Infections with Cephapirin

Transcription

1 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Sept. 1974, p Americn Society for Microbiology Vol. 6, No. 3 Printed in U.S.A. Tretment of Pneumoni nd Other Serious Bcteril Infections with Cephpirin HUGH G. ROBSON AND M. IAN BOWMER Infectious Disese Service, Deprtments of Medicine nd Microbiology, Royl Victori Hospitl, Montrel, Quebec, Cnd Received for publiction 21 December 1973 Nineteen ptients with pneumoni due to Streptococcus pneumonie, Stphylococcus ureus, Klebsiell pneumonie, or Escherichi coli were treted with 4 to 18 g of cephpirin dily. There were three tretment filures. One ptient ech with pneumoni due to E. coli or S. pneumonie died despite pprent erdiction of the pthogen. Lobr pneumoni due to K. pneumonie progressed during therpy in third ptient to lung gngrene, necessitting pneumonectomy. Five dditionl ptients with pneumococcl pericrditis or septic bursitis, empyem, cnnul-ssocited bcteremi, nd thorctomy wound infection due to S. ureus were cured. All isoltes of S. ureus, S. pneumonie, nd group A Streptococcus were inhibited by.8,ug of cephpirin per ml; miniml inhibitory concentrtions of cephlothin were similr. Ninety percent of K. pneumonie, 85% of Proteus mirbilis, 73% of E. coli, nd 3% of Enterobcter were inhibited by 12.5 ug cephpirin per ml. All isoltes of Pseudomons, Serrti nd indole-positive Proteus hd cephpirin miniml inhibitory concentrtion of 1 gg/mg. Serum concentrtions fter intrvenous nd intrmusculr injection were similr to those reported for cephlothin. The intrmusculr injections were modertely pinful, nd intrvenous infusions cused phlebitis in three of nine ptients treted with doses up to 18 g per dy. Cephpirin ppers comprble to cephlothin in vitro nd is n effective gent in tretment of infection due to S. ureus nd S. pneumonie. 274 Cephpirin is new cephlosporin ntibiotic with n in vitro ntibcteril spectrum similr to tht of cephlothin (1, 6). Cephpirin is poorly bsorbed following orl dministrtion nd must be given prenterlly. Erly reports suggested tht the drug produced moderte pin fter intrmusculr dministrtion but cused little pin or phlebitis when given by the intrvenous route (3, 4, 7). In prticulr, it ws reported to be better tolerted by the intrvenous route thn cephlothin (9). However, three recent comprisons of the incidence of phlebitis ssocited with cephpirin nd cephlothin therpy hve not resulted in consistent findings (5, 8, 13). Other dverse effects hve been infrequent in ptients receiving cephpirin therpy (1). In prticulr, renl toxicity hs not been noted, in contrst to it being commonly ssocited with cephloridine nd infrequently with cephlothin (2). Experimentl nephrotoxicity in lbortory nimls hs not been observed with cephpirin (11, 15). A serum-sickness-like syndrome hs been documented in volunteers who received intermittent intrvenous injections of either cephpirin or cephlothin in doses of 8 g per dy for up to 28 dys (13). The present study ws undertken to evlute the clinicl efficcy of cephpirin in ptients with modertely severe nd severe bcteril infections, especilly pneumoni. We lso compred the in vitro ctivities of cephpirin, cephlothin, nd cephloridine ginst lrge number of clinicl isoltes nd mesured cephpirin serum levels in ptients on vrious dose regimens. MATERIALS AND METHODS Clinicl nd microbiologicl studies. Twentyfour ptients with infections due to Streptococcus pneumonie, Stphylococcus ureus, Escherichi coli, nd Klebsiell pneumonie were treted. Of these, 18 hd significnt underlying disese nd 12 were 6 yers of ge or older. All but 2 hd intrthorcic infections. Cultures of sputum were obtined in ll pneumoni ptients prior to therpy except for three (numbers 9, 2, nd 21) in whom trnstrchel spirtions were performed becuse of their inbility to produce de- Downloded from on June 28, 218 by guest

