Streptococcus pyogenes

S. pyogenes is the predominant cause of group A infections of people and is the type species for this group. The sites of greatest carriage of group A streptococci in people are the caudal aspects of the pharynx and tonsillar region. Group A streptococci can survive extremes in environmental temperature and humidity; however, most infections are associated with direct or close contact among susceptible individuals (Fig. 33-1). Shedding occurs most commonly through respiratory droplets or oropharyngeal secretions. As is true with many streptococcal infections, some individuals can harbor the infection for extended periods in the absence of clinical illness. Prevalence rates for group A streptococci are higher in young children, especially those in daycare or classroom situations. The prevalence of positive throat culture findings in such circumstances may approach 50%, even in the absence of an obvious epidemic.⁷⁸ Symptomatic rather than carrier children are most likely to bring infection into the home. Under such circumstances the isolation rate in other people in the household approaches 25% to 50%. If the child is asymptomatic, the rate is only 9%.⁹⁶ Dogs and cats have been suggested as possible sources of reinfection of treated household members, but no convincing evidence shows that dogs and cats are significant reservoirs of infection for people. However, veterinarians may need to be consulted on this topic.

Whenever streptococcal typing has been performed on the oropharyngeal regions of dogs and cats, groups G, C, L, and M have been present (in order of decreasing frequency). However, screening for group A streptococcal colonization of the tonsils of dogs and cats from random households in urban environments has shown the apparent prevalence to range between 1% and 10%.33,36,109,138 In one study in which recurrent group A streptococcal pharyngitis occurred in people, the prevalence for households was said to be 42% for dogs and 36% for cats.³³ However, because only bacitracin susceptibility was used to distinguish group A from non–group A strains in many of these studies, these findings of high prevalence must be regarded as outdated. When Lancefield typing has been done, the prevalence of true group A streptococcal carriage has varied from 0% to 3% of dogs and has not correlated with the presence of infection in the owner.^36,242 Biochemical testing of isolates from dogs and cats cannot accurately distinguish between those from groups A and G.¹⁶⁹ There is no convincing evidence that dogs or cats are a source of S. pyogenes for people, although the possibility cannot be completely dismissed, but the suggestion still persists in the less well informed medical literature.^176,177

When domestic pets come into close contact with infected individuals, some pets may apparently develop pharyngeal colonization with group A streptococci. Infected pets show no clinical illness or tonsillar enlargement and usually lose their infection within 2 to 3 weeks after they are removed from the household. Infected people are carriers of group A streptococci for much longer periods.¹⁷¹ It is not acceptable to consider culturing and treating a dog and/or cat in a household in which reinfection occurs without doing so for the human contacts. See Chapter 99 for a further discussion of this zoonotic infection in humans.

The recovery of group A streptococci is affected by the method used when swabbing the throat, because overgrowth by indigenous microflora can result in the death of group A streptococci. Sedation may be needed, because sterile swabs should be rubbed over the surface of the exposed tonsils in their crypts. Swabs that are unrefrigerated during transport should be kept dry, otherwise overgrowth by contaminating microflora occurs. Latex agglutination and enzyme-linked immunosorbent assay tests are available for rapid detection of group A streptococci in children. Their value in detection of asymptomatic group A infections in dogs and cats is likely to be low.

The spectrum of effective antimicrobials for treatment of group A streptococcal infection in pets is the same as that for human strains. It is judicious to treat pets when they may be a source of recurrent infection of household members. Isolates of group A streptococci from dogs have shown the greatest susceptibility to penicillin, erythromycin, and chloramphenicol. Recommended total daily dosages are listed in Table 33-2. Resistant strains can be treated with cephalosporins.

