Neonatal Meningitis Due to Enterobacter cloacae Churku Mohan Reddy, MD, Lionel F. Willoughby, MD, Saburo Hara, MD, and E. Perry Crump, MD Nashville, Tennessee
Enterobacter species, in recent years, have been divided into E aerogenes, E hafniae, E liquefaciens, and E cloacae. Early reviews of neonatal meningitis include some cases due to KlebsiellaAerobacter,1 and recent reviews2'3 include Enterobacter which did not divide them into species of Enterobacter. Reported here is a case of neonatal meningitis due to a gram-negative organism, Enterobacter cloacae.
Case Report A 15-day-old, 3,600 gm female infant was hospitalized with a four-day history of lethargy, irritability, hypothermia, and anorexia. She had been seen by her private physician three days prior to admission where she had received erythromycin estolate
From the Department of Pediatrics, Meharry Medical College, Nashville, Tennessee. Requests for reprints should be addressed to Churku Mohan Reddy, MD, Associate Professor, Department of Pediatrics, Meharry Medical College, Nashville, TN 37208.
(Ilosone) and sodium butabarbitol (Butisol sodium) elixir. Pregnancy, delivery, and previous neonatal course had been unremarkable. At birth, she weighed 3,750 gm and her head circumference measured 35 cm. Her length was 51 cm. No other members of the family were ill at the time of the infant's hospitalization. On admission, examination revealed a lethargic and irritable infant with a weak cry and poor sucking reflex. Her temperature was 38.8 C, pulse 120 per minute, and respiration 50 per minute. The anterior fontanelle was bulging and pupils were equally reactive. Her head circumference was 36 cm. The admission lumbar puncture revealed a cloudy cerebrospinal fluid with 1,800 WBC/mm3, which showed 98 percent polymorphonuclear forms. The protein was 850 mg/100 ml. The
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 5, 1978
cerebrospinal fluid (CSF) glucose was 8 mg/100 ml and the serum glucose was 62 mg/100 ml. The gram stain demonstrated gram-negative bacilli. The peripheral white blood cell (WBC) count was 12,033/mm3 with 10 percent band forms, 60 percent segmented neutrophils, 28 percent lymphocytes, and 2 percent eosinophils. The hemoglobin level was 16.4 gm/100 ml. The results of the chest roentgenogram, serum chemistry analysis, and urinalysis were normal. Subdural fluid (1.5 ml), obtained 36 hours after admission, revealed tenacious mucopurulent fluid and a gram stain demonstrated gram-negative bacilli. Cultures of the throat, nasopharynx, cerebrospinal fluid, and subdural fluid grew Enterobacter cloacae and were sensitive gentamicin. Blood and urine cultures were negative. 347
Initial therapy consisted of intravenous infusion of gentamicin 7 mg/kg/day and methicillin 200 mg/kg/ day. She was placed in an isolette because of hypothermia. At the receipt of the sensitivity data, administration of methicillin was deleted from the therapeutic regimen and gentamicin was continued for 30 days. On the day following admission, the infant developed an episode of apnea and cyanosis and required resuscitation. By day five, marked progress in her clinical condition was hoticed. The anterior fontanelle became flat and the temperature returned to normal five days after the initiation of treatment. After seven days of hospitalization, she developed generalized convulsions which continued to occur for another eight days but with less intensity. The infant was also maintained on phenobarbital to control her seizure activity. By day 18, a bulging anterior fontanelle was noted and head circumference measured 38 cm. Subdural tap was performed on both sides and 19 ml of subdural fluid (left side, 14 ml and right side, 5 ml) was obtained. The subdural fluid was xanthochromic and contained a total white blood cell count of 143,800/mm3. There were 100 percent polymotwhonuclear leukocytes. The red blood cell count was 2,877/mm3, protein level 3000 mg/100 ml, and glucose level 32 mg/100 ml. Subdural taps were repeated every 48 to 72 hours and yielded no fluid by day 28. Culture and gram stain were negative. By day 23, the infant was noted to have enlargement of head circumference, 38 cm, but diagnostic studies were postponed because of diarrhea. Skull x-rays revealed bulging of the anterior fontanelle and widely separated sutures. By day 33, head circumference measured 40 cm. A neurosurgeon performed a right ventriculogram which demonstrated hydrocephalus. A right ventriculoperitoneal shunt was inserted subsequently. Lumbar punctures showed a progressive decrease in the WBC count. But glucose and protein values did not return to normal levels at the time of discharge from the hospital. All repeat CSF cultures remained sterile. She had some feeding difficulties and some stiffness of the extremities. The infant was discharged after an eight-week hospital stay and was referred to the child development center for further follow-up. 348