2 VOL. 6, 1974 qute sputum spontneously. All spirte nd sputum specimens were Grm-stined nd exmined by one of the investigtors to determine the predominnt orgnism. At lest one blood culture ws obtined in every ptient before institution of cephpirin therpy. Chest roentgenogrms were obtined before, during, nd fter tretment to determine the extent of pneumoni nd to ssess response to therpy. In ptients with pericrditis, empyem, wound infection, nd septic bursitis, specimens for Grm stin nd culture were obtined by spirtion of the involved site. Sputum nd direct spirte specimens were cultured erobiclly on sheep blood nd McConkey grs. Pneumococci were identified on blood gr nd confirmed by optochin (ethylhydrocupreine) sensitivity. Isoltes of S. ureus were cogulse nd mnnitol positive. E. coli nd K. pneumonie were identified by their typicl colony ppernce on McConkey gr, the presence or bsence of motility, nd their chrcteristic performnce in the indole, methyl red, Voges-Proskuer, nd citrte biochemicl rections. The K. pneumonie isolted in ptient 23 ws identified s type 1 by the Center for Disese Control, Atlnt, G. Miniml inhibitory concentrtions (MIC) for S. ureus nd grm-negtive bcilli were determined by n gr dilution method in Mueller-Hinton gr. Antibiotic-contining pltes were inoculted by multiple inocultor pprtus (14) with 1-fold dilution of n overnight Trypticse soy broth culture. The MIC for pneumococci nd group A streptococci were determined in Mueller-Hinton gr contining 5% defibrinted sheep blood. These pltes were inoculted with 1-fold dilution of n overnight Todd- Hewitt broth culture. Lbortory studies performed in ll ptients before, during, nd fter cephpirin therpy included hemtocrit, leukocyte count nd differentil, urinlysis, blood ure nitrogen, serum cretinine, lkline phosphtse, serum glutmic oxlocetic trnsminse (SGOT), nd serum bilirubin. Serum level studies. Blood ws drwn t vrying times during courses of therpy from selected ptients for determintion of cephpirin concentrtion. Antibiotic levels were determined by the method of Brn et l. (4), except tht 6-mm filter pper disks were loded with 25 Mliters of serum from cpillry tubes nd ssy pltes were incubted t 37 C for 18 h. All ssys were performed in qudruplicte. Tretment schedules. Intrmusculr injections of 1 g in 2 ml of sterile wter were dministered into the glutel muscle mss. For intrvenous infusions, ech grm of the drug ws dissolved to concentrtion of 1 g/2 ml in 5% dextrose in wter. The infusions were given over 2 to 3 min through smll-guge steel needles mintined t given infusion site for 48 to 72 h. RESULTS Clinicl results. Tble 1 summrizes clinicl dt on the ptients treted with cephpirin. All but 1 of the 11 ptients with pneumococcl TREATMENT OF PNEUMONIA WITH CEPHAPIRIN 275 pneumoni were cured. They defervesced within 1 to 7 dys (men, 2.8 dys) fter institution of therpy. In ddition to the isoltion of pneumococci from sputum or spirtes in ll ptients with pneumoni, nd from blood cultures of two ptients, exmintion of pretretment sputum or trnstrchel spirtes showed predominnce of grm-positive diplococci in ll ptients. The dose of cephpirin employed for pneumococcl pneumoni ws 4 g per dy except in ptient 9, who received 6 g per dy. Five ptients, including one with pneumococcl bcteremi (ptient 5), were treted for 5 dys or less. All defervesced bruptly