In vitro activity of difloxacin against canine bacterial isolates.

The in vitro activity of difloxacin against canine bacterial isolates from clinical cases was studied in the United States and The Netherlands. Minimal inhibitory concentrations (MIC), the postantibiotic effect, the effect of pH on antimicrobial activity, and the bacterial killing rate tests were determined according to standard techniques. The MICs of American and Dutch isolates agreed in general. The MICs of the American gram-negative isolates ranged from 0.06 to 2.0 microg/ml, and the MICs of the Dutch gram-negative isolates ranged from 0.016 to 8.0 microg/ml. A few European strains of Proteus mirabilis and Klebsiella pneumoniae had relatively high MICs. Bordetella bronchiseptica also was less susceptible to difloxacin. The MICs of the American gram-positive cocci ranged from 0.125 to 4.0 microg/ml, and the MICs of Dutch isolates ranged from 0.125 to 2.0 microg/ ml. Difloxacin induced a concentration-dependent postantibiotic effect that lasted 0.2-3 hours in cultures with Escherichia coli, Staphylococcus intermedius, Streptococcus canis, Proteus spp., and Klebsiella pneumoniae. There was no postantibiotic effect observed against canine Pseudomonas aeruginosa. Decreasing the pH of the medium increased the MIC of Proteus mirabilis for difloxacin. The MICs of Escherichia coli and Klebsiella pneumoniae were lowest at neutral pH and were slightly increased in acid or alkaline media. At a neutral pH, most tested bacterial species were killed at a difloxacin concentration of 4 times the MIC. Similar results were obtained when these same bacteria were tested against enrofloxacin. A Klebsiella pneumoniae strain in an acidic environment was readily killed at difloxacin or enrofloxacin MIC, but at neutral pH the drug concentration had to be raised to 4 times the MIC for a bactericidal effect. After 24 hours of incubation at pH 7.1, difloxacin and enrofloxacin had similar bactericidal activity for all bacteria tested except Staphylococcus intermedius. Against S. intermedius, difloxacin was more bactericidal than enrofloxacin.     

Comparison of pharmacodynamic and pharmacokinetic indices of efficacy for 5 fluoroquinolones toward pathogens of dogs and cats

BACKGROUND: Fluoroquinolones are often used interchangeably in dogs and cats. HYPOTHESIS: Predicted therapeutic efficacy differs among fluoroquinolones. ANIMALS: Bacterial pathogens isolated from dogs and cats. METHODS: Using microtube-dilution procedures, percent resistance and 2 pharmacodynamic/pharmacokinetic indices (maximum concentration/minimum inhibitory concentration [Cmax/MIC] [target 0.10] and area under curve/minimum inhibitory concentration [AUC/MIC] [target 0.125]) were compared prospectively at low and high doses (mg/kg) for ciprofloxacin (5 and 20), difloxacin (5 and 10), enrofloxacin (including enrofloxacin+ciprofloxacin) (5 and 20), marbofloxacin (2.5 and 5), and orbifloxacin (2.5 and 7.5). Indices were calculated for organisms represented by < or = 15 isolates. RESULTS: Percent resistance for all Gram-negative (n = 180; 20+/-3%; 39+/-5% for Escherichia coli) and Gram-positive isolates (n = 66; 18+/-3%) did not differ among drugs or organisms. The pattern of Cmax/MIC was generally enrofloxacin+ciprofloxacin > or = enrofloxacin or ciprofloxacin > or = marbofloxacin > or = orbifloxacin > or = difloxacin; and for AUIC/ MIC, enrofloxacin+ciprofloxacin > or = marbofloxacin > or = ciprofloxacin > or = enrofloxacin > difloxacin > orbifloxacin. Among susceptible Gram-negative isolates studied (n = 117), targeted Cmax/MIC or AUC/MIC were achieved in 88% of E. coli, 53% of Proteus mirabilis, and 35% of Pseudomonas aeruginosa; and for susceptible Gram-positive isolates studied (n = 49), 53% of Streptotoccus spp. and Staphylococcus intermedius and 27% of Staphylococcus spp. At the high dose, the proportion of isolates for which a target was reached was: ciprofloxacin, enrofloxacin+ciprofloaxin, and marbofloxacin (77%), enrofloxacin (73%), orbifloxacin (51%), and difloxacin (40%); and at the low dose, enrofloxacin+ciprofloxacin and enrofloxacin (43%), ciprofloxacin (40%), marbofloxacin (39%), orbifloxacin (29%), and difloxacin (28%). CONCLUSIONS: E. coli resistance to fluoroquinolones approximated 40%. For susceptible isolates, enrofloxacin, marbofloxacin, and ciprofloxacin more consistently reached indices associated with predicted efficacy, but only at the high dose.     