Comment Enterobacter cloacae is a motile gram-negative bacillus. Generally speaking, most infections with Enterobacter are hospital acquired and are associated with altered host resistance. E cloacae is most commonly recovered from the urinary tract of catheterized patlents.4 5 However, in studies of gram-negative septicemia in which Enterobacter has been speciated, E cloacae has seldom been found.6-10 Recently, a nationwide outbreak of bacteremias associated with intrinsic contamination of commercial intravenous fluids11 and bacteremia in dialysis patients12 has been reported with this organism as the pathogen. lannini and his associates13 reported a case of suppurative arthritis and osteomyelitis in a 47-year-old woman resulting from Fcloacae. She had an underlying condition of leukemia and was receiving chemotherapy. They implicated the platelet-rich plasma she was receiving as the source for the Enterobacter bacteremia in this patient. Lerer14 reported the case of a 13-year-old girl who developed E cloacae endocarditis following open aortic valvotomy. Therapy with carbenicillin and kanamycin sulfate resulted in a rapid cure. A case of a premature infant with multiple joint infections15 and two cases of osteomyelitis16 have been reported during the neonatal period. A review of the literature revealed reports of neonatal meningitis due to Enterobacter1-3 but these were not divided into species. The majority of survivors have neurologic and developmental handicaps1 17 despite the use of effective chemotherapeutic agents. The above presented case developed hydrocephalus, subdural effusion, some feeding difficulties, and stiffness of the extremities even though she was treated effectively with gentamicin.
Summary A 15-day-old female infant, with neonatal meningitis due to Enterobac-
ter cloacae, has been reported. She developed hydrocephalus, subdural effusion, soite feeding difficulties, and stiffness of the extremities despite the use of effective chemotherapeutic agents.
Acknowledgement This study was supported in part by Grant Number 440 from the Health Service and Mental Health Administration, US Public Health Service. We thank Miss Jo Ann Bunch for her secretarial assistance.
Literature Cited
1. Groover RV, Sutherland JM, Landing BH: Purulent meningitis of newborn infants. N Engl J Med 264:1115-1121, 1961 2. McCracken GH, Mize SG: A controlled study of intrathecal antibiotic therapy in gramnegative enteric meningitis of infancy. J Pediatr 89:66-72, 1976 3. Fitzhardinge PM, Kazemi M, Ramsay M, et al: Long-term sequelae of neonatal meningitis. Dev Med Child Neurol 16:3-10, 1974 4. Steiner BW, Eickhoff TC, Kislak JW, et al: Klebsiella-Enterobacter-Serratia division: Clihical, epidemiologic characteristics. Ann Intern Med 65:1180-1194, 1966 5. Dans PE, Barrett FF, Casey JI, et al: Klebsiella-Enterobacter at Boston City Hospital, 1967. Arch Intern Med 125:94-101, 1970 6. Hodgin UG, Sanford JP: Gram-negative tod bacteremia. Am J Med 39:952-960, 1965 7. Maiztequi JI, Biegelseisen JZ, Cherry WB, et al: Bacteremia due to gram-negative rods: A clinical, bacteriologic, serologic, and immunofluorescent study. N Engl J Med 272:222-229, 1965 8. Martin CM, Cuomo AJ, Geraghty MJ, et al: Gram-negative rod bacteremia. J Infect Dis 119:506-517, 1969 9. McCabe WR, Jackson GG: Gramnegative bacteremia. Arch Intern Med 110:847-855, 1962 10. Crowley N: Some bacteremias encountered in hospital practice. J Clin Pathol 23:166171, 1970 11. Maki DG, Rhame FS, Mackel DC, et al: Nationwide epidemic of septicemia caused by contaminated intravenous products. Epidemiologic and clinical features. Am J Med 60:471485, 1976 12. Borobio MV, Perea EJ: Enterobacter cloacae bacteremia in dialysis patients. Rev Clin Esp 137:517-520, 1975 13. lannini PB, Hull SF, Quintiliani R: Severe sepsis from Enterobacter. Arch Surg 107:854-856, 1973 14. Lerer RJ: Postoperative endocarditis due to Enterobacter cloacae. Am J Dis Child 126:352-353, 1973 15. Gordon SL, Maisels MJ, Robbins WJ: Multiple joint infections with Enterobacter cloacae. Clin Orthop 125:136-138, 1977 16. Voss HV, Gobel U, Kemperdick H, et al: Enterobacter-osteomyelitis bei zwei Sauglingen. Klin Pediatr 187:465-470, 1975 17. Overall JC: Neonatal bacterial meningitis. J Pediatr 76:499-511, 1970
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 5, 1978
Enterobacter species, in recent years, have been divided into E aerogenes, E hafniae, E liquefaciens, and E cloacae. Early reviews of neonatal meningitis include some cases due to KlebsiellaAerobacter,1 and recent reviews2'3 include Enterobacter which did not divide them into species of Enterobacter. Reported here is a case of neonatal meningitis due to a gram-negative organism, Enterobacter cloacae.
