A technician's guide to antibiotic usage in orthopedic cases (Proceedings)

As a referral veterinary surgeon working closely with private practitioners over the last 25 years I have noticed that there are a number of questions regarding common surgical conditions that occur frequently.  Many years ago I began accumulating these questions in a file.  The purpose of this lecture is to open the file, and see if we can answer as many of these questions as possible.  I will present common orthopedic conditions tomorrow, so tonight is directed at soft tissue topics.  Possible general topics/issues include mammary tumors, anal gland tumors, ear canal problems in cats, pawpaw lesions, bladder tumors and management of pain in pets after aggressive soft tissue surgery.

History

The search for antibiotics began in the late 1800's, with the growing acceptance of the germ theory of disease, a theory that linked bacteria and other microorganisms to the causation of a variety of ailments.  Although several early antibacterial agents were identified, it was Alexander Fleming's discovery of the antibacterial properties of the penicillium mold in 1928 that would revolutionize modern medicine.  While Fleming made the initial discovery, he was never able to purify significant quantities of penicillin, and it wasn't until the 1940's that other scientists in the United States and United Kingdom we able to develop methods to mass-produce the drug.  Initially penicillin was used almost exclusively to treat soldiers injured in WWII, but by the end of the war in 1946 the drug had become widespread for clinical use. Penicillin was in fact available without prescription until the mid 1950's.

Resistance

Indiscriminate and inappropriate use of antibiotics results in rapid development of bacterial resistance.  While resistance can occur by many different mechanisms, consider the case of penicillin.  Penicillin and penicillin-like antibiotics all have a B-lactam ring as part of their chemical structure.  Unfortunately, certain bacteria are able to produce a protein  (B-lactamase ) that destroys the B-lactam ring, rendering penicillin ineffective.  When penicillin is given to a patient, bacteria that are not able to produce B-lactamase are quickly killed, but those that are able to produce B-lactamase survive and reproduce. Eventually, only bacteria resistant to the effects of penicillin are present in the environment, and the antibiotic is completely useless.

While one human hospital reported about 14% of strains of staph were resistant to penicillin in 1946, the same hospital reported 59% of strains were resistant by 1950.  Scientists have attempted to combat this problem in several ways. One method is to chemically modify penicillin to produce B-lactamase resistant drugs (ampicillin and cephalosporins).  Another method is to create antibiotics that do not have a B-lactam ring (chloramphenicol, tetracycline, sulfonamides, fluoroquinolones, and aminoglycosides).

Specific antibiotics

The plethora of antibiotics available on the veterinary and human market makes an in-depth understanding of all of them impossible.  The trick is to know a few basic features about the most commonly used drugs that are important in clinical decision making.  Specific features of importance include whether the drug is bactericidal or bacteristatic, cost, spectrum, route of elimination, and specific toxicities.

Table 1. Classification of operative wounds in relation to contamination Clean Non-traumatic, elective procedure   No acute inflammation encountered   No break in aseptic technique Clean contaminated Entry into the gastrointestinal, urogenital, or respiratory tracts with significant contamination   Minor break in aspectic technique Contaminated Fresh traumatic wounds (< 4 hours old)   Spillage from the gastrointestinal or urogenital tracts   Major break in aseptic technique Dirty (infected) Traumatic wound > 4 hours old or with devitalized tissue or foreign bodies   Perforated viscus encountered   Acute bacterial inflammation or pus encountered   "Clean" tissues transected for access to an abscess

Preventing Bacterial Resistance

Bacterial resistance exists as one of the major problems facing both the human and veterinary medical professions today.  Irrational and indiscriminate antibiotic usage for many years has created this situation.  Several important guidelines must be adhered to if this problem is to be curtailed.

1.              Antibiotic usage with the premise that “it can't hurt” is patently wrong.

2.              When the organism and sensitivity is known, use the least expensive, least toxic, most narrow spectrum antibiotic effective.

3.              Antibiotics should be given at full dose for at least 3 days before changing, and at least 3 days after clinical cure.

4.              Do not use an antibiotic as an antipyretic.  Fever does not mean infection

5.              Newer is not better.

6.              Broad spectrum is rarely better.

MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a newly emerging bacterial pathogen, and infections with MRSA are becoming an increasingly common problem in veterinary patients.  MRSA are resistant to all beta-lactam antibiotics and because of indiscriminate antibiotic usage have acquired resistance to many other antimicrobials including fluoroquinolones and aminoglycosides.  In humans, MRSA strains are classified as either hospital acquired (HA-MRSA) or community acquired (CA-MRSA). A 2007 report in Emerging Infectious Diseases, a publication of the Center for Disease Control (CDC), estimated that the number of MRSA infections treated in hospitals doubled nationwide, from approximately 127,000 in 1999 to 278,000 in 2005, while at the same time deaths increased from 11,000 to more than 17,000.

