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Original Articles Analysis of Long Term (20 Years) In Vitro Susceptibility to Antibacterial Drugs of the Most Prevalent Animal Bacterial Pathogens Isolated in Israel. Part 2: Multi-Drug Resistance
Elad, D.,* Blum, S., Fleker, M., Zukin, N., Weissblit, L. and Shlomovitz, S.
Department of Clinical Bacteriology and Mycology, the Kimron Veterinary Institute, P.O. Box 12, Bet Dagan, 50250 Israel
* Corresponding author: Daniel Elad, DVM, PhD. Kimron Veterinary Institute P.O.Box 12, Bet Dagan, Israel, 50250; Phone: +972-(0)3-9681688; Fax: +972-(0)3-9688965. Email: danielad@moag.gov.il
AB ST RAC T
This part of the study is based on the data presented in Part 1 in the Israel Journal of Veterinary Medicine. Changes in the number of antibacterial drugs to which each microorganism was susceptible and possible correlation between all the combinations of susceptibility curves were evaluated. Results indicated a decrease in the number of drugs to which the microorganisms were resistant to, for Salmonella enterica serogroup B and Proteus spp. The number of drugs to which E. coli showed resistance decreased but returned to the original level. The low number of drugs (n=4) that were used for Pseudomonas aeruginosa made the identification of variations difficult. It was found that while stability was maintained until 2007, the number of resistant drugs decreased steeply in 2008 and somewhat increased in 2009. For Pasteurella multocida and Mannheimia haemolytica, the number of antibacterial drugs to which there was a resistance remained practically unchanged. No noteworthy patterns of correlation between susceptibility curves were observed with the exception of chloramphenicol and sulfamethoxazole/trimethoprim that had a high correlation coefficient for 3 out of the 6 included microorganisms: E. coli, Proteus spp. and P. multocida. These findings are in general in agreement with those of Part 1 of this study and stress the importance of conducting long term surveys before reaching conclusions regarding the evolution of bacterial resistance and multi-resistance.
Key words: Multi drug resistant, long term, in vitro susceptibility, animal.
During the last decades, multi-drug resistant (MDR) bacteria have become one of the most problematic topics of human and veterinary medicine (1). A clear definition of the term exists for Mycobacterium tuberculosis – an isolate resistant at least to isoniazid and rifampin is considered multidrug resistant (2). The definition of other bacteria as MDR is more vague (3). In addition to the term MDR other expressions such as Extensive Drug Resistant (XDR) (4) and Pan Drug Resistant (PDR) (5) have been used to define, respectively, strains of Mycobacterium tuberculosis (4) and Gram
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INTRODUCTION
negative bacteria showing exceptionally marked resistance to antibacterial drugs (3). The establishment of MDR bacteria has been associated with the intensive subtherapeutic concentrations of antibacterial drugs in hospitals (6, 7), but more recently such strains have been reported with increased frequency in the community as well (8, 9). Bacteria may become MDR following prolonged exposure to the relevant drugs (10), horizontal gene transfer (11) or by a resistance mechanism that develops for one drug but affects indirectly several others as well (12). The latter may be assessed by evaluating eventual
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associations between the resistances to two or more drugs. In this second part of the study we examined the long term variations in the prevalence of MDR bacteria and associations between their resistance patterns. This part of the study is based on the data presented in Part 1 (13). The following parameters were assessed: 1. Changes over time of the number of antibacterial drugs to which each microorganism was susceptible. Annual trends were assessed by the LINEST() function of MS Excel® and their statistical significance determined according to F percentile distribution tables (Dixon, 1957). Only antibacterial drugs examined during the whole period of 20 years were included and presented in Table 1. 2. Correlations between all the combinations of susceptibility curves were evaluated by the CORREL() function of MS Excel®.
