Feline pyothorax - new insights into an old problem_part 2. Treatment recommendations and prophylaxi

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Review

Feline pyothorax – new insights into an old problem: Part 2.

Treatment recommendations and prophylaxis Vanessa R. Barrs *, Julia A. Beatty Valentine Charlton Cat Centre, Faculty of Veterinary Science, University of Sydney, Sydney NSW 2006, Australia Accepted 19 March 2008

Abstract Until recently, pyothorax in the cat has been generally considered to have a poor prognosis. However, it has become clear that most cats that survive the first 48 h following presentation can be successfully treated with aggressive medical management. In this second part of a two-part review, logical guidelines for the management of the disease are discussed, with particular emphasis on antimicrobial selection. Patient stabilisation and supportive care, techniques for pleural space drainage and lavage and indications for surgery are reviewed. Ó 2008 Elsevier Ltd. All rights reserved.

Keywords: Thoracostomy; Antimicrobial; Treatment; Review

Introduction Early reports describing feline pyothorax were pessimistic about the likelihood of a successful outcome, although in many instances treatment was not attempted (Wilkinson, 1956; Holzworth, 1958; Piermattei and Gowing, 1964; Anon, 1974). This situation has changed dramatically. Aggressive medical management (Leighton and Cordell, 1961; Withrow et al., 1975; Crane, 1976; Brodrick, 1983) is widespread and has been accompanied by an improvement in the prognosis for this disease (Demetriou et al., 2002; Waddell et al., 2002; Barrs et al., 2005). The improved prognosis is likely also as a consequence of an increased willingness to have feline disorders investigated and treated, as well as the increased availability of highquality veterinary care.

This is the second part of a two-part review. The first part considered aetiopathogenesis and diagnostic investigation of feline pyothorax (Barrs and Beatty, 2009). Here we consider recommendations for treatment and prophylaxis although evidence on which to base treatment recommen-

*

DOI of original article: 10.1016/j.tvjl.2008.03.011.

Corresponding author. Tel.: +61 2 9351 3437; fax: +61 2 9351 4261.

E-mail address: vbarrs@vetsci.usyd.edu.au (V.R. Barrs).

1090-0233/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2008.03.019

dations for feline pyothorax is lacking. For example, there are no retrospective analytical studies comparing different treatments protocols with outcome. However, polymicrobial pyothorax is conceptually similar to a cat fight abscess and the same basic principles of drainage, antimicrobial therapy and supportive care apply. While future studies may shed light on the optimum treatment schedules, these basic principles are unlikely to change. We have reported a success rate of 95% for cats treated using closed tube thoracostomy (Barrs et al., 2005). The treatment recommendations outlined below are based on our findings and other available evidence as indicated. It is worth noting that even in human medical practice, controversies still exist as to the best treatment for pyothorax (Davies et al., 2003; Rahman and Gleeson, 2006).

Stabilisation and supportive care Excluding cats that are euthanased because treatment is declined, most non-survivors (60–100%) die or are euthanased in the first 48 h after presentation (Gruffydd-Jones and Flecknell, 1978; Pidgeon, 1978; Jonas, 1983; Brady et al., 2000; Demetriou et al., 2002; Waddell et al., 2002; Barrs et al., 2005). Respiratory decompensation, sepsis or

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the systemic inflammatory response syndrome may contribute to these deaths. In some studies, death occurred during clinical examination or shortly after presentation (Pidgeon, 1978; Gruffydd-Jones and Flecknell, 1978; Jonas, 1983; Barrs et al., 2005), highlighting the importance of careful patient handling and initial stabilisation.

Where respiratory distress is recognised, minimal handling, assessment for, and treatment of, reduced oxygen saturation, using supplemental oxygen and therapeutic thoracocentesis is of paramount importance, since these patients are at imminent risk of respiratory failure (Haskins, 1992; Purvis and Kirby, 1994; Brady et al., 2000).