Streptococcus pneumoniae

Streptococcus pneumoniae can produce pneumonia, bacteremia, otitis media, endocarditis, and meningitis in people but is of uncertain significance in dogs and cats. Although it possesses no Lancefield antigens, it is mentioned in this section because, like S. pyogenes, it is almost exclusively a human pathogen. A single report of bacteremia and septic arthritis in a cat attributed the infection to transmission of S. pneumoniae from a human infant in the same household.¹⁹⁴ Necrotizing fasciitis caused by S. pneumoniae was reported in a cat that received trauma while playing with children.²⁴⁹ A French bulldog developed hyperesthesia and central vestibular disease from meningoencephalitis caused by S. pneumoniae.⁹³

Dogs

Group G streptococci are the major streptococcal type isolated as commensal flora from the skin and mucosa of dogs.17,18 The majority of group G isolates from dogs are S. canis. Nevertheless, some group G isolates have the biochemical characteristics of human group G streptococci. More work is needed to define the biotypic variation within S. canis and the identity of unusual group G streptococci isolated from dogs. Historically, the veterinary literature has contained numerous reports of diseases in dogs caused by these organisms, including abortion, infertility, sterility, and neonatal death. In addition, cellulitis, keratitis, mastitis, pharyngitis, arthritis, pericarditis, tonsillitis, pneumonia, polysynovitis, necrotizing fasciitis, endocarditis, cholangiohepatitis, meningoencephalitis, and genital infections have been described (see Table 33-1). Metaphyseal osteomyelitis may occur in growing pups.⁶⁶ Some of the historical descriptions of disease, especially pharyngitis, tonsillitis, infertility, and sterility, caused by group G streptococci should be carefully considered because of the frequency with which these organisms are isolated from clinically healthy animals and the lack of clear description of the microbiology of the infections. However, it is also likely that, as in other animals and in people, β-hemolytic streptococcal infections have declined in importance in the past 50 years with the widespread use of penicillin and its derivatives.

S. canis is generally an opportunistic pathogen of dogs and is isolated from an array of nonspecific infections, including genitourinary tract, wound, mammary gland, and skin (especially otitis externa). In addition, it may cause bacteremia or septicemia and polyarthritis in neonatal puppies, forming part of the fading puppy syndrome, in which the pup is predisposed because of lack of warmth, improper navel disinfection, and lack of nursing. Infection in these pups may come from microflora or the environment; no correlation was found between the organisms found in the milk of bitches with those isolated from dead septicemic pups.¹⁷⁹ Group G streptococci have also been associated with a rapidly progressive systemic infection in older dogs (see streptococcal toxic shock syndrome discussion in this chapter). S. canis is a common commensal of the genital tract. It may be an opportunistic organism associated with vaginitis, but its historical role in infertility in bitches is not supported by current findings. Historical but no current accounts exist of the association of this organism with acute tonsillitis and suppurative cervical lymphadenitis in dogs in kennels and other settings. Group G streptococci have also been isolated from the cerebrospinal fluid (CSF) of dogs with meningoencephalomyelitis as a result of hematogenous spread or penetrating injuries.²⁸ Polymerase chain reaction (PCR) has been used to detect these organisms in CSF of a dog with bacterial meningoencephalitis.¹⁴² Space-occupying abscess formation may occur within the confines of the central nervous system (CNS) in some cases. Results of CSF analysis are marked pleocytosis (usually greater than 100 cells/µL) with a predominance of neutrophils and in some cases, intracellular bacterial cocci. Antimicrobial choices for group G infections are similar to that for group A streptococcal infections (see Tables 33-2). Organisms of this group are generally susceptible to erythromycin, clindamycin, and penicillin (as well as other β-lactams). Aminoglycoside susceptibility is variable. Although highly effective, vancomycin use is not recommended, because it is reserved for resistant human infections. For CNS infections, therapeutic options include high-dose intravenous penicillins, trimethoprim-sulfonamide, clindamycin, or intravenous third-generation cephalosporins (see Bacterial Infections of the Central Nervous System, Chapter 91).