within 24 h of institution of cephpirin nd remined well fter therpy ws discontinued. Follow-up sputum cultures invribly showed bsence of pneumococci within 72 h of institution of therpy, nd seril chest roentgenogrms showed complete resolution of the pneumonic processes within 3 weeks in ll ptients. Ptient 1, 73-yer-old mn, dmitted moribund with pneumoni nd congestive hert filure, died suddenly on dy 4 of therpy. At utopsy, some resolution of the pneumoni ws evident, nd cultures of lung, spleen, nd blood were sterile. Ptient 12, with lymphosrcom, purulent pericrditis, nd bcteremi, required emergency pericrdiectomy nd dringe in ddition to 6 g of cephpirin per dy. Therpy resulted in resolution of the pericrditis nd erdiction of pneumococci from blood nd pericrdil dringe fluid. Ptient 24 hd lobr pneumoni involving three lobes, presumed due to pneumococci. Initil sputum Grm stin showed predominnce of grm-positive diplococci. Although sputum nd blood cultures did not grow out the pneumococci, this ptient defervesced within 5 dys, nd complete resolution ws observed on chest roentgenogrphy by dy 1 fter institution of cephpirin. Seven ptients with S. ureus infections were treted with cephpirin. In three ptients with pneumoni (numbers 15 to 17), pretretment Grm stin of sputum showed the predominnt orgnism to be lrge grm-positive cocci in clumps. These three ptients were only modertely ill, nd ll defervesced within 72 h of institution of cephpirin therpy. Follow-up sputum cultures showed disppernce of stphylocci within 5 to 11 dys, nd the pulmonry infiltrtes clered within 5 to 14 dys. Ptient 14 with cnnul-ssocited phlebitis nd bcteremi defervesced within 48 h of removl of the cnnul nd institution of cephpirin therpy; locl signs of inflmmtion disppered within 1 dys. Three ptients with closed-spce infec- Downloded from on June 28, 218 by guest

3 276 ROBSON AND BOWMER ANTIMICROB. AG. CHEMOTHER. I ~4-6.. co Y Y 2E2E 2 2 E r = r 2 l"l v 6 L.1: 4Q ^. 4.. I Cs ci' C -4 A '4.' O~ -- LO LO) CO OM O 4 4;~~~~~~~~~~~~C CD t C ~~~~~ " o ~~~~~~~~~~~~~~~~~~~~~~~~~~~6 Obi > l ci S E ~ ~~~~~~~~~~~~~~ E6'4- ' *CDywi 3-~ E 14 C1 No c c o o o.: O _ >O- -._ o. _ co o -N cis <rd CS C S Co o ~~~~~~~~~~~~~~~ ~ = O O o O O O O O O O O ' ", ~ ~~~ - " ~~~~~~~~~ " C. -c ci'i8> > r oo srcd NCO c 6 _ o o~~~~~~~~ O CCO '1' C 6 C~ l Cot coo co co~~~~~~~~~y)c E ~~~~~~~~~~~~~~~~~ s d ~~~~~~~~~' ) ; Mr ) V v vzv v vc O v X "C] o V4 c v Cl C)..C. C> 3 ~~~~~~~~~~~~~~~~~~~~~~~~~4 6 ~~~~~~~~~~~~ ~ " o ~~~~~~~~~~~~~~~n. 4x O Downloded from on June 28, 218 by guest o OVL c) cc. O ~C E- o ~ C cqloo C DCco v- I", le,t-- t.3 CO 'locd-i t-- CO '-4 c-i :s ' J $2.. t Ci: -

4 VOL. 6, 1974 TREATMENT OF PNEUMONIA WITH CEPHAPIRIN 277 > > I -. C It~~ Cl o &4~~~~~~~4 C 4- Cu )CZ ~ C. 2c;=2Xi E e 3 ; Cu~~~~~~~~~~~~~~~~~~~~~~~~~~~~&.Y~~~A X ~~~~~~ oc) C.) _ O C Cu.45" Ooi z^r co o m co cs Ocs :* oc C c5 C mc-4 cq 11-t c ~~~~~~~~~~~~ = ti "o~~ ~~~~~~~~~~ EJ ve" o~ CZC C ~ C ' > CS &C H"o o co- ci. 4 C) C) 3 C) O ^ bf CZ~~~~~~~~u C6C - ~ CO CO co ccrr > C' -,. ~ cu _ N Cl - W In cs~~~~~~~~~~~c Q Cu3 o cq co ;_ Cu3 q co -,ce Cu3 m cis X- Cu.Ct " o ~ b42.c Downloded from on June 28, 218 by guest - C- Lo ~C- 4. " 4 ) U~~~~~~~~~~~~~~~~~--l 4. O) 8 ~ 4 Cl -ZH ' Cli Cl Cl4 Cl uc

