Minimum Inhibitory Concentrations of Different Antibiotics for Pasteurella Multocida, Pasteurella Haemolytica and Corynebacterium Pyogenes of Bovine Origin, and Therapeutic Considerations
H. Specht II. Medizinische Tierklinik, Universitat MiXnchen W. Gedek Tiergesundheitsdienst Bayern, Grub G. Dirksen II. Medizinische Tierklinik, Universitat MiXnchen
A wide range of microorganisms with varying In 38 swab samples P. multocida as well as P. haemolytica pathogenicity has been isolated from the lungs of cattle were detected. affected by enzootic bronchopneumonia (transport The minimum inhibitory concentrations of the tested pneumonia, shipping fever); nevertheless there is no doubt antibiotics for the isolated germs are listed in the following that P. haemolytica and P. multocida are the main causes two tables. of this disease. In the advanced stage of the condition C. pyogenes is frequently also present as a secodary invader. It is therefore of practical and therapeutic significance to regularly review the sensitivity of these bacteria to the antibiotics available for the treatment of pneumonia. Tab le 1: Minimum inhibitory concentrations of the tested antibiotics for 50 strains of P.multocida and 22 strains of P.Haemolytica Materials and Methods
Nasal swabs (n = 392) were taken from the airways of mg/1 0.125 0.25 0.5 1 2 4 8 16 32 64 128 >128 calves which were afflicted by, or had died of enzootic Amoxicillin bronchopneumonia (EBP), as well as from calves which P.h. 4 10 2 1 2 3 P.m. 45 5 were initially healthy but later became affected by EBP. O xacillin The samples were examined for the above-mentioned P.h. 1 14 7 organisms by the procedure described previously8 and the P.m. 7 6 22 8 2 2 1 2 minimal inhibitory concentration (MIC) of the following N eom ycin antibiotics for 22 strains of P. haemolytica (P.h.), 50 strains P.h. 1 7 14 P.m. 5 14 16 14 1 of P. multocida (P.m) as well as for 15 C. pyogenes (C.p.) K anam ycin strains were determined: amoxycillin trihydrate, oxacillin P.h. 7 15 sodium, neomycin sulphate, kanamycin sulphate, P.m. 5 9 13 21 2 spectinomycin sulphate, tylosin tartrate, spiramycin, Spectinomycin lincomycin hydrochloride, oxytetracycline hydrochloride P.h. 20 1 1 P.m. 6 44 and also a chinoloncarbonic acid ester (Baytril-Bayer) (only T ylosin for C.p.). P.h. 13 9 P.m. 3 5 7 12 8 14 1 Results S piram ycin P.h. 3 16 3 Total number o f isolated bacterial types P.m. 4 7 5 11 19 3 1 From the 392 swab samples the named organisms were Lin co m ycin P.h. 2 9 11 isolated in the following distribution: P.m. 1 9 36 4
P. multocida — 121 strains Oxytetracyclin P. haemolytica — 74 strains P.h. 12 2 5 3 C. pyogenes — 15 strains P.m. 1 2 12 11 13 6 5
NOVEMBER, 1988 35 Table 2: Minimum inhibitory concentrations of the tested antibiotics for 15 strains Spectinommycin: 20 mg/kg i.m. at 8-hours intervals — of Corynebacterium pyogenes. limit value of 8 mg/'l — should inhibit all C.p. strains but
mg/1 0.125 0.25 0.5 1 2 4 8 16 32 64 128 >128 merely 8% Pasteurellae. Amoxicillin Dosage 30-40 mg/1 — limit value of 16 mg/1 — would C.p. 15 inhibit 97% of the Pasteurellae. O xacillin Oxacillin: dosage 25 mg/ kg i.m. at 12-hours intervals C.p. 2 7 6 — Limit value 0.5 mg/1 — 50% of Pasteurellae (only P.m.) N eom ycin C.p. 10 5 inhibited and all C.p. strains. (Fig. 3)
K anam ycin Neomycin: doses of 12 mg/kg or 22 mg/kg i.m./s.c. at C.P. 8 7 12-hours intervals — limit value 4 mg/1 or 8 mg/1 — 50%/ Spectinomycin 80% Pasteurellae inhibited; only 8 mg/1 inhibit 66% of C.p. 11 1 3 C.p. At 22 mg/kg already risk of toxicity. Better effect Tylosin C.p. 5 5 1 1 1 1 1 on intratracheal application? (Fig. 4) S piram ycin Oxytetracycline-HCl: dosage 11 mg/kg/die i.v./i.m./ C.p. 1 9 1 1 3 s.c. —• limit value 2 mg/1 — 38% of Pasteurellae inhibited, L in com ycin 33% C.pyogenes. C.p. 4 6 1 1 3 Provided that the limit value in the lungs is 4 mg/1 — Oxytetracyclin C.p. 5 2 3 5 55% Pasteurellae inhibited. Significantly higher
