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EVE 08-131 Widmer:Layout 1 10/07/2009 16:22 Page 2 EVE 08-131 Widmer:Layout 1 10/07/2009 16:22 Page 2 430 EQUINE VETERINARY EDUCATION / AE / august 2009 Original Article Comparison of the clinical efficacy of cefquinome with the combination of penicillin G and gentamicin in equine patients A. Widmer*, M. Kummer, M. Wehrli Eser† and A. Fürst Equine Department Vetsuisse - Faculty Zurich, Section Surgery; and †Section Medicine, University of Zurich, Winterthurerstr. 260, CH-8057 Zurich, Switzerland. Keywords: horse; cefquinome; antibiotic treatment; cephalosporins Summary dihydrothiazine ring. The differences among cephalosporin derivatives in antimicrobial activity, stability This prospective, randomised, nonblinded study against β-lactamases, protein binding, intestinal compared the clinical efficacy of cefquinome to that of a absorption, metabolism and toxicity are the result of the combination of penicillin and gentamicin. Patients presence of different groups at the R position (Vaden and (374 horses and 13 donkeys) at the equine hospital of the Riviere 2001). Vetsuisse-Faculty of Zurich, presented from February– The division of cephalosporins into 4 generations is October 2007, were divided into prophylactic and largely based on the time of introduction of the specific therapeutic treatment groups. Equids from these groups cephalosporin, although some generalities can be made were randomly treated either with cefquinome or with the for each group regarding their spectrum and combination of sodium penicillin and gentamicin. pharmacological behaviour. In general, first-generation There was no significant difference between the cephalosporins are effective against Gram-positive 2 treatment groups for prophylactic indications. In the organisms. Their spectrum is similar to that of therapeutic group, cefquinome showed better efficacy, as aminopenicillins. Second-generation cephalosporins are demonstrated by fewer complications of wound healing active against the same bacteria as first-generation and fewer treatment failures with subsequent change to cephalosporins, but their spectrum is extended to Gram- another antibiotic. Side effects were very rare in both negative bacteria. Third-generation cephalosporins are treatment groups. Cefquinome can be used with safety known to be less active against Gram-positive cocci, but and efficacy in equids. Cefquinome had greater efficacy have a wider range of activity against Gram-negative than the combination of penicillin and gentamicin in the pathogens than other cephalosporins. Some of them also therapeutic group. However, there was no difference have good activity against anaerobic bacteria (Vaden between the 2 antibiotic treatments in the prophylactic and Riviere 2001). Ceftiofur is a commonly used third- group. In order to minimise the development of resistance, generation cephalosporin. It shows good activity against cefquinome should therefore not be used for routine Gram-positive and Gram-negative anaerobes, including prophylactic treatment. Enterobacteriaceae, and against many anaerobes such as Clostridium spp. and Fusobacterium spp. (Yancey et al. Introduction 1987; Samitz et al. 1996). It should be administered by the i.m. route (Haggett and Wilson 2008). This fact makes Since the discovery of penicillin in 1928, many antibiotics ceftiofur less suitable for perioperative prophylaxis. In have been developed. The first cephalosporin, horses that are treated for several days, administration of ‘cephalosporin C’, was isolated in 1945, and was derived antibiotics through an indwelling venous catheter is also from a fungus (Cephalosporium acremonium). All other preferred over i.m. administration. The side effects of cephalosporins are semi-synthetic derivatives of this ceftiofur are diarrhoea and colitis after high dosages, as cephalosporin C. Cephalosporins have the same basic well as minor irritation at the injection site (Mahrt 1992). composition, which contains a β-lactam ring and a Two cases of fatal enteritis have been seen after i.v. administration of ceftiofur in horses (A. Fürst, unpublished *Author to whom correspondence should be addressed. report). The occurrence of antimicrobial resistance EVE 08-131 Widmer:Layout 1 10/07/2009 16:22 Page 3 EQUINE VETERINARY EDUCATION / AE / august 2009 431 against ceftiofur in equine pathogens has been reported concentration-dependent manner (Riviere and Spoo (Vo et al. 2007). Most of the isolates (Escherichia coli and 2001). There are few published reports of side effects Klebsiella pneumoniae) were resistant to multiple following administration of cephalosporins to horses in antibiotics (Vo et al. 2007). clinical situations. Anecdotally, however, there are The fourth-generation cephalosporins have a wider concerns about gastrointestinal tract