A THESIS ROBERT HAROLD FEATHERSTON. Department of Surgery and Medicine KANSAS STATE COLLEGE OF AGRICULTURE AND APPLIED SCIENCE

Transcription

1 THE COMPARATIVE EFFICACY OF SOME OF THE COMMONLY USED URINARY ANTIBACTERIAL AGENTS IN THE TREATMENT OF EXPERIMENTAL CANINE BACTERIAL NEPHRITIS by ROBERT HAROLD FEATHERSTON B. S., Kansas State Cllege f Agriculture and Applied Science, D. V. M., Kansas State Cllege 1953 f Agriculture and Applied Science, 1955 A THESIS submitted in partial fulfillment f the requirements fr the degree MASTER OF SCIENCE Department f Surgery and Medicine KANSAS STATE COLLEGE OF AGRICULTURE AND APPLIED SCIENCE 1958

2 J 2<#C 8 11 c 7 TABLE OF CONTENTS INTRODUCTION 1 REVIEW OP LITERATURE 8 MATERIAL AND METHODS l6 RESULTS OF EXPERIMENTATION 20 Results f Penicillin-Dihydrstreptmycin Therapy Results f Chlramphenicl Therapy 22 Results f Sulfisxazle Therapy... 2$ Results f Cntrl Animals 28 DISCUSSION 30 SUMMARY 35 ACKNOWLEDGMENTS 37 BIBLIOGRAPHY 38

3 INTRODUCTION Nephritis in the canine patient is a basic prblem in veterinary medicine and prbably ccurs mre cmmnly than presently diagnsed. Veterinary pathlgists have recrded that frm five t ten percent f the dgs underging rutine autpsies have characteristic lesins f nephritis (2), (10). Clinically, nephritis may be divided int acute and chrnic types. The acute type is characterized by a sudden nset, 11stlessness, a disinclinatin t mve abut, inappetence, vmiting, and plydipsia. The temperature is usually elevated at the nset, but may drp t nrmal in a few days withut the benefit f treatment. Lumbar tenderness may cause an arching f the back and a stilted gait. Partial r cmplete anuria is frequently nted and hematuria Is nt uncmmn. Results f urinalysis usually reveals a high specific gravity ranging frm 1,030 t and prteinuria. Examinatin f the urine sediment may reveal an increased number f leukcytes and the presence f erythrcytes and urinary casts. As the disease cnditin prgresses, the specific gravity f the urine usually decreases t what is called a pint f "fixatin" (1.010 t 1.012) (1J4.). Chrnic nephritis is cmmnly seen in dgs ver eight years f age (2), The nset is slw with a perid f time passing befre marked symptms are evident. Early cases shw increased thirst with ccasinal perids f sickness. The patient is usually dehydrated and the hair cat has an unthrifty appearance.

4 There may be a prnunced diarrhea in the later stages f the cnditin. Cardiac hypertrphy with dilatatin f the left ventricle may result frm the increased wrk lad placed upn the heart (3). Cpius amunts f a pale urine with lw specific gravity (1,010 t 1.012) may be vided. Labratry tests may reveal nly a trace f prtein r nne at all. A few leukcytes and granular casts may be nted upn micrscpic examinatin f the urinary sediment* Uremia is a cmmn sequel and is characterized by cngestin f the cnjunctiva, ulceratin f the mucsa, a fetid muth dr, a full and buncing pulse, and nervus symptms varying frm cnvulsins t a cmatse state. Other symptms which may be seen are muscle twitchings f a fibrillary type, cnstipatin r diarrhea, emaciatin and smetimes eczema. Canine nephritis cmmnly results frm an acute infectin, which may initiate a ldgment f micr-rganisms in the glmerular r intertubular vessels, r the damage t renal tissue frm bacterial txins and Inflammatry prducts passing thrugh the kidney (9)«In the past, it was cmmnly believed that bacterial nephritis was established by bacteria ascending by way f the lumen f the ureter int the renal pelvis and parenchymal tissues f the kidney, mre recently it has been assumed that unless there is an urinary bstructin r stasis that mst infectins are hematgenus (2). Theretically, rganisms may als reach the kidney by way f the ureteral lymphatics. Bacterial nephritis is mre cmmnly due t Escherichia cll and Prteus vulgaris, and less cmmnly t streptccci,

5 staphylccci, r ther specific rganisms (2), In a reprt by Msier and Cles (15) they fund that in a ttal f 53 cases f clinical urinary tract infectins that 22,6 percent were due t Escherichia cli, 32,1 percent were caused by Prteus sp., 20.7 percent due t streptccci, and 18,9 percent were infected with Micrcccus pygenes. Bth human and veterinary medical literature cntain numerus enthusiastic reprts f the clinical efficacy f the urinary antibacterial agents in the treatment f urinary tract infectins. Cntrlled bacterilgical tests have shwn that the favrable clinical effects may be nly temprary with the infecting rganism still present in the urinary tract fllwing treatment (l5)» It is generally agreed that the successful treatment f kidney infectins will depend nt nly n the selectin f a suitable antibacterial agent, but als bstructive lesins must be crrected and infecting fci such as pymetra, vaginal infectins, peritnitis, pneumnia, prstatitis, gastr-intestinal, and ther infectins eliminated. The rate f relapse and reinfectin after any type f drug therapy is apparently very high, making the treatment f urinary tract infectins a definite prblem (12), Sme f the mre cmmn urinary antibacterial agents used in the therapy f bacterial canine nephritis are penicillin, chlramphenicl, tetracyclines, sulfnamides, nitrfurans, and streptmycin. Penicillin, streptmycin, sulfisxazle, and

6 \ hlraraphenicl were selected as representatives f this grup fr this study. Penicillin is prduced cmmercially by the culturing f the Penicillium mld strains f Peniillium n ta turn r f Penicillium hrys genum (17)«Penicillin has prven t be relatively specific in its actin against Gram-psitive bacteria, but has shwn t be ineffective against mst Gram-negative rganisms. Penicillin is bth bactericidal and bacteristatic. Bacterial multiplicatin is inhibited at lw cncentratins f penicillin and the bacterial cells are killed with higher cncentratins. The perid f the highest antibacterial actin is when the multiplicatin f the bacteria is the greatest. Sme bacteria, which are riginally susceptible, develp a resistance t penicillin. This drug is cnsidered active in the presence f bld, serum, pus, and large numbers f bacteria (11), The mde f actin f penicillin against bacteria is unknwn. It is believed t inhibit the metablic activities vital t the bacterial cell by blcking the assimilatin f prtein which is essential fr grwth and reprductin (11), Penicillin is excreted primarily by the urinary system. It is cnsidered a relatively nntxic substance, and appraches the ideal therapeutic agent in relatin t the antibacterial actin and the wide margin f safety in which it pssesses (11), The administratin f penicillin in animals is largely by the intramuscular rute. The minimal dsage f penicillin fr the canine is cnsidered t be 5,000 units f penicillin per pund f bdy weight intramuscularly. This dsage may be