Table 1: Bacteria and antibacterial drugs included in the study: Pseudomonas. Salmonella aeruginosa enterica sgr. B Escherichia coli Proteus spp. + + + + + + + + + + + +
MATERIALS AND METHODS
Gentamicin Amikacin Polimixin B Fluoroquinolones Ampicillin Chloramphenicol Sulfamethoxazoletrimethoprim Cefotaxime Cephalothin Tetracyclines
Pasteurella multocida Mannheimia haemolytica + + + + + +
Results
Results of the changes in the number of antibacterial drugs to which each microorganism was susceptible are shown in Tables 2-7 and Figures 1-3. For Salmonella enterica serogroup (sgr.) B (Figure 1) a decrease in the statistical mode from resistance to 4 drugs in 1990 to 1 in 2004 (0 in 2003) was noted. This decrease was highly significant (p<0.01). Interestingly, this decrease was not uniform in time, but proceeded in a stepwise mode between 1990 and 1993 (with a temporary increase in 1993) and 2001 and 2003, remaining stable between the years 1993 to 2001. A highly signifi-
Figure 2: Mode of number of antibacterial drugs Proteus spp. isolates were resistant to.
Figure 1: Mode of number of antibacterial drugs Salmonella enterica sgr. B isolates were resistant to. Decrease statistically highly significant (p<0.01)
Figure 3: Mode of number of antibacterial drugs Escherichia coli isolates were resistant to.
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cant (p<0.01) decrease in the number of resistant drugs was observed for Proteus spp. (Figure 2) as well, but, unlike S. enterica sgr. B, this decrease was more or less constant. An increase in the statistical mode was observed between 1993 and 1997 and starting 2007. The number of resistant drugs to E. coli followed a completely different pattern to that of other drugs. While the mode values for S. enterica sgr, B and Proteus spp. followed a general trend, E. coli values evolved in a curve (Figure 3): mode values went from resistance to 5 drugs in 1992, decreased to 0 in 1999 and returned to 4 drugs in 2009. Due to its intrinsic resistance to most antibacterial drugs used in our laboratory, the susceptibility of Pseudomonas aeruginosa was tested to only 4 drugs. While this low number could make it difficult to identify the more subtle variations, in this survey we found that until 2007 the mode was stable (without resistance to any drug between 1993 and 2007). Interestingly within one year the mode increased to resistance to 3 out of 4 tested drugs, returning to one drug in 2009. For the respiratory pathogens, Pasteurella multocida and
Mannheimia haemolytica, the mode remained practically unchanged at a resistance of only one to two drugs. Correlation coefficients between the various susceptibility curves are presented in Tables 8-13. While high (>0.7) coefficients were found in several cases, no noteworthy patterns emerged. The only couple of drugs that showed a high correlation coefficient in more than one microorganism were those observed between chloramphenicol and sulfamethoxazole/trimethoprim: 0.822, 0.717 and 0.772 in E. coli, Proteus spp. and P. multocida, respectively. DISCUSSION