5 278 ROBSON AND BOWMER tions (numbers 13, 18, nd 19) required surgicl procedures in ddition to cephpirin therpy, including lung decortiction, dringe of n extrpleurl bscess, nd incision of n olecrnon burs, respectively. Ptient 13 becme febrile by dy 7 of cephpirin tretment (dy 4 post-lung decortiction); ptients 18 nd 19 both were febrile on dy 3 of cephpirin therpy. S. ureus could no longer be recovered from dringe from the infected sites by 5, 15, nd 15 dys, respectively, fter institution of cephpirin. Four ptients (numbers 2 to 23) with grm-negtive bcillry pneumoni received cephpirin. The dignosis ws estblished by the demonstrtion of grm-negtive rods in predominnce in smers nd recovery of E. coli or K. pneumonie in cultures from trnstrchel spirtes in ptients 2 nd 21, nd from sputum nd pleurl fluid or lung tissue in ptients 22 nd 23. Ptient 2, 74-yer-old womn, died of E. coli pneumoni on dy 5 of tretment. Exmintion of the pretretment trnstrchel spirte showed sprse grmpositive cocci nd numerous grm-negtive bcilli, but only E. coli ws recovered on culture. On dy 4 of tretment repet trnstrchel spirte showed only grm-negtive bcilli nd culture gin grew out only E. coli. The MIC of both isoltes ws 25 Mg/ml. Autopsy showed severe confluent bronchopneumoni involving three lobes, but lung cultures were sterile nd no bcteri were seen in tissue sections. Two of three ptients with K. pneumonie infections were cured, including ptient 22, n lcoholic mle with severe lobr pneumoni. He required severl thorcenteses for mngement of erly empyem nd received concurrent knmycin therpy. He defervesced within 8 dys nd K. pneumonie ws erdicted from sputum nd pleurl fluid within 1 dys of institution of therpy. Ptient 23 with severe lobr pneumoni due to type 1 K. pneumonie fred less well. He hd been ill for 5 dys before institution of therpy nd developed gngrene of most of the right lung, necessitting pneumonectomy. Despite therpy with lrge doses of cephpirin nd knmycin which erdicted K. pneumonie from sputum, the ptient remined febrile. The pthogen ws recovered from necrotic lung resected on dy 27 of illness, 7 dys fter cephpirin therpy ws discontinued. MIC of pre- nd post-tretment isolted ws 3.1 jg/ ml Ȧdverse effects. There were no instnces of drug-induced nemi, neutropeni, eosinophili, or renl toxicity. There were, however, ANTIMICROB. AG. CHEMOTHER. nine ptients who developed elevted SGOT vlues during therpy. Seven hd been given cephpirin intrmusculrly nd two (ptients 14 nd 22) hd been treted intrvenously. In the ltter two, elevted SGOT levels were noted before tretment s well, but significnt elevtions (greter thn 5 units) occurred during intrvenous therpy. In ll cses, SGOT vlues diminished fter therpy ended. Serum cretinine phosphokinse levels were not mesured. The most striking dverse effect ws severe wtery dirrhe in ptient 12 treted with 6 g per dy intrvenously for 7 dys. Culture of dirrhe fluid yielded no pthogenic microorgnism. The dirrhe subsided 3 dys fter cephpirin therpy ended. Locl tolernce on injection ws good in mny ptients; however, 1 of 23 who received some or ll of their doses intrmusculrly reported some pin fter the injection. In only one cse ws the pin severe enough to necessitte stopping therpy. Evidence of phlebitis (redness nd plpble venous cord t the infusion site) developed in three of nine ptients given intrvenous cephpirin. Of the two ptients who developed severe phlebitis, one received 6 g dily for nine dys nd the other received 12 to 18 g dily for 16 dys. Another ptient who ws given 12 to 18 g intrvenously dily for 16 dys hd evidence of mild phlebitis. In vitro results. All pneumococcl isoltes from study ptients hd MIC of.1,ug or less per ml. Ptients' S. ureus isoltes were ll inhibited by.4,g of cephpirin per ml, nd the K. pneumonie isoltes by 6.25 Mg or less per ml. These orgnisms were included with other concurrent hospitl isoltes in studies of the comprtive in vitro ctivity of