Case Report A 15-day-old, 3,600 gm female infant was hospitalized with a four-day history of lethargy, irritability, hypothermia, and anorexia. She had been seen by her private physician three days prior to admission where she had received erythromycin estolate
From the Department of Pediatrics, Meharry Medical College, Nashville, Tennessee. Requests for reprints should be addressed to Churku Mohan Reddy, MD, Associate Professor, Department of Pediatrics, Meharry Medical College, Nashville, TN 37208.
(Ilosone) and sodium butabarbitol (Butisol sodium) elixir. Pregnancy, delivery, and previous neonatal course had been unremarkable. At birth, she weighed 3,750 gm and her head circumference measured 35 cm. Her length was 51 cm. No other members of the family were ill at the time of the infant's hospitalization. On admission, examination revealed a lethargic and irritable infant with a weak cry and poor sucking reflex. Her temperature was 38.8 C, pulse 120 per minute, and respiration 50 per minute. The anterior fontanelle was bulging and pupils were equally reactive. Her head circumference was 36 cm. The admission lumbar puncture revealed a cloudy cerebrospinal fluid with 1,800 WBC/mm3, which showed 98 percent polymorphonuclear forms. The protein was 850 mg/100 ml. The
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 5, 1978
cerebrospinal fluid (CSF) glucose was 8 mg/100 ml and the serum glucose was 62 mg/100 ml. The gram stain demonstrated gram-negative bacilli. The peripheral white blood cell (WBC) count was 12,033/mm3 with 10 percent band forms, 60 percent segmented neutrophils, 28 percent lymphocytes, and 2 percent eosinophils. The hemoglobin level was 16.4 gm/100 ml. The results of the chest roentgenogram, serum chemistry analysis, and urinalysis were normal. Subdural fluid (1.5 ml), obtained 36 hours after admission, revealed tenacious mucopurulent fluid and a gram stain demonstrated gram-negative bacilli. Cultures of the throat, nasopharynx, cerebrospinal fluid, and subdural fluid grew Enterobacter cloacae and were sensitive gentamicin. Blood and urine cultures were negative. 347
Initial therapy consisted of intravenous infusion of gentamicin 7 mg/kg/day and methicillin 200 mg/kg/ day. She was placed in an isolette because of hypothermia. At the receipt of the sensitivity data, administration of methicillin was deleted from the therapeutic regimen and gentamicin was continued for 30 days. On the day following admission, the infant developed an episode of apnea and cyanosis and required resuscitation. By day five, marked progress in her clinical condition was hoticed. The anterior fontanelle became flat and the temperature returned to normal five days after the initiation of treatment. After seven days of hospitalization, she developed generalized convulsions which continued to occur for another eight days but with less intensity. The infant was also maintained on phenobarbital to control her seizure activity. By day 18, a bulging anterior fontanelle was noted and head circumference measured 38 cm. Subdural tap was performed on both sides and 19 ml of subdural fluid (left side, 14 ml and right side, 5 ml) was obtained. The subdural fluid was xanthochromic and contained a total white blood cell count of 143,800/mm3. There were 100 percent polymotwhonuclear leukocytes. The red blood cell count was 2,877/mm3, protein level 3000 mg/100 ml, and glucose level 32 mg/100 ml. Subdural taps were repeated every 48 to 72 hours and yielded no fluid by day 28. Culture and gram stain were negative. By day 23, the infant was noted to have enlargement of head circumference, 38 cm, but diagnostic studies were postponed because of diarrhea. Skull x-rays revealed bulging of the anterior fontanelle and widely separated sutures. By day 33, head circumference measured 40 cm. A neurosurgeon performed a right ventriculogram which demonstrated hydrocephalus. A right ventriculoperitoneal shunt was inserted subsequently. Lumbar punctures showed a progressive decrease in the WBC count. But glucose and protein values did not return to normal levels at the time of discharge from the hospital. All repeat CSF cultures remained sterile. She had some feeding difficulties and some stiffness of the extremities. The infant was discharged after an eight-week hospital stay and was referred to the child development center for further follow-up. 348