Haemoglobin saturation can be monitored non-invasively with pulse oximetry, securing the probe to a non-pigmented area of skin, usually the pinna in cats. Haemoglobin saturations of <90% in patients breathing room air indicate severe hypoxaemia and humidified nasal oxygen supplementation should be provided. Arterial blood gas analyses enable evaluation of both oxygenation and ventilation, but are more invasive to procure. Arterial catheters can be placed during general anaesthesia for tube thoracostomy (Tseng and Waddell, 2000). Other considerations for initial patient stabilisation include identification and correction of fluid and electrolyte imbalances. Treatment of hypoglycaemia, hypothermia and hypotension may be necessary in patients with advanced sepsis (Brady et al., 2000; Waddell et al., 2002).

Drainage of the pleural space Indwelling thoracostomy versus needle thoracocentesis Although there are reports of successful management of feline pythorax using single or repeated needle thoracocentesis combined with antimicrobial therapy (Gruffydd-Jones and Flecknell, 1978; Brodrick, 1983; Jonas, 1983; Waddell et al., 2002; Barrs et al., 2005), mortality rates of 50–80% have been reported (Anon, 1974; Bauer, 1986). Placement of indwelling thoracostomy tubes is simple and cost-effective, provides superior drainage and is well tolerated. This technique has been recommended by many sources (Holzworth, 1958; Leighton and Cordell, 1961; Crane, 1976; Holmberg, 1979; Sherding, 1979; Padrid, 2000; Waddell et al., 2002; Barrs et al., 2005) and is the authors’ preferred

method for pleural drainage in cats. Needle thoracocentesis may be useful when the effusion is of small volume and pneumonia is the primary problem or when euthanasia is the only other option. It is worth noting that a single ultrasound-guided pleural drainage procedure using a temporary thoracostomy tube, followed by antibiotic treatment was successful in 15/16 consecutive dogs with pyothorax (Johnson and Martin, 2007).

The authors recommend closed-tube thoracostomy for treatment of feline pyothorax unless diagnostic imaging studies reveal indications for exploratory thoracotomy (see ‘indications for surgery’ below). To facilitate drainage and decrease the likelihood of mechanical complications, such as kinking or obstruction, the thoracostomy tube of greatest diameter that can fit comfortably between the intercostal spaces should be used (generally 14–16 Fr; Fig. 1). It should be noted that emerging evidence has suggested that smaller drains with regular flushes are adequate in the treatment of empyema in adult humans (Rahman and Gleeson, 2006). Commercially available paediatric thoracic trocar catheters are inserted under general anaesthesia. Mortality is reduced by use of therapeutic preanaesthetic needle thoracocentesis prior to tube thoracostomy and reducing the time between diagnosis and thoracic drain insertion (Barrs et al., 2005).

The chest tube should enter the skin two or more intercostal spaces (ICS) caudal to where the tube enters the thoracic cavity to minimise pneumothorax from leakage of air around the tube. The surgical site is prepared and a small stab incision is made in the dorsal third of the tenth or eleventh ICS. The trocar is advanced cranially through a subcutaneous tunnel and then driven into the pleural space through the eighth ICS. The tube is advanced over the trocar in a cranio-ventral direction parallel to the thoracic wall for a distance of 12–18 cm (Fig. 2). As the trocar is removed, the end of the tube is clamped to prevent pneumothorax. Alternatively, thoracostomy tubes without stylets may be placed in the same location using large haemostats to perforate the intercostal muscles. The tube is secured to the thoracic wall by a purse-string suture to provide an airtight seal and a Chinese-finger trap suture is placed to prevent the tube from slipping. A plastic tube connector attached to a three-way tap is placed in the end of the tube and any remaining exudate or air that

Fig. 1. Fenestrated thoracic catheters (14 G and 16 G) with stylet removed, with plastic-tube connector, three-way tap and clamp.

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Fig. 2. Correct positioning of a thoracostomy tube within the pleural space.

entered during the procedure is evacuated (Sherding, 1979; Fossum, 2002). For safety, when the tube is not being drained it is sealed with a clamp (Figs. 1 and 2). Hygienic precautions should be used when draining the tube to prevent nosocomial infection (McCaw et al., 1984).