The results of the survey on multidrug resistance are generally in accordance with those found the previous study covering drug resistance of bacteria in Israel (13), namely that the number of antibacterial drugs the microorganisms were resistant to did not increase. In fact in two cases, Salmonella enterica sgr. B and Proteus spp., these values decreased. In the case of E. coli, the importance of long term surveys emphasized in Part 1 of this study was underscored once more
N 0 1 2 3 4 5 6 7 8
1990 19.1 2.2 7.9 13.5 23.6 15.7 12.4 4.5 1.1
Table 2: Number of antibacterial drugs Salmonella enterica sgr. B isolates were resistant to (percent). Mode emphasized. 1991 12.2 7.0 7.8 12.2 34.8 14.8 6.1 3.5 1.7 1992 12.0 9.8 9.8 21.7 19.6 16.3 7.6 3.3 0.0 1993 12.4 15.2 15.2 15.2 14.3 17.1 8.6 1.9 0.0 1994 24.5 9.6 28.7 16.0 13.8 6.4 0.0 1.1 0.0 1995 19.5 8.6 28.9 19.5 17.2 5.5 0.8 0.0 0.0 1996 13.8 10.6 38.1 17.5 9.4 5.6 4.4 0.6 0.0 1997 14.4 8.5 31.4 20.3 10.2 8.5 3.4 2.5 0.8 1998 14.3 11.7 35.1 16.9 11.7 6.5 3.9 0.0 0.0 1999 18.5 11.1 24.1 22.2 14.8 5.6 3.7 0.0 0.0 2000 19.4 18.1 23.6 20.8 12.5 2.8 0.0 2.8 0.0 2001 24.7 20.8 29.9 11.7 7.8 1.3 3.9 0.0 0.0 2002 27.7 34.9 15.7 10.8 4.8 6.0 0.0 0.0 0.0 2003 26.2 23.8 21.4 9.5 7.1 7.1 4.8 0.0 0.0
2004 12.5 22.5 15.0 17.5 7.5 5.0 15.0 5.0 0.0
N: number of antibacterial drugs N 0 1 2 3 4 5 6 7 8 1990 1.5 3.1 21.5 23.1 23.1 12.3 9.2 3.1 3.1 1991 0.0 5.9 8.8 27.9 32.4 10.3 7.4 7.4 0.0 1992 0.0 0.0 8.5 23.7 23.7 23.7 15.3 5.1 0.0 Table 3: Number of antibacterial drugs Proteus spp. isolates were resistant to (percent). Mode emphasized. 1993 0.0 3.6 14.3 25.0 21.4 21.4 8.9 3.6 1.8 1994 3.2 16.1 12.9 19.4 19.4 14.5 11.3 3.2 0.0 1995 0.0 12.7 25.4 15.5 29.6 7.0 7.0 1.4 1.4 1996 0.0 7.9 15.8 17.1 23.7 22.4 6.6 6.6 0.0 1997 1.3 6.3 11.3 15.0 20.0 21.3 13.8 6.3 5.0 1998 0.0 8.7 15.2 14.1 18.5 25.0 9.8 7.6 1.1 1999 2.1 8.2 27.8 18.6 18.6 16.5 7.2 1.0 0.0 2000 2.6 12.8 24.8 25.6 22.2 10.3 0.9 0.9 0.0 2001 1.8 10.1 21.1 22.0 16.5 14.7 11.9 1.8 0.0 2002 0.0 6.4 28.0 22.4 18.4 13.6 8.8 1.6 0.8 2003 0.0 5.3 19.5 25.7 22.1 18.6 3.5 4.4 0.9 2004 2.4 4.9 23.2 18.3 17.1 13.4 9.8 7.3 3.7 2005 3.4 24.1 26.4 12.6 18.4 10.3 3.4 0.0 1.1 2006 3.9 28.4 22.5 19.6 13.7 4.9 4.9 2.0 0.0 2007 0.0 43.8 25.0 12.5 10.4 4.2 4.2 0.0 0.0 2008 0.0 18.0 31.1 16.4 19.7 8.2 4.9 1.6 0.0 2009 1.1 26.9 17.2 28.0 14.0 9.7 1.1 1.1 1.1
N: number of antibacterial drugs
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N 0 1 2 3 4 5 6 7 8
1990 3.6 8.9 17.2 16.7 18.8 17.7 11.5 3.6 2.1
1991 7.4 11.9 15.6 32.6 14.8 9.6 3.7 1.5 3.0
