several Mycoplasma spp. to be inhabitants of the mucosal surfaces of the respiratory and genital tracts, as well as the eyes, alimentary canal, mammary glands, and joints of animals; some of these studies also provide evidence that Mycoplasma spp. may be a causal factor of inflammation in these areas.^28–10

By 1956, at least 15 species of the pleuropneumonia-like organisms had been identified, and the genus Mycoplasma was assigned.¹¹ Many of the Mycoplasma spp. were isolated from the respiratory tract.¹²¹³ It is now accepted that Mycoplasma spp. are normal flora of the upper airway (i.e., pharynx, larynx, oral cavity, and nasal cavity).^814–16 Mycoplasma spp. are not thought to colonize the lower airways (i.e., trachea and lungs) of normal dogs or cats.²⁵⁸¹⁶ However, Mycoplasma spp. have been isolated alone and in combination with other bacteria from the lungs of dogs and cats with pulmonary disease.^{4–61015–17}

In most reported cases with Mycoplasma spp. isolated from the lower airways, the affected dogs or cats had underlying syndromes such as hyperadrenocorticism, laryngeal paralysis, megaesophagus, or vomiting.^15–17 In these cases, organism presence may be explained by aspiration of the bacteria from the oropharynx with colonization secondary to other primary causes of airway inflammation or immunosuppression. In humans, Mycoplasma pneumoniae (M. pneumoniae) has been recognized as a primary cause of pneumonia in otherwise healthy individuals for almost 20 years.⁹¹⁸ In one study of 613 children with lower respiratory tract infections, 210 were diagnosed with M. pneumoniae.¹⁹ Mycoplasma spp. are also well-recognized primary causes of respiratory tract disease in cattle, goats, swine, and poultry.⁹¹⁵ The purpose of this study was to describe the clinical findings of dogs and cats with lower respiratory disease from which Mycoplasma spp. was the sole bacterial isolate, in an attempt to determine whether members of this genus serve as primary respiratory pathogens.

Materials and Methods

Results

Between January 1988 and July 1999, 272 cases with lower airway disease were identified. Of these cases, 224 (82%) had airway samples collected by transtracheal aspiration, transoral airway washing, or BAL and were cultured for Mycoplasma spp. and aerobic bacteria. Of these 224 samples, 113 (50.5%) were negative for Mycoplasma spp., and 111 (49.5%) were positive for Mycoplasma spp. alone or in combination with one or more aerobic bacterial isolates. Concurrent isolation of Mycoplasma spp. and aerobic bacteria was reported in 94 (85%) of the 111 positive cultures. In 17 of these animals with lower airway disease, Mycoplasma spp. was the sole isolate [Table 1].

Of the 17 cases, 14 (82.4%) were dogs; multiple breeds were reported. Two of the three cats were Siamese. Patient age ranged from 0.3 to 15 years (median, 7 years). All sexes were represented (male castrated, 6/17; female spayed, 6/17; male intact, 2/17; female intact, 2/17; not reported, 1/17). Coughing was the most common presenting complaint (13/17; 76.5%), followed by labored breathing (7/17; 41.2%). Coughing was also a common physical examination finding (13/17; 76.5%), with the majority of animals having coughs that were easily elicited on tracheal palpation (9/13; 69.2%).

Complete blood counts were performed on 16 of the animals. The most frequently detected hematological abnormalities were neutrophilia (9/17; 52.9%), leukocytosis (7/17; 41.2%), lymphopenia (6/17; 35.3%), and eosinophilia (4/17; 23.5%). Radiographic findings were available for all cases [Table 1]. Thoracic radiographs were interpreted as normal in three of 17 (17.6%) cases. Radiographic patterns consistent with pneumonia (11/17; 64.7%) were the most common finding. Collapsing trachea or collapsing bronchi (4/17; 23.5%) were also common findings on both radiographs and endoscopic examinations.

Cytopathological examination (16/17) and culture results (17/17) on fluid obtained from transtracheal aspiration or transoral airway washings (14/17) or BAL (3/17) were also reported. Seven of the 16 cytopathological examinations listed differential counts. The predominant cell types were nondegenerate neutrophils (3/7; 42.9%), large mononuclear cells (2/7; 28.8%), or eosinophils (2/7; 28.8% [both from cats]). A variety of cytopathological examination interpretations were reported; however, suppurative inflammation (6/16; 37.5%) was the most common finding. Two of the cytopathological examinations were deemed to have no cytopathological abnormalities. Mycoplasma spp. growth was subjectively assessed and ranged from 1+ to 4+, with 1+ (10/17; 58.8%) being the most common finding [Table 1].

