Moxalactam for obstetric and gynecologic infections

Moxalactam for obstetric and gynecologic infections

Moxalactam for obstetric and gynecologic infections In vitro and dose-finding F. GARY CUNNINGHAM, M.D. DAVID L. HEMSELL, M.D. RALPH T. DEPALM...

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Moxalactam for obstetric and gynecologic infections In vitro and dose-finding F. GARY

CUNNINGHAM,

M.D.

DAVID

L.

HEMSELL,

M.D.

RALPH

T.

DEPALMA,

M.D.

SHERYL

KAPPUS,

MICKI

ROARK,

BRENDA Dallas,

studies

M.S. R.N.

NOBLES

Texas

Moxalactam (LY 127935) a “third-generation” p-lactam antimicrobial, has been shown to have promising in vitro activity against a wide spectrum of pathogens similar to those isolated from women with pelvic infections.’ Pharmacodynamic studies have shown that its serum half life is longer than 2 hours, which permits less frequent dosing. The current investigation was carried out in two parts: In the first phase, the minimal inhibitory concentration of moxalactam against 519 clinical isolates was determined and compared to antimicrobials used in infections caused by these microbes. In vitro activity of moxalactam comparable to that of clindamycin was demonstrated against B. fragilis and other Bacteroicfes species. There was similar activity to penicillin G and clindamycin against anaerobic gram-positive cocci and activity superior to amikacin was demonstrated against Enterobacteriaceae. The second part of this investigation was a clinical one and 100 women with pelvic infections were given treatment with moxalactam. With an initial dose of 3 gm/day, women with posthysterectomy cellulitis and pelvic inflammatory disease did well. Women with pelvic infections following cesarean section responded less readily to this dose; however, when the initial dose was increased to 6 gm/day, a 91% cure rate was effected. The results of these investigations indicate that moxalactam is useful as a single-agent antimicrobial for treatment of polymicrobial female pelvic infection. (AM. J. OBSTET. GYNECOL. 139:915, 1981.)

THE POLYMICROBIAL NATURE of female pelvicinfections has been well documented, and most authors recommend combined microbiocides for their treatment to ensure coverage against most pathogens isolated in these infections.le7 For example, penicillin or one of its cogeners is generally given with an aminogly-

From the Department of Obstetrics and Gynecology University of Texas Health Science Center

The

Presented in part at the Interscience Antimicrobial and Chemotheraputic Massachusetts, 1979.

Conference of Agents, Boston,

Supported Indiana.

& Co., Indianapolis,

by a grant

Received

for

Accepted

December

from

publication

Eli Lilly November

26,

1980.

3 I, 1980.

Reprint requests: Dr. F. Gary Cunningham, Department of Obstetrics and Gynecology, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235. 0002-9378/81/080915+07$00.70/0~

1981The

C.V.MosbyCo.

coside, and in severe infections either clindamycin or chloramphenicol is added for expanded anaerobic coverage.2, 8-11 More recently, the “second-generation” p-lactam antimicrobials, cefamandole and cefoxitin, have been used successfully as single-drug therapy for mixed infections in both surgicali’ and female pelvic infections.i3. is Further modification of the /3-lactam structure has yielded yet a “third generation” of antimicrobials with promising in vitro activity against a wide spectrum of pathogens. 16-18 Moxalactam (Compound LY 127935, Shinogi 6059-S) is such an antimicrobial which has a longer serum half time than parent cephalosporins and may, therefore, prove effective for treatment of these polymicrobial infections. The purpose of the present study was first to determine in vitro bacterial susceptibilities to moxalactam and compare these with those of antimicrobials commonly given for infections caused by these organisms. Second, we 915

916

Cunningham

et al.

April Am. J. Obstet.

100

loogo-

Bacferoides N=179

fragilis

Bactgipos

15, 1981 Gynecol.

/’

sp.

90

/ 80-

60

i

70-

E .-al 60$8 50v;

605040-

30 . Chloramphemcol 4 Clindamycin 3 LY127935 A Cefovltln o Cefamandole

20 10 01

.03

I

I

06

.I25

9’7

.25

.5 MIC

Chloramphenicol 0 Penicillm . LY127935 A Clmdamycln

l

I

I

I

I

I

I

I

OL

1

2

4

0

16

32

64

.03

sought to determine the clinical efficacy and appropriate dose of moxalactam given for moderate to severe obstetric and gvnecologic infections.