Table 4: Number of antibacterial drugs Escherichia coli isolates were resistant to (percent). Mode emphasized. 1992 0.0 16.3 12.6 17.8 14.8 22.2 10.4 5.2 0.7 1993 6.7 13.5 19.0 15.3 20.9 13.5 8.6 2.5 0.0 1994 11.5 20.9 22.1 19.1 14.9 6.4 2.6 0.9 1.7 1995 0.0 12.1 27.2 23.8 20.0 8.6 6.2 1.4 0.7 1996 5.2 17.6 20.5 18.8 13.9 10.7 9.0 2.3 2.0 1997 6.4 16.5 21.9 17.2 13.8 11.1 8.1 3.0 2.0 1998 11.4 17.8 22.1 19.2 11.4 13.2 3.6 1.1 0.4 1999 21.2 17.0 18.7 15.7 12.9 11.5 1.9 0.8 0.3 2000 18.5 17.3 18.5 17.0 15.0 9.1 3.5 1.2 0.0 2001 19.4 15.8 21.2 13.7 12.8 10.4 4.5 0.9 1.2 2002 16.8 17.4 22.6 13.9 16.0 8.2 4.1 1.1 0.0 2003 16.5 19.6 18.3 16.5 13.0 9.3 3.3 1.8 1.8 2004 9.0 21.1 17.5 19.8 14.1 9.5 5.7 2.8 0.5 2005 12.3 19.6 19.6 15.8 12.5 8.4 5.7 5.2 0.8 2006 14.2 21.8 16.2 14.2 12.7 12.5 4.4 3.4 0.5
2007 15.2 19.1 17.3 14.4 16.2 8.7 5.1 2.9 1.1
2008 5.6 12.4 17.4 19.1 12.9 15.7 9.0 6.2 7.3
2009 4.5 10.7 10.4 16.2 16.4 15.7 13.7 9.0 3.5
N: number of antibacterial drugs
Table 5: Number of antibacterial drugs Pseudomonas aeruginosa isolates were resistant to (percent). Mode emphasized. Note steep increase in multi-drug resistant isolates in 2008. N 0 1 2 3 4 1990 27.6 37.9 31.0 1.7 1.7 1991 33.3 24.0 36.0 6.7 0.0 1992 31.1 37.8 24.4 6.7 0.0 1993 51.9 22.2 20.4 5.6 0.0 1994 60.9 20.3 17.2 1.6 0.0 1995 68.4 17.5 10.5 3.5 0.0 1996 57.1 23.4 13.0 5.2 1.3 1997 48.0 24.0 16.0 10.7 1.3 1998 61.9 31.0 6.0 1.2 0.0 1999 49.6 29.9 12.0 7.7 0.9 2000 49.1 35.3 10.3 4.3 0.9 2001 51.0 31.5 8.7 7.4 1.3 2002 47.9 24.8 18.8 7.7 0.9 2003 42.7 32.1 18.3 6.1 0.8 2004 34.3 30.5 22.9 11.4 1.0 2005 55.9 20.7 13.5 6.3 3.6 2006 67.6 20.9 5.4 6.1 0.0 2007 68.2 22.7 4.5 4.5 0.0 2008 2.7 9.5 25.7 47.3 14.9 2009 9.6 69.3 7.0 9.6 4.4
N: number of antibacterial drugs
N: number of antibacterial drugs
N 0 1 2 3 4 5 6
1990 43.0 26.0 11.0 10.0 7.0 3.0 0.0
1991 66.7 17.5 10.5 3.5 1.8 0.0 0.0
Table 6: Number of antibacterial drugs Pasteurella multocida isolates were resistant to (percent). Mode emphasized. 1992 51.6 26.6 9.4 9.4 3.1 0.0 0.0 1993 58.4 18.2 11.7 5.2 3.9 2.6 0.0 1994 39.4 38.4 11.1 6.1 4.0 1.0 0.0 1995 39.5 34.0 11.6 8.8 4.8 1.4 0.0 1996 44.6 27.3 17.4 3.3 1.7 4.1 1.7 1997 27.8 37.3 16.7 8.7 4.8 4.0 0.8 1998 43.4 22.1 18.0 5.7 5.7 3.3 1.6 1999 41.7 35.2 12.0 5.6 2.8 2.8 0.0 2000 58.4 23.8 6.9 6.9 3.0 1.0 0.0 2001 53.8 28.8 9.6 2.9 2.9 1.0 1.0 2002 59.6 24.1 7.8 4.3 3.5 0.7 0.0 2003 40.5 35.1 14.4 4.5 3.6 0.9 0.9 2004 49.0 32.7 10.2 5.1 1.0 2.0 0.0 2005 41.3 34.9 12.8 6.4 2.8 1.8 0.0 2006 54.0 27.0 9.5 7.3 0.0 2.2 0 2007 67.6 16.7 10.2 3.7 0.0 0.9 0.9
2008 40.6 31.3 18.8 6.3 3.1 0.0 0.0
2009 71.1 15.6 6.7 4.4 0.0 0.0 2.2
N: number of antibacterial drugs
N 0 1 2 3 4 5 6
1990 63.2 22.6 6.6 3.8 2.8 0.9 0.0