Chinoloncarbon- concentration on intratracheal administration? (Fig. 5) saure-Ester Tylosin: dosage 10 mg/kg/die i.m. should inhibit 2/3 C.p. 9 5 1 of the C.p. strains for sevral hours, not however the Pasteurellae. Increasing the dosage to 20 mg/44 mg/kg or intratracheal administration (50 mg Tylosin-base/kg) Discussion do not result in a significant increase in effectiveness. (Fig. Of initial interest is the high proportion of P. haemolytica 6) in the Pasteurella isolates, that is, 38%. A higher Spiramycin: dosage 50 mg/kg/die — limit value 2 mg/ pathogenicity is ascribed to P. haemolytica than to P. 1 — inhibits approx. 11/15 of the C.p. strains, but not multocida; in addition the organism is, as these results also the Pasteurellae. (Fig. 7) show, less sensitive to most antibiotics and Lincomycin: dosage 10 mg/kg i.m. in 12-hours intervals chemotherapeutic agents. — limit value 2 mg/1 — should inhibit 11/15 C.p. strains, In evaluating the therapeutic usefulness of a drug from but not the Pasteurellae. (Fig. 8) the MIC values must not only the size and duration of the active agent concentration in a feasible dosage be Conclusions considered, but also a number of other influencing factors The results show that P. haemolytica and P. multocida such as degree of binding to protein, tissue concentration proved to be very often sensitive to amoxycillin, often in the lungs, pH dependency, bacteriostatic or bacteriocidal sensitive to kanamycin and only relatively high method of action, post-antibiotic effect, inhibiting fibrin concentrations sensitive to neomycin and spectinomycin; barriers etc. The establishing of criteria for evaluating a both bacteria were frequently resistant to oxacillin and compound is therefore restricted by uncertainties. oxytetracycline and always resistant to tylosin, spiramycin Nevertheless the gradings based on the MIC values have and lincomycin. C. pyogenes proved to be always sensitive proved to be valuable guidelines for practitioners. to amoxycillin, oxacillin, kanamycin and spectinomycin, Bearing in mind the provisos listed above, the antibiotics frequently sensitive to tylosin, spiramycin and lincomycin, which were tested can be assessed as follows (in line with frequently resistant to oxytetracycline and neomycin. the recommendations of the Medical Standards Committee Considering the results of the in vitro testing as well as (1981) the effective agent concentration is taken as that the achievable drug concentrations in vivo amoxycillin and reached in serum half-way through an application period kanamycin seem to be good candidates for the treatment at the recommended dosage): of EBP. With the other drugs tested different restrictions Amoxycillin: at a dosage of the trihydrate of 7 mg/kg/ have to be considered. die i.m. a limit value of 1 mg/1 is obtained, at which 92% of the Pasteurellae and all C.p. strains should be inhibited. Summary (Fig. 1) Kanamycin: dosage 10 mg/kg i.m. at 8-hours intervals, For 50 strains of Pasteurella multocida (P.m.), 22 strains giving limit value of 4 mg/1 — should inhibit 75% of the of Pasteurella haemolytica (P.h.) and 15 strains of Pasteurellae and 100% of the C.p. (Fig. 2) Corynebacterium pyogenes (C.p.), isolated from the