Material and methods studies.

isolates. All bacteria were isolated from patients hospitalized at Parkland Memorial Hospital. Somr were isolated in our laboratory from women with pelvic infections, while others were taken from patients hospitalized on the Medical or Surgical Service and submitted to the Parkland Memorial Hospital Microbiology Laboratory. A total of 339 anaerobes were isolated by means of the roll-tube technique and identified and classified according to the Virginia Polytechnzc Institure Manual. ” These organisms included 179 Bacteroides f+agilzS, 50 Hact~m/rlrs sp. (including former subspecies of B. fragih), and 77 anaerobic gram-positive cocci (44 Peptostreptococr us, .50 Peptococcus, 15 Streptococcus, and 3 Har~trrial

Gaffly

).

Aerobic organisms were isolated and identified by standard microbiological techniques and included 197 Enterobucteriaceae. There were 105 species of E. coli, 52 Enferobacter sp., and 18 Klebsiella; the remainder were Salmonella-Shigella sp.. Srrratia, and Citrobacter. AntimicrobiaL

and

suxeptibility

testing.

Growth was allowed in prereduced, anaerobically sterilized chopped meat carbohydrate broth for 24 to 48 hours at 35’ C, and turbidity was ad-justed to the McFarland Nephelometer StanA&AEROBIC

ISOLATES.

I .25

(’

I

I

.5

1

2

MIC

I 4

1 6

I

I

I

16

32

64

(pg/ml)

Fig. 2. Antimicrobial susceptibilities of 50 strains ofhcleroides species. These include Bacteroides d&soak, Bacteroides thetaiotamicron,

and Bacteroides

vitro

I 125

(@g/ml)

Fig. 1. Susceptibilities of’ 179 strains of Bacteroidesfragih to five antimicrobials. LY 127935 (moxalactam) inhibited 46% of’ these strains in concentrations of 0.5 pg/ml or less.

In

I .06

Bacteroides corrodens.

vulgatus,

Bacteroides

melaninogenicus,

dard No. 1. These were inoculated onto agar plates containing increasing concentrations of antimicrobials according to the method of Sutter and associates.*” The plates were used on the day of preparation. To Brucella broth with 2%: agar-agar were added laked blood (5%), menadione (0.05 pg/ml), hemin (5 pg/ml), and concentrations of the antimicrobials to be tested, all after autoclaving and before the plates were poured. An inoculum of 10’ to 10” viable organisms was delivered by means of the Steers replicator. The plates were incubated in Gaspak jars at 35” C for 48 hours and then examined for growth. Drugs used for testing of’ anaerobes included moxalactam, penicillin G, tetracycline hydrochloride, cefamandole, cefoxitin, chloramphenicol, and clindamycin. The minimal inhibitory concentration was defined as the lowest drug concentration which resulted in no macroscopic growth on plates at 48 hours. AEROBIC ISOLATES. After incubation in trypticase soy broth at 35’ C for 3 to 4 hours, the inoculum was adjusted to approximately 3 x 1OVml with the No. 1 McFarland Nephelometer Standard. This inoculum was then diluted 1: 10 with saline and a suspension was inoculated onto the surface of antibiotic-containing Mueller-Hinton agar with the Steers replicator used to deliver approximately 10” bacteria per spot. These plates were incubated at 35” C for 18 to 24 hours and examined for growth. The minimal inhibitory concentration was the lowest drug concentration showing no macroscopically visible growth. Susceptibility testing was done with the use of

Volume Number

139 8

Moxalactam

loo-

90 -

917

loo-

Anaerobic Positive Cocci (N = 77)

Gram

for infections

Enterobacteriaceae

N=197

QO-

80-

80-

70-

70-

. LY127935 l

Gentamlcm

0 Cefamandole

. 0 . A 0

ot

.03

'

06

'

'

125

.25

'

5

Chloramphenicol Cefamandole LY127935 Clindamycin Penicillin

1

1

I

1

I

I

I

1

2

4

8

16

32

64

MIC (pg/ml)

.03

.06

.l25

.25

.5

1

I

I

I

I

I

,

2

4

8

16

32

64

MIC (fig/ml)

Fig. 3. Cumulative minimal inhibitory concentrations of 5 antimicrobials against 77 anaerobic gram-positive cocci including 44 Peptostreptococcw, 15 Peptococcus, and 15 Streptococcus.

