Volume 92 Number 2

B r i e f clinical a n d laboratory observations

The necessity for monitoring chloramphenicol levels when treating neonatal meningitis

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Steven B. Black, M.D., Peter Levine, M.D.,

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and Henry R. Shinefield, M.D.,* S a n Francisco, Calif.

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NEONATAL

GRAM-NEGATIVE

MENINGITIS

is often

associated with a p o o r p r o g n o s i s in spite o f r e c e n t a d v a n c e s in n e w b o r n intensive care a n d the use o f n e w e r a n t i b i o t i c s ? R e c e n t studies have s h o w n that the use o f

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i n t r a t h e c a l as well as p a r e n t e r a l antibiotics offers n o

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I I I I I I I I I I I I I I ) h 1 2 3 4 5 6 7 8 9101112131415161718192021

m e n i n g i t i s w h i c h did n o t r e s p o n d well to intra;cenous ampici!!in a n d p a r e n t e r a l g e n t a m i c i n b u t did r e s p o n d to c h l o r a m p h e n i c o [ is r e P o r t e d . I n t r a v e n o u s c h l o r a m p h e n icol t h e r a p y Was m a d e feasible by close m o n i t o r i n g o f s e r u m c h l o r a m p h e n i c o l levels.

CASE REPORT A 2,020 gm female infant was delivered at 35 weeks' gestation to a mother with idiopathic thrombocytopenic purpura. At delivery the Apgar scores were 2 at one minute and 8 at five minutes. The plat~ count was 97.000/ram: at birth and fell to 47.000/mm 3 when the infant was 72 hours of age. At this time the infant's temperature rose to 37.4 ~ C. A lumbar puncture at that time revealed 573 red blood cells and 53 white blood cells (84% lymphocytes and 16% polymorphonuclear leukocytes). Amplcillin at 200 mg/kg intravenously daily and gentamicin at 7.5 mg/kg intravenously daily were administered at 12-hour intervals. Blood and CSF cultures repeatedly yielded E. call which was by disc resistant to ampicillin, but sensitive to gentamicin and chloramphenic01. Because of the infant's clinical condition and persistently positive CSF cultures, the intraventricular use of gentamlc m was considered, but it was decided that this was too ha.zardous because of the low platelet count. As an alternative. chloramphenicol at 50 mg/kg daily was administered intraven~,usly every 12 hours, and serum levels were determined by the modified calorimetric method before each dose.' The blood level From the Depar[mem q~ Pediatrics, Kaiser Permanente Medical Center. *Reprint address." Department of Pediatrics. Kaisei'-Permanente Medical Center. 2200 O'Farrell St. San Francisco. CA 94115.

0022-3476/78/0292-0235500.20/0

9 1978 T h e C. V. M o s b y Co.

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Day of therapy

a d v a n t a g e o v e r the use o f p a r e n t e r a l antibiotics a l o n e 7 O t h e r s h a v e a d v o c a t e d the use o f i n t r a v e n t r i c u l a r instillation o f a n t i b i o t i c s ? A n i n f a n t w h o h a d E s c h e r i c h i a coli

. o .

)Therapy

begun

on 5th doy of life)

Fig. 1. Chloramphenicol dose response curve. Chloramphenicol was administere d every 12 hours. Total daily dose is sum of the AM and I'M doses. [] = Serum level; A = CSF level; o = AM dose; 9 = PM dose. drawn 12 hours after the first dose was 9 ffg/ml (therapeutic fang~ 10 to 20 ffg/ml). By the third dose, the level had risen to 25 ffg/ml,.with a simultaneous CSF level of 14 ffg/ml. At that time the dose%vas decreased to 20 mg/kg daily, and the blood level fell to 7 ffg/ml (Fig. 1). Forty-eight hours after the initiation of chloramphenicol therapy, seizures had ceased and repeat CSF culture was siLerile. To maintain therapeutic levels, the dose of chloramphenicol was steadily increased over the 3-week course of therapy (Fig. 1). The final dose needed to maintain blood levels in the low therapeuuc range was 95 m s / k s daily. After the 21-day course of therapy, the infant was thriving and CSF culture remained sterile. Abbreviation used CSF: cerebrospinal fluid

DISCUSSION W e elected to use c h l o r a m p h e n i c o l in this p a t i e n t b e c a u s e o f t h e a p p a r e n t lack o f r e s p o n s e to ampicillin a n d gentamicln.