7 Increased t 10,000 units per pund f bdy weight in the presence f a virulent infectin (17)«Streptmycin is prduced frm a species f actinmyces belnging t the genus Streptmyes griseus (11). It Is a valuable therapeutic agent as it is effective against Gram-negative bacteria and supplements the drugs which are active nly against Gram-psitive rganisms. The actin f streptmycin against the micr-rganisms seems t be that f interference with ne r mre f the cellular enzyme systems essential fr bacterial cell divisin (11). It was fund that streptmycin sulfate culd be cnverted int D I hydr streptmycin Sulfate by reducing the carbnyl grup by catalytic hydrgenatin (11) Di hydrstreptmycin is a mre stable, less txic prduct and has an antibacterial activity cmparable t that f streptmycin. Streptmycin and di hydr streptmycin are readily absrbed Int the bld stream and distributed t the varius bdy tissues and fluids fllwing intramuscular Injectin, Streptmycin is indicated fr treatment f systemic infectins due t sensitive Gram-negative and acid fast Gram-psitive bacteria. Streptmycin and d i hydrstz'eptmycin are reprted t be effective In the treatment f urinary infectins, especially thse due t Escherichia cll, Prteus vulgaris. Aerbe cter aergenea, and Pseud mnas aeruginsa (17)«Prlnged streptmycin therapy has the tendency t prduce the develpment f resistant strains f bacteria and chrnic txicity. The mst serius txic actin f streptmycin Is the neurtxic effect upn the vestibular and auditry mechanism (11),

8 6 The develpment f dihydrstreptmycin reduced the txicity prblem smewhat, but it still is wrthy f serius cnsideratin. Streptmycin is excreted primarily in the urine in abut ne-half the cncentratin f the bld stream (11) This may cause unduly high cncentratins f streptmycin in the bld f individuals with renal dysfunctin and result in serius txic effects. The dsage shuld be adjusted accrdingly in the treatment f these patients (17) The minimal therapeutic dse f streptmycin r dihydrstreptmycin fr mammals is cnsidered t be five mg. per pund f bdy weight, injected intramuscularly in aqueus slutin at 12 t 2l\. hur intervals (11), Chlramphenicl (Chlrmycetin) is prduced frm cultures f a sil-brne actinmycete, Streptmyces venezuelae (17)* It has a brad spectrum f activity against bth Gram-psitive and Gram-negative bacteria, rickettsia, and the larger viruses (11). Apparently, little is knwn abut the mde f actin f chlramphenicl against these pathgens. Chlramphenicl is administered bth rally and intramuscularly. When given rally in the dg, it des nt cause vmitin r diarrhea, but it may induce anrexia. It is readily absrbed fllwing ral administratin in dgs, and appears in practically all tissues within ne and ne-half hurs fllwing administratin. It reaches the highest cncentratin in the liver, bile, and the kidneys (11), Chlramphenicl is excreted in an active and inactive frm, Y/ith nly 6,3 percent f the ttal drug

9 excreted in the active frm (II). The active frm is excreted mainly by the renal glmeruli, the inactive frm is excreted by the renal tubules and bile in the dg. Chlramphenicl may be preferred t streptmycin in the treatment f urinary tract infectins because f its lack f txicity (17). The ral dsage f chlramphenicl recmmended fr small animals is 2$ t $0 mg. per pund f bdy weight per day, administered in tw r three divided dses. Sulfisxazle (3,l -dimethyl-5'-sulfanilamidisxazle) is a sulfnamide marketed under the trade name Gantrisin by Hffmann La Rche, Inc. It Is a highly sluble sulfnamide cmmnly used in treating urinary tract infectins f man (18). Previus studies have shwn sulfisxazle t have abut the same range f bacteristatic activity as sulfadiazine. The slubility f sulfisxazle in ph ranges f \*$ t 6.0 is cnsiderably greater than that f sulfadiazine (18). It Is believed that when sulfnamides are administered, they exert a bacteristatic actin n the micr-rganisms. The retiul-endthelial system and the sulfnamide appear t cmbine actins, the sulfnamides exert a bacteristatic actin in viv and aid the retlcul-endthelial system in cmbating and remving the Invading pathgenic rganisms. The exact mechanism f the antibacterial actin f the sulfnamides has been pstulated in several theries (11). The excretin f the sulfnamides is primarily thrugh the urinary tract. The sulfnamides which are nt readily absrbed

10 by the intestinal tract are excreted by the feces. There are small amunts excreted in bile, pancreatic juice, gastric juice, intestinal juice, saliva, and in the milk (11). Sulfisxazle has becme ne f the drugs f chice in treating urinary tract infectins in man (18), Its use has becme ppular because f its slubility and lw txicity (lb). Sulfisxazle is administered rally t small animals, usually in a dsage range f ne grain per pund f bdy weight per day divided int three dses, A number f cntrlled tests have been made in human medicine, in which bacterilgical studies have accmpanied the treatment f the urinary tract infectins with varius urinary antibacterial agents. Mst f the reprts in regard t the treatment f urinary tract Infectins In veterinary medicine are clinical In nature, and bacterilgical studies have nt been dne. Apparently much f the infrmatin In regard t the treatment f bacterial nephritis and infectins f the urinary tract In veterinary medicine has been adapted frm the human medical literature. On this basis the fllwing survey f the efficacy f the selected urinary antibacterial agents bacterial nephritis was made, n experimental canine REVIEW OF LITERATURE Kidney disease has been cnsidered a prblem in veterinary medicine fr a number f years, Wright (23), in 1932, stated that kidney disease was such a cmmn finding in the dg, that

11 it shuld be cnsidered first in the diagnsis f what therwise were bviusly alimentary symptms. King (13), in 1937, reprted that althugh kidney disease was a cmmn cnditin seen upn autpsy f the dg, that there was much wrk t be dne bth n preventive and curative lines* Haines (8) reprted n a clinical case f bacterial nephritis which was treated with penicillin. The animal died and upn autpsy the renal tissue revealed multiple abscesses and cludy degeneratin, Escherichia cli was cultured frm the renal abscesses* Rllag (19) indicated in a clinical reprt the difficulty in btaining a bacterilgical cure in a case f bacterial nephritis due t Escherichia cli * In this reprt it was indicated that imprvement f the clinical symptms was accmplished by treatment with antibitics and the usual urinary tract agents, but recurrence f the symptms wuld arise at abut tw-week intervals* Euthanasia was perfrmed and upn autpsy a diagnsis f suppurative nephritis was made* Results f a screening survey by Msier and Cles (lj?), Invlving apprximately 300 dgs, indicated a bacterial etilgy in an estimated 25 percent f the animals presented with a suspected urinary tract disrder* In subsequent wrk by Msier and Cles (15), 25> dgs, diagnsed bth by clinical and labratry means as having bacterial urinary tract infectins, were used t evaluate the clinical effectiveness f Furadantin (nitrfurantin) in urinary tract infectins. Frty percent f the dgs treated in this study had

12 10 sterile urine upn pst treatment bacterilgical examinatins. Clinical manifestatins were imprved in ver 90 percent r the animals by treatment, but recurred in sme instances after treatment was discntinued. Cles and Hsier (7) established bacterial urinary tract infectins in 27 dgs by experimental means t evaluate the effect f nitrfurantin n experimental canine nephritis. After treatment, with relative high dsages f nitrfurantin fr perids up t 20 days, nly three dgs, r percent, had sterile urine upn a bacterilgical examinatin at the time f necrpsy Blm (2) states that there is a species difference In tne types f renal inflammatry disease between man and canine. With this in mind we review sme f the literature pertaining t the use f antibacterial agents in the treatment f urinary infectins in human medicine. Adcck and Plumb (l) reprted n 11 cases f urinary tract infectins treated with streptmycin. In five patients with, infectin due t rganisms f the Aerbacter grup, prmpt relief f symptms ccurred, pyuria disappeared and the urine became and remained sterile. Pretreatment tests had shwn these rganisms t be sensitive t streptmycin in vitr. Pseud mnas aeruginsa was islated alne r in cmbinatin with ther bacteria in five cases. Upn treatment there was relief f symptms and pyuria diminished r disappeared. tfnf rtunately, the results f treatment were temprary and bacilluria persisted in each case. In vitr tests had indicated that these rganisms

