Clinical Perinatal/Neonatal Case Presentation ⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢⅢ Bacteremia, Meningitis, and Brain Abscesses in a Hospitalized : Complications of Pseudomonas aeruginosa

Samir S. Shah, MD dosis. The white blood cell count was 50,900/mm3 with 59% seg- Peter Gloor, MD mented neutrophils and 17% band forms. The platelet count was 3 Patrick G. Gallagher, MD 20,000/mm , and prothrombin and partial thromboplastin times were prolonged at 26.5 seconds and Ͼ2 minutes, respectively. Cere- This report describes a preterm infant hospitalized in a neonatal brospinal fluid examination revealed a glucose of 22 mg/dl, a protein 3 3 intensive care unit who developed Pseudomonas aeruginosa of 164 mg/dl, 5/mm erythrocytes, and 387/mm leukocytes. Blood, conjunctivitis associated with bacteremia, meningitis, and multiple urine, endotracheal secretion, and cerebrospinal fluid cultures were brain abscesses. P. aeruginosa conjunctivitis can rapidly progress to an obtained. Cranial ultrasonography was normal. Treatment included invasive eye infection, such as corneal ulceration or endophthalmitis, intravenous fluid boluses, dopamine infusion, mechanical ventila- leading to poor vision or blindness. Progression of this infection may tion, and transfusion with packed red blood cells, fresh frozen plasma, lead to systemic disease. However, as illustrated in this report, P. and platelets. Intravenous ampicillin and were prescribed. aeruginosa conjunctivitis may be associated with the development of These were subsequently changed to intravenous gentamicin and systemic complications such as bacteremia and meningitis in the ceftazidime when Pseudomonas aeruginosa was isolated from absence of invasive . P. aeruginosa is a relatively common blood, endotracheal, and conjunctival cultures. Both eyes were treated cause of conjunctivitis in hospitalized preterm and low birth weight with ophthalmic gentamicin ointment. . Given the severity of the ocular and systemic complications of The infant’s condition remained poor over the next week. Al- Pseudomonas conjunctivitis, clinicians are reminded that prompt though his conjunctivitis had resolved, he was still lethargic with poor detection and treatment of neonatal conjunctivitis is critical. perfusion. He continued to require mechanical ventilation and pressor support as well as multiple packed red blood cell, platelet, and fresh frozen plasma transfusions for treatment of ongoing disseminated CASE REPORT intravascular coagulation. On day 20 of life, he was noted to be irrita- ble with increased lower extremity extensor tone, a depressed anterior An infant boy was born by cesarean section at 27 weeks’ gestation fontanelle, and an absent right plantar grasp. Repeat cranial ultra- due to a prolapsed . The infant’s birth weight was sonography revealed a new left-sided grade I germinal matrix hemor- 910 gm, and Apgar scores were 5 and 6 at 1 and 5 minutes, respec- rhage and two 3- to 5-mm spherical, cystic lesions in the left cerebral tively. The infant required mechanical ventilation for treatment of hemisphere consistent with brain abscesses (Figure 1, left). Electroen- respiratory distress syndrome for the first 11 days of life. On day 12 cephalogram was abnormal, with excessive asynchrony and diffuse of life, a purulent conjunctivitis of the right eye was noted and a slowing without evidence of focal or epileptiform abnormalities. Ab- conjunctival bacterial culture was obtained. dominal ultrasonography, echocardiography, and fundoscopic exam- On day 13 of life, the infant developed signs and symptoms of ination did not reveal any other sites of infection. A new 2-mm cavi- septic shock. Physical exam was remarkable for a heart rate of 220 tary lesion was noted in the right frontoparietal region on day 26 of beats per minute, respirations at 40 to 50/min, and blood pressure life (Figure 1, right), but repeat blood, endotracheal secretion, and at 30/20 mm Hg. The infant was lethargic but had normal upper cerebrospinal fluid cultures were sterile. The brain abscesses were not and lower extremity tone. The anterior fontanelle was flat. There considered to be large enough for surgical aspiration. was decreased perfusion with cold extremities and delayed capil- The infant had a gradual improvement in his clinical status with lary refill. This deterioration was accompanied by metabolic aci- resolution of his cerebrospinal fluid pleocytosis by day 28 of life. The infant received a 6-week course of intravenous gentamicin and cefta- Departments of and Ophthalmology, Yale University School of Medicine, New zidime. Magnetic resonance imaging performed on day 58 of life Haven, CT. showed brain abscesses without evidence of active inflammation (Fig- Address correspondence and reprint requests to Patrick G. Gallagher, MD, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208064, New Ha- ure 2). At discharge on day 65 of life, the infant had increased exten- ven, CT 06520-8064. sor tone of both lower extremities but no focal neurological deficits.