cephpirin, cephlothin, nd cephloridine. Cephpirin ws somewht more ctive thn cephlothin ginst group A streptococci nd pneumococci, but less ctive thn cephloridine (Fig. 1). Cephpirin inhibited ll strins of pneumococci t concentrtion of.1 Mg/ml nd ll group A streptococci t.5 Mg/ml. Cephpirin nd cephlothin showed lmost identicl nti-stphylococcl ctivity, inhibiting ll 1 strins of S. ureus t.8 Mg/ml (Fig. 2). Cephpirin ws less ctive thn cephlothin nd cephloridine ginst isoltes of E. coli, inhibiting 73% of the isoltes t concentrtion of 12.5 Mg/ml compred to 8% nd 96% of strins inhibited by cephlothin nd cephloridine, respectively (Fig. 3). The ctivities of the three cephlosporins did not differ significntly ginst isoltes of K. pneumonie, Proteus mirbilis, or Enterobcter. Cephpirin inhib- Downloded from on June 28, 218 by guest

6 VOL. 6, I so S 4 I I 2 U Group A SREPTOCOCCUS (16) 1~~~~ - I I * Co*phpirin._Coo - Mphothin I *---- * Cph, slorldine 1 / ~~~~~~~I I~~~~~~~~~ I, -/1 II TREATMENT OF PNEUMONIA WITH CEPHAPIRIN 279 ited 9% of K. pneumonie, 85% of P. mirbills, nd 3% of Enterobcter t concentrtion of 12.5,ug/ml. MIC of the three cephlosporins ws 1,ug or greter per ml for 15 strins ech of Pseudomons eruginos nd indole-positive Proteus nd 1 strins of Serrti. Serum levels. Pek serum levels in ptients S. AUREUS (1) 1 L4 ( S & PNEUMONIAE (3) too_ij/ ~so I 4 z / 12 / / /I Minimum Inhibitory Concontrtion (WMi) FIG. 1. Cumultive percentge of inhibition of isoltes of group A Streptococcus nd S. pneumonie. Numbers in prentheses refer to the number of isoltes tested. 1 E.COLI (3).C c 1. C U ( R E U2 * * Cephpirin *-A- Cephlothin *----- Cephloridine Minimum Inhibitory Concentrtion (Ag/mi) FIG. 2. Cumultive percentge of inhibition of 1 S. ureus isoltes. P.MIRABILIS (3) Downloded from I I - 6 x Bās 4 U A KLEBSIELLA (3) so oo 4 2 F 1 r so8 - t/ _// /,,.'! ENTEROBACTER (2) on June 28, 218 by guest Ic I S 6 E Minimum Inhibitory Concentrtion (IO/ml) SO 1 Minimum Inhibitory Concontrtion (," 'ni) FIG. 3. Cumultive percentge of inhibition of isoltes of E. coli, Klebsiell, P. mirbilis, nd Enterobcter. Numbers in prentheses refer to the number of isoltes.

7 28 ROBSON AND BOWMER given 1-g intrmusculr doses were mesured 1 h fter injection (Tble 2). The vlues rnged from 4.3 to 4. Ag/ml, with men of 1.1 jgg/ml. Cephpirin ctivity disppered rpidly from the blood in most cses so tht 4 h fter injection the men level ws 1.3,ug/ml. Significnt elevtions of serum cephpirin levels were observed in two ptients. Ptient 2 hd concentrtions of 4., 34. nd 12.2 ug/iml 1, 2 nd 3 h fter 1-g intrmusculr dose on dy 4 of tretment. At the time, she ws in hert filure nd hd blood ure nitrogen content of 42 mg/1 ml. Ptient 21 hd twice weekly hemodilysis for chronic renl filure nd received 1-g intrmusculr doses every 6 h for K. pneumonie bronchopneumoni. On dy 8 of tretment, immeditely prior to beginning dilysis, nd 6 h fter his lst dose, he hd cephpirin serum level of 78.4 Mg/ml. At the beginning of the dilysis he received 1 g of cephpirin intrvenously. Subsequent serum levels during the dilysis were: 3 min postdose, Ag/ ml; 1 h postdose, 7.4 ug/ml; nd 4 h postdose, 52. ug/ml. No untowrd effects were noted in these two ptients s result of the elevted levels. DISCUSSION Cephpirin is highly ctive in vitro ginst isoltes of S. ureus, pneumococci, nd group A Streptococcus. Its nti-stphylococcl ctivity ws virtully identicl to tht of cephlothin. Lrge inocul of ll stphylococcl isoltes were inhibited by.8 gg of both gents per ml. In nother study lrge inocul of penicillin-resistnt S. ureus were killed in vitro t