disturbances spectrum than all other cephalosporins (Hornish and (gastrointestinal discomfort, anorexia, diarrhoea) (Mahrt Kotarski 2002). Cefepime, a cephalosporin of the fourth 1992; Guglick et al. 1998). generation that is used in human medicine, has been Antibiotics are used in man and domestic animals for shown to be active against most clinically important Gram- the treatment of infections and also for prophylactic positive and Gram-negative organisms and it is resistant to indications to prevent infections. The therapeutic use of hydrolysis by β-lactamases (Holloway and Palmer 1996). antibiotics is not questioned, because antibiotics are, in However, methicillin-resistant Staphylococcus aureus combination with surgical techniques, of great (MRSA) and multi-resistant Entercoccus should be importance in treating infections. It is important to select considered intrinsically resistant (Sood et al. 2008). an appropriate antibiotic in order to combat the infection Cefquinome is a cephalosporin of the fourth effectively, as well as to reduce the prevalence of generation that is used only in veterinary medicine. It has resistance. New antibiotics, such as cefquinome, have zwitterionic characteristics, which allow rapid been developed in an attempt to find an antibiotic with penetration of the Gram-negative outer membrane better efficacy against multi-resistant pathogens. (Murphy et al. 1994). Cefquinome has been found to be However, antimicrobial resistance develops fast, and effective against most major equine pathogens, prudent use of antimicrobials is the only way to combat including Staphylococcus spp., Streptococcus spp., the development of multi-resistant pathogens. Guidelines Actinobacillus equuli, enterobacteriaceae and for the prudent use of antibiotics are available elsewhere pasteurellaceae. In an in vitro study, it was less effective (Traub-Dargatz and Dargatz 2009). against Clostridium perfringens and Rhodococcus equi The aim of this study was to compare the clinical (Thomas et al. 2006). Cefquinome showed more limited in efficacy of cefquinome with a combination of penicillin vitro activity against Gram-negative and Gram-positive and gentamicin for therapeutic as well as for prophylactic anaerobic pathogens (Limbert et al. 1991; Murphy et al. use. 1994). The same in vitro study showed that cefquinome was more stable than other cephalosporins against Materials and methods β-lactamase (Limbert et al. 1991). In a study involving treatment of bovine mastitis, cefquinome showed good Patients presented to the equine hospital of the Vetsuisse- activity against Streptococcus spp., Staphylococcus spp. Faculty of Zurich from the beginning of February until the and enterobacteriaceae. Enterococcus spp. and end of October 2007 were divided into a prophylactic and Pseudomonas spp. were less susceptible (Shpigel et al. a therapeutic treatment group. These 2 groups were then 1997). Another clinical study showed that cefquinome split into groups representing different diagnoses. The also was efficient for the treatment of foals with therapeutic treatment group was divided into cases of septicaemia (Rohdich et al. 2007). peritonitis, respiratory tract infection, alveolar periostitis, Like that of other β-lactam antibiotics (e.g. penicillin), orthopaedic infections and infected soft tissue injuries the activity of cefquinome is time rather than (Table 1). The prophylactic treatment group comprised concentration dependent (Thomas et al. 2006). In patients undergoing colic surgery, colic patients without contrast, aminoglycosides, such as gentamicin, act in a surgery (e.g. caecal puncture), patients with noninfected TABLE 1: Patient groups Total number Indication Patient group Percentage (n = 387) Therapeutic group Orthopaedic infections 11.9 46 Infected soft tissue injuries 17.3 65 Alveolar periostitis 4.4 17 Respiratory infections 2.8 11 Peritonitis 0.5 2 Prophylactic group Different elective surgeries (neurectomies, annular ligament 19.9 77 desmotomies, open castrations) Sterile closed castrations 10.6 41 Noninfected soft tissue injuries 9.6 37 Arthroscopies 9.3 36 Colic surgeries 7 27 Closed fractures 3.6 14 Colic patients without surgery (e.g. caecal puncture) 3.1 12 EVE 08-131 Widmer:Layout 1 10/07/2009 16:22 Page 4 432 EQUINE VETERINARY EDUCATION / AE / august 2009 soft tissue injuries, those undergoing arthroscopies, sterile nasal discharge, enlarged submandibular lymph nodes, closed castrations, different elective surgeries, and those cough, as well as evaluation of the surgery site or wound with closed fractures (Table 1). For each group of diseases and the ability to bear weight (good, fair, poor), as (e.g. colic surgery) we created a randomisation list using appropriate, according to a scoring system (Table 2). Any Microsoft Excel1.
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