Susceptibility of rapidly growing mycobacteria and Nocardia isolates from cats and dogs to pradofloxacin

Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory infections in cats and dogs. Prolonged antibacterial therapy is required to cure these infections. As fluoroquinolones have been used in combination therapy for treating RGM infections, isolates from the Mycobacterium smegmatis cluster (n=64), Mycobacterium fortuitum cluster (n=17), and M. mageritense cluster (n=2), collected from feline and canine patients, underwent susceptibility testing to pradofloxacin. The MIC(50), MIC(90) and tentative epidemiological cut-off (ECOFF) values as determined by microbroth dilution susceptibility testing that inhibited growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and ≤ 0.25; and 0.125, 0.250 and ≤ 1.0 μg/mL, respectively. E-Test results showed similar trends but MICs were lower than those for microbroth dilution. In summary, pradofloxacin demonstrated effective in vitro activity against RGM isolates. Additionally, veterinary isolates of Nocardia nova (n=18), Nocardia farcinica (n=3) and Nocardia cyriacigeorgica (n=1) underwent microbroth dilution testing to ciprofloxacin, enrofloxacin and pradofloxacin. The MIC(50) and MIC(90) of pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of Nocardia nova isolates were 2 (4), 8 (16), 16 (32) μg/mL, respectively. The tentative ECOFF values for pradofloxacin and ciprofloxacin were 32 μg/mL and for enrofloxacin 64 μg/mL. The MIC or MIC range for the three N. farcinica isolates of pradofloxacin, ciprofloxacin and enrofloxacin were 0.25-0.5, 2 and 2 μg/mL and for the single N. cyriacigeorgica isolate were 1, 4 and 4 μg/mL, respectively. On the basis on these results, fluoroquinolones appear to have limited therapeutic potential for most Nocardia infections.     

In vitro susceptibility of canine and feline Escherichia coli to fosfomycin

Therapeutic options for multi-drug resistant (MDR) Escherichia coli in dogs or cats are limited. The objective of this study was to establish in vitro susceptibility of canine and feline E. coli to fosfomycin. Two sources of isolates were categorized based on susceptibility as to no resistance (NDR), single drug resistance (SDR), multidrug resistance (MDR) or extreme drug resistance (XDR). Clinical isolates were collected from throughout the US from dogs (n=157) or cats (n=43) with naturally occurring infection between March 2008 and January 2010. Experimental isolates were collected from fecal samples of dogs treated with no drug (NDR), amoxicillin (expressing SDR) or enrofloxacin (expressing MDR or XDR). Fosfomycin minimum inhibitory concentrations (MIC) were determined using E-Test(?). For clinical isolates, most (165/200) originated from the urinary tract, with the number of isolates per resistant category being: NDR (N=44, 22%), SDR (N=65, 32.5%), MDR (N=74, 37%), and XDR (N=17, 8.5%). Of these isolates, 99% (197/200) were susceptible to fosfomycin with the MIC(90) and MIC(50) being 2 and 1 μg/ml, respectively (range: 0.25-196 μg/ml). The number of experimental isolates in each category was NDR (3), SDR (23), MDR (38), and XDR (11) (29.3, 44, and 14.7%, respectively). Of these, 100% were susceptible to fosfomycin with MIC(90) and MIC(50) being 1.5 and 1 μg/ml (range: 0.38-4 μg/ml), respectively. The susceptibility of canine and feline MDR and XDR E. coli to fosfomycin at concentrations well below the susceptible breakpoint supports further investigation for its use when treating E. coli resistant to alternative antimicrobials.     

