Introduction

Critically ill dogs and cats may require antimicrobials if their underlying disease process is bacterial in origin, or if they have developed bacterial infections secondary to immunosuppression or medical interventions. However, the indiscriminant use of antimicrobials in every critically ill patient is inappropriate, and will contribute to bacterial resistance in your hospital. This presentation will cover reasonable criteria for instituting empirical antimicrobials in the critical care unit, protocols for managing nosocomial and resistant infections and rational use of prophylactic antimicrobials prior to surgery.

Criteria for Antimicrobial Use in the Critically Ill Patient

There are three major questions that need to be addressed in antimicrobial decision-making:

 Is there good clinical evidence of a bacterial infection?

 If so, what are the likely organism(s) involved?

 Will my chosen antibiotic reach the site of infection?

The first two questions can be addressed by physical examination findings, urine sediment, imaging and cytology of any cavity effusions. The third question is important for infections in privileged sites, such as the central nervous system, eye, prostate or testes. Antimicrobials should be chosen that penetrate these sites, such as fluoroquinolones, doxycycline, potentiated sulphonamides or chloramphenicol. In addition, if an infection is necrotic or abscessed, aminoglycosides will have poor activity in the presence of high calcium (tissue necrosis) or acidic pH (abscess).

In dogs and cats with evidence of sepsis (fever, hypovolaemia, hypoglycaemia), Escherichia coli is the most common organism cultured; however, blood and/or urine cultures are important to guide long-term treatment. In the meantime, identifying the potential source of sepsis (e.g., aspiration pneumonia (mixed organisms), or an ingested carcass (anaerobes)) can narrow the likely organisms involved (Figure 1).

In patients with fever and neutropenia (especially 1 x 10⁹/l), such as dogs with parvovirus or patients undergoing chemotherapy, coverage should be aimed at bacteria that translocate from the gut, to include gram-negative enterics, anaerobes, and Enterococcus spp. This typically requires more than one drug; for example, ampicillin (which covers many anaerobes and also Enterococcus) and a fluoroquinolone (which covers most gram-negative enterics).

Figure 1. Common isolates from life-threatening bacterial infections in dogs and cats.

Optimising Antimicrobial Dosing

Beta lactam antibiotics exhibit time-dependent killing; bacterial kill is optimised when tissue concentrations are maintained above the organism's minimum inhibitory concentration (MIC) for the majority of the dosing interval. Therefore, some beta lactams with relatively short half-lives, such as ticarcillin and ceftazidime, need to be given as a continuous rate infusion. This is particularly important in an immunocompromised patient or in the presence of an organism with a high MIC.

Aminoglycosides exhibit concentration-dependent killing, such that higher peak serum concentrations (obtained with q24h dosing) are associated with greater bacterial kill. Aminoglycosides should therefore be given once daily in most circumstances. Once daily dosing is associated with less toxicity in some animal models; this is because lower urinary concentrations at the end of the dosing interval means less uptake into renal tubular cells. Aminoglycoside use should be accompanied by daily urine sediment evaluation for granular casts; treatment should be limited to 3–5 days, if possible, to limit nephrotoxicity.

Like aminoglycosides, fluoroquinolones also exhibit concentration-dependent bacterial killing, and have a post-antibiotic effect for many bacteria. Therefore, once- daily dosing is recommended in order to reach high peak plasma concentrations. Ciprofloxacin has increased activity towards Pseudomonas compared to enrofloxacin, but it is not as well absorbed (enrofloxacin has approximately 50% bioavailability; ciprofloxacin, approximately 10% bioavailability in dogs). However, ciprofloxacin can be given intravenously to dogs (5–20 mg/kg i.v.) to target organisms with an MIC of 1–2 µg/ml. Seizures may result from high doses of enrofloxacin or ciprofloxacin given intravenously, so use caution and infuse the drug slowly over 30 minutes.

Treatment of Resistant Bacterial Isolates

Hospital-acquired, or nosocomial, infections are defined as those that develop after 48 hours or more of hospitalisation. Typical routes of infection are intravenous catheters, open wounds and the lower urinary tract (particularly in patients with indwelling urinary catheters). Because nosocomial infections are acquired from hospital flora, these organisms are more likely to be resistant to antimicrobials that are commonly used in the unit.

Critically ill patients are also more likely to present with resistant bacterial infections, since they have often been treated with other antimicrobials prior to presentation. Therefore, localisation of the source of infection, with culture and sensitivity, is important in critical patients. If possible, it is helpful to obtain MICs with your sensitivity results; you may need to ask for additional antimicrobial sensitivities before you can compare all available antimicrobial options for potential side effects, cost and convenience. Figure 2 provides guidance on which additional sensitivities to request for common resistant isolates.

Figure 2. Antimicrobial options for resistant bacterial infections in dogs and cats.

Perioperative Antimicrobial Use in the Critical Patient

Prophylactic antibiotics are indicated for certain surgical procedures and in patients with individual risk factors for infection. In other situations, perioperative antimicrobials are not rational, will add to the cost of hospitalisation, may lead to gastrointestinal upset and can encourage the selection of resistant bacteria.

Procedures of short duration that do not enter a contaminated viscus do not require antibiotic prophylaxis. Examples of this include ovariohysterectomy, castration and uncomplicated splenectomy. However, even short surgical procedures that enter the gastrointestinal, lower urinary or upper respiratory tracts require prophylaxis to prevent infection of the surgical site. For these situations, the following recommendations are the standard of care in humans:

 Parenteral antimicrobials within 1 hour before incision

 Re-dosing every 1–2 elimination half-lives during prolonged procedures

 For most procedures, discontinue prophylactic antimicrobials after wound closure.

In addition, prolonged anaesthesia alone has been correlated with an increased risk of postoperative infection in dogs and cats. This may be due to hypothermia, hypo-tension and decreased tissue perfusion. According to one study of more than 1000 surgeries in dogs and cats in Switzerland, infection risk doubles for every 70 minutes of surgery. In addition, the presence of devitalised tissue or tissue desiccation also increases the risk of postoperative infection. Therefore, surgeries with an anticipated prolonged duration (> 60–90 minutes), such as major fracture repair or reconstructive surgery, or surgeries involving substantial tissue trauma, require prophylaxis even if a contaminated viscus is not entered (Figure 3).

Figure 3. Procedures in critical patients, with recommended perioperative antimicrobial prophylaxis.

Other Strategies to Minimise Acquired Infections in Critical Patients

The most important, but often neglected, step in preventing opportunistic infections in critical patients, or in preventing spread of infection from one patient to another, is hand washing. Keep hand sanitisers throughout the clinic, and adhere to the protocol of having all personnel wash hands or use hand sanitiser before and after every patient. Have all staff use examination gloves, every time, when placing catheters or examining wounds. Other measures that have been shown to decrease infection rates in the hospital are minimising duration of indwelling urinary catheters, avoiding antibiotic prophylaxis during indwelling urinary catheterisation, consistent hygiene during intravenous catheter placement and maintaining patient core body temperature during anaesthesia.