Table 7: Number of antibacterial drugs Mannheimia haemolytica isolates were resistant to (percent). Mode emphasized. 1991 60.0 20.0 8.0 10.7 1.3 0.0 0.0 1992 66.7 17.5 6.3 6.3 3.2 0.0 0.0 1993 50.5 16.5 6.6 16.5 5.5 4.4 0.0 1994 41.2 21.6 18.6 14.4 1.0 3.1 0.0 1995 46.1 32.4 12.7 6.9 1.0 1.0 0.0 1996 46.9 21.9 10.9 15.6 1.6 3.1 0.0 1997 36.6 31.0 9.9 14.1 2.8 4.2 1.4 1998 43.8 20.3 7.8 20.3 1.6 4.7 1.6 1999 54.8 21.0 8.1 12.9 3.2 0.0 0.0 2000 50.0 16.0 12.0 16.0 0.0 2.0 4.0 2001 54.0 14.3 19.0 11.1 1.6 0.0 0.0 2002 53.8 26.9 3.8 9.6 3.8 1.9 0.0 2003 39.6 39.6 15.1 3.8 1.9 0.0 0.0 2004 36.8 40.4 10.5 8.8 0.0 3.5 0.0 2005 40.7 37.3 10.2 6.8 3.4 1.7 0.0 2006 42.4 39.0 13.6 3.4 0.0 1.7 0.0 2007 49.3 21.9 19.2 9.6 0.0 0.0 0.0
2008 32.7 26.5 18.4 14.3 6.1 2.0 0.0
2009 46.3 39.0 9.8 2.4 2.4 0.0 0.0
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SxT: Sulfamethoxazole-trimethoprim, Ceph: Cephalothin, Amp: Ampicillin, AmC: Amoxicillin/clavulanic acid, Gen: Gentamicin, Flq: Fluoroquinolones, Ctx: Cefotaxime, PB: Polymyxin B, Clm: Chloramphenicol, Amk: Amikacin; *Starting 1992 Table 9: Correlation coefficients for Escherichia coli susceptibility curves. Values above 0.7 emphasized. Ceph* Amp AmC* Gen Flq Ctx PB
Ceph* Amp AmC* Gen Flq Ctx PB Clm Amk
SxT 0.368 0.214 -0.460 0.891 0.310 0.631 0.472 0.122 0.539
Table 8: Correlation coefficients for Salmonella enterica sgr. B susceptibility curves. Values above 0.7 emphasized. Ceph* Amp AmC* Gen Flq Ctx PB
Clm
0.157 0.175 0.544 0.284 0.522 0.592 -0.414 0.715
0.639 0.503 0.099 0.129 -0.222 0.723 0.344
-0.124 -0.157 -0.037 -0.450 0.447 0.326
0.377 0.547 0.421 0.261 0.578
0.265 0.115 -0.007 0.104
0.281 -0.128 0.568
-0.619 0.145
0.203
SxT: Sulfamethoxazole-trimethoprim, Ceph: Cephalothin, Amp: Ampicillin, AmC: Amoxicillin/clavulanic acid, Gen: Gentamicin, Flq: Fluoroquinolones, Ctx: Cefotaxime, PB: Polymyxin B, Clm: Chloramphenicol, Amk: Amikacin; *Starting 1992 Table 10: Correlation coefficients for Proteus spp. susceptibility curves. Values above 0.7 emphasized. Ceph* Amp AmC* Gen Flq Ctx PB Clm Amk SxT Ceph* Amp AmC* Gen 0.754 0.725 0.674 0.505 0.792 0.593 0.130 0.218 0.259 0.430 -0.237 -0.433 -0.076 -0.354 0.082 0.806 0.835 0.643 0.459 0.029 -0.407 -0.521 -0.387 -0.270 0.344 0.717 0.806 0.574 0.712 0.403 0.400 0.565 0.437 0.745 0.463 Flq Ctx PB Clm
Ceph* Amp AmC* Gen Flq Ctx PB Clm Amk
SxT 0.055 0.411 0.175 0.239 -0.454 0.467 0.340 0.822 0.639
Clm
0.418 0.604 0.349 0.547 0.136 0.691 -0.180 0.198
0.255 0.338 0.064 0.582 0.521 0.321 0.278
0.336 0.069 -0.023 0.150 -0.027 0.430
0.179 0.311 0.523 0.152 0.239
-0.347 0.072 -0.751 -0.624
0.638 0.673 0.689
0.352 0.484
0.798
-0.329 0.337 -0.517 -0.486 0.649 -0.365 -0.206 0.362 0.191 0.548
SxT: Sulfamethoxazole-trimethoprim, Ceph: Cephalothin, Amp: Ampicillin, AmC: Amoxicillin/clavulanic acid, Gen: Gentamicin, Flq: Fluoroquinolones, Ctx: Cefotaxime, PB: Polymyxin B, Clm: Chloramphenicol, Amk: Amikacin; *Starting 1992
since the decrease in the number of antibacterial drugs this microorganism was susceptible to was followed by an increase during the following years, to a level almost identical to the original stage.
