Department of Medicine & Epidemiology, University of California-Davis, Davis, CA, USA
Streptococci and enterococci are gram-positive cocci that occur in pairs and chains. They are facultative to strict anaerobes. Over 40 species of Streptococcus exist that vary in host tropism and virulence properties. β-hemolytic streptococci cause complete lysis of red blood cells and result in a zone of clearing around the colony on blood agar. α-hemolytic streptococci reduce hemoglobin, causing a green discoloration of the agar around bacterial colonies. γ-hemolytic or non-hemolytic streptococci do not produce hemolysis. Pyogenic streptococci are β-hemolytic streptococci that belong to Lancefield groups A (Streptococcus pyogenes), B (Streptococcus agalactiae), C (includes Streptococcus dysgalactiae and Streptococcus equi subsp. zooepidemicus) and G (includes Streptococcus canis). Viridans streptococci are often non-hemolytic or α-hemolytic and are often commensal organisms that have low virulence. Many Group D streptococci have now been classified as Enterococcus.
Streptococci typically invade tissues opportunistically when there is a breach in normal host barriers and cause a variety of disease manifestations, such as pyoderma, pneumonia, endocarditis, arthritis, osteomyelitis, meningoencephalitis, cellulitis and UTIs. Severe and life-threatening manifestations of streptococcal infection include necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). STSS is any streptococcal infection associated with the sudden onset of shock and organ failure. Shock and organ failure results from elaboration of pyrogenic exotoxins by streptococci, which cause fever and act as superantigens. Superantigens stimulate T cell responses by binding to, and cross-linking, the MHC class II complex of antigen presenting cells, and the T cell receptor, which bypasses normal MHC-restricted antigen processing. This leads to massive cytokine release, with signs of fever, vomiting, and hypotension, together with tissue damage, DIC, and multiple organ dysfunction. Death can occur within 48 hours after the onset of illness.
NF is a bacterial infection of the deep subcutaneous tissues and fascia, characterized by extensive necrosis and gangrene of the skin and underlying tissues (‘flesh-eating bacteria’), which can begin as a small wound and progress rapidly over 24 to 72 hours, sometimes accompanied by STSS. Lesions usually involve a limb, and are intensely painful, with accumulation of exudate along fascial planes that requires drainage and debridement. Outbreaks of NF, arthritis, sinusitis and meningitis caused by S. canis have been reported in cats in shelters and breeding colonies.
S. canis is the most frequently isolated streptococcal species from dogs and cats. It colonizes the skin, genital and gastrointestinal tracts of healthy dogs and cats. Infection with S. canis may be associated with neonatal bacteremia, pharyngitis, cervical lymphadenitis, bacteremia and endocarditis, UTIs, wound infections, otitis externa, bronchopneumonia, pyometra or metritis, meningoencephalitis, NF, STSS, necrotizing sinusitis, pyothorax, discospondylitis, arthritis, osteomyelitis, mastitis, cholangiohepatitis and peritonitis. Although opportunistic infections with S. canis occur sporadically, outbreaks of Group G streptococcal infection have been reported in group-housed animals, which have suggested spread of virulent strains.
Severe manifestations of S. canis infection, such as STSS and NF, have been increasingly described in dogs and cats in recent years, sometimes in the absence of obvious immunosuppressive underlying conditions or wounds. Little is known about virulence factors of S. canis. A protein analogous to M protein, a major virulence factor of S. pyogenes, has been identified in S. canis.
Streptococcus equi subspecies zooepidemicus
S. equi subsp. zooepidemicus is a commensal of the upper respiratory and lower genital tracts of horses, and can cause disease in dogs and cats. Different strains of S. equi subsp. zooepidemicus exist. Infected horses may have been a source of infection for some dogs.
Several outbreaks of S. equi subsp. zooepidemicus hemorrhagic, fibrinosuppurative, and necrotizing pneumonia have been described in group-housed dogs. The pneumonia can progress rapidly and been accompanied by signs suggestive of STSS. In some dogs, death occurs within 48 hours of the onset of respiratory signs. Other infected dogs have shown only mild signs of upper respiratory disease. Chronic lymphoplasmacytic rhinitis, sometimes with turbinate lysis in association with S. equi subsp. zooepidemicus infection has also been described in several dogs, which resolved after specific antimicrobial treatment. Outbreaks of pneumonia, rhinosinusitis and meningoencephalitis have also occurred in cats.
The pathogenesis of S. equi subsp. zooepidemicus in dogs and cats is still unclear. Co-infection with other contagious respiratory pathogens and bacterial virulence factors may contribute to the severity of disease. Other environmental factors such as overcrowding may also contribute to stress and severe disease manifestations.
Other Streptococcal Species
Other streptococcal species reported to cause disease in dogs and cats are S. dysgalactiae, Streptococcus suis, Streptococcus constellatus, Group B streptococci (S. agalactiae), and S. bovis group organisms (now reclassified as Streptococcus gallolyticus and Streptococcus infantarius).