Invasive Infections: Streptococcal Toxic Shock Syndrome and Necrotizing Fasciitis and Myositis

The past decade has had a resurgence of severe invasive group A human streptococcal infections characterized by septic shock associated with multiple organ failure and with or without necrotizing fasciitis and myositis (NFM) (Box 33-1).⁸⁷ In dogs and cats, S. canis is usually responsible for this syndrome. With NFM, bacteria at the inoculation site synthesize proteolytic and other products that facilitate the organism’s spread via fascial planes and into muscles. Periosteal involvement, adjacent to involved muscle, has also been reported.¹⁰⁸ S. canis isolates that resisted phagocytosis were examined for virulence genes comparable to those found in group A (S. pyogenes) human isolates. Only M-protein genes associated with surface fibrillar material and streptolysin O genes were identified in most of the canine isolates.⁵⁰ Increased invasiveness of streptococci correlates with a change in the M-protein, which inhibits phagocytosis by neutrophils and macrophages. Once the streptococci develop this new protein, they can enter the body and avoid host defenses.

Multiple organ involvement in streptococcal toxic shock syndrome (STSS) suggests that a toxin produced by the pathogenic bacteria might also be involved in the pathogenesis.¹⁶⁴ Bacterial superantigens, a family of highly mitogenic proteins secreted by the organisms, are suspected. Superantigens simultaneously bind to major histocompatibility complex class II molecules and T-cell receptors, resulting in sudden high cytokine levels. In vitro, enrofloxacin (a quinolone) caused bacteriophage-induced lysis of an S. canis strain that had been isolated from a dog with STSS.⁹² Bacteriophage induction was associated with an enhancement of expression of a superantigen gene relative to the same organism in noninduced cultures. The presence of this gene on enrofloxacin-induced bacteriophages may explain the association between this drug treatment and the occurrence of STSS in dogs. Most of the dogs reported with this type of infection had received enrofloxacin in the early stages of disease; however, the drug was not effective in halting the progression of the disease, despite in vitro susceptibility in some cases. In fact, enrofloxacin may have been responsible for triggering the pathologic events caused by these virulent streptococci.

The dramatic and severe multisystemic STSS and locally invasive NFM group A streptococcal infections in people have been dubbed toxic shock infections and flesh-eating bacterial infections, respectively, in the popular media. A similar clinical picture caused by various isolates of S. canis has been identified in dogs* and cats.^{157,202,206,234,249} In most cases, affected animals were previously healthy adult dogs or cats younger than 1 year of age. The dogs had a history of mild trauma, bite wound, or respiratory disease or UTI. Affected kittens had suppurative lymphadenomegaly typical of group G infection. In addition, they had multifocal purulent ulcerative skin lesions. They were generally depressed but afebrile.²³⁴ All the dogs were febrile (40° C to 41° C [104° F to 105.8° F]) at admission. Dogs with NFM had severe, rapidly developing cellulitis, usually of a limb, but in one case it occurred in the ventral thorax. The most consistent clinical sign in the history and on physical examination was intense, excruciating pain localized around the affected area but sometimes involving the whole body. Localized heat and swelling were identified at presentation or within 2 days of hospitalization. Once evident, the cellulitis developed rapidly (Fig. 33-4). A left shift, with variable leukocyte count and toxic granulation, is frequent. Serum creatinine kinase activities are usually increased in cats with muscle involvement. Colonies of streptococci in chains can be readily demonstrated in fluid aspirated from the cellulitis or in underlying tissues or internal organs by histopathologic examination (Fig. 33-5). Pulmonary interstitial or alveolar densities resulting from bacterial or hypercoagulable emboli may be detected with thoracic radiography. Cytologic examination of fine-needle aspirates from swollen areas is essential to speed confirmation of infection and institute early appropriate antimicrobial therapy, because virulent strains of gram-negative bacteria can also cause this syndrome.²⁴⁴ Bacteriologic culture should also be performed on portions of the aspirated material; however, results are often delayed. Dogs with NFM were extremely depressed when examined and eventually went into shock. They had extensive exudate accumulation along fascial planes. The fascia required surgical debridement. In two dogs, acute onset of posterior paresis with lower motor neuron deficits developed because of the presence of septic emboli in blood vessels of the gray matter of the spinal cord and because of extension of infection into the surrounding connective tissue, muscle, and peripheral nerves.