Where pyothorax is bilateral, the placement of bilateral thoracostomy tubes is recommended (Bjorling, 2001; Barrs et al., 2005). Bilateral chest tubes are more likely to provide effective drainage in cases of persistent loculation of fluid or where the mediastinum is complete. Given the high mechanical complication rates that have been reported with thoracostomy tubes, placement of bilateral tubes reduces the likelihood of a second general anaesthesia for tube replacement in case of unilateral tube failure (Barrs et al., 2005). Radiographs should be taken after thoracostomy tube placement to assess drain position and the presence of underlying bronchopulmonary disease. If only one tube has been placed and there is minimal residual effusion, unilateral drainage may be sufficient for treatment. However, if effusion persists on the opposite side, a second thoracostomy tube should be placed.

Tube complications can include pneumothorax, failure of drainage due to incorrect placement, kinking or adhesions, subcutaneous oedema or abscesses and thoracic wall abscess at the site of drain insertion (Barrs et al., 2005).

Continuous suction versus closed-tube thoracostomy Indwelling tube thoracostomy can be managed with continuous water seal suction or closed-tube with intermittent suction. Continuous suction offers the advantage of maximal drainage, but does not decrease the time needed to manage pyothorax (Hawkins and Fossum, 2000). Continuous water seal suction is not necessary for effective pleural drainage in most cases of feline pyothorax (Demetriou et al., 2002; Waddell et al., 2002; Barrs et al., 2005). In addition, water-seal chest drainage units require continuous monitoring, since leakage between the pleural cavity

and water seal can be fatal (Hawkins and Fossum, 2000).

Closed-tube thoracostomy with intermittent suction is simpler, less expensive, requires less monitoring and is adequate for most cases.

Thoracic lavage Intermittent thoracic lavage is recommended by many studies (Crane, 1976; Pidgeon, 1978; Holmberg, 1979; Sherding, 1979; Tomlinson, 1980; Jonas, 1983; Padrid, 2000; Bjorling, 2001; Barrs et al., 2005). No prospective studies have evaluated whether thoracic lavage is associated with shorter indwelling thoracostomy tube times.

However, Demetriou et al. (2002) reported shorter duration of tube placement for patients with lavage than those managed without lavage.

The theoretical benefits of lavage include facilitation of exudate drainage, prevention of thoracostomy tube obstruction by thick exudates, hydraulic debridement of the pleura including breakdown of adhesions, and dilution of bacteria and inflammatory mediators (Crane, 1976; Anon, 2006). Furthermore, instillation of lavage solution allows rapid detection of failure of thoracostomy tubes to drain the pleural space adequately. Recovery of 75% or more of instilled lavage solution is expected. If smaller volumes of fluid are recovered, radiology and/or ultrasonography are indicated to investigate for thoracostomy tube complications or loculation of pockets of fluid due to adhesions.

After the initial thoracostomy tube placement, intermittent suction and lavage should be carried out every 4 h for the first 24–48 h. Thereafter, suction and lavage two to three times daily is usually adequate. The volume and gross characteristics of the aspirated fluid are useful to guide frequency of suction and lavage. For thoracic lavage, 0.9% sodium chloride or Hartmann’s solution warmed to body temperature can be safely instilled into one thoracostomy tube using volumes from 10–25 mL/kg per lavage (Padrid,

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2000; Barrs et al., 2005). The volume of ďŹ&#x201A;uid instilled and aspirated should be recorded. The procedure is then repeated using the thoracostomy tube on the opposite hemithorax. Hypokalaemia is a potential complication of lavage of the thoracic cavity (Barrs et al., 2005). Use of volumes of lavage ďŹ&#x201A;uid not exceeding 25 mL/kg and of a lavage solution containing potassium (e.g. Hartmannâ&#x20AC;&#x2122;s solution) may prevent this complication (Sherding, 1994).

Indwelling thoracostomy tubes are generally removed after 4â&#x20AC;&#x201C;6 days when the following criteria have been met: reduction of pleural eďŹ&#x20AC;usion to approximately 2 mL/kg/ day; resolution of pleural eďŹ&#x20AC;usion on thoracic radiographs, and cytological resolution of infection, as indicated by absence of micro-organisms, reduction of neutrophil numbers with loss of their degenerative appearance and appearance of macrophages. The median duration of thoracic drainage was 5â&#x20AC;&#x201C;6 days, in recent studies (Demetriou et al., 2002; Waddell et al., 2002; Barrs et al., 2005).