Antibacterial activity of marbofloxacin. A new fluoroquinolone for veterinary use against canine and feline isolates

Marbofloxacin is a new fluoroquinolone developed exclusively for veterinary use. Minimum inhibitory concentrations of marbofloxacin were assessed for 816 recent isolates associated with canine or feline diseases. Marbofloxacin showed a broad spectrum of activity against gram-negative and gram-positive bacteria. In vitro rates of killing of marbofloxacin and enrofloxacin were compared against strains of Staphylococcus intermedius and Pasteurella multocida , and the results showed no marked difference between the two antibiotics. The duration of bactericidal activity was evaluated ex vivo in the urine of dogs and cats treated with marbofloxacin and lasted from 2 to 5 days after a single administration according to the dosages. Post-antibiotic effect durations were determined with Escherichia colt, PasteureUa multocida, Staphylococcus aureus and Staphylococcus intermedius and were found almost equal to those of enrofloxacin or ciprofloxacin. These results predict a great potential for marbofloxacin in the treatment of a wide range of diseases in dogs and cats.     

Comparative quantification of the in vitro activity of veterinary fluoroquinolones

The aim of this study was to compare the in vitro antimicrobial activity of the veterinary fluoroquinolones against a panel of recently isolated porcine and bovine bacterial pathogens. The study used enrofloxacin as a benchmark against which other agents were compared, being the most common fluoroquinolone used in treatment of bovine and porcine infections. The activity of ciprofloxacin was also assessed as it is the main metabolite of enrofloxacin in cattle. Enrofloxacin and ciprofloxacin generally showed higher antibacterial activity, in terms of MIC(50) values, for most pathogen species when compared with marbofloxacin, difloxacin, danofloxacin and norfloxacin. Ciprofloxacin showed significantly greater in vitro antibacterial activity than enrofloxacin against M. haemolytica, P. multocida and E. coli, whereas enrofloxacin showed greater activity than ciprofloxacin against S. aureus. Marbofloxacin was significantly more active than enrofloxacin against M. haemolytica, E. coli and B. bronchiseptica but less active against P. multocida, S. aureus, coagulase negative Staphylococci, S. dysgalactiae, S. uberis, A. pleuropneumoniae and S. suis. Danofloxacin was significantly less active than enrofloxacin against P. multocida, E. coli, S. uberis, A. pleuropneumoniae and S. suis. Enrofloxacin and its metabolite ciprofloxacin showed the highest in vitro activities against most bovine pathogens tested and the porcine pathogens also showed a high degree of sensitivity to enrofloxacin. These data facilitate further pharmacokinetic/pharmacodynamic comparison of fluoroquinolones currently used in veterinary medicine.     

In vitro susceptibilities to fluoroquinolones in current and archived Mycoplasma gallisepticum and Mycoplasma synoviae isolates from meat-type turkeys

Monitoring of susceptibility to antibiotics in field isolates of pathogenic avian mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility to enrofloxacin and difloxacin in recent (2005-2006) isolates of Mycoplasma gallisepticum and Mycoplasma synoviae from meat-type turkey flocks with archived (1997-2003) isolates and reference strains. Comparison of minimal inhibitory concentration (MIC) values determined by microtest, agar dilution and commercial Etest showed good agreement, but underscored the need for standardized methods for testing. Notably, while the commercial Etest was convenient and accurate for determining MICs for enrofloxacin in the range 0.002-0.094mug/ml, the endpoint of inhibition for M. gallisepticum and M. synoviae strains with MIC values >/=1.0mug/ml could not be determined. A decrease in susceptibility to both fluoroquinolones was detected in archived strains but to a greater degree in recent isolates, most of which had MICs above the NCCLS susceptibility breakpoint for these antibiotics (相似文献   

In vitro antimicrobial activity of orbifloxacin against Staphylococcus intermedius isolates from canine skin and ear infections

The objective of the study was to evaluate the in vitro activity of orbifloxacin against Staphylococcus intermedius strains isolated in France from canine skin and ear infections. The minimum inhibitory concentrations (MICs) of orbifloxacin against 240 field S. intermedius isolates (69 skin and 171 ear isolates) ranged from 0.016 to 8 mg l(-1), with MIC50 and MIC90 equal to 0.5 and 1 mg l(-1), respectively. Only one strain, a pyoderma isolate was resistant (MIC=8 mg l(-1)). Orbifloxacin was tested at different concentrations for killing rate against five isolates obtained from pyoderma cases and against a reference strain (Staphylococcus aureus ATCC 29213). Orbifloxacin expressed a concentration-dependent bactericidal activity against the S. aureus reference strain, but a time-dependent bactericidal activity against S. intermedius. Orbifloxacin induced bactericidal effect against the S. intermedius strains tested with concentrations equal to or two times MIC.     