cephpirin TABLE 2. Cephpirin serum levels P- Dose Serum level (ug/ml) Tretment tient vler no. (h) l Intrmusculr dose (1 g) Intrvenous dose (1 g) Intrvenous dose (2 g) Time (hour) fter dose. ANTIMICROB. AG. CHEMOTHER. concentrtions of 5 gg or less per ml (15). This suggests tht cephpirin my, like cephlothin, be resistnt to stphylococcl penicillinse. The in vitro ctivity of cephpirin ginst pneumococci nd group A streptococci ws intermedite between tht of cephloridine nd cephlothin. All isoltes were inhibited by the three cephlosporins t concentrtions of.2,g or less per ml. The smll differences in ntibcteril ctivity of the three gents re unlikely to be importnt fctors in the successful mngement of infections due to these orgnisms. Isoltes of Enterobctericee were much less susceptible to cephpirin. This gent nd cephlothin showed similr in vitro ctivity ginst isoltes of P. mirbilis nd K. pneumonie, but cephpirin ws less ctive ginst E. coli. The ltter finding grees with the results of other studies (3, 7). Pseudomons, indole-positive Proteus, nd Serrti were highly resistnt. The pek serum level ws mesured in our ptients bout 1 h fter 1-g intrmusculr dose. In ptients with norml renl function, little drug ws present longer thn 4 h fter 1-g prenterl dose. The men serum concentrtion 1 h fter 1-g intrmusculr dose ws 1.1 Mg/ml, very similr to the men serum level ttinble with comprble dose of cephlothin. This concentrtion ws well bove the MIC of ll isoltes of S. ureus, pneumococci, nd group A Streptococcus, but ws below the MIC of mny isoltes of Enterobctericee. Two ptients with bnorml renl function, one of whom ws nuric nd on hemodilysis progrm, hd considerbly elevted serum levels without recognized toxicity. Hemodilysis ws effective in prtilly removing cephpirin from the blood, s documented by McCloskey et l. (12). Hlf of the ptients treted were 6 yers of ge or older, nd mny hd severe underlying disese. Despite these dverse prognostic fctors the infectious processes of 21 of the 24 ptients were erdicted. The clinicl results observed with cephpirin therpy were stisfctory in ptients with infection due to S. pneumonie nd S. ureus. All seven ptients with stphylococcl infection were cured, lthough removl of foreign body in one nd surgicl dringe of bscesses in three others ws certinly of mjor therpeutic importnce. One elderly mle died during therpy of pneumococcl pneumoni despite erdiction of the pneumococci from the lungs. Eleven others with proven nd one with suspected pneumococcl infections were cured. Although only four ptients with grm-negtive Downloded from on June 28, 218 by guest

8 VOL. 6, 1974 bcillry pneumoni were treted, the results were disppointing. One elderly femle died during therpy of E. coli pneumoni from hypoxi, severe congestive hert filure, nd uncontrollble ventriculr rrhythmis despite pprent erdiction of the pthogen from lung tissue. In nother ptient severe lobr pneumoni (Klebsiell) progressed to virtully totl gngrene of one lung despite cephpirin tretment of 12 g or more dily. The responsible pthogen ws isolted in pure culture from surgiclly resected tissue nd showed identicl cephpirin MIC to the pretretment isolte. Seven ptients who received cephpirin by the intrmusculr route developed elevted SGOT vlues. This bnormlity my be relted to muscle dmge t injection sites nd hs been observed by others (4). We did not observe ny instnces of rsh, eosinophili, or neutropeni, dverse rections which hve been reported by other investigtors (3, 4, 1, 15). Only two ptients received long-term intrvenous dministrtion of cephpirin. In neither cse ws there ny