Fibrinolytics Intrapleural ďŹ brinolytics, such as streptokinase and urokinase, have been used to treat thoracic empyema in humans with the intention of improving pleural drainage and preventing loculations. More recently, their eďŹ&#x192;cacy has been questioned and their routine use has fallen from favour (Anon, 2006; Bouros et al., 2007). While the use of ďŹ brinolytics has been described in treating feline pyothorax, the eďŹ&#x192;cacy of these agents has not been evaluated (Crane, 1976; Withrow et al., 1975; GruďŹ&#x20AC;ydd-Jones and Flecknell, 1978; Holmberg, 1979; Sherding, 1979; Tomlinson, 1980).

Patient monitoring and analgesia Constant monitoring is mandatory while thoracic drains are in place where continuous water seal suction systems are used, and is ideal where closed tube thoracostomy with intermittent suction is used. Thoracic radiography should be performed every 48 h whilst chest tubes are in place to ensure early detection of pleural space drainage failure and other indications for exploratory thoracostomy.

Daily monitoring, additional to that described earlier, should include measurement of electrolytes, haematocrit, serum albumin, total plasma protein, volume of thoracostomy-tube ďŹ&#x201A;uid lavaged and aspirated, and changes in bodyweight. Anorexia usually resolves within 48 h of commencing pleural space drainage and antimicrobial therapy.

Provision of early enteral nutrition through a feeding tube should be considered in cachectic or critically ill patients.

Oesophagostomy tubes are an appropriate choice for the short duration of nutritional support required (Chan and Freeman, 2006).

Analgesia is recommended after placement of indwelling thoracostomy tubes. InďŹ ltration of a local anaesthetic (e.g.

1% lignocaine or 0.25% bupivacaine) through the skin to the pleura should be used before tube placement, even in

the anaesthetised patient (Mathews and Dyson, 2005).

Intrapleural analgesia, using bupivacaine buďŹ&#x20AC;ered with sodium bicarbonate, has been advocated as an adjunct to opioid analgesia in small animal patients with indwelling chest tubes (Hansen, 2000; Mathews and Dyson, 2005).

However, intrapleural analgesia should be avoided in patients with poor respiratory reserve because of the potential for diaphragmatic paralysis. Also, absorption is unreliable in the presence of eďŹ&#x20AC;usion. Systemic opioids are not contraindicated in the presence of respiratory compromise in cats, since clinically signiďŹ cant respiratory depression is uncommon (Hansen, 2000).

Indications for surgery Indications for exploratory thoracostomy at the time of diagnosis of pyothorax include detection of a pulmonary or mediastinal abscess, or extensively loculated eďŹ&#x20AC;usions on thoracic ultrasonography or post-drainage radiographs (Demetriou et al., 2002; Waddell et al., 2002; Doyle et al., 2005). Surgical exploration of the thorax is also indicated when medical management fails, as determined by persistence of loculated or generalised eďŹ&#x20AC;usion 3â&#x20AC;&#x201C;7 days after instigation of thoracostomy drainage, or the development of pneumothorax or drain obstructions caused by pleural adhesions (Holmberg, 1979; Crane, 1976; Hawkins and Fossum, 2000; Bjorling, 2001; Demetriou et al., 2002; Doyle et al., 2005).

Two studies have demonstrated that where medical management fails, in 5% and 9% of cases, respectively (Barrs et al., 2005; Waddell et al., 2002), exploratory thoracotomy is likely to be curative. Recurrence rates of 5â&#x20AC;&#x201C;14% after medical management have been reported in retrospective studies but diďŹ&#x20AC;erent treatment modalities were used (GruďŹ&#x20AC;ydd-Jones and Flecknell, 1978; Jonas, 1983; Waddell et al., 2002; Barrs et al., 2005). The aims of exploratory thoracotomy are to: Identify and remove any primary cause, such as grass awn foreign body, which may act as a nidus of infection; Remove isolated areas of necrotic tissue, including grossly abnormal lung lobes; break down ďŹ brinous or ďŹ brous adhesions that may be isolating areas of the thoracic cavity; and ensure proper positioning of bilateral thoracostomy tubes.