喹诺酮类药物对嗜水气单胞菌体外生物被膜形成能力的影响

采用微量肉汤稀释法测定3种喹诺酮类药物对21株嗜水气单胞菌的最小抑菌浓度(MIC),体外建立其生物被膜(BF),采用结晶紫法和扫描电镜的方法研究生物被膜的形成和结构,并观察喹诺酮类药物对生物被膜形成能力的影响。结果表明:喹诺酮类药物对嗜水气单胞菌有较强的抑制作用,诺氟沙星、环丙沙星、恩诺沙星的抑菌率分别为90.5%,95.25%和85.7%,其中环丙沙星的抑菌作用最强,对21株菌的最小抑菌浓度均在0.7813μg/mL以下。21株嗜水气单胞菌均可在24～48 h内体外形成较为稳定的BF,但不同菌株之间形成BF的能力有所不同。嗜水气单胞菌对喹诺酮类药物较为敏感,环丙沙星浓度在1倍MIC以上即可抑制嗜水气单胞菌生物被膜的早期形成,但细菌形成成熟的生物被膜后,较高浓度药物对生物被膜的影响不明显。     

Antimicrobial susceptibility of Actinobacillus pleuropneumoniae, Escherichia coli, and Salmonella choleraesuis recovered from Taiwanese swine.

Minimum inhibition concentrations (MICs) were determined for ampicillin, ceftiofur, cephalothin, chloramphenicol, enrofloxacin, gentamicin, lincomycin, lincospectin (lincomycin/spectinomycin), neomycin, premafloxacin, spectinomycin, sulfamethoxazole/trimethoprim, and tetracycline against a total of 180 isolates of Actinobacillus pleuropneumoniae, Escherichia coli, and Salmonella choleraesuis (60 each) clinically isolated from pigs on farms in Taiwan from 1994 to 1996. No more than 3 isolates per farm were used. Ceftiofur had the highest activity in vitro against isolates of A. pleuropneumoniae, E. coli, and S. choleraesuis, with MIC90 values of 0.03, 2, and 1 microg/ml, respectively. Premafloxacin was highly active against isolates of A. pleuropneumoniae, E. coli, and S. choleraesuis, with MIC90 values of 2, 8, and 0.5 microg/ml, respectively, which were lower than those with enrofloxacin (MIC90 8, 32, and 2 microg/ml, respectively). Neomycin was moderately active against A. pleuropneumoniae and E. coli, with MIC90 values of 8 and 64 microg/ml, respectively, but was inactive with S. choleraesuis. Gentamicin showed high activity against A. pleuropneumoniae (MIC90 of 2 microg/ml) but was only moderately active with E. coli and S. choleraesuis (MIC90 of 64 and 32 microg/ml). Cephalothin was highly active against isolates of A. pleuropneumoniae (MIC90 of 1 microg/ml) but was inactive with E. coli (MIC90 of 128 microg/ml). Lincomycin had moderate activity (MIC90 of 32 microg/ml) against A. pleuropneumoniae. Chloramphenicol, lincomycin, and tetracycline were inactive with E. coli and S. choleraesuis (MIC90 > 128 microg/ml). In conclusion, ceftiofur and premafloxacin were highly active against isolates of A. pleuropneumoniae, E. coli, and S. choleraesuis, enrofloxacin and gentamicin were highly to moderately active; cephalothin was highly active against A. pleuropneumoniae and moderately active against S. cholearesuis; chloramphenicol, lincomycin, and tetracycline were active only with A. pleuropneumoniae; neomycin was moderately active against A. pleuropneumoniae and E. coli. The other antimicrobials tested were inactive.     