Other dogs with severe invasive S. canis infection developed STSS without clinically apparent NFM. The dogs with STSS had severe depression, fever, and rapidly developing hypotension and shock. In most, the lungs were considered the primary site of infection, and acute infection appeared to be superimposed on chronic preexisting pulmonary infection. In one dog a UTI was the presumed source.¹⁴⁴ Similarly, cats with STSS that did not develop NFM had bacterial embolic localization with lesions in the lungs, heart, and liver.²⁰⁶

Some cats with NFM responded favorably to treatment with amoxicillin-clavulanate, supportive care, and wound management with topical antibacterial application, whereas in other cases, the cats were moribund or dead.²³⁴ The dogs with STSS died or were euthanized within 48 hours of hospitalization, but those with NFM survived. All dogs had full-thickness skin sloughs and required aggressive debridement of necrotic tissue, incision of fascia of affected muscles, appropriate antibacterial treatment, and intensive supportive medical care (crystalloids, colloids, plasma, low-dose heparin) aimed at treating shock with disseminated intravascular coagulation. Intravenous plasma has been used in people to control hypotension and neutralize bacterial toxins.¹⁰³ Intravenous IgG therapy has also shown some benefit in clinical improvement and reduction of mortality in treated versus control human patients.^39,198 Less commonly, glucocorticoid treatment was used. More appropriate antibacterials for treatment of this condition are penicillin G, aminopenicillins (ampicillin, amoxicillin), erythromycin, and clindamycin. In human STSS or NFM, clindamycin is regarded as the drug of choice. In addition to its antibacterial activity, clindamycin is a potent suppressor of bacterial toxin synthesis, inhibits M-protein synthesis (which facilitates phagocytosis), and suppresses lipopolysaccharide-induced monocyte synthesis of TNF.¹⁹⁶ The authors (CEG and JFP) have found this drug to be valuable in the treatment of affected pets. Surviving animals often must have extensive skin grafting or dermoplasty to close open wounds created by the necrotic process.

Public Health Considerations

In general, public health risks from S. canis colonization of infection in dogs or cats are low. Only rarely have people been infected with this organism.69,233 Nevertheless, when veterinarians drain and debride NFM lesions, they should recognize the extreme risk of inadvertent infection of cuts on their hands. This risk can probably be contained by wearing latex gloves and protective clothing when handling dogs with STSS or NFM. One report has been made of this syndrome in a person; the source was group G streptococci.²²⁷ Group G streptococci are normal inhabitants of the skin, oropharynx, GI tract, and female genital tract of people but are rarely S. canis. Asymptomatic pharyngeal carriage of group G streptococci is found in up to 23% of people. The organisms commonly colonize human skin, and approximately 5% of asymptomatic puerperal women harbor them on the genital mucosa. Group G streptococcal infections in people are not common and involve primarily dermatitis and pharyngitis; however, bacteremia and septicemia, endocarditis, peritonitis, peripheral sepsis, soft-tissue infection, and septic arthritis are unusual.

There is no evidence that dogs and cats are a significant source of infection for humans,21,69 although human infection with S. canis presumably acquired from animals may sometimes occur In this report, dogs were mentioned as a possible source of group G streptococcal arthritis in people, but the association was speculative. The source of infection was more likely autogenous. In one report of meningitis,⁹⁵ the isolate was not completely characterized. In another report, S. canis was isolated from the blood of a person with septicemia.¹³ The organism was specifically typed on the basis of biochemical and genetic analysis. It was presumably transmitted from the family dog and colonized the varicose ulcers of the person’s legs. Similar wound infections were reported in three dog owners.¹¹² One had concurrent S. canis bacteremia and another had concurrent infection with Pasteurella multocida. The occurrence of such infections probably involves close contact between the animal and open skin wounds. Routine hand washing after animal contact and not allowing dogs to lick people, especially their wounds, are always advisable.