Decortication refers to the removal of thick ďŹ brinous material that forms on the pleural surfaces in response to inďŹ&#x201A;ammation. Although it may be necessary to remove some material from the visceral pleural surfaces to facilitate lung expansion, complete decortication (including the parietal pleural surfaces) carries a risk of severe haemorrhage and is not recommended (Crane, 1976). In dogs, thoracotomy has been recommended if Actinomyces spp. is isolated from pleural ďŹ&#x201A;uid, because of poor outcomes associated with medical therapy alone (Rooney and Monnet, 2002).

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In both dogs and cats Actinomyces spp. are members of normal oropharyngeal flora (Love et al., 1990; Edwards, 2006). Pyothorax in dogs has been associated with inhalation or penetration of grass awns or florets that are contaminated with this bacterium (Edwards, 2006). In cats, pyothorax involving Actinomyces spp. in combination with other oropharyngeal flora is less likely to be associated with grass awn foreign bodies (Brennan and Ihrke, 1983) and has been shown to resolve without thoracotomy (Thompson et al., 1992; Waddell et al., 2002; Barrs et al., 2005).

Antimicrobial therapy Initial antimicrobial therapy is empiric and based on cytology of the pleural fluid. Therapy should be modified, if necessary, after culture and susceptibility testing results.

Factors to consider when choosing an antibiotic regimen for initial treatment are whether to use a bactericidal or bacteriostatic antimicrobial, spectrum of activity, combination therapy, dose, route, frequency and duration of administration.

Selection of antimicrobials for empiric therapy Since the majority of cases are synergistic polymicrobial infections caused by oropharyngeal flora, antimicrobials should ideally be effective against both obligate anaerobes and facultative bacteria. Obligate anaerobes are inherently resistant to aminoglycosides. Fluoroquinolones marketed for veterinary use include the current generation fluoroquinolones (enrofloxacin, orbifloxacin, ciprofloxacin, danofloxacin, marbofloxacin and difloxacin) and the new generation fluoroquinolone, pradofloxacin (Martinez et al., 2006; Silley et al., 2007). Earlier generation fluoroquinolones have low activity against obligate anaerobes (Silley et al., 2007).

New data have indicated that methoxyfluoroquinolones, such as pradofloxacin, have high activity against isolates of anaerobic bacteria from dogs and cats, including Clostridia spp., Bacteroides spp., Fusobacterium spp., Prevotella spp., Porphyromonas spp., Sporomusa spp. and Propionibacterium spp. (Silley et al., 2007). The use of pradofloxacin as monotherapy for mixed aerobic and anaerobic infections in small animals has been proposed. However, the expansion in use of newer generation fluoroquinolones in the treatment of human anaerobic infections has raised concerns because of reports of increasing resistance in Bacteroides spp. group isolates (Stein and Goldstein, 2006).

Penicillin and its derivatives are reliably effective against non b-lactamase producing obligate anaerobes (Jang et al., 1997; Roy et al., 2007). Antibiotics effective against most blactamase producing anaerobes, such as the Bacteroides fragilis group, include the potentiated penicillins, such as amoxicillin–clavulanic acid and ticarcillin–clavulanic acid, and metronidazole. In one study of obligate anaerobes from dogs and cats, all isolates were susceptible to amoxicillin–clavulanic acid and 98% were susceptible to metroni-

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dazole (Jang et al., 1997). Only 71% of Bacteroides isolates were susceptible to ampicillin, and only 83% were susceptible to clindamycin (Jang et al., 1997). But in feline pyothorax, Bacteroides tectum is a more common isolate than Bacteroides fragilis and b-lactamase producing strains of this species are uncommon (Love et al., 1989; Love and Wigney, 1997). Also, polymicrobial infections are synergistic and concurrent facultative bacteria scavenge oxygen, creating a more suitable environment for the proliferation of anaerobes. Therefore, the combination of drainage and antibiotics effective against only non-b-lactamase producing anaerobes and facultative bacteria is often adequate.