Mutant-prevention concentrations of enrofloxacin for Escherichia coli isolates from chickens

OBJECTIVE: To investigate the development of enrofloxacin resistance among Escherichia coli isolates obtained from chickens by determining mutant-prevention concentrations (MPCs) and sequence the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes in selected isolates. SAMPLE POPULATION: 15 chicken-derived E coli isolates. PROCEDURES: For all isolates, MPC and minimal inhibition concentration (MIC) of enrofloxacin were determined. The MPCs and maximum serum drug concentrations attained with enrofloxacin doses recommended for treatment of E coli infections in chickens were compared. Mutation frequencies and QRDR sequence changes in gyrA and parC were also determined. RESULTS: In 2 of 15 E coli strains, MPCs were low (0.016 and 0.062 microg/mL), MPC:MIC ratios were 2 and 4, and the GyrA and ParC proteins had no mutations. In 9 susceptible isolates with a GyrA point mutation, MPCs ranged from 2 to 16 microg/mL. For isolates with double mutations in GyrA and a single mutation in ParC, MPCs were > 32 microg/mL (several fold greater than the maximal plasma concentration of enrofloxacin in chickens); mutation frequencies were also much lower, compared with frequencies for single-mutation isolates. CONCLUSIONS AND CLINICAL RELEVANCE: For E coli infections of chickens, MPC appears to be useful for determining enrofloxacin-dosing strategies. The high MPC:MIC ratio may result in enrofloxacin-treatment failure in chickens infected with some wild-type gyrA E coli isolates despite the isolates' enrofloxacin susceptibility (MICs 0.125 to 1 microg/mL). For infections involving isolates with high MPCs, especially those containing mutations in gyrA and parC genes, treatment with combinations of antimicrobials should be adopted.     

In vitro antimicrobial activity of nitrofurantoin against Escherichia coli and Staphylococcus pseudintermedius isolated from dogs and cats

Minimum inhibitory concentrations (MIC) of nitrofurantoin were determined by agar dilution in 269 canine and feline isolates of Escherichia coli and Staphylococcus pseudintermedius, two of the most common bacterial species associated with urinary tract infection (UTI) in small animals. The MIC90 for E. coli and S. pseudintermedius were 32 and 16 μg/ml, respectively. All isolates, including multidrug-resistant strains of known genetic background, displayed MICs below the drug concentrations reported in canine urine following oral administration of nitrofurantoin. Preliminary data on mutant prevention concentration (MPC) and many years of nitrofurantoin usage in human medicine suggest that emergence of resistant mutants during treatment is not a critical issue for this drug. The study provides species-specific data on nitrofurantoin MIC distribution that can be used for setting dog- and cat-specific breakpoints. Although nitrofurantoin is not an appropriate first-line agent for empirical treatment of canine UTI due to toxicity and poor pharmacokinetic properties, it may be indicated for treatment of UTI caused by multidrug-resistant bacteria, which are otherwise difficult to treat using conventional veterinary antimicrobial agents.     

Fluoroquinolone resistance in Staphylococcus intermedius

Four canine isolates of S. intermedius resistant to enrofloxacin were isolated amongst a total of 429 screened. Two of these were shown to exhibit resistance also to marbofloxacin and ciprofloxacin. Whilst molecular studies have shown the mechanism of resistance to these quinolone antibiotics to be similar in a number of staphylococcal species, it was not possible to confirm this mechanism in Staphylococcus intermedius .     

Comparative mutant prevention concentration and mechanism of resistance to veterinary fluoroquinolones in Staphylococcus pseudintermedius