Diagnosis and treatment protocols are outlined in Table 2. Multiple clinical diagnoses were made. All of the feline cases were diagnosed with feline asthma, bronchitis, or both. Pneumonia was diagnosed in seven of the 14 (50%) canine cases. The remainder of the canine cases were diagnosed with airway collapse (4/14; 28.6%), bronchitis (1/14; 7.1%), or airway collapse and bronchitis (2/14; 14.3%). Of the six cases diagnosed with airway collapse, four (66.7%) were diagnosed with tracheal collapse and two (33.3%) were diagnosed with collapsed bronchi. Several different treatment protocols were used. Enrofloxacin^d was the most commonly used antibiotic (8/17; 47.1%). Combinations of drugs were used in some (8/17; 47.1%); enrofloxacin and amoxicillin made up the most common (3/8; 37.5%) combination. Of the single drugs, doxycycline was used most commonly (3/9; 33.3%), followed by tetracycline (2/9; 22.2%). Chloramphenicol, enrofloxacin, prednisone, and clindamycin were used as the sole drug in one case each (11.1%).

Recheck information and clinical outcome are also listed in Table 2; three cases were lost to follow-up. Of the 14 treated animals with follow-up information available, two (14.3%) responded completely and had no recurrence; six (42.9%) of the cases had either partial improvement or complete resolution, but recurred; and six (42.9%) cases had no improvement. Recurrence was defined as the return of clinical signs or presenting complaint at any time during the follow-up period. The follow-up periods for these cases ranged from 4 months to 9 years. Cases with favorable outcomes had follow-up periods that were longer than those for cases with poor outcomes.

Discussion

Mycoplasma spp. was the sole bacterial isolate from airway washings collected from 17 animals presented for evaluation of cough or labored breathing. Since other bacteria were not cultured, the authors feel that the positive Mycoplasma spp. results were unlikely to have been from oropharyngeal contamination during the collection procedure. For discussion, based on clinical, radiographic, and endoscopic findings, these cases were grouped into three categories: airway collapse, bronchitis, and pneumonia. Each category will be discussed separately as to the potential role Mycoplasma spp. played in the disease process. Mycoplasma spp. are considered to be susceptible to macrolides, azalides, tetracyclines, chloramphenicol, lincosamides, and fluoroquinolones;²²⁰²¹ therefore, tylosin, enrofloxacin, chloramphenicol, tetracycline, doxycycline, and clindamycin were all considered antimycoplasmal drugs.

Airway collapse can be due to congenital weakness or acquired weakness.²² Airway collapse can be predisposed by chronic infections and allergic or irritant airway disease. In the six dogs (case nos. 1, 7, 9–11, 13) with airway collapse described here, five were treated with an antimycoplasmal drug alone or in combination with other drugs. A positive response was suspected to be due to the antimycoplasmal drug in three dogs; two had no response. The one Mycoplasma spp.-infected dog that was treated with prednisone only (case no. 11) died 2 weeks later. It is possible that the dogs had airway collapse induced by chronic airway disease from a pathogenic Mycoplasma spp. infection. Alternately, chronic airway disease may have resulted in decreased airway clearance of nonpathogenic Mycoplasma spp. inhaled into the airways from the oropharynx. It cannot be determined from this study which of these hypotheses is most likely. However, if preexisting airway collapse predisposed to bacterial colonization from the oropharynx, it would have been expected that multiple bacteria would have been cultured, not just Mycoplasma spp. These findings support airway washings and culture for animals with airway collapse, particularly if they are poorly responsive to drugs other than antimicrobials. Doxycycline has anti-inflammatory effects²³ as well as antimycoplasmal effects and, therefore, may be a good choice empirically.