It is has been recommended that empiric therapy for the Gram-negative facultative bacterial component of pyothorax in cats and dogs should include either an aminoglycoside (gentamicin or amikacin) or a fluorinated quinolone (Hawkins and Fossum, 2000; Walker et al., 2000). This recommendation has merit for empiric treatment of canine pyothorax where Enterobacteriaceae spp., especially Escherichia coli, are isolated relatively commonly (Walker et al., 2000; Demetriou et al., 2002; Rooney and Monnet, 2002; Johnson and Martin, 2007). However, in feline pyothorax Enterobacteriaceae are uncommon, with E. coli being isolated in 0–7% of cases (Barrs et al., 2005; Jonas, 1983; Love et al., 1982; Walker et al., 2000; Demetriou et al., 2002).

The most common facultative Gram-negative rod likely to be isolated from cats with pyothorax is Pasteurella spp.

(Love et al., 1982). Pasteurella spp. were isolated from 63% of cultures from feline pyothorax in a recent case series (Demetriou et al., 2002). Cephalexin and other first generation cephalosporins have poor activity against Pasteurella spp. and have only intermediate activity against many anaerobes (Goldstein et al., 1988; Dow et al., 1986). Their use in empiric therapy of feline pyothorax is therefore not recommended. Similarly, monotherapy with clindamycin is not suitable since it is ineffective against Pasteurella spp. (Goldstein et al., 1988). Clindamycin and penicillin G or an aminopenicillin could be used in combination, although the use of a b-lactam antibiotic together with a protein synthesis inhibitor may result in antagonism both in vitro and in vivo.

Pasteurella spp. are susceptible to penicillin and its derivatives as well as to fluoroquinolones and aminoglycosides. Therefore, the addition of a fluoroquinolone or aminoglycoside is unnecessary for initial empiric therapy.

Furthermore, aminoglycosides are potentially ototoxic and nephrotoxic; they have poor penetration of the pleural space and have a weaker action in an acidic environment (Clark, 1977; Chapman and Davies, 2004). Enrofloxacin can be retinotoxic (Gelatt et al., 2001; Ford et al., 2007) and in some geographic regions many isolates of E. coli are not susceptible to fluoroquinolones (Boothe et al., 2006; Clarke, 2006; Farca et al., 2007). Of 50 E. coli isolates obtained from cats examined at a veterinary teaching hospital, 75% were susceptible to amoxicillin–clavulanate, whilst only 55% were susceptible to enrofloxacin (Walker et al., 2000).

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Antibiotics should be administered parenterally, preferably intravenously (IV) rather than intramuscularly (IM) or subcutaneously (SC), in the initial stages. Antimicrobials suitable for empiric treatment of polymicrobial feline pyothorax (Table 1) include penicillin G (e.g. benzylpenicillin potassium or benzylpenicillin sodium) or an aminopenicillin (e.g. ampicillin or amoxicillin) – either alone or in combination with metronidazole. Another alternative is parenteral monotherapy with a potentiated penicillin, e.g. amoxycillin–clavulanic acid or ticarcillin–clavulanic acid (Timentin, SmithKlineGlaxo). These agents are effective against both b-lactamase producing anaerobes and Pasteurella spp. IV preparations of amoxycillin–clavulanic acid (Augmentin Intravenous, SmithKlineGlaxo) and ampicillin with sulbactam (Unasyn, Pfizer Animal Health) are available in some regions.

Adjunctive, targeted antimicrobial therapy can be administered if indicated by the results of antimicrobial susceptibility testing, or if Gram-negative rods only are seen in smears of pleural fluid.

Susceptibility testing Whilst susceptibility testing for aerobic organisms is routine, antimicrobial susceptibility testing of obligate anaerobic bacteria is not a standard procedure in many clinical microbiology laboratories because of time constraints, technical complexity and the relatively low incidence of b-lactamase producing organisms. Also, in pyothorax, where 2–5 species of facultative and anaerobic bacteria are often present, each species must be systematically isolated and tested separately. Disk diffusion or disk elution testing to determine antimicrobial susceptibility of anaerobes is unreliable.

Agar dilution is the reference method recommended by the Clinical and Laboratory Standards Institute (2007).