Background – The problem of antibacterial drug resistance is increasing worldwide, in part due to the therapeutic concentrations currently used based on the minimal inhibitory concentration (MIC) as a measure of potency are often the very concentrations required to selectively enrich the resistant mutant portion of the population. A mutant prevention concentration (MPC)‐based dosing strategy is suggested to improve the therapeutic outcome based on the MIC. Objective – Our aim was to investigate the MPC and mechanism of resistance to various fluoroquinolones using recent Staphylococcus pseudintermedius isolates from canine pyoderma. Methods – The broth microdilution method for MIC and a series of agar plates containing different concentrations of fluoroquinolones were inoculated with ～10¹⁰ colony‐forming units of the bacterial culture for MPC were used. PCR was used to identify mutation in the resistant isolates. Results – The rank order of potency based on MIC and MPC was ciprofloxacin = enrofloxacin ≥ marbofloxacin > difloxacin ≥ orbifloxacin. Integrating our data with reported pharmacokinetic data at the recommended dose ranges revealed that only high doses of ciprofloxacin, enrofloxacin and marbofloxacin could achieve a maximal plasma concentration (C_max) greater than the MPC of 90% of isolates (C_max/MPC₉₀). The overall rank of potency against S. pseudintermedius, based on C_max/MIC, C_max/MPC, the area under concentration–time curve (AUC)/MIC and AUC/MPC values, was in decreasing order: enrofloxacin > ciprofloxacin ≥ marbofloxacin ≥ orbifloxacin = difloxacin. Sequencing of the quinolone resistant determining region of gyrA, gyrB, grlA and grlB of resistant strains showed a base‐pair substitution in both gyrA and gyrB that resulted in Ser‐84 to Leu and Ser‐80 to Arg amino acid changes, respectively. Conclusions and clinical importance – High doses of ciprofloxacin, enrofloxacin and marbofloxacin could minimize the selection of resistant mutants, whereas the possibility of selecting mutants with the conventional doses of difloxacin and orbifloxacin, and low clinical doses of all fluoroquinolones, seems high.     

Reduced in vitro adherence of Staphylococcus species to feline corneocytes compared to canine and human corneocytes

It is apparent that in-contact humans and animals exchange commensal staphylococci. Previous in vitro studies, however, indicate that staphylococci preferentially adhere to corneocytes from host species. This study compared adherence of meticillin-sensitive and -resistant Staphylococcus aureus (MSSA/MRSA), S. intermedius, S. felis and S. hominis to feline, canine and human corneocytes acquired from 10 healthy subjects using adhesive tape discs. Adherent bacteria were counted using an image processing and analysis programme. Mean adherence of MSSA (P = 0.0009), MRSA (P = 0.0162) and S. intermedius (P = 0.0117), but not S. felis or S. hominis, to feline corneocytes was significantly lower than that to canine and human corneocytes. All the isolates had similar adherence to both human and canine corneocytes. S. felis was the most adherent species to feline corneocytes followed by S. intermedius, and then MSSA, MRSA and S. hominis. For dogs and humans, S. intermedius and S. felis were the most adherent, followed by MRSA and MSSA, and then S. hominis. These results do not reveal any preferential adherence of staphylococci to canine or human corneocytes. Poor adherence to feline corneocytes could suggest that cats are relatively resistant to pyoderma and cross-species transmission of staphylococci.     

Antimicrobial activity of enrofloxacin against Staphylococcus intermedius strains isolated from canine pyodermas

This study examined and compared the minimal inhibition concentrations (MICs) of enrofloxacin against 393 Staphylococcus intermedius strains isolated in France from canine pyodermas during three different years, 1995 (174 isolates), 1997 (101 isolates) and 1999 (118 isolates). The MICs of enrofloxacin against these strains ranged from 0.063 to 64 mg L^?1, with MIC₅₀ and MIC₉₀ equal to 0.125 and 0.25 mg L^?1, respectively. Two resistant strains were found, but only among isolates collected in 1999. The data show that resistance to enrofloxacin among S. intermedius strains is still rare in dogs, but the selection in vitro of variants in which the MICs were increased 4–16‐fold after 10 serial passages in subinhibitory concentrations of enrofloxacin suggests that inappropriate use might favour the development of resistant strains in vivo.     

In vitro antibacterial activity of enrofloxacin and ciprofloxacin in combination against Escherichia coli and staphylococcal clinical isolates from dogs

The objective of the study was to determine the in vitro interaction between enrofloxacin and ciprofloxacin against Escherichia coli and staphylococcal isolates from dogs. The microdilution checkerboard assay was used to determine the interaction of the drugs against 50 E. coli and 50 beta-haemolytic staphylococcal clinical isolates. The checkerboard assay revealed that the activity of enrofloxacin and ciprofloxacin was additive against E. coli and staphylococcal clinical isolates. It was concluded that for bacterial species against which ciprofloxacin is more potent than enrofloxacin, the in vivo transformation of enrofloxacin to ciprofloxacin may enhance the efficacy of enrofloxacin, if additivity of the drugs is confirmed in vivo.     