Fig. 4. Cumulative susceptibilities of 197 strains of Enterobacteriaceae against five antimicrobials. At concentrations of 0.25 pg/ml or less, more than 50% were sensitive to Compound LY 127935 (moxalactam) and at 1.0 fig/ml 75% were inhibited.

moxalactam, amikacin, gentamicin, penicillin G, tetracycline hydrochloride, cefamandole, cefoxitin, and chloramphenicol. Clinical studies. Women considered for treatment with moxalactam were those hospitalized at Parkland Memorial Hospital and who had one of the following infections: (1) posthysterectomy vaginal cuff and pelvic cellulitis, (2) acute pelvic inflammatory disease with peritonitis, or (3) post-cesarean section metritis with pelvic cellulitis. The study was approved by the Human Research Committee and informed consent was obtained. Microbiological methods. In women with pelvic infection following hysterectomy, specimens were obtained by aspiration above the vaginal cuff after cleansing with povidone-iodine. Peritoneal fluid was obtained from women with pelvic inflammatory disease by culdocentesis, as previously described.’ In women with infections following cesarean section, a transcervical endometrial aspiration was obtained after cleansing with povidone-iodine. Liquid specimens were injected into rubber-stoppered vials and swabs were placed into screw-top vials, both containing anaerobic carbon dioxide. Almost immediately, or within 12 hours, these specimens were plated onto blood agar for isolation of aerobes and onto a roll-tube for isolation of anaerobes. Subcultures were performed after 48 hours, as previously described.13 Antimicrobial administration. Women with clinical findings of postoperative infection were given treatment if the temperature was 38.6” C (101.5” F) or greater dur-

ing the first 24 hours or if it was 38.3” C (101” F) on two occasions 4 hours apart thereafter. Women with nonsurgical infections were given treatment if the temperature was 38.3” C or higher. During the first part of the study, moxalactam was given by intermittent intravenous infusion, 2 gm initially followed by 1 gm every 8 hours. These women were then seen twice daily by one of us, and if there was no clinical improvement within 72 hours, the dose of moxalactam was increased to 2 gm every 8 hours. For those who failed to respond to this dose after a total of 4 or 5 days of therapy, chloramphenicol, 50 mglkglday, was added and given in divided doses by intermittent intravenous infusion. Wound abscesses were drained upon their discovery and other appropriate surgical procedures were performed as necessary. Women whose clinical condition improved with intravenous moxalactam were then given the drug intramuscularly, 500 mg every 8 hours. After the woman was afebrile for 24 to 48 hours, she was discharged and given cephalexin, 500 mg to be taken orally to complete a lo- to 14day course of antimicrobial therapy. After 57 women had completed treatment with this 3 gm daily dose, their responses were analyzed and a decision was made to increase the initial daily dose to 6 gm for another group of women with post-cesarean section infections. In these women, the initial 2 gm dose was followed by 2 gm every 8 hours. Following improvement, these women were given moxalactam, 500 mg intramuscularly every 8 hours, and discharged on a regimen of oral cephalexin as described above.

918

Cunningham

Table

April Am. J. Obstet.

et al.

I. Demographic

characteristics

of 100 women

given moxalactam

for pelvic infections

Age Infection

Mean

Mean temperature * (72)

Range

Mean

18-40

29.6

2.7

38.4

15-31 14-35

20.8 21.9

1.6 1.2

38.9 39

14-40

22.6

1.4

38.9

Posthysterectomy pelvic cellulitis Pelvic inflammatory disease Post-cesarean section metritis and cellulitis Total

15, 1981 Gynecol.

parity

*Prior- to moxalactam therapy. Table

II. Clinical

response

and complications

in 100 women

treated

with moxalactam

for pelvic infections

Chloramphenicol added Infettion

Posthysterectomy pelvic cellulitis (n = 11) Pelvic inflammatory disease (n = 10) Post-cesarean section metritis 3 g-m/day (n = 36)

6 am/day (n = 43) Total (n = 100) *Prior to treatment. tTAH + BSO = Hysterectomy

Complication

Incisional abscess, 1 abscess,* 5

Tubo-ovarian

Phlegmon, 4 Subfascial abscess, 1 Phlegmon,

5

Response without surgery

ivo.