Another method, broth microdilution, although well suited to clinical laboratories, is currently recommended for susceptibility testing of the Bacteroides fragilis group only because of poor growth and unreliable results for other anaerobic species. The development of the ‘E-test’ (epsilon test) method for susceptibility testing of anaerobic bacteria offers a simple, albeit expensive, rapid alternative for rap-

Table 1 Parenteral antimicrobial agents useful in treatment of pyothorax (see text for appropriate combination); (Hardie, 2000; Plumb, 2005) Antibiotic

Dosage and frequency

Penicillin G potassium/sodium Ampicillin Amoxicillin Ticarcillin–clavulanic acid Ampicillin–sulbactam Amoxycillin–clavulanic acid Clindamycin Metronidazole

20,000–40,000 IU/kg IV q 6 h 20–40 mg/kg IV q 6–8 h 10–20 mg/kg IV q 12 h 40–50 mg/kg (combined) IV q 6–8 h 50 mg/kg (combined) IV q 8 h 12–20 mg/kg (combined) SC/IM q 12 h 11 mg/kg IV q 12 h 15 mg/kg IV q 12 h

idly growing organisms, such as the B. fragilis group and Filifactor villosus, and results are available after overnight incubation (Citron et al., 1991; Love and Wigney, 1997; Jorgensen and Ferraro, 2000).

Use of intrapleural antimicrobial therapy Adding antimicrobials, such as penicillin, to thoracic lavage solution is controversial and would appear to offer no advantage because comparable tissue levels are attained with IV administration. This practice is no longer recommended in treatment of human thoracic empyema (Falagas and Vergidis, 2005). In the two largest treatment studies of feline pyothorax, antibiotics were not administered intrapleurally (Waddell et al., 2002; Barrs et al., 2005). In one early report, mortality rates were considered to be higher with intrapleural antimicrobial administration (Piermattei and Gowing, 1964). In a more recent study of canine and feline pyothorax, duration of thoracostomy tube placement was 6.3 days without intrapleural antibiotics compared with 4.8 days with intrapleural antibiotic administration.

No statistical significance was ascribed to this finding (Demetriou et al., 2002).

Duration of antimicrobial therapy Treatment of anaerobic infections associated with devitalised tissue requires high doses of antimicrobials administered for extended periods. There is risk of relapse if therapy is discontinued prematurely (Dow and Jones, 1987). For ongoing treatment once clinical improvement is seen and the patient is eating well, oral antibiotics may be substituted for IV antibiotics. Mean duration of antimicrobial therapy in two recent studies of feline pyothorax was 5–7 weeks (Demetriou et al., 2002; Barrs et al., 2005). This is similar to current recommendations that antimicrobial therapy for treatment of feline pyothorax should be administered for 4–6 weeks (Hawkins and Fossum, 2000; Greene and Reinero, 2006). The British Thoracic Society recommends a minimum duration of antimicrobial therapy for treatment of pleural infections in humans of 3 weeks providing pleural drainage is adequate (Davies et al., 2003).

Thoracic radiographs should be taken 1–2 weeks after discharge from hospital and at the completion of antimicrobial therapy to ensure complete resolution of infection.

Prophylaxis The majority of cases of pyothorax involve oropharyngeal flora (Barrs and Beatty, in press). Routine antimicrobial prophylaxis should therefore be considered where cats are at risk of microbial colonisation of the lower respiratory tract, such as during viral upper respiratory tract infections or after dental procedures under general anaesthesia.

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Conclusions Careful handling and early consideration of stabilisation, including supplemental oxygen and therapeutic thoracocentesis, are essential to avoid respiratory failure.

Closed-tube thoracostomy, twice daily aspiration and lavage and antimicrobial therapy can be expected to result in complete resolution of disease in most cases. Guided by in house cytological findings, empiric therapy for most cases will involve agent/s effective against obligate and facultative anaerobes. At least initially, the IV route is preferred. Suitable choices include penicillin combined with metronidazole or ticarcillin–clavulanate monotherapy.

Results of culture and susceptibility testing guide ongoing treatment. Where medical treatment fails and surgical intervention is required, the prognosis for resolving infection is good to excellent. Clinicians should consider routine antimicrobial prophylaxis in cats with viral upper respiratory tract infections and after dental procedures under general anaesthesia.

Conflict of Interest Statement None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.

Acknowledgements The authors thank Bozena Jantulik and Keith Ellis for preparation of the figures, and Dr. Katherine Briscoe for assistance in preparation of the manuscript.

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