Rational Approach to Antimicrobial Therapy: The Gastrointestinal System
World Small Animal Veterinary Association World Congress Proceedings, 2003
Craig E. Greene
University of Georgia
Athens, GA, USA

Oral Cavity

The resident microbial flora of the canine and feline oral cavity is composed of a wide variety of both aerobic, and facultative and obligate anaerobic bacteria. From a clinical standpoint, bacterial culture of specimens from the oropharyngeal region is meaningless because of the diversity of commensal organisms and the lack of accurate quantitative methods. However, antimicrobial agents used in treating oral infections such as gingivitis and stomatitis should be chosen with the composition of the resident microflora in mind. Inflammation and recession of perialveolar gum margins, is a common finding in dogs and cats. Microflora involved with supragingival and subgingival plaque in healthy mucosal sites in dogs are generally gram positive; however, as periodontal inflammation progresses with associated calculus (tartar) formation, gram-negative motile, obligate anaerobic rods and spirochetes proliferate.

In cats, differences in the microflora between clinically healthy animals and those with gingivitis have not been appreciated.

Treatment includes the extraction of severely affected teeth, debriding necrotic or proliferative gum margins, and the scaling of calculus from the remaining involved dental surfaces. Systemic antimicrobials such as tetracycline, metronidazole, and tinidazole, and topical chlorhexidine have been evaluated for treatment of periodontitis in experimentally affected dogs. Tetracycline or metronidazole have been beneficial in reducing dental calculus or preventing its reformation when they have been used with or without mechanical cleansing. Flushing dental surfaces once daily with antibacterial solutions or brushing has also been effective. Preventative antimicrobial therapy may be needed during dental manipulations.

Gingivostomatitis and pharyngitis

Oral and pharyngeal ulceration may be a manifestation of systemic or immunosuppressive illness. Similar to periodontitis, motile (predominantly anaerobic) bacteria including spirochetes often proliferate and may invade tissues in advance of necrotic lesions.

Cats subclinically infected with FCV and feline rhinotracheitis virus may develop oral ulceration with or without respiratory signs following stress or immunosuppression such as with concurrent FIV infection. Hard, dry cat food also appears to have a role in exacerbating palatine ulceration in cats with acute FCV infection. The pattern of oral ulceration may be helpful in determining its underlying cause.

With ulcerative lesions underlying disease processes should be eliminated or treated when they are encountered. Topical or systemic antimicrobial therapy appears to hasten the resolution of NUG significantly, perhaps by inhibiting the overgrowth of anaerobic and spirochetal bacteria that colonize and impair healing of ulcerated lesions in the oral cavity. Historically, tetracycline, chloramphenicol, ampicillin, or penicillin solutions have been applied topically for bacterial stomatitis, although the first two drugs may cause anorexia in cats. Systemic antibiotic therapy directed primarily against anaerobic bacteria appears to be more efficacious in treating stomatitis. Relapse may occur in some cases following termination of antimicrobial therapy, and a repeated course of therapy may be required.

Esophagus and Stomach

The oral cavity and ingested material are the primary sources of microorganisms that colonize the lower portions of the GI tract. The oral cavity, esophagus, stomach, and proximal small intestine are colonized primarily by gram positive aerobic and anaerobic bacteria, which are usually susceptible to penicillin or its derivatives. For gastric helicobacteriosis, several antimicrobial and antacid preparations are administered. An in depth coverage of gastric helicobacteriosis is beyond the scope of this discussion.

Small Intestinal Infections

Concentrations of bacteria in the proximal small bowel are relatively low because of the influence of gastric acid and bile and gradually increase toward the ileocecal region. Excessive use of antacids, obstruction or stasis of intestinal or bile flow, or a decrease in mucosal or IgA secretions can result in bacterial overgrowth of the small intestine. Anaerobes are known to make up a majority of the intestinal microflora, greatly outnumbering aerobic bacteria. The duodenum and upper jejunum primarily harbor gram-positive bacteria, including streptococci and lactobacilli. Anaerobes and gram-negative organisms predominate in the distal portions of the small bowel and colon. Numbers of microorganisms reach their maximum in the cecum, colon, and feces. The GI tract is a known reservoir of microorganisms which under certain circumstances can spread by portal blood vessels or intestinal lymphatics to extraintestinal sites including the mesenteric lymph nodes, liver, spleen, pancreas and by the systemic circulation to other organs

Collection of fecal samples for culture of aerobic bacteria is easier when commercially prepared, sterile, cotton-tipped applicators are used. These are supplied with transport media or enrichment broth in which the swab is placed immediately following specimen collection. When organisms such as Salmonella, Shigella, Helicobacter or Campylobacter are suspected the laboratory can be notified because selective media or special cultural conditions may improve yields.