%

,v’o.

7c

Drainage of abscess

0

-

10

91

None

0

-

10

100

5

14

32

89

4 9

9 9

43 95

100 95

Other

treatment

Chloramphenicol, 4; TAH + BSO,t 3 Chloramphenicol + I celiotomy Chloramphenicol, 4

J

+ adnexectomy.

hborrrtory SW&L Laboratory studies were performed prior to therapy with moxalactam and several times ~hereal’~er, including upon completion of treatment. Kenal function was evaluated by measurement of serum creatinine and by urinalysis. Hematologic changes were monitored by hemogram, platelet count, and Coombs test. Liver function was monitored by the determination of serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin.

Results In vitro studies. The minimal inhibitory concentrations f’or most of the 5 19 clinical isolates are summarized in Figs. 1 to 1. The cumulative susceptibility of Ho&roido~ f~u~lis to five antimicrobials is illustrated in Fig. I. At 8 and 16 &ml, there was comparable antibacterial activity of‘ moxalactam and clindamycin; cefamandole and cefoxitin were similar to each other but were less effective. C~hloramphenicol activity teas greater than any of these; 92% of strains were inhibited at 16 @g/ml. Of’ particular interest is the number of organisms sensitive to very 101~ levels of’ moxalactam, e.g., at O.OY pgiml, :32%, of’strains were inhibited and at 0.5 @g/ml, 46% of these 179 stains were inhibited.

As illustrated in Fig. 2, chloramphenicol was the most effective drug against non-JLa&s Rnrtvroidps species and 96% of strains were inhibited by 16 ~giml. At concentrations from 3 to 16 pgiml, moxalactam, penicillin G, and clindamycin activities were similar. Once again, the susceptibility of these isolates at low levels of moxalactam is noted; almost 30% were sensitive at 0.25 pgiml. In Fig. 3, the minimal inhibitory concentrations of five antimicrobials against 77 anaerobic gram-positive coccal isolates are compared. Moxalactam, cefamandole, clindamycin, and penicillin were almost equally effective at concentrations of 4 to 16 pg/ml. Chloramphenicol inhibited 96% of these strains at 16 pglml. At a concentration of 0.125 yglml, nearly 40% of these were susceptible to moxalactam. The cumulative susceptibilities of 197 Erlterobnctuiucear to five antimicrobials are depicted in Fig. 4. Cefoxitin and cef’amandole activities were almost identical at 16 @g/ml but were less effective than gentamitin. At 16 &ml, 93% of strains were sensitive to moxalactam and 83% were sensitive to amikacin. In vitro susceptibility to low concentrations ofmoxalactam was again demonstrated: At 0.25 pg/ml, slightly more

Volume Number

139 8

Table

III. Results of 253 bacterial

Moxalactam

isolates from

Anaerobes Peptostreptococcus Peptococcus sp.

Other gram-positive Clostndium

Aerobes

48

11 11 I

cocci

sp.

28

10 6

Bacteroides fragilis B. melaninogenicw Bacteroides sp.