13 11 were fairly resistant t streptmycin. The eleventh patient was a case f chrnic cystitis due t Escherichia cll, which temprarily imprved frm the streptmycin therapy. In three cases it was fund that the strains f bacteria islated after therapy were mre resistant t streptmycin in vitr than the strains Islated prir t treatment. In a series f f>0 patients treated with Chlramphenicl by Chittenden, et al, (6), it was fund that 13 (26 percent) were Infected by a single invader, while in the thr 37 (7if percent) the infectin was caused by tw r mre bacilli r cmbinatins f bacilli and ccci. In the patients with simple bacillary urinary infectin the treatment usually returned the elevated temperature t nrmal within a few hurs and grssly purulent urine became clear, free f leukcytes, and bacilli within 2i\. t 36 hurs. In the 50 cases treated, infectin was bacterilglcally cntrlled in 19 cases (3<3 percent), clinically imprved in 22 (1(4 percent), and the infectin was unimprved in nine cases (10 percent). In this study Escherichia cll, Aerbacter argenes. Pseudmnas aeruginsa, Klebsiella pneumniae. Salmnella schttmuelleri, and Prteus vulgaris were the cmmn urinary tract pathgens that respnded t chlramphenicl treatment, ischweinburg and Rutenburg (20) evaluated the therapeutic activity f W 1 45 (Sulf isxazle) in 20 unselected patients which had varius urinary tract infectins due t Gram-negative bacilli. They received tw types f respnses, a clinical and

14 12 bacterilgical cure was btained in seven patients (35 percent)* Thirteen patients (65 percent) were listed as clinical and bacterilgical failures. Three f this grup indicated temprary imprvement, but had a recurrence. Twelve f the patients that were nt cured had mixed infectins. On the basis f this clinical trial, these wrkers stated that sulfisxazle was a safe and effective drug in the treatment f uncmplicated mnvalent infectins due t Escherichia cll and B, prteus and was apparently ineffective in plyvalent infectins. In a study n the antibacterial management f urinary tract infectins made by Rhads, Billings, and O'Cnr (18), 325 cases were studied that were knwn t have bacterial urinary tract infectins. The bject f the study was t btain the cmparative results f different antibacterial agents cmmnly used in treating urinary tract infectins, A grup f patients with urinary tract infectins, due t Escherichia cli, were surveyed in regard t the effectiveness f treatment with varius antibacterial agents. Seven patients were treated with streptmycin, three patients (I4.3 percent) develped negative urine cultures, with a bacterilgical cntrl f the infectin in nly ne patient. Nine patients were treated with chlramphenicl, three patients (33 percent) develped negative urine cultures, with the infectin cntrlled permanently in tw patients. Twenty-three ases were treated with Gantrisin, six patients (26 percent) develped negative urine cultures, with the infectin permanently cntrlled in tw

15 13 patients. This survey shwed a remarkably lw incidence f permanent cures with any type f drug therapy except in patients having cystitis withut bvius bstructin. Results indicated that cmbined therapy f tw r mre agents were mre effective than treatment with a single drug, Sulfisxazle was cnsidered by these authrs t be the sulfnamide f chice in mst urinary tract infectins, Waisbren and Carr (21) reprted n 23 ases f clinical urinary tract infectins due t Prteus rganisms which were treated with chlramphenicl, penicillin, and the cmbinatin f the tw agents. Five cases respnded t chlramphenicl, three cases respnded t penicillin, and fur cases respnded t the cmbinatin f the tw agents. Eight cases did nt respnd t chlramphenicl, 12 f the patients did nt respnd t penicillin, and five cases shwed n respnse t the cmbinatin f chlramphenicl and penicillin in spite f an apparent in vitr sensitivity. It is the pinin f this authr that chlramphenicl, penicillin, gantrisin, and nemycin may be cnsidered effective against sme infectins due t Prteus rganisms. The cmbinatin f penicillin and chlramphenicl may cure Infectins that have nt respnded t either drug given alne, Nesbit and Baum (l6) in a reprt n the treatment f infectins f the geniturinary tract stated that the physician tday, despite the many chem therapeutic and antibitic agents available, cntinues t encunter a number f urinary infectins that fail t imprve under therapy r that recur. They were f

16 lfc the pinin that inadequate dsage f the antibacterial agent was ften the reasn fr the therapeutic failure. Infectins f the kidney are primarily lcated in the tissues, therefre successful treatment f kidney infectins will depend n selectin f nt nly the prper antibacterial agent but als the maintenance f a tissue level that will be adequate t destry the rganism. Anther cause f failure f treatment is the resistance f the rganisms t the agent used in treatment. Resistant strains f bacteria appeared mre cmmnly under situatins where there was pr cntact f the drug with the rganism, either as a result f inadequate dsage r because f the nature f the tissues where the rganisms are lcated. Als the develpment f crss resistance against drugs having similar bacterial spectra was cnsidered highly significant. These authrs state that it is very imprtant t identify the bacteria befre treatment, A Gram stain f the urine sediment may be sufficient as a preliminary guide t the selectin f a treatment agent. When streptccci are demnstrated the use f penicillin is Indicated, If Gram-negative rganisms r staphylccci are identified in the urine sediment, the use f a sulfnamide such as sulfadiazine, triple sulfnamides, r sulfisxazle is advisable. This prcedure reserves the mre expensive antibitics fr instances in which penicillin r the sulfnamides are ineffective and allw time fr the use f sensitivity tests in selectin f the mst suitable agent. It is suggested that chlramphenicl shuld be given fr a minimum f seven days, and that it has been fund t be effective against

17 15 Escherichia cll and Streptcccus faecalis, with a bacteristatic effect n Aerbacter aergenea. Bacillus prteus, and Klebsiella pneumniae, They cncluded that cmbinatins f the varius antibacterial agents may eventually prve t be mst effective in the treatment f urinary tract infectins. Carrll (5) maintains that because f mderate side reactins, lw cst, and gd tlerance the cmpunds Gantrisin, Elksin, Thisulfil, and Kynes are preferable in acute cases f urinary tract infectin where the infecting rganism has nt been identified. He reprts that Gantrisin is effective against Prteus as well as against the cccal infectins. This is imprtant in the treatment f urinary tract infectins as Prteus splits the urea in the urine and causes a cnstant alkaline cnditin which renders methenamine and mandelic acids ineffective* Carrll 1 s studies shwed penicillin t be ineffective against Prteus, and streptmycin and the tetracylines were nly mderately effective. Carrll suggests that the persistence and recurrence f urinary infectins are due t failure f drainage r the presence f bstructive lesins. In chrnic pyelnephritis bstructins f the tubular structures belw the lesin are nt usually demnstrable. It is his pinin that multiple small infected areas are transfrmed int clnies f rganisms surrunded by fibrus tissue that makes them inaccessible t the drug. Lng cntinuus therapy must be used t reach these rganisms with an effective tissue level f the antibacterial agent, Carrll