Comment Enterobacter cloacae is a motile gram-negative bacillus. Generally speaking, most infections with Enterobacter are hospital acquired and are associated with altered host resistance. E cloacae is most commonly recovered from the urinary tract of catheterized patlents.4 5 However, in studies of gram-negative septicemia in which Enterobacter has been speciated, E cloacae has seldom been found.6-10 Recently, a nationwide outbreak of bacteremias associated with intrinsic contamination of commercial intravenous fluids11 and bacteremia in dialysis patients12 has been reported with this organism as the pathogen. lannini and his associates13 reported a case of suppurative arthritis and osteomyelitis in a 47-year-old woman resulting from Fcloacae. She had an underlying condition of leukemia and was receiving chemotherapy. They implicated the platelet-rich plasma she was receiving as the source for the Enterobacter bacteremia in this patient. Lerer14 reported the case of a 13-year-old girl who developed E cloacae endocarditis following open aortic valvotomy. Therapy with carbenicillin and kanamycin sulfate resulted in a rapid cure. A case of a premature infant with multiple joint infections15 and two cases of osteomyelitis16 have been reported during the neonatal period. A review of the literature revealed reports of neonatal meningitis due to Enterobacter1-3 but these were not divided into species. The majority of survivors have neurologic and developmental handicaps1 17 despite the use of effective chemotherapeutic agents. The above presented case developed hydrocephalus, subdural effusion, some feeding difficulties, and stiffness of the extremities even though she was treated effectively with gentamicin.
Summary A 15-day-old female infant, with neonatal meningitis due to Enterobac-
ter cloacae, has been reported. She developed hydrocephalus, subdural effusion, soite feeding difficulties, and stiffness of the extremities despite the use of effective chemotherapeutic agents.
Acknowledgement This study was supported in part by Grant Number 440 from the Health Service and Mental Health Administration, US Public Health Service. We thank Miss Jo Ann Bunch for her secretarial assistance.
Literature Cited
1. Groover RV, Sutherland JM, Landing BH: Purulent meningitis of newborn infants. N Engl J Med 264:1115-1121, 1961 2. McCracken GH, Mize SG: A controlled study of intrathecal antibiotic therapy in gramnegative enteric meningitis of infancy. J Pediatr 89:66-72, 1976 3. Fitzhardinge PM, Kazemi M, Ramsay M, et al: Long-term sequelae of neonatal meningitis. Dev Med Child Neurol 16:3-10, 1974 4. Steiner BW, Eickhoff TC, Kislak JW, et al: Klebsiella-Enterobacter-Serratia division: Clihical, epidemiologic characteristics. Ann Intern Med 65:1180-1194, 1966 5. Dans PE, Barrett FF, Casey JI, et al: Klebsiella-Enterobacter at Boston City Hospital, 1967. Arch Intern Med 125:94-101, 1970 6. Hodgin UG, Sanford JP: Gram-negative tod bacteremia. Am J Med 39:952-960, 1965 7. Maiztequi JI, Biegelseisen JZ, Cherry WB, et al: Bacteremia due to gram-negative rods: A clinical, bacteriologic, serologic, and immunofluorescent study. N Engl J Med 272:222-229, 1965 8. Martin CM, Cuomo AJ, Geraghty MJ, et al: Gram-negative rod bacteremia. J Infect Dis 119:506-517, 1969 9. McCabe WR, Jackson GG: Gramnegative bacteremia. Arch Intern Med 110:847-855, 1962 10. Crowley N: Some bacteremias encountered in hospital practice. J Clin Pathol 23:166171, 1970 11. Maki DG, Rhame FS, Mackel DC, et al: Nationwide epidemic of septicemia caused by contaminated intravenous products. Epidemiologic and clinical features. Am J Med 60:471485, 1976 12. Borobio MV, Perea EJ: Enterobacter cloacae bacteremia in dialysis patients. Rev Clin Esp 137:517-520, 1975 13. lannini PB, Hull SF, Quintiliani R: Severe sepsis from Enterobacter. Arch Surg 107:854-856, 1973 14. Lerer RJ: Postoperative endocarditis due to Enterobacter cloacae. Am J Dis Child 126:352-353, 1973 15. Gordon SL, Maisels MJ, Robbins WJ: Multiple joint infections with Enterobacter cloacae. Clin Orthop 125:136-138, 1977 16. Voss HV, Gobel U, Kemperdick H, et al: Enterobacter-osteomyelitis bei zwei Sauglingen. Klin Pediatr 187:465-470, 1975 17. Overall JC: Neonatal bacterial meningitis. J Pediatr 76:499-511, 1970
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 70, NO. 5, 1978