6

Other gram-negative

bacilli

Group B streptococci Group D streptococci

15 9

Streptococcus

26 28 3

faecalis

Staphylococcus

I

6 108

aweus

10

Neisseria

13

gonorrhoeae

Table IV. Minimal pelvic infections

inhibitory

concentrations

of moxalactam

Minimal

Bacterial Anaembet

:

Gram-positive

zsolates

sp.

cocci (78)

Clostridium SD. f 14) B. melaninogkus ‘(7) B. fragilti (10) Aerobes:

1.0 I%‘&

47 64 71

53 86

60 -

10

-

-

79 20

-

-

63

13

-

-

_ 64 -

_ -

-

37

S. auretu (8) N. gonorrhoeae (9) E. coli (11) Klebsiella-Enterobacter Proteus sp. (10)

25 100

Z _ 55

-

-

45 _

(18)

(3)

-

than 50% of’ strains were susceptible, while at a concentration of 1.0 PgIml, almost 75% were inhibited. Clinical studies. During the l-year period from July, 1979, through June, 1980, 100 women with pelvic infections were given treatment with moxalactam. Of these, 2 1 were hospitalized on the Gynecology Service; 11 were treated for posthysterectomy pelvic infections and 10 were treated for pelvic inflammatory disease. The remaining 79 women were treated for postcesarean section metritis; 36 were given 3 gmiday of moxalactam and 43 were given 6 gm/day. The demographic characteristics of these women are presented in Table I. PELVIC

inhibitory

0.5 pghnl

Group B streptococci (16) S. ,faccalis (3 1)

Clinicnl response. POSTHYSTERECTOMY

for bacteria

0.25 &ml

CELLULITIS.

these women responded to single-drug (Table 1I). In one woman, an incisional was drained on the fifth day following

Infection in therapy alone wound abscess abdominal hys-

2.0 &ml

10 135

coli

sp. Other gram-negative

bacilli

isolated

from

concentration

(%)

women

8.0 &ml

16 pgiml

72 -

86 -

91 50

81 32 _ 56 70

94 50 -

100 48 -

91

100

-

16

12 145

4.0 &ml

=

32

9

Other staphylococci Escherichia Enterobacter Klebsiella

% All isolates

NO.

Viridans streptococci Other Streptococcus sp.

10

919

with pelvic infections

% All isolates

NO.

sp.

100 women

for infections

-

32 pglml

95

100 70

61 -

with

64 pgJm1

x4 &ml

-

5

100 100

-

-

50 -

-

-Yi 80

28 20

terectomy. These women were hospitalized for a mean of 6.8 days and received moxalactam intravenously for a mean of 2.2 days and intramuscularly for a mean of 2.6 days. PELVIC INFLAMMATORY DISEASE. Infection in these women also responded to single-drug therapy. In five, a tuboovarian abscess was apparent on clinical examination at admission and this was confirmed by sonographic evaluation. In one woman, treatment was begun after exploratory celiotomy for hemoperitoneum demonstrated acute salpingitis with peritonitis. These 10 women were hospitalized for a mean of 5 days and were given intravenous moxalactam for 2.6 days and intramuscular drug for 1.8 days. CESAREAN

SECTION

METRITIS

AND

PELVIC

CELLL'LITIS.

Risk factors were compared for the 36 women given 3 gm/day of moxalactam to those 43 women given 6 gm/day. The data were analyzed for the number of

920

Cunningham

April Am. J. Obstet.

et al.

cervical examinations, length of membrane rupture, and presence of active labor, and no differences between the two groups were ascertained. For example, 20% of those women in the 3 gm group had intact membranes and no labor, whereas 30% of those in the 6 gm group had these criteria. In each group, half of the women had ruptured membranes and two thirds had begun active labor. Clinical responses for each group are summarized in Table II. 3 CM/DAY DOSE. These 36 women were hospitalized for a mean of 8.8 days after operation. In five (14%), chloramphenicol was added to moxalactam therapy because of poor clinical response. In three of these women, abdominal hysterectomy with adnexectomy was necessary to eradicate infection characterized by intense cellulitis and necrosis of the uterine incision. In a fourth patient, celiotomy was performed and an intraabdominal abscess was drained. The fifth had a parametrial phlegmon and responded to the addition of chloramphenicol. The four women who required operative intervention were encountered over a 6-week interval and prompted cessation of the study until analysis of the study drug was performed. Several vials from each drug lot were selected randomly and assayed and found to contain between 99% and 105% of moxalactam activity. The decision was then made to increase the initial daily dose to 6 gm. 6 CM/DAY DOSE. The 43 women completing this protocol were hospitalized for a mean of 6.8 days after cesarean section (p < 0.05 compared to 3 gmiday group). Of these, 39 (91%) responded to moxalactam given alone. In the other four (9%) women, chloramphenicol was added for treatment of parametrial phlegmons and these women responded to combined therapy. Adwrsr clinical and laboratory ejferts. Superficial phlebitis at the site of infusion was demonstrated in 8% of these 100 women. Neither its onset nor its severity appeared to be related to dosage or duration of therapy. There were no adverse renal, hepatic, or hematologic changes noted. Microbiological studies. A total of 253 organisms were isolated from these 100 women (Table III). In 567c these were mixed isolates; in 1570 they were anaerobes only, and in 29% only aerobic pathogens were isolated. Anaerobic (28%) and aerobic (32%) streptococcal species were found in 6070 of all isolates. Enterobactpriaceae ( 16%) and Bacteroides species (9%) were the next most common isolates. Barteroides fragilis was isolated in at least one specinen from 10% of all women. The minimal inhibitory concentrations of moxalactam to 2 12 bacterial isolates from these 100 women are presented in Table IV. There was no correlation with