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Whether the increase in multiresistance observed for Proteus spp. in 2008-2009 indicates a trend or a temporary fluctuation, similar to the rise observed between 1993 and 1996, may be determined in the future. The same considerations may be made for Pseudomonas aeruginosa regarding the results of 2008 in which almost half of the isolates tested were resistant to 3 out of 4 drugs examined and 14.9% were resistant to all 4. Although the results of 2009 indicate that this may have been an exceptional phenomenon, its amplitude (decreasing from a mode of 0 resistances to 3/4) is significant enough to warrant further monitoring. Correlation coefficients between the various susceptibility curves did not indicate a noteworthy pattern. Interestingly when high correlation coefficients were found they were between different drug groups while high coefficients between drugs belonging to the same (the aminoglycoside gentamicin and amikacin) or similar (the beta-lactam penicillins and cephalosporins) groups were rare. Another noteworthy observation regards the correlation between chloramphenicol
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Table 11: Correlation coefficients for Pseudomonas aeruginosa susceptibility curves. Values above 0.7 emphasized. Gen Flq PB Amk Gen Flq PB
other hand, a third microorganism for which a high correlation coefficient was found, Pasteurella multocida, belongs to a completely different family, the Pasteurellaceae.
1. French, G. L.: The continuing crisis in antibiotic resistance. Int. J. Antimicrob. Agents. 36 Suppl 3:S3-7, 2010. 2. Frieden, T. R., Sherman, L. F., Maw, K. L., Fujiwara, P. I., Crawford, J. T., Nivin, B., Sharp, V., Hewlett, D. Jr., Brudney, K., Alland, D. and Kreisworth, B. N.: A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA. 276:1229-1235, 1996. 3. Falagas, M. E., Koletsi, P. K. and Bliziotis, I. A.: The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa. J. Med. Microbiol. 55:1619-1629, 2006. 4. Kang, M. W., Kim, H. K., Choi, Y. S., Kim, K., Shim, Y. M., Koh, W. J. and Kim, J.: Surgical treatment for multidrug-resistant and extensive drug-resistant tuberculosis. Ann. Thorac. Surg. 89:1597-1602, 2010. 5. Tsioutis, C., Kritsotakis, E. I., Maraki, S. and Gikas, A.: Infections by pandrug-resistant gram-negative bacteria: clinical profile, therapeutic management, and outcome in a series of 21 patients. Eur. J. Clin. Microbiol. Infect. Dis. 29:301-305, 2010. 6. Lee, A. S., Huttner, B. and Harbarth, S.: Control of methicillin-resistant Staphylococcus aureus. Infect. Dis. Clin. North Am. 25:155-179, 2011. 7. Mihu, M. R. and Martinez, L. R.: Novel therapies for treatment of multi-drug resistant Acinetobacter baumannii skin infections. Virulence. 2:97-102, 2011. 8. Telang, N.V., Satpute, M. G., Dhakephalkar, P. K., Niphadkar, K.B. and Joshi, S.G.: Fulminating septicemia due to persistent pan-resistant community-acquired metallo-β-lactamase (IMP-1)-positive Acinetobacter baumannii. Indian J. Pathol. Microbiol. 54:180-182, 2011. 