18 16 reprts the administratin f Gantrlsin ver perids f three mnths with favrable effect n the infectin and n deleterius effect n the patient. The literature reviewed appears t indicate that althugh there is prbably sme species difference between man and the canine in the inflammatry lesins f urinary tract infectins, the prblem f treatment and cntrl f these infectins are similar, MATERIAL AMD METHODS A ttal f l)\. dgs were used in this study. The dgs were f cmmn mixed breeds ranging in age frm six mnths t tw years, and weighing between 13 and 32 punds. There were seven males and seven females. Urine was cllected frm each animal by abdminal puncture and examined bacterilgically prir t use in this study t eliminate any previusly Infected animals. The llj. dgs were divided int fur grups. Grup I, cnsisting f three dgs, was inculated with Escherichia cll. Grup II, cnsisting f three dgs, was inculated with Streptcccus canis. Grup III, which cnsisted f fur dgs, was Inculated with Escherichia cll. Grup IV, cnsisting f fur dgs, was inculated with Prteus sp_. In each instance the rganism used was riginally islated frm a clinical case f canine urinary tract infectin. After the rganism was islated and Identified, it was tested fr sensitivity t antibitics by adding apprximately ne ml, f a 2l.-hur brth culture t fur ml. f melted tryptse-dextrse

19 17 agar cled t \\$ degrees Centigrade. This agar mixture was pured nt the surface f a plate cntaining five percent sheep bld agar. After slidificatin, the antibiti discs cntaining penicillin, streptmycin, auremycin, chlramphenicl, tetracycline, terramycin, plymyxin, and erythrmycin were placed n the surface f the plate. The results f antibitic sensitivity were determined after the plate had been incubated fr 18 hurs at 37 degrees Centigrade, The rganism selected fr use in the establishment f bacterial nephritis was cultured in brth fr a perid f 2l\. hurs at 37 degrees Centigrade, and this culture used as the inculum. The technique used in establishing the infectin was essentially the same as that described by earlier investigatrs (7), (22), The dgs were anesthetized with sdium pentbarbital and prepared fr surgery in the rutine manner, A lngitudinal incisin f abut three inches in length, parallel t the thirteenth rib, was made n the left side f the animal. The external blique, internal blique, and transverse abdminal muscles were separated in the directin f their fibers. The peritneum was divided with the transverse abdminal muscle and the left kidney lcated and elevated t the surface f the incisin. The renal artery was islated by separating the adipse tissue away frm the kidney and expsing the structures at the hilus f the kidney, A frcep was placed under the renal artery thereby islating it frm the ther structures. The bacterial suspensin was then inculated int the kidney by injectin f 0,5 ml, f the

20 18 inculum Int the renal artery thrugh a curved 28-gauge hypdermic needle. A frcep was immediately plaed n the renal vein Tr a shrt perid t insure cmplete spread f the bacterial suspensin thrughut the renal tissues. The kidney was then replaced int the abdminal cavity and the incisin clsed in the usual manner. Urine samples were cllected daily after the injectin f the bacterial suspensin t determine if the infectin was established. Since specimens cllected by catheterizatin are likely t be cntaminated by the micr-rganisms nrmally present in the external genitalia f bth sexes, the urine was btained by abdmincentesis with a 20-gauge, 1-^-inch hypdermic needle (Ij.), Examinatin f the urine cnsisted f a bacterilgical examinatin by culture f the urine n five percent sheep bld agar media, rutine urinalysis fr prtein, glucse, specific gravity, and ph, and a micrscpic examinatin f the urinary sediment. Fllwing islatin f the rganisms frm the urine, a perid f five t 20 days was allwed t elapse befre treatment was initiated, thus enabling the bacterium t becme firmly established in the renal tissues, and therefre t mre clsely apprximate a clinical cnditin. Treatment cnsisted f at randm selectin f ne animal frm each grup fr treatment with penicillin-streptmycin cmbinatin, ne with sulfisxazle, and ne with chlramphenicl.

21 19 The number fur dg in Grups III and IV served as a cntrl and was nt treated. The dsage f penicillin-streptmycin used was 10,000 units f Penicillin G Prcaine, crystalline, and five mgm. f Dihydrstreptmycin sulfate per pund f bdy weight administered intramuscular each 12 hurs. Chlramphenicl was administered rally in a dsage f 25 mgm. per pund f bdy weight divided int three dses daily, with the exceptin f Grup I, in which lf> mgm. per pund f bdy weight was administered, and Grup II, in which 10 mgm. per pund f bdy weight was administered. Sulfisxazle was used in tw preparatins, Renzl tablets and Gantrisin tablets. Renzl Is a cmpund prepared by Allied Labratries, Inc., Indianaplis, Indiana. It cntains Ingrains sulfisxazle, mgm. f hydrcyamine hydrbrmide, 0.007ii-5 mgm. f atrpine sulphate, and ;. mgm. f scplamine per tablet. The recmmended dsage f ne tablet per ten punds f bdy weight three times a day was used In Grups I and II. Sulfisxazle (Gantrisin), used in Grups III and IV, was administered rally at the rate f ne grain per pund f bdy weight per day divided int three equal dses. Grups I, II, and IV were treated fr a perid f five days. Grup III was treated fr a ten-day perid. Seven t ten days fllwing the terminatin f the treatment perid, urine samples were cllected and examined, by means f bacterial cultures, fr cntinued presence, pssible recurrence, r change f rganisms.

22 20 Fllwing euthanasia f the dgs, cultures f bth kidneys and the mucsa f the urinary bladder were made, RESULTS OP EXPERIMENTATION Results f Penicillin-Dihydrstreptmycln Therapy Experimental animal number 5 was a male dg f mixed breed weighing 32 punds. This animal was injected with hemlytic Escherichia cll rganisms int the left renal artery n March 22, Cultures f the urine later Indicated that a urinary tract Infectin due t hemlytic Escherichia 00 II had been established, A cmbinatin f peniclllin-dihydrstreptmycin was selected as the drug fr treatment. Treatment was initiated eight days fllwing the date f injectin and was cntinued fr a five-day perid. Hemlytic Escherichia cli was nt present n the urine culture made 2ij. hurs pst treatment. The urine was cultured ten days fllwing treatment and hemlytic Us c herihia cli was islated. Fllwing euthanasia, culture f the right kidney was negative fr bacterial grwth, but hemlytic Escherichia cli rganisms were present n the culture f the left kidney. Experimental animal number 8 was a female f mixed breed weighing 20 punds. This animal was injected with hemlytic Streptcccus cania Int the left renal artery n May 7# 1958, Cultures f the urine later Indicated that a urinary tract infectin due t hemlytic Streptcccus canls had been established, A cmbinatin f penicillin and di hydrs treptmycin