Enterococci are commensals of the gastrointestinal tract of humans and other animals, and important nosocomial pathogens. Enterococci survive harsh environmental conditions and are often resistant to a wide variety of different antimicrobial drug classes. Multidrug resistant enterococcal infections, especially those that are resistant to vancomycin (vancomycin-resistant enterococci or VRE) are a significant problem in human medicine. Resistance among enterococci occurs as a result of both intrinsic and acquired resistance mechanisms. Intrinsic resistance to low levels of most β-lactam antimicrobials occurs because enterococci possess low affinity penicillin binding proteins. In addition, all enterococci have intrinsic resistance to cephalosporins. Enterococci also have low-level intrinsic resistance to aminoglycosides, which results from decreased drug uptake. However, uptake of aminoglycosides is enhanced when enterococci are exposed to β-lactams, which explains the synergistic activity of this combination. Enterococci are also resistant to trimethoprim-sulfamethoxazole because they utilize exogenously produced folate. Enterococcal resistance to other antimicrobials, such as macrolides and vancomycin, results from acquired resistance mechanisms.
E. faecium is more likely to show high-level resistance to penicillins and carbapenems than E. faecalis. However, E. faecalis is more likely to produce biofilms than E. faecium. An increase in the prevalence of multidrug resistant E. faecium infections has occurred in human medicine.
In healthy dogs and cats, enterococci can be found on the skin and within the oral cavity, nasal cavity and gastrointestinal tract. Although less pathogenic than many streptococci, enterococci possess virulence factors that enable them to invade tissues and cause disease. Their ability to form biofilms means they can be difficult to eradicate.
Because enterococci are intrinsically resistant to a number of antimicrobials, treatment with broad-spectrum antibiotics may select for gastrointestinal colonization by enterococci. Enterococci can contaminate the hospital environment and survive for long periods on fomites. Inoculation may occur via urinary, intravenous, or other invasive devices. Enterococci can be isolated from dogs and cats with UTIs, cholangiohepatitis, pancreatitis, hepatic abscesses, peritonitis, mastitis, bacteremia and endocarditis, wound infections, and diskospondylitis. There have been rare reports of gastrointestinal illness in association with Enterococcus infection in dogs and cats.
In general, Streptococcus spp. infections should be treated with a β-lactam drug. In animals with severe disease, initial treatment should be with a broad-spectrum antimicrobial drug combination, such as a β-lactam and an aminoglycoside. Prompt surgical exploration and debridement is of critical importance for NF. Aggressive fluid resuscitation with crystalloids and blood products may also be required. In human patients, NF and STSS are treated with both high-dose penicillin and clindamycin. This is because clindamycin suppresses exotoxin production by GAS, is more active than penicillin in experimental NF, and has a longer half-life than penicillin, but clindamycin resistance exists in some GAS, whereas all GAS remain susceptible to penicillin.
Meningitis/meningoencephalitis. Penicillins typically have limited CSF penetration. Trimethoprim-sulfamethoxazole was used with apparent success to treat some dogs and cats with streptococcal meningitis. Ceftriaxone has been used as an alternative to benzylpenicillin for treatment of human streptococcal meningitis.
Enterococcal infections. Aminopenicillins such as ampicillin generally have more potent activity against enterococci than penicillin or carbapenems. Bactericidal regimens should be used for treatment of systemic infections such as endocarditis or bacteremia, which consist of a β-lactam and gentamicin. Enterococci are usually resistant to aminoglycosides at dilutions used in routine broth microdilution methods (low-level resistance). When the synergistic combination of an aminoglycoside and penicillin is indicated, but low-level resistance is present, isolates can be tested for high-level resistance (HLR) to aminoglycosides. Aminoglycoside HLR has been reported in E. faecium and E. faecalis isolated from dogs and cats. When enterococci are penicillin resistant, the glycopeptide vancomycin can be substituted, but this requires prolonged hospitalization for intravenous administration. Single-agent treatment with linezolid represents an oral alternative. However, resistant strains have appeared. Chloramphenicol may be successful for treatment of resistant enterococcal bloodstream infections when administered orally, but is bacteriostatic and concerns regarding adverse effects exist.
Nitrofurantoin has been useful for treatment of resistant enterococcal UTIs in humans, and routine treatment of MOR enterococcal UTIs that are not accompanied by clinical signs of lower urinary tract disease is not recommended. When enterococci are present with other bacteria, especially in the urinary tract, anecdotal evidence suggests that treatment of the nonenterococcal pathogen may be sufficient to resolve the infection.
Appropriate shelter and kennel management and hygiene, as well as vaccination against other respiratory pathogens, may help to prevent streptococcal infections. Resistant enterococcal infections may be prevented through restricted and appropriate use of antimicrobial drugs and management of underlying disorders that predispose to bacterial infections.