evidence of the serum-sickness type of dverse rection noted by Snders et l. (13). The only severe dverse effect noted ws profuse wtery dirrhe in one ptient tht subsided fter cephpirin tretment ws discontinued. Cephpirin is n effective ntimicrobil gent in the tretment of pneumococcl nd stphylococcl infection, but my be less stisfctory in the tretment of grm-negtive bcillry infection involving sites other thn the urinry trct. In contrst to erly opinions (4, 9), it my not be better tolerted by ptients thn cephlothin. Mny of our ptients who received intrmusculr cephpirin complined of pin t injection sites, nd severe phlebitis ws observed in two ptients who received intrvenous cephpirin. Recent evidence from one double-blind, crossover design tril suggests tht the potentil of cephpirin to produce phlebitis my be equivlent to tht of cephlothin (5), though in nother study of different design cephpirin produced less phlebitis thn cephlothin (8), nd in third study phlebitis ws seldom observed fter dministrtion of either gent (13). The eventul role of cephpirin in ntibcteril chemotherpy will likely depend on further comprtive trils of efficcy nd toxicity. TREATMENT OF PNEUMONIA WITH CEPHAPIRIN 281 ACKNOWLEDGMENTS We thnk Ev S. Hwkins for skillful technicl ssistnce. This investigtion ws supported by grnt from Bristol Lbortories, Syrcuse, N.Y. LITERATURE CITED 1. Axelrod, J., B. R. Meyers, nd S. Z. Hirschmn Cephpirin: in vitro ntibcteril spectrum. Appl. Microbiol. 22: Benner, E. J Renl dmge ssocited with prolonged dministrtion of mpicillin, cephloridine, nd cephlothin, p Antimicrob. Ag. Chemother Bodner, S. J., nd M. G. Koenig Clinicl nd in vitro evlution of cephpirin: new prenterl cephlosporin. Amer. J. Med. Sci. 263: Brn, J. L., M. E. Levison, nd D. Kye Clinicl nd in vitro evlution of cephpirin, new cephlosporin ntibiotic. Antimicrob. Ag. Chemother. 1: Crrizos, J., M. E. Levison, nd D. Kye Doubleblind controlled comprison of phlebitis produced by cephpirin nd cephlothin. Antimicrob. Ag. Chemother. 3: Chisholm, D. R., F. Leitner, M. Misiek, G. E. Wright, nd K. D. Price Lbortory studies with new cephlospornic cid derivtive, p Antimicrob. Ag. Chemother Gordon, R. C., F. F. Brrett, D. J. Clrk, nd M. D. Yow Lbortory nd phrmcologic studies of BL-P1322 (cephpirin sodium) in children. Curr. Ther. Res. 13: Ingki, J., nd G. P. Bodey Phlebitis ssocited with cephlosporins: cephpirin versus cephlothin. Curr. Ther. Res. 15: Lne, A. Z., J. G. Tggrt, nd R. L. Iles Reltive incidence of phlebitis cused by continuous intrvenous infusion of cephpirin nd cephlothin. Antimicrob. Ag. Chemother. 2: Levison, M. E., J. L. Brn, J. H. Jepson, nd D. Kye Neutropeni ssocited with cephpirin therpy. Antimicrob. Ag. Chemother. 1: Linton, A. L., R. R. Biley, nd D. I. Turnbull Reltive nephrotoxicity of cephlosporin ntibiotics in n niml model. Cn. Med. Ass. J. 17: McCloskey, R. V., E. E. Terry, A. W. McCrcken, M. J. Sweeney, nd M. F. Forlnd Effect of hemodilysis nd renl filure on serum nd urine concentrtions of cephpirin sodium. Antimicrob. Ag. Chemother. 1: Snders, W. E. Jr., J. E. Johnson III, nd J. G. Tggrt Adverse rections to cephlothin nd cephpirin. Uniform occurrence on prolonged intrvenous dministrtion of high doses. N. Engl. J. Med. 29: Steers, E., E. L. Foltz, nd B. S. Grves An inocul replicting pprtus for routine testing of bcteril susceptibility to ntibiotics. Antibiot. Chemother. (Wshington D.C.) 9: Wiesner, P., R. McGregor, D. Ber, S. Bermn, K. Holmes, nd M. Turck Evlution of new cephlosporin ntibiotic, cephpirin. Antimicrob. Ag. Chemother. 1: Downloded from on June 28, 218 by guest