23 21 was selected as the drug fr treatment. The treatment was started 20 days after the date f injectin. Strep te cus aais was nt islated frm the urine when cultured within 2l\. hurs after the terminatin f treatment. The urine culture made seven days fllwing the terminatin f the treatment perid shwed the Streptcccus canis rganism present. After euthanasia was perfrmed, cultures were made f the right and left kidneys and mucsa f the urinary bladder, all f which revealed the presence f hemlytic Streptcccus canis. Experimental animal number l6 was a female dg f mixed breed weighing 30 punds. The animal was injected int the left renal artery with hemlytic Escherichia cli rganisms n June 21, 1958* Cultures f urine speimens later indicated that an infectin, due t Escherichia cli. had been established in the urinary tract. The cmbinatin f penicillin and dihydrstreptmycin was selected fr use ver a perid f ten days. Treatment was started six days fllwing the date f injectin. The urine culture made within A\. hurs fllwing the terminatin f the treatment perid was negative t bacterial grwth. Cultures f the urine seven days pst treatment, f the right and left kidneys, and the mucsa f the urinary bladder were negative t bacterial grwth. Experimental animal number 17 was a male dg f mixed breed weighing 20 punds. This animal was injected int the left renal artery with a culture f Prteus sp. n June 22, Urine cultures, made frm specimens cllected a few days after injectin f the. rganisms, indicated the establishment f

24 22 Prteus sp» in the urinary tract. Penicillin and dihydrstrept* mycin cmbinatin was used ver a perid f five days fr treatment. The treatment was started eight days fllwing the date f injectin. Urine cultures at the terminatin f the treatment perid were negative fr bacterial grwth. Cultures f the urine, right and lft kidneys, and mucsa f the urinary bladder were made seven days af br the terminatin f treatment and did nt reval a bacterial grwth. (Table 1.) Results f Chlramphenicl Therapy Experimental animal number 1 was a female dg f mixed breed weighing 20 punds. This animal was injected with a culture f hemlytic Escherichia cll rganisms int the renal artery n March 22, Cultures f the urine indicated a urinary tract infectin du t Escherichia cli rganisms had been established. Chlrampnenicl was selected as the drug t be used in treatment. Treatment was initiated eight days fllwing the date f injectin f the micr-rganisms. The urine culture made within 2i{. hurs after the terminatin f treatment revealed the presence f hemlytic Escherichia cli rganisms. The urine was again cultured ne week pst treatment, this culture als revealed the presence f hemlytic Escherichia cli rganisms. Fllwing euthanasia, cultures were made f the right and left kidneys. The culture f the right kidney was negative fr bacterial grwth, the culture f the left kidney revald the presence f hemlytic Escherichia c l i in the tissues.

25 . P : 23 r-» O as P H 1 gp H 3 p as P 034: O c Ah (t 1 03 P >»«as a p 03 P c a. g s O.i 5 «8 XJ H Ti-rt * H O O p p d P O Xi cj H 55 8b > - CP t=> aj bo I H ^ H q CJ 1 CJ 3 a «H 1 ' a P. 1 d H C«<Vh fc k p P & CO *-3 c > CJ P H cj u 5 65 I!>i *H CJ CJ ttf P CO 1 h> I CJ IB 0) H >T 1 «H X-ri H <D P P d aj P CJ H fa <H J C< >!? t-3s H h ; Jh bo C3 I Bb H CEJSS d cj I h t fep d T3 tj H H > 5 ^ H p P P aj ej G S25 «Jh H P M 5 52! > -H dp th j ij bo P P XJ as 01 a 03 B 1» xi -p & P ft -P p CO w p C! I OS u * P C5 s cj a) C3 O Q 03 at x> 1A p 85 dxsq 03 g «C-h -a h cj ^a a ~ ftp p ft O H u B xj CJ p C01ACQ O M dx> Q H H H 03 as *A m P i>> CJ-H'3 f ftp OXi O r-l p ft p C0U\S p. O H a, H P-, (Q dx>p CQ a p ft M P a- COIAfQ p p 0J P S a h»b ftp H OX3 O H d 3 01 l» a) XJ \A dxiq 03 H H H P >s O CQ d -rj'cj H CJ XI & H 3 ftp p P ft E d p O CO COIAfQ H OX> O O H m O H hph m [ H r-t H O H d ft y 03 P H 0J rt d 03 -H H P C O ' t* u a O H P Xi bo «H C) 3: XJ 03 pa p ft! p EQ n St a d p u (±4 Xl a! EH u\ CO

26 ttk Experimental animal number 6 was a dg f mixed breed weighing 30 punds. This animal was injected Int the renal artery with a culture f hemlytic Streptcccus anis n May 7# urine cultures f specimens cllected at later dates indicated the establishment f Streptcccus canls In the tissues f the urinary tract. Chlramphenicl was used in treatment fr a perid f five days, Treatment was initiated 20 days fllwing the date f injecting the micr-rganisms. The urine specimen cllected and cultured within 2l\. hurs f the terminatin f the treatment perid revealed the presence f Streptcccus canis, Euthanasia was perfrmed seven days fllwing the terminatin f treatment, cultures f the urine, right kidney, and mucsa f the urinary bladar were psitive fr Streptcccus canls rganisms. The culture f the left kidney was negative fr bacterial grwth, experimental animal number llj. was a female dg f mixed breed weighing l punds. This animal was injected int the left artery with a culture f hemlytic Escherichia cll n June 21, 1958, Cultures f the urine indicated that Escherichia li rganisms had becme established in the tissues f the urinary tract. Chlramphenicl was used in the treatment fr a perid f ten aays. Treatment was initiated five days after injectin f the rganisms. Urine cultures made frm specimens cllected within 2l± hurs f the terminatin f the treatment perid indicated the prsence f Escherichia cli rganisms. Euthanasia was perfrmed seven days fllwing terminatin f treatment. The cultures made f the urine, right and left

27 25 kidney, and mucsa f the urinary bladder revealed the presence f hemlytic Escherichia cli. Experimental animal number 19 was a female dg f mixed breed weighing 13 punds. This animal was injected with Prteus sp. culture int the renal artery n June 2I4., Urine cultures revealed that Prteus sp. rganisms had becme established in the tissues f the urinary tract. Chlramphenicl was selected fr treatment. The treatment perid was started six days after treatment and cntinued fr a perid f five days. The urine specimen cllected and cultured within 2lj. hurs f terminatin f the treatment perid indicated the presence f Prteus sp. rganisms. Fllwing euthanasia, seven days after treatment, the urine culture revealed the presence f Prteus sp. rganisms. The culture f the right and left kidney, and mucsa f the urinary bladder was negative fr bacterial grwth. (Table 2.) Results f Sulf isxazle Therapy Experimental animal number 3 was a female dg f mixed breed weighing 2$ punds. This animal was injected with a culture f hemlytic Escherichia cli rganisms int the left renal artery n March 22, The cultures f the urine indicated that Escherichia cli rganisms had becme established in the tissues f the urinary tract. Sulfisxazle was selected fr treatment. The treatment was initiated eight days fllwing the injectin f the rganisms and cntinued fr a perid f five days. The culture f the urine cllected within 2ij. hurs after the terminatin f treatment revealed the presence f

28 t 26 H d p a P< a t P }>>3S at Q Sh H! H O d H Jh l h q fa H <H Jx!H I fa > Oj-P ^ -P &PfcQ H I I P cu p CO I t! d d S3 as 9 -O as TJ H > P X! P as >H-P 5*3 I fco &» H I O fl O H b PW I W I h I fa -P O xi t H CCF3 03 I d C P H O PA< l i S3 -d H > P P as I h a d > P P d as t V C > P p «S 4> m-p -! J u it* H H as H H d d H O H rl O fa fc ft P Z3 w fc Sh P M SI 3 P O p w H P aj «1A CQ aj a in O ft as si -p H -p a1 a +9 as SW-P a b N h a. g mx* a k 1AX1 1 CvJ H Ck JU-P 1AX1 CVJ H ft si ft Si O ra th h P d as U d OH xi H Sh O.r; H H D9 -I n P a C p ftlca H 05 I H Si m p 3 «H. a! H as p dn a a Sh d <a; M ** p Xi t H vq 2 s