Five animals (case nos. 4, 5, 15–17, including all three cats in the study) had small airway disease (i.e., bronchitis) without obvious tracheal or bronchial collapse. Eosinophils were the predominant cells in the airway washings of two of the cats, leading to the clinical diagnosis of asthma. However, some clinically normal cats have a high number of eosinophils present in BAL specimens.²⁴²⁵ Additionally, it has been shown that small airway disease in general can result in an increased number of eosinophils in the airways.²⁶ Thus, it is possible that Mycoplasma spp. infection could have induced the increased numbers of eosinophils in the BAL specimens of these two cats. Of the four cases with available follow-up information, three (case nos. 4, 5, 17) had clinical evidence of response to antimycoplasmal drugs, suggesting that Mycoplasma spp. was playing a primary or secondary role in the disease process. In case no. 5, glucocorticoids were required chronically, suggesting that the Mycoplasma spp. infection was secondary to another primary cause. Case no. 17 was a cat with a clinical illness of 3 years’ duration; clinical signs resolved and never recurred after a 6-week course of prednisone and clindamycin. In this case, it is likely that Mycoplasma spp. was the primary cause of the disease. If the primary cause was allergic disease, the authors would have expected continued use of medication to be required, especially considering a 3-year previous history. These results suggest that some Mycoplasma spp. may be capable of inducing chronic bronchitis as primary pathogens.

Pneumonia was the clinical diagnosis in six dogs (case nos. 2, 3, 6, 8, 12, 14). Mycoplasma spp. has commonly been cultured from the lower airways of animals with pneumonia, usually in combination with other bacteria. This is likely a result of aspiration from the mouth, where Mycoplasma spp. are considered normal flora.^814–16 Most animals with Mycoplasma spp. infection and pneumonia have had an underlying cause, such as immunosuppression or aspiration due to vomiting or regurgitation. In the six dogs with pneumonia and Mycoplasma spp. cultures described here, two (case nos. 3, 14) had likely primary causes (i.e., pulmonary thromboembolic disease and aspiration) predisposing them to pneumonia. For case nos. 6 and 8, it is possible that hypothyroidism predisposed the dogs to infection, aspiration, or both. This endocrine disease is thought to decrease neutrophil numbers²⁷ and affect neutrophil function by reducing the cell’s protein synthesis, lowering its rate of respiration and heat production, decreasing the amount of enzymes, and changing intracellular concentrations and handling of ions.²⁸²⁹ These factors could be responsible for predisposing to Mycoplasma spp. infection by reducing the bactericidal capacity of neutrophils. The possibility also exists that these cases suffered from aspiration since hypothyroidism also predisposes to laryngeal paralysis and megaesophagus.³⁰³¹ Both of these dogs had an apparent response to antimycoplasmal drugs. In case nos. 2 and 12, there was no obvious cause for pneumonia. Case no. 2 did initially respond to enrofloxacin and amoxicillin. Case no. 12 was recently adopted from a local humane shelter and so may have been exposed to a pathogenic Mycoplasma spp. The dog had failed to respond to amoxicillin, a drug that theoretically should not treat Mycoplasma spp. Amoxicillin is a cell wall synthesis inhibitor, and Mycoplasma spp. have no cell wall.⁹

This study showed that 49.5% of the cases with lower airway disease that were cultured were positive for Mycoplasma spp. The findings of this study emphasize the importance of airway washings and culture (aerobic and mycoplasmal), especially in cases that are poorly responsive to empirical treatment. Samples obtained from airway washings should be collected and placed into either a solid transport medium^a or a sterile, red-topped tube for transport to a laboratory. Some diagnostic laboratories prefer the samples not be collected with wooden or cotton-tipped swabs, as there is anecdotal evidence these substances may have an inhibitory effect on the growth of Mycoplasma spp. Samples should be kept cool (not frozen) during shipment. Positive results are usually reported within 5 to 7 days, but this can vary depending on the laboratory used. However, it may take up to 14 days to obtain results of a negative culture, because some laboratories will hold or re-plate samples with no growth in order to assure the accuracy of the report. Specific species identification and antibiotic sensitivities are not routinely available for Mycoplasma spp.

At least three other cases of pneumonia due to Mycoplasma spp. in dogs³² and three other cases of pneumonia due to Mycoplasma spp. in cats have been reported.³³ In each of these cases, Mycoplasma spp. were suspected to be a primary pathogen. Several studies agree that Mycoplasma spp. are not found in the lower airways of healthy dogs and cats.^2581624 Although uncertainty remains about whether Mycoplasma spp. play a primary or secondary role in lower airway disease, it can be stated that the presence of Mycoplasma spp. on transtracheal or BAL specimens is indicative of disease. To definitely prove whether Mycoplasma spp. are capable of primarily inducing respiratory disease in dogs and cats will require the isolation of strains from clinically affected animals for inoculation into healthy animals.