36 THE BOVINE PRACTITIONER — NO. 23 OEBR 1988 NOVEMBER, Figure 1: Serum concentration of Amoxycillin in healthy calves after Figure 2: Serum concentration of Kanamycin sulphate in healthy calves i.m. application of different doses (YEOMAN, 1977) in relation after s.c. application of different closes (H JERPE and ROUTEN, to the minimum inhibitory concentrations for Pasteurella 1976) in relation to the minimum inhibitory concentrations for multocida (50 strains), Pasteurella haemolytica (22 strains) Pasteurella multocida (50 strains), Pasteurella haemolytica (22 and Corynebacterium pyogenes (15 strains). strains) and Corynebacterium pyogenes (15 strains). . . C Q. Q. “a) "® « E a E -«= - co v- o o to to to + o + X D CD O O £=O C CD c ® o o co co co c a m O C 0 0 CO CC £ ® ® 3 o j co 2 E ® - O ^5 E O CC o O I I II II II c E Q, E -c 2^ "O ‘o "o 'o O Q- CL co
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c CO • § Copyright American accessdistribution.of Bovineopen Practitioners;Association *CO 5 .2 .2 a> <1) 0 ) (5 g o ffl m ™ 12 -o 8 i f s l £ o CO s i g CD c co CD S i * o CD CO O CQ CO TO co . E o O CL i ! 03 c 03 E O E ® -g CD _D o .2 ~ CO 3 w « o r a " 1 j z E . 2 CO CD .fc; ® ’ - c m JO JO O }" O - C D ’- CO "® 3 JQ Z3 D CD 0 ) 0 ) C g ® o o B CO t o CO CO o (D . t CL o . O O C L m- CD .Q O o o § ° c cz c ° « CO CO CO .2 D >■. o o I 1 "co CO CO E -2. E CD CD ® o E | c C c E ® o o o O° CO2 o II II II c i= CD . 2 >> E E CL X + o CO CD THE BOVINE PRACTITIONER — NO. 23 respiratory tract of calves with enzootic bronchopneumonia basis of the results, listed in two tables, the usefulness of (EBP) or from affected lung tissue of animals that had the drugs for the treatment of EBP has been evaluated died, the sensitivity (respectively the resistance) was and discussed. determined on the basis of minimum inhibitory concentration (MIC) to the following antibiotics: amoxycillin trihydrate, oxacillin sodium, neomycin References sulphate, kanamycin sulphate, spectinomycin sulphate, 1. Amstutz, H.E., R.L. Morter and C.H. Armstrong (1982). Bov. Pract. tylosin tartrate, spiramycin, lincomycin hydrochloride, 17, 52-55. 2. Burrows, G.E. (1980a). Bov. Pract. 15, 99-102. 3. Burrows, oxytetracycline hydrochloride and to a new G. E. (1980b). Bov. Pract. 15, 103-110. 4. Endres, A. (1983). Minimale chinoloncarbonic acid ester (only for C.p.). The results Hemmkonzentrationen von Oxytetracyclin, Penicillin G, Chloram show that P. haemolytica and P. multocida proved to be phenicol, Erythromycin, Sulfamethazin und Sulfadoxin-Trimethoprim fur very often sensitive to amoxycillin, often sensitive to Pasteurella haemolytica, Pasteurella multocida und Corynebacterium pyogenes boviner Herkunft. Vet. Med. Diss., Miinchen. 5. Hjerpe, C.A. kanamycin and only at relatively high concentrations (1979). Bov. Pract. 14, 18-26. 6. Hjerpe, C.A. (1983). Proc. 15th Ann. sensitive to neomycin and spectinomycin; both germs were Conv. Amer. Assoc. Bov. Pract., 122-126.7. Hjerpe, C.A. and T.A. Routen frequently resistant to oxacillin and oxytetracycline and (1976). Proc. 9th Ann. Conv. Amer. Assoc. Bov. Pract., 94-140. 8. Specht, to tylosin, spiramycin and lincomycin. C. pyogenes proved H. (1986). Minimale Hemmkonzentrationen von Amoxicillin, Oxacillin, to be always sensitive to amoxycillin, oxacillin, kanamycin Neomycin, Kanamycin, Spectinomycin, Tylosin, Spiramycin, Lincomycin und Oxytetracyclin fur Pasteurella haemolytica, Pasteurella multocida and spectinomycin, frequently sensitive to tylosin, und Corynebacterium pyogenes boviner Herkunft. Vet. Med. Diss., spiramycin and lincomycin, frequently resistant to Miichen. 9. Ziv, G. (1982). Proc. Xllth World Congr., Dis, Cattle, The oxytetracycline and always resistant to neomycin. On the Netherlands, Vol. I, S. 111-119. NOVEMBER, 1988 41