29 27 Escherichia cll rganisms and a Streptccci, Euthanasia was perfrmed ten days fllwing the terminatin f treatment. The cultures f the urine, rirht and left kidneys were absent f bacterial grwth. Experimental animal number 7 was a male dg f mixed breed weighing 25 punds. This animal was injected with a culture f hemlyti Streptcccus canis int the left renal artery n May 7» 1958, The cultures f the urine indicated the Streptcccus canis rganisms had becme established in the tissues f the urinary tract, Sulfisxazle was selected as the therapeutic agent. The treatment was initiated 20 days after injectin fr a perid f five days, A culture f the urine within 2I4. hurs after the terminatin f treatment revealed the presence f Streptcccus cania rganisms, Fllwing euthanasia, ne week after the terminatin f treatment, the urine, left kidney, and mucsa f the urinary bladder shwed the presence f Strept - cccus canis n bacterial culture. The culture f the rie;ht kidney was negative fr bacterial grwth. Experimental animal number 12 was a female dg f raided breed weighing 20 punds. This dg was injected with a culture f hemlytic Escherichia cll rganisms int the left renal artery n June llj., 1958«Cultures r the urine indicated that Escherichia rganisms had becme established in the tissues f the urinary tract, Sulfisxazle was selected as the treatment agent. The treatment perid was started 13 days after injectin and was cntinued fr ten days, A culture f the urine taken within 2l\. hurs after the terminatin f treatment was

30 28 negative fr bacterial grwth. Fllwing euthanasia, seven days pst treatment, cultures were made f the urine, left and right kidney, and mucsa f the urinary bladder. These cultures were all negative fr bacterial grwth. Experimental animal number 18 was & female dg f mixed breed and weighed 15 punds. This animal was injected with a culture f Prteus sn. int the left renal artery n June 22, 1958* Cultures f the urine indicated the Prteus sj. had becme established in the tissues f the urinary tract. Suliisxazle was selected as the drug fr treatment. Treatment was started n the eighth day fllwing injectin f the rganisms and was cntinued fr a five-day perid. A culture f the urine made witain 2lj. hurs after the terminatin f treatment was negative fr bacterial grwth. Seven days after the terminatin f treatment, euthanasia was perfrmed. Cultures f the urine and mucsa f the urinary bladder revealed the presence f Prteus sp. rganisms, xhe cultures f the right and left kidneys were negative fr bacterial grwth. (Table 3.) Results f Cntrl Animals Experimental animal number 15 was a male dg f mixed breed weighing 30 punds. This animal was injected with a culture f hemlytic Escherichia li rganisms int the renal artery n June 21, Cultures f the urine later indicated that a urinary tract infectin due t hemlytic Escherichia li rganisms had been established. This animal was selected t serve as a cntrl animal. Cultures f the urine were made at the same

31 etl tsj i '.1 r P H O P 03 P O fl Oh O a P. fa I 1 ha 'd ^ > O P -P P -P P ^5 d c5 bo 8) u H 5 tses «fas I in. S«H 9 d a d «j -j T5 O H H I d 9J+2 p O d rj 43 H S3 fa O P Art tf tao H ft; s -p ro I fa ' 5 : :-. l H P 3 9 H > -! -P t s H 1 i s p d p. ra d d a T5 tj l 03 H > ^ > fa ra 1 3 XLt* h d P P -P «T3 dp P 5> 3 P H O «H «u B 01 O u u O «H H fa >» i-^affiizi cn a. P aj -p C3P fl Ph 6 p 3 a fa H «H O I p< d fa H P fa c0 > H a) > «H 43 SI U H ON -p ra a p c p d H P «61 fa 01 c5 1A P P. t»> H Xt P O bo C* XI CJ +J i-t «X> H «J 03 m p x> N H d d p X O H 3: ra & >4 p,:>> rh 13 P P O aj XI P r- XI ih OS n O P,. i H 3 i d «OHS p g> O H f«p > d --< 5^g?-. aj Xi u 43 E 3 Xi t e> ih^i 0. R \A fcp w d H N ra dx b H -H i k aj Xi U P U d h.'- aj OHrift * O ra «H < H P* M <M O CO P rh d a Ti m -h jd H P d H at ID Sh fcflt"j fa J H O M,-1 ra 3 Si v4 X! O H O ra --1 SI -P * '* S3 O «ra th X> E-i H i P si p &0 xrv d rh H CM tf 1 a s«^4 nh ^ d li «aj A 1 f^ * H a VA C\i 8 3 CO H

32 30 intervals as the animals that were treated. The urine culture made at the time f terminatin f treatment f the ther animals indicated the presence f Escherichia cll rganisms. The cultures made fllwing euthanasia indicated Escherichia cli rganisms were present in the urine, tissues f the left kidney, and mucsa f the urinary bladder. The culture f the right kidney was negative fr bacterial grwth. Experimental animal number 20 was a male dg f mixed breed weighing 2$ punds. This animal was injected with a culture f Prteus s. int the left renal artery n June 21}., Urine cultures later indicated the establishment f Prteus s. rganisms in the tissues f the urinary tract. This animal was selected t serve as a cntrl. Urine Maples were taken at crrespnding times with the animals being treated. The urine culture cllected at the crrespnding time with the terminatin f the treatment perid f the animals being treated revealed the presence f Prteus sp. rganisms. Fllwing euthanasia cultures f the urine and mucsa f the urinary bladder indicated the presence f Prteus s. Cultures f the right and left kidneys did nt reveal bacterial grwth. (Table I}..) DISCUSSION Penicillin and d 1 hydrstrp tmy in cmbinatin prduced a negative culture f the urine in all fur ases upn the bacterilgical examinatin f the urine made within 2i± hurs after the terminatin f treatment. In tw cases, experimental animals $ and 8, the infecting rganism, Escherichia cll r

33 : 31 -p H O P OS" CQ P 43 c g p ss Q & EH P W P O fl d, pi K H 1 i k 1 b >» I & CJ 'd Q< a d T3 H xi H X > CO H >J4 > *: H 1 3 MH H P P p P P p si a CJP p a xi cd H 1 H O u K A rl k u O tj&q si «!25 m n H > CM «S5 p J p CO SI C a H 3 xi fc p S> P xi p n -< H n u p CO P GS I g P c! a CQ H P C 0) a p O d c Q»«* H O is 1 I O (X m U E p OS H n H CU P *-* <H O CJ P H CO H 1 H P d & a O f-t * H P C! H <; I P xl 6(0 H O S3 as 3 H P. i jd H H n M a si p h Oh P H H OO P P CJ It O P CO > «rl C] H O f*