Hepatic

maturity

varies

widely

in

the

n e w b o r n i n f a n t : toxic levels o f c h l o r a m p h e n i c o 1 c a o readily occur a n d result in severe or fatal side effects? T h e fact that s t a n d a r d i z e d doses o f c h l o r a m p h e n i c o l in t h e n e w b o r n i n f a n t m a y result in ineffective b l o o d levels h a s n o t b e e n Widely publicized. In o u r patient, the availability o f a r a p i d m e a n s for determination

of chloramphenicol

b l o o d levels m a d e

23 6

Brief clinical and laboratoty observations

possible the establishment of an appropriate dosage. Doses of chloramphenicol required to achieve therapeutic levels ranged from 20 to 95 mg/kg daily. Our experience demonstrates the importance of monitoring serum levels and then individualizing dosage of the drug during the course of the illness. Unmonit0red dosage schedules can quickly result either in inadequate therapeutic or in toxic levels of chloramphenicol. Weiss has recommended treating all newborn infants with 25 mg/kg daily of chloramphenicol, and increasing the dose to 50 mg/kg daily by one month of age? Such a standardized regimen may be unsafe in some cases or may result in ineffective blood levels in others. It is possible that the concomitant use of phenobarbital and Dilantin in our patient may have stimulated increased hepatic conjugation of chloramphenicol and thus increased dosage requirements. Since newborn infants with meningitis commonly require treatment with phenobarbital, this drug interaction might affect chloramphenicol dosage requirements. 7 SUMMARY Chloramphenicol can be an effective agent in the treatment of ampicillin-resistant E. colt meningitis due to

The Journal of Pediatrics February 1978 susceptible organisms in the premature or term infant. However, it can be used safely and effectively only if careful monitoring of serum levels is undertaken. The authors gratefully acknowledge the assistance of Dr. George McCracken and his laboratory for studies related to the E. colt.

REFERENCES 1. Overall JC Jr: Neonatal bacterial meningitis, J PEDIATR 76:499, 1970. 2. McCracken GH Jr, and Mize SG: A controlled study of intrathecal antibiotic therapy in gram-negative enteric meningitis of infancy, J PEDIATR89:66, 1976. 3. Moellering RC Jr, and Fischer EG: Relationship of intraventricular gentamicin levels to cure of meningitis, J PEDIATR81:534, 1972. 4. Hughes DW, and Diamond LK: Chloramphenicol in blood: Simplechemical estimations in patients receiving multiple antibiotics, Science 144:296, I964. 5. Sutherland JM: Fatal cardiovascular collapse of infants receiving large amounts of chlorampbenicol, Am J Dis Child 97:761, 1959. 6. WeissCF, Glazko A J, and Weston JK: Chloramphenicol in the newborn infant, N Engl J Med 262:787, 1960. 7. Palmer DL, Despopoutos A, and Rael ED: Induction of chloramphenicol metabolism by phenobarbital, Antimicrob Agents Chemother 1:112, 1972.

Comparison of bacterial contamination with two methods of human milk collection

pasteurization decreases the immune factor content of the milk.'. ~ Twenty percent of the 40,000 ounces of human milk collected per year requires such treatment. We compared milk collected by two methods, hand expression and suction breast pump, to quantify differences in the degree of bacterial contamination.

Myron Liebhaber, M.D.,

We did a retrospective study of 195 samples of breast milk brought to the Mother's Milk Unit of the Northern California Transplant Bank, Sat/Jose, CA. Donors, with a mean age of 26 years and a mean lactation period of three months, provided milk either by direct expression into a sterile 4-ounce bottle or by the use of a rubber bulb breast pump (Davol pump, Davol Company, Providence, RI) oi" Faultless pump, (Abbott Laboratories, Chicago, IL) with transfer into a sterile container. Donors were directed io immerse the pumps in boiling water for !0 minutes Or place them in the home dishwasher, provided that tile water temperature was 60~ The milk was stored in the home refrigerator freezer compartment at - 2 3 ~ for two to three days and brought to the milk bank. Milk Was diluted 1"100 with buffer, added to 15 ml tryptoneglucose-yeast agar, and incubated at 32~ for 48 hours.

Norman J. Lewiston, M.D., Maria Teresa Asquith, and Philip Sunshine, M.D., Stanford, Calif. THE FEEDING of banked human milk to premature infants has become popular. In Santa Clara County this milk is pasteurized if the bacterial count is greater than i0,000 colonies/ml. We and others have shown that

From the Children's Hospital at Stanford, Northern California Transplant Bank, and Stanford University Hospital. *Reprint address: Stanford University Medical Center, Stanford, CA 94305.

MATERIALS AND METHODS

0022-3476/78/0292-0236500.20/0 9 1978 The C. V. Mosby Co.