MRSA is transmitted through direct contact with an individual who is colonized with the bacteria, or contact with fomites in contaminated environments. Nasal passages, throat, and the skin surface are the most common areas colonized by MRSA. The CDC estimates about 1% of all people carry MRSA.  When veterinary personnel were studied at an international conference, both veterinarians and technicians were much more likely to be MRSA carriers than the general population

MRSA is a zoonotic pathogen. Studies have shown that it is possible for MRSA to move from humans to animals and from animals to humans. MRSA infections have been reported in many domestic animal species including dogs, horses, and cats, producing in many cases sub-clinical infections (colonization).  When a person or animal is healthy, MRSA often causes no significant illness. However, if a person or animal is immunocompromised (cancer, recent surgery, steroid therapy), has skin damage, or has undergone an invasive medical procedure, MRSA can cause illness; ranging from skin and superficial soft tissue infections to severe disease including bacteremia, pneumonia, urinary tract infections, or infection of a surgical site. Infections may be life threatening.

MRSA infection should be suspected in a dog when any condition is not responding to routine antimicrobial therapy and diagnostic testing indicates infection with Staphylococcus aureus. Specific conditions of worry include pyoderma, otitis externa, recurrent urinary tract infections, post-surgical wound infections, and persistent surgical implant or catheter-site infections.

MRSA is resistant to all beta-lactam antimicrobials in vivo, irrespective of the result of the in vitro susceptibility testing. Some strains of MRSA show resistance to all antimicrobials on routine susceptibility testing. Studies suggest that the antibiotics most likely to be effective against CA-MRSA are vancomycin and sulfa-trimethoprim.  HA-MRSA are even more resistant to multiple antibiotics, and only vancomycin appears to be uniformly effective.

If a MRSA case is identified, it is important to properly inform the client and other hospital personnel about the risks associated with this infection.  Untrained front-desk and kennel staff may be particularly worried.   If you have any concerns about a potential MRSA case, you should bring them to the veterinarians at your practice.     

Classification of surgical wounds

Surgical wounds and procedures have been classified by the National Research Council (NRC) as clean, clean/contaminated, contaminated, and dirty (Table 1).

Surgical prophylaxis

Surgical prophylaxis represents a special situation of antibiotic usage, in that the goal is to prevent, rather than treat infection.  In humans, antibiotic prophylaxis is recommended only for contaminated and clean-contaminated wounds, because data has not supported decreased infection rate if the procedure is clean.  In veterinary patients, there is great debate regarding the use of antibiotic prophylaxis in clean procedures.  The data is quite limited, so I prefer to use antibiotic prophylaxis even in clean procedures. 

Studies demonstrate repeatedly that if antibiotic prophylaxis is to be effective, the antibiotic must have therapeutic levels at the time the incision is made.  To accomplish this, the antibiotic must be given intravenously sometime between 30 and 60 minutes before surgery.  Antibiotics given by other routes or at different times have no effect on infection rates. In fact, if an antibiotic is given inappropriately not only does it not decrease the rate of infection, but if an infection does occur, it is more likely to be with a resistant organism.

Factors associated with infection in clean veterinary surgical procedures

The ONLY factor that has been consistently associated with infection rate in clean surgical procedures in veterinary patients is surgery/anesthesia time.  In one study, risk of postoperative infection was reported to double for every hour of operation.  In a second study, each minute of additional anesthesia time over 60-minutes was associated with a 0.5% increased risk of wound infection.  Factors that have been reported less consistently to increase surgical infection rates are propofol use, surgical sites clipped any time before anesthetic induction, older animals (> 8-years), and animals with body condition scores other than normal.       

Postoperative fever

A common clinical situation is the patient with a fever after surgery.  Fevers that occur within the first 24-36 hours after a surgical procedure do NOT indicate infection.  Bacteria require a period of time to reproduce and produce fever-inducing toxins.  If the temperature is elevated in the first two days after surgery, inflammation and pain are the most likely causes.  Fevers indicating surgical infection typically develop 3-4 days after surgery.

Antibiotic usage with open granulating wounds

Open granulating wounds are extremely resistant to developing deep tissue infection.  Topical application of an antibiotic generally decreases epithelialization, and systemic antibiotic usage increases bacterial resistance.

Anaerobic infections

Anaerobic bacteria are found primarily in areas with mucosal surfaces, such as the oral cavity and the urogenital and gastrointestinal tracts.  In the gastrointestinal tract, anaerobic bacteria greatly outnumber the aerobic bacteria.  Abscesses and chronic draining tracts are common sites for culture of obligate anaerobic bacteria.  More than 70% of the obligate anaerobic isolates are of the Bacteroides species.  In addition to appropriate antimicrobial therapy, treatment of anaerobic infections generally requires some form of surgical debridement or drainage to increase oxygen levels within the tissue.  Drugs of choice for anaerobic infections in veterinary patients are metronidazole and clindamycin.  Most anaerobic bacteria are NOT sensitive to fluoroquinolone or aminoglycoside antibiotics.