34 32 Streptcccus cards, were present In the urine and kidney tissues at the time f necrpsy. The duratin f treatment may be f significance In cmparing the results btained in the treatment f experimental animals 5 and l6 In animal 16 the ten-day perid f treatment appeared t prduce a bacterilgical cure, while the infecting rganisms reappeared n bacterilgical culture after the fiveday treatment perid f animal 5. Chlramphenicl therapy, in this series, did nt prduce negative urine cultures in spite f the fact that the rganisms used Indicated a sensitivity t chlramphenicl in vitr. Upn necrpsy f experimental animal number llj., a severe suppurative pyelnephritis f the left kidney was bserved. Cnsequently, this case was prbably nt a true indicatin f the efficacy f chlramphenicl fr a ten-day perid f treatment. In the series using sulfisxazle therapy the urine was sterile upn bacterilgical examinatin 2if hurs after the terminatin f the treatment in tw cases, experimental animals number 12 and 18. A psitive culture f the urine was btained upn necrpsy f experimental animal number 18 The ten-day treatment f experimental animal number 12 apparently prduced a bacterilgical cure. The five-day treatment perid f experimental animal number 3# infected with the same strain f rganisms, did nt prduce a sterile urine specimen upn bacterilgical examinatin within 2l\. hurs after the treatment perid. A secnd rganism, identified as a

35 33 Streptcccus, appeared n the cultures f the urine f animal number 3. This was a cmmn finding f Rhads, Billings, and O'Cnr (18). Sulfisxazle is usually effective against Escherichia cli, but apparently it is ineffective against sme strains f Streptcccus. The absence f rganisms upn the bacterilgical examinatin f the urine and kidney tissues at necrpsy f experimental animal number 3 can nly be therized. The treatment may have reduced the number f infecting rganisms and allwed the nrmal bdy defenses t vercme the infectin. Obstructive lesins may have been prduced by the enlargement f the kidney tissues due t inflammatin caused by the infectius rganism. These inflammed tissues may have been reduced in size by treatment, in turn crrecting the bstructive lesins and allwing the infected areas t be repaired by the nrmal bdy prcesses. There are several factrs which have a direct relatin n the effectiveness f an antibactial agent upn urinary tract infectins and may be the cause f a bacterilgical failure in the treatment f infectins f the urinary system. A fci f infectin may be the primary lesin which cntinually sheds the rganisms which gain entrance t the urinary tract tissues by way f the bld and lymphatics. If this cnditin des exist it must be eliminated befre a permanent bacterilgical cure f the urinary tract infectin can be accmplished. Stasis f the urine due t bstructive lesins may be a cause f urinary tract therapeutic failures. Obstructive

36 34 lesins f the urinary system may be due t neplasms, injuries, inflammatry debris, prstatitis, urinary calculi, and disease cnditins. Obstructive lesins must be crrected befre bacterilgical cures can be attaind with antibacterial agents* Inadequate dsage f the antibacterial agent may be a cmmn cause f therapeutic failure. The rganisms are usually situated within the tissues f the kidneys. The cmmnly cnsidered dsage schedules may sterilise the urine, but the antibacterial level in the tissues may nt be sufficient t be effective against the rganisms. The duratin f treatment is an imprtant factr in the treatment f urinary tract infectins. In chrnic infectins barriers frm cellular infiltratin and cicatrix frmatin may reduce the antibacterial level reaching the infecting rganisms. The maintenance f an antibacterial level fr a sufficient perid f time t allw Infiltratin int these areas is necessary fr a bacterilgical cure. Anther cause f therapeutic failure may be the resistance f the rganisms t the antibacterial agent. An antibacterial drug has limitatins in usefulness based upn its bacterial spectrum. Unfrtunately, sme rganisms which are nrmally cnsidered susceptible t a drug may nt be cntrlled by this drug upn its use in treatment. The identificatin f the infecting rganism and determining the drug f chice fr the treatment by the use f antibitic sensitivity testing generally increases the rate f bactrilgical cures f urinary tract infectins.

37 35 There is the pssibility that the manner in which the antibacterial agent is excreted may have an effect upn therapeutic respnse. Jnes (11) states that 80 percent f penicillin is excreted thrugh the renal tubules. Organisms which are lcated in sme areas f the kidneys may be expsed t an insufficient level f the antibacterial t create a therapeutic respnse. The use f cmbined antibacterial agents appear t increase the number f bacterilgical cures. It is reasnable t assume that tw agents may attack the bacterial cell frm different metablic standpints, bth cntributing t a mre cmplete therapeutic respnse. Cmbined antibacterial agents may als be f benefit in treating urinary tract infectins which are caused by mre than ne micr-rganism. SUMMARY The results f this series indicates that chlramphenicl is nt effective against urinary tract infectins in the canine due t Escherichia cli. Streptcccus canis. and Prteus sp_. when used in the cmmnly applied dsages and perid f treatment, Sulfisxazle wuld appear t be f benefit in the treatment f urinary tract infectins f the canine due t Gramnegative rganisms. Based n this series, therapy shuld be maintained fr a perid f at least ten days t prvide fr maximum effectiveness. Due t the lw cst f this drug, in cmparisn with many f the s-called brad spectrum antibacterials, the expense f effective treatment shuld nt be

38 36 cnsidered prhibitive. Of the antibacterial agents used, the cmbinatin f penicillin and dihydrstreptmycin was the mst effective against Escherichia cjli, Streptcccus canis, and Prteus sp. In this series, the ten-day perid f treatment was the mst effective. The results f this study indicate that the prcedure f treatment generally administered by veterinary practitiners, using penicillin, dihydrstreptmycin, chlramphenicl, and sulfisxazle, may nt be effective in prducing bacterilgical cures in urinary tract infectins due t Escherichia cll, Prteus sp, and Streptcccus canis.

39 37 ACKNOWLEDGMENTS Grateful acknwledgment t Dr. J, E. Msier, Department f Surgery and Medicine, fr his valuable cuncil and guidance. Acknwledgment t Dr. E. H. Cles, Department f Pathlgy, fr his aid and use f labratry facilities. Sincere appreciatin t the Department f Surgery and Medicine fr the use f their facilities.

40 38 BIBLIOGRAPHY (1) Adcck, J. D., and R. T. Plumb. Streptmycin fr urinary tract infectins. Med. Assc. 133:579* 19^7. Jur, Am, (2) Blm, Frank, Pathlgy f the dg and cat. Evanstm American Veterinary Publicatins, 1951J-* (3) Bddie, Gerge F. Diagnstic methds in veterinary medicine. l.th ed. Philadelphia! LIppinctt, (ij.) Brdey, R. S. Canine urlethiasis. A survey and discussin f fiftytw cases. Jur, Am, Vet, Med, Assc. 126: «(5) Carrll, Graysn. Current use f sulfnamides in urlgy. Ann. New Yrk Acad. Sci (6) Chittenden, G, E., E. A. Sharp, E. C, Vnder Heide, A, C, Brattn, A, J, Glazk, and F, D, Stimpert, The treatment f bacillary urinary infectins with Chlrmycetin. J. Url. 62*771. I9I+.9. (7) Cles, E. H and J, E. Msier. Effect f nitrfurantin n experimental canine bacter - ial nephritis. Unpublished material. (8) Haines, Harld M. Clinical reprt. Cllfrm nephritis in the dg. Vet. Med. i 2t319«19^5 (9) Hutyra, Franz, Jseph Marek, and Rudlph Manninger. Special pathlgy and therapeutics f th diseases f dmestic animals. Chicag: Alexander Eger, 19^9. (10) Institute f Animal Pathlgy (Lndn). Vet. Med. 35:63. 19^-0. (11) Jnes, L. Meyer. Pharmaclgy and therapeutics. 2nd ed. Ames: Iwa State Cllege Press, 1957 (12) Kass, E, H. C hmtherapeutic and antibitic drugs in the management f infectins f the urinary tract. Am J. Med. 18: 76I4.-78I