organisms for failure

that proved resistant of clinical cure.

15, 1981 Gynecol.

in vitro when analyzed

Comment Female pelvic infections are usually polymicrobial with a predominance of anaerobic pathogens.‘-’ In vitro data indicate that moxalactam, a semisynthetic p-lactam antimicrobial, is effective against a wide spectrum of bacteria that are similar to those isolated from women with pelvic infections.‘“. Ii More recently, Gibbs and associates’” reported a 90% cure rate when moxalactam was given to women with pelvic infections. These data support those of previous investigations showing that p-lactam derivatives may be given alone for treatment of women with moderate to severe pelvic infections.1”~ 15 In the first part of the current investigation, we determined the in vitro activity of moxalactam against 5 19 clinical isolates and demonstrated findings similar to those already reported. The MI& of moxalactam to B. fragilis was 1.0 pgiml, and at 8 and 16 pg/ml, this drug had activity similar to that of clindamycin. Against anaerobic gram-positive cocci, moxalactam activity was similar to that of clindamycin, penicillin, and cefamandole; against Enterobacteriaceae it was superior to amikacin, gentamicin, cefamandole, and cefoxitin. Delgado and associates ” have reported that minimal bactericidal levels with this drug are generally the same as the minimal inhibitory concentrations. Compared to most /3-lactam drugs, moxalactam has a longer serum half time (2.4 hours), which results in higher serum levels and permits longer intervals between dosing. Parsons and associate? demonstrated peak serum levels following a 1 gm dose given intravenously and intramuscularly to be 70 and 52 pg/ml respectively. At 8 hours these levels were 3.8 and 4.8 pgiml. With its active in vitro antibacterial activity, moxalactam should have advantages over other /3-lactams given for single-agent therapy. The second part of this study was a clinical investigation in which 100 women with pelvic infections were given moxalactam. A 3 gm daily intravenous dose proved effective for women with posthysterectomy pelvic infections or salpingitis with peritonitis. In the latter group, half had tuboovarian abscesses, yet none required surgical intervention. Women with metritis following cesarean section at Parkland Memorial Hospital usually have severe infections,23 and such a group treated with 3 gm of moxalactam daily did less well than women given 12 gm of cefamandole daily.i3, 24 When the initial daily dose was increased to 6 gm, these women had good clinical responses, and in only 9% was the addition of chloramphenicol necessary. Moreover,

Volume Number

139 8

none required surgical intervention. These results are comparable to those of Gibbs and associates,rs who used a 6 gm/day dose. They are also similar to our results with high-dose cefamandole,r3. 24 and to these of diZerega and associates,25 who treated such women with clindamycin and gentamicin. In conclusiop, from the clinical and laboratory data presented here, moxalactam appears to be effective