Antibacterial therapy is indicated in selected instances of intestinal disease where it is usually combined with supportive care such as dietary modification, fluid therapy, motility modifiers, and antiemetics. Antimicrobials should be used systemically when episodes of diarrhea or vomiting are accompanied by signs of systemic illness, including fever, depression, impending shock, and the presence of leukopenia or leukocytosis with a marked left shift, findings that indicate there has been absorption of microbes or, more likely, their toxins. The choice of drugs depends on a knowledge of the susceptibilities of both the usual pathogens and the normal intestinal flora.

Small intestinal bacterial overgrowth (SIBO) is a syndrome of bacterial proliferation in the upper intestinal lumen accompanied by chronic or recurrent small bowel diarrhea. Chronic SIBO may result in protein loosing enteropathy which can be controlled by antimicrobial therapy. Oxytetracycline and tylosin are recommended for dogs and metronidazole for cats. Because of the development of overgrowth in some dogs with PEI, antimicrobial therapy may be required in those that do not respond to enzyme supplementation alone.

Inflammatory bowel diseases. Chronic intestinal inflammation, characterized by bowel inflammation, have been attributed to pathogenic microorganisms There are also numerous helminthic and noninfectious causes for these inflammatory intestinal disorders. Therapy of lymphocytic plasmacytic enteritis is very similar to that of chronic colitis which is covered under that section later.

Large Intestinal Infections

The cecum and colon are the richest source of intestinal microflora. Anaerobic bacteria, which usually compose more than 90% of the colonic microflora, include clostridia, lactobacilli, Bifidobacterium, and Bacteroides. Aerobic or microaerophilic bacteria primarily consist of streptococci, members of the Enterobacteriaceae, and spirochetes. Colitis, whether acute or chronic, usually involves the microflora as a secondary phenomenon.

The antibiotics that have been useful in treating canine and feline ulcerative colitis are primarily those that are effective against anaerobic bacteria. The lesions usually do not resolve spontaneously. Drugs that have been most effective in dogs and cats include oral sulfasalazine, oral chloramphenicol, and oral metronidazole.

Pancreatitis

Pancreatic infection by bacteria develops in less than10% of humans with acute pancreatitis but up to 40% of those with severe pancreatitis. Bacterial contamination may arise from hematogenous spread from the systemic circulation, duodenal reflux up the pancreatic duct, contamination from the biliary tree or bacterial translocation from the lower bowel via the portal circulation. Common enteric organisms are usually involved causing secondary infection of acutely inflamed or necrotic pancreatic tissue. In dogs with acute experimental pancreatitis, significant differences in bioactive levels were found between antibiotics in pancreatic tissue. Ampicillin, gentamicin, and cefazolin reached therapeutic levels in blood, but not in normal or inflamed pancreatic tissue. Of other drugs tested, clindamycin, metronidazole, and chloramphenicol achieved penetrance in normal and inflamed pancreas.

Hepatobiliary Infections

Cholecystitis and cholangiohephalitis are the most common infectious disorders of the biliary system in small animals. Broad spectrum antibiotics reaching high concentrations in the bile should be considered. Organisms usually responsible for these infections include aerobic coliforms and occasionally anaerobic bacteria. Antibiotics which are effective include ampicillin (broad spectrum), clindamycin (anaerobes) and cephalosporins (gram positives). These may be considered immediately prior and during hepatobiliary surgery where infection has been established to lessen the risk of contamination. However, if evidence of severe biliary obstruction is present then antibiotics excreted primarily in the bile such as nafcillin, clindamycin, erythromycin, doxycycline, chloramphenicol and rifampin should be avoided. When a hepatic abscess is likely, the drainage should be performed at surgery followed by the use of kanamycin and clindamycin since these are concentrated in hepatic tissues.

Peritonitis and intra-abdominal abscesses

Peritonitis and intra-abdominal abscess formation are frequent complications of intestinal perforation caused by postsurgical wound dehiscence of the GI tract, foreign bodies, severe ulcerative enteritis, penetrating abdominal wounds, or rupture of abscesses of intra-abdominal organs. Antibiotic therapy is important in the management of intra-abdominal infections. Organisms in all cases are a mixture of facultative anaerobic bacteria, usually Enterobacteriaceae, and obligate anaerobes. A combination of antimicrobial therapy and surgical drainage is required for treating most cases of intra-abdominal infection. Drugs such as aminoglycosides or fluoroquinolones have been recommended because of their effect against gram-negative bacteria. Drugs effective against anaerobic bacteria such as clindamycin are needed to control abscesses and adhesions that result from these organisms. Antimicrobial drugs or combinations used in treating intraabdominal sepsis must be effective against both aerobic and anaerobic intestinal flora to decrease both mortality and abscess formation following peritonitis. Regimens in which a third generation cephalosporin is substituted for the aminoglycoside or metronidazole is substituted for clindamycin give similarly favorable results.

Speaker Information
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Craig E. Greene
University of Georgia
Athens, GA, USA


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