41 39 (13) King, Nevill S. Stuggart disease and nephritis. Vet, Med. 32tij.Ol-l4.O (II4.) Lenard, E. P., G. G. Richard, and K. MEntee. The urgenital system. Canine medicine. Evanstn: American Veterinary Publicatins, 1953 (15) Msier, J. E,, and E, H. Cles. Clinical effectiveness f furadantin in urinary tract infctin f small animals. Vet. Med. Unpublished material. (16) Nesbit, R. M., and W. C. Baum. Antibitic and chen therapeutic agents in infectins f the genl t-urinary tract. Jur. Am. Med. Assc. 150: (17) Pratt, Rbertsn, and Jean Dufreny. Antibitics. Philadelphia: Lippinctt, (18) Rads, P. S., C. E. Billing, and V. P. O'Cnr. Antibacterial management f urinary tract infectins. Jur. Am. Med. Assc, llj.8 : (19) Rllag, Ole. Clinical reprt. Nephritis due t escherichia cli infectin. Vet. Med. Ij.2j1j lj-7. (20) Schweinburg, B., and A. M. Rutenburg. NUl i[.5 in treatment f infectin due t gram negative bacilli. Prc. Sc. Exper. Bil, and Med. 71:20. (21) Waisbren, Burtn A., and Clair Carr. Penicillin and chlramphenicl in the treatment f infectins due t prteus rganisms. Am. Jur. Med. Sc (22) Winternitz, M. C, and W. C. Puinby. Experimental nephrpathy in the dg. Lesins prduced by injectin f the bacillus brnchisepticus int the renal artery. J. Url. I:139-l (23) Wright, J. G. The diagnsis f gastric diseases in the dg and cat. Vet. Rec. 12:

42 THE COMPARATIVE EFFICACY OF SOME OF THE COMMONLY USED URINARY ANTIBACTERIAL AGENTS IN THE TREATMENT OF EXPERIMENTAL CANINE BACTERIAL NEPHRITIS by ROBERT HAROLD FEATHERSTON B. S#, Kansas State Cllege f Agriculture and Applied Science, D, V. M», Kansas State Cllege 1953 f Agriculture and Applied Science, 1955 AN ABSTRACT OF A THESIS submitted in partial fulfillment f the requirements fr the degree MASTER OF SCIENCE Department f Surgery and Medicine KANSAS STATE COLLEGE OF AGRICULTURE AND APPLIED SCIENCE 1958

43 Bacterial nephritis is frequently encuntered in canine urinary tract infectins. It is nt uncmmn fr this nditin t recur fllwing treatment, thus, btaining a bacterilgical cure may be a definite prblem t the veterinary practitiner. The purpse f this study was t attempt t evaluate the efficacy f the mre cmmnly used antibacterial agents and their prcedure f use as generally administered by veterinary practitiners in the treatment f canine urinary tract infectins, A ttal f lij. dgs f cmmn mixed breeds, seven males and seven females, ranging in age frm six mnths t tw years, weighing between 13 and 32 punds, were used. The dgs, after urine cultures were made and fund t be negative, were divided int fur grups. Grup I, cnsisting f three dgs, was inculated with Escherichia cll rganisms. Grup II, cnsisting f three dgs, was Inculated with Streptcccus anis. Grup III, cnsisting f fur dgs, was Inculated with Escherichia cll. Grup IV, cnsisting f fur dgs, was inculated with Prteus sp_. The rganisms used fr inculatin were riginally islated frm clinical cases f canine urinary tract Infectins, After the rganism was islated, identified, and tested fr sensitivity t antibitics, it was cultured In brth fr 2l\. hurs prir t Its use as an inculum. The Infectin was established by surgically expsing the left kidney and injecting 0.5 ml. f the bacterial inculum int the left renal artery. Fllwing the injectin f the bacterial

44 2 culture, urine specimens were cllected daily t determine if a urinary tract infectin had been established The urine specimens were cllected by abdmincentesis t eliminate pssible cntaminatin frm the rganisms nrmally present in the external genitalia. The urine samples were cultured n five percent sheep bld agar and a rutine urinalysis fr prtein, glucse, specific gravity, and ph was perfrmed, A micrscpic examinatin was made f the urinary sediment. Treatment was initiated five t 20 days fllwing islatin f the rganisms frm the urine after injectin. This perid allwed the rganisms t becme firmly established in the tissues f the kidney. Treatment cnsisted f the randm selectin f ne animal in each grup fr treatment with penicillin and dihydrstreptmycin cmbinatin, ne with sulf isxazle, and ne with chlramphenicl. Tw animals, ne in Grup III and ne in Grup IV, were selected t serve as cntrl animals and were nt treated. The recmmended dsage fr each drug was used fr a perid f five days in Grups I, II, and IV, and fr ten days in Grup III, The urine specimens were cllected and examined daily during the treatment perid, within 2^ hurs after terminatin f treatment, and at the time f necrpsy seven t ten days fllwing terminatin f treatment. Chlramphenicl, in this series, did nt prduce negative urine cultures in spite f the fact that the rganisms used indicated a sensitivity t chlramphenicl in vitr. These results indicate that chlramphenicl is nt effective against

45 urinary tract infectins in the canine due t Escherichia cll, Streptcccus canis, and Prteus sp. when used in the cmmnly applied dsages and perid f treatment. In the series using sulf isxazle therapy, the urine was sterile upn bacterilgical examinatin within 2l\. hurs fllwing terminatin f therapy in tw cases, experimental animals number 12 and 18. Only ne case, experimental animal number 12, had a sterile urine culture upn necrpsy seven days fllwing terminatin f treatment. The ten-day perid f treatment f animal number 12 apparently prduced a bacterilgical cure. The five-day treatment perid f experimental animal number 3, infected with the same strain f rganisms, did nt prduce a sterile urine culture. A secnd rganism, identified as a Streptcccus, appeard n the urine cultures f animal number 3 at the terminatin f the treatment perid. This has been reprted a cmmn finding with sulf isxazle therapy. Based n this series, sulfisxazle is f benefit in the treatment f urinary tract infectins f the canine due t Gramnegative rganisms, and treatment with this drug shuld be maintained fr at least ten days t btain maximum effectiveness. Penicillin and dihydrstreptmycin cmbinatin prduced a negative urine culture in all fcur experimental animals n bacterilgical examinatin made within 2l\. hurs fllwing treatment perid. Tw animals, experimental animals number l6 and 17, had sterile urine cultures at the time f necrpsy. A bacterilgical cure was apparently btained in experimental animal number l6, when treated fr a ten-day perid. The

46 five-day treatment perid f experimental animal 5, infected with the same strain f rganisms, did nt prduce a sterile urine culture at the time f necrpsy. In this series the cmbinatin f penicillin and dihydrstreptmycin was effective against urinary tract infectins due t Escherichia cli. Streptcccus canis. and Prteus sp, t and was mst effective when used fr a ten-day treatment perid. The results f this study indicate that the prcedures f treatment generally administered by veterinary practitiners, using penicillin, dihydrstreptmycin, chlramphenicl, and sulfisxazle, may nt be effective in prducing bacterilgical cures in urinary tract infectins due t Escherichia cell, Prteus sp». and Streptcccus canis.