REFERENCES

1. Ledger, W. J.: Infections in obstetrics and gynecology: New developments in treatment. Sum. Clin. North Am. 52: 1447, 19’72. 2. Thadepalli, H., Gorbach, S., and Keith, L.: Anaerobic infections of the female genital tract: Bacteriologic and therapeutic aspects, AM. J. OBSTET. GYNECOL. 117: 1034, 1973. 3. Swenson, R. M., Michaelson, T. C., Daly, M. J., and Spaulding, E. I-I.: Anaerobic bacterial infections of the female genital tract, Obstet. Gynecol. 42:538, 1973. 4. Sweet, R. L., and Ledger, W. J.: Puerperal infectious morbidity: A two-year review, AM. J. OBSTET. GYNECOL. 117:1093, 1973. 5. Gorbach, S. L., and Bartlett, J. G.: Anaerobic infections, N. Engl. J. Med. 290: 1177, 1974. 6. Chow, A. W., Marshall, J. R., and Guze, L. B.: Anaerobic infections of the female genital tract: Prospects and perspectives, Obstet. Gynecol. Surv. 30:477, 1975. 7. Cunningham, F. G., Hauth, J. C., Strong, J. D., et al.: Evaluation of tetracycline or penicillin-ampicillin for treatment of acute pelvic inflammatory disease, N. Engl. J. Med. 296:1380, i977. 8. Sweet. R. L.: Anaerobic infections of the female rzenital tract, AM. J. OBSTET. GYNECOL. 122:891, 1973. 9. Gorbach, S. L.: Antibiotic therapy of obstetric and gynecologic infections, Surg. Clin. North Am. 55:1373, 1975. 10. Schwarz, R. H., and Fruiterman, N. P.: Life-threatening infections in pregnancy, Clin. Obstet. Gynecol. 19:561, 1976. 11. Ledger, W. J.: Hospital acquired gynecologic infections, in Infections in the Female, Philadelphia, 1977, Lea & Febiger, chap. 8, pp. 142-176. 12. Stone, H. H., Guest, B. S., Geheber, C. E., and Kolb, L. D.: Cefamandole in treatment of peritonitis, J. Infect. Dis. (Suppl.) 137:SlO3, 1978. 13. Cunningham, F. G., Gilstrap, L. C., and Kappus, S. S.: Treatment of obstetrics and gynecologic infections with cefamandole, AM. J. OBSTET. GYNECOL. 133:602, 1979.

Moxalactam

for infections

921

when given for polymicrobial obstetric and gynecologic infections. Dose-finding studies indicate that for more severe infections an initial dose of 6 gm/day should be given. More experiences are needed before treatment with moxalactam alone can be recommended for the patient with life-threatening sepsis of polymicrobial origin.

14. Sweet, R. L., and Ledger, W. J.: Cefoxitin: Single-agent treatment of mixed aerobic-anaerobic pelvic infections, Obstet. Gynecol. 54: 193, 1979. 15. Gibbs, R. S., and Huff, R. W.: Cefamandole therapy of endomyometritis following cesarean section, AM. ‘j. OBSTET. GYNECOL. 136:32. 1979. 16. Barza, M., Tally, F. P., Jacobs, N. V., and Gorbach, S. L.: In vitro activity of LY127935, Antimicrob. Agents Chemother. 16:287, 1979. 17. Fass, R. J.: In vitro activity of LY127935, Antimicrob. Agents Chemother. 16:503, 1979. 18. Gibbs, R. S., Blanco, J. D., Castaneda, Y. S., and St. Clair, P. I.: Theranv of obstetrical infections with moxalactam, Aitimicrob.‘Agents Chemother. 17: 1004, 1980. 19. Staff of Anaerobe Laboratory: Anaerobe Laboratory Manual, Blacksburg, Virginia, 1977, Virginia Polytechnic Institute. 20. Sutter, V. L., Kivok, Y. Y., and Finegold, S. M.: Standardized antimicrobial disc susceptibility testing of anaerobic bacteria, Appl. Microbial. 23:268, 1972. 21. Delgado, D. G., Brau, C. J., Cobbs, C. G., and Dismukes, W. E.: In vitro activity of LY127935, a new I-oxa cephalosporin, against aerobic gram-negative bacilli, Antimicrob. Agents Chemother. 16:864, 1979. 22. Parsons, J. N., Romano, J. M., and Levison, M. E.: Pharmacology of a new I-oxa+-lactam LY 127935) in normal volunteers, Antimicrob. Agents Chemother. 17:226, J980.

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