9. Pichereau, S. and Rose, W. E.: Invasive community-associated MRSA infections: epidemiology and antimicrobial management. Expert Opin. Pharmacother. 11:3009-3025, 2010. 10. Davies, J. and Davies, D.: Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev. 74:417-433, 2010. 11. Babic, A., Berkmen, M. B., Lee, C. A. and Grossman, A. D.: Efficient gene transfer in bacterial cell chains. MBio. 2:pii: e0002711, 2011. 12. Guardabassi, L. and Courvalin, P.: Modes of Antibacterial Action and Mechanisms of Bacterial Resistance. in: Aarestrup FK. (ed.) Antimicrobial Resistance in Bacteria of Animal Origin. ASM Press, Washington DC, 2006, pp 1-18. 13. Elad, D., Blum, S., Fleker, M., Zukin, N., Weissblit, L. and Shlomovitz, S.: Analysis of long term (1990-2009) in vitro susceptibility to antibacterial drugs of the most prevalent animal bacterial pathogens isolated in Israel. Part 1: Trends and fluctuations. Isr. J. Vet. Med. 66:134-142, 2011. 14. Correlation Correl() & Percentiles of distribution of r Introduction to Statistical Analysis, WJ Dixon, FJ Massey Jr., 2nd ed, 1957, McGraw Hill, New York.
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Gen: Gentamicin, Flq: Fluoroquinolones, PB: Polymyxin B, Amk: Amikacin Table 12: Correlation coefficients for Pasteurella multocida sceptibility curves. Values above 0.7 emphasized. Ceph Amp AmC* Gen Flq* Ctx* Tet Clm SxT 0.389 -0.173 -0.268 -0.048 0.258 -0.278 0.445 0.772 Ceph Amp AmC* Gen -0.051 0.194 -0.220 0.183 -0.179 -0.442 Flq* Ctx* Tet
-0.176 0.552 0.866
0.048 -0.177
REFERENCES
0.540
SxT: Sulfamethoxazole-trimethoprim, Ceph: Cephalothin, Amp: Ampicillin, AmC: Amoxicillin/clavulanic acid, Gen: Gentamicin, Flq: Fluoroquinolones, Ctx: Cefotaxime, Tet: Tetracyclines, Clm: Chloramphenicol; *Starting 1992 Table 13: Correlation coefficients for Mannheimia haemolytica susceptibility curves. Values above 0.7 emphasized. SxT Ceph -0.070 Amp 0.677 AmC* -0.313 Gen -0.101 Flq* 0.415 Ctx* 0.470 Tet 0.302 Clm 0.068 Ceph Amp AmC* Gen -0.315 -0.016 0.430 0.524 0.289 -0.108 Flq* Ctx* Tet
0.371 0.163 0.281 -0.226 -0.273 0.148 0.357
0.729 0.024 0.461 -0.148 -0.194
0.033 0.356 0.556 -0.239 0.569 0.262 -0.120 0.334 -0.280 0.480
0.234 0.553 -0.074 0.273 -0.102 0.116 -0.040
-0.246 -0.114 -0.012 0.326 -0.118
-0.043 0.181 0.240 -0.240 -0.089 0.015 -0.049 0.053 -0.182 -0.063
SxT: Sulfamethoxazole-trimethoprim, Ceph: Cephalothin, Amp: Ampicillin, AmC: Amoxicillin/clavulanic acid, Gen: Gentamicin, Flq: Fluoroquinolones, Ctx: Cefotaxime, Tet: Tetracyclines, Clm: Chloramphenicol; *Starting 1992
and sulfamethoxazole/trimethoprim. The curves of these two antibacterial drugs were the only ones to be significant in more than one case. In fact they correlated for E. coli, Proteus spp. and P. multocida. Interestingly this seems to indicate that if a common mechanism of resistance exists, the microorganisms' taxonomic affiliation is not the only determining factor: the correlation was observed for E. coli, Proteus spp. which belongs to the Enterobacteriaceae but not for another member of the same family, Salmonella enterica sgr. B. On the
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