Trends in fluoroquinolone resistance of bacteria isolated from canine urinary tracts.

Fluoroquinolone (FQ) antimicrobial agents are used extensively in human and veterinary medicine. Widespread use of any antimicrobial agent can apply selective pressure on populations of bacteria, which may result in an increase in the prevalence of antimicrobial-resistant isolates. Antimicrobial-susceptibility data on bacteria isolated from the canine urinary tract by the University of Missouri-Columbia Veterinary Medical Diagnostic Laboratory, Columbia, MO, were used to determine whether there has been an increase in the prevalence of FQ-resistant bacteria over time. Between January 1992 and December 2001, minimum inhibitory concentrations of either ciprofloxacin (1992-1998) or enrofloxacin (1998-2001) were determined for 1,478 bacterial isolates from the canine urinary tract. The predominant bacterial species isolated were Escherichia coli (547 isolates), Proteus mirabilis (156), and Staphylococcus intermedius (147). In all, there were 13 bacterial species with more than 25 isolates each. A significant increase in the overall proportion of resistant bacterial isolates was documented from 1992 to 2001 (Cochran-Armitage test for trend, P < 0.0001). The same increase in resistant isolates was documented when either ciprofloxacin or enrofloxacin was analyzed separately (P < 0.0001 and P < 0.0002, respectively). No difference was detected in rates of bacterial FQ resistance with regard to the sex of the dog from which the bacteria were isolated. The frequency with which some bacterial species were isolated differed with the sex of the infected dog. Proteus mirabilis was found more often in females (P < 0.0001), whereas beta hemolytic Streptococcus spp., were found more often in males (P = 0.0003). Although the overall efficacy of FQ antimicrobials remained high with greater than 80% of isolates being susceptible, the data demonstrated an increase in the proportion of resistant bacteria isolated from the urinary tract of the dog.     

Adherence of Staphylococcus intermedius to canine corneocytes in vitro

This study investigated the in vitro adherence of Staphylococcus intermedius to canine corneocytes, collected from a healthy dog using double-sided adhesive tape. Adherence was shown to depend on duration (P < 0.001) and temperature of incubation (P < 0.001) and the concentration of bacteria (P < 0.001). Isolates of S. intermedius from lesions of pyoderma were not generally more adherent to healthy canine skin than were isolates from healthy dogs. Significant differences in adherence were demonstrated between individual isolates within both groups (P < 0.001). The study suggests that among S. intermedius there is no correlation between virulence and adherence to canine corneocytes in vitro. The finding may be important for the potential use of avirulent variants of S. intermedius as antagonistic strains against canine pyoderma. However, more studies are needed to compare the adherence of the isolates to skin cells obtained from dogs with diseases predisposed to pyoderma.     

In vitro killing of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin in combination with its active metabolite ciprofloxacin using clinically relevant drug concentrations in the dog and cat

Enrofloxacin is a fluoroquinolone antibacterial agent used to treat infections in companion animals. Enrofloxacin's antimicrobial spectrum includes Gram positive and Gram-negative bacteria and demonstrates concentration-dependent bacteriocidal activity. In dogs and cats, enrofloxacin is partially metabolized to ciprofloxacin and both active agents circulate simultaneously in treated animals at ratios of approximately 60-70% enrofloxacin to 30-40% ciprofloxacin. We were interested in determining the killing of companion animal isolates of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin and ciprofloxacin combined using clinically relevant drug concentrations and ratios. For E. coli isolates exposed to 2.1 and 4.1μg/ml of enrofloxacin/ciprofloxacin at 50:50, 60:40 and 70:30 ratios, a 1.7-2.5log(10) reduction (94-99% kill) was seen following 20min of drug exposure; 0.89-1.7log(10) (92-99% kill) of S. pseudintermedius following 180min of drug exposure; 0.85-3.4log(10) (98-99% kill) of P. aeruginosa following 15min of drug exposure. Killing of S. pseudintermedius was enhanced in the presence of enrofloxacin whereas killing of P. aeruginosa was enhanced in the presence of ciprofloxacin. Antagonism was not seen when enrofloxacin and ciprofloxacin were used in kill assays. The unique feature of partial metabolism of enrofloxacin to ciprofloxacin expands the spectrum of enhanced killing of common companion animal pathogens.