Journal of Perinatology (1999) 19(6) 462–465 © 1999 Stockton Press. All rights reserved. 0743–8346/99 $12 462 http://www.stockton-press.co.uk Complications of Pseudomonas aeruginosa Conjunctivitis Shah et al.

Figure 1 Cranial ultrasonography of an infant with P. aeruginosa conjunctivitis and brain abscesses. Left, Two white matter lesions, a 2- to 3-mm cavitary frontal lobe lesion and a 4-mm parietal lobe lesion, are seen in this left sagittal view. Right, A 2-mm cavitary lesion in the parietal lobe white matter is seen in this right sagittal view.

tent and are more likely to require invasive procedures and prolonged hospitalization. In this population, P. aeruginosa may be a virulent pathogen. A 50% fatality rate in very low birth weight infants with systemic P. aeruginosa infection has been reported.1 Pseudomonas species account for ϳ9.1% of all neonatal noso- comial infections,2 including malignant external otitis, endocarditis, meningitis, pneumonia, bacteremia, urinary tract infections, derma- titis, and conjunctivitis.3 P. aeruginosa comprises 1.2% to 5.9% of all cases of neonatal conjunctivitis,4–6 and extraocular colonization with P. aeruginosa, particularly in the respiratory tract, may be a predis- posing factor.7 P. aeruginosa conjunctivitis in infancy may be associated with significant morbidity and mortality due to the development of both ophthalmic and systemic complications (Table 1). The infection begins as a purulent conjunctivitis and may progress to infiltration of the corneal stroma. Infiltrating polymorphonuclear leukocytes and the itself may also produce collagenases that contribute to Figure 2 Magnetic resonance imaging with gadolinium of the brain of an infant 17,18 with P. aeruginosa conjunctivitis and brain abscesses 6 weeks after antibiotic therapy corneal ulceration. Continued spread of the infection may lead to was initiated. A coronal view is shown. Small cystic changes representing sequelae of corneal perforation, endophthalmitis, panophthalmitis, and orbital prior microabscesses are seen in the periventricular white matter (arrows). A 7-mm cellulitis. Poor vision or blindness may result.3,9,19 In some cases, focus of hyperintensity representing a right germinal matrix hemorrhage with intra- subsequent systemic complications such as bacteremia and death ventricular extension is also seen. occur.19–21 On follow-up examination at 3 years of age, the child was found to P. aeruginosa conjunctivitis has also been associated with sys- 6,8 have severely delayed receptive and expressive language skills. He temic complications in the absence of invasive eye infection. In one suffered no long-term ophthalmologic complications. study, 7 of 18 hospitalized infants with P. aeruginosa conjunctivitis, one of whom is the subject of this detailed report, developed systemic P. aeruginosa infection without evidence of invasive eye disease.6 Of DISCUSSION these 18 infants, 5 were bacteremic and 3 also had meningitis. The Pseudomonas aeruginosa, an aerobic Gram-negative bacillus, is a reason for the association between P. aeruginosa conjunctivitis and readily recognizable nosocomial pathogen capable of causing infec- systemic infection is not known. The conjunctivae may serve as the tion among susceptible hospital patients. Preterm infants are at risk portal of entry for systemic infection. Alternatively, the presence of P. for infection with this organism because they are immunoincompe- aeruginosa conjunctivitis in infants who later develop systemic P.

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of conjunctivitis due to P. aeruginosa are similar to the clinical Table 1 Complications in 37 Infants With P. aeruginosa Conjunctivitis* manifestations of other bacterial causes of conjunctivitis and include fibrinopurulent exudate, edema, and reactive hyperemia.28 In addi- Type of complication Number of infants tion, there can be significant overlap in both incubation period and Ocular clinical findings with conjunctivitis due to other causes such as Corneal 7 chemically induced, gonococcal, and chlamydial conjunctivitis. How- perforation/ulceration ever, unlike other causes of neonatal conjunctivitis, P. aeruginosa Endophthalmitis 3 appears to have a predilection for preterm infants (Table 2). Panophthalmitis 4 Because neonatal conjunctivitis can lead to permanent visual Systemic loss and significant systemic infection even in full-term infants, Bacteremia 13 prompt, careful evaluation and aggressive treatment are needed for Meningitis 3 Brain abscess 1 all cases of neonatal conjunctivitis. Ophthalmic consultation should Other 3 be considered an important part of this evaluation, as it improves the Death 6 chances that adequate conjunctival scrapings are obtained for Gram stain, bacterial cultures, chlamydial studies, and herpes simplex stud- *Data compiled from reported cases of complications associated with P. aeruginosa conjunc- 34 tivitis in infants.6,8–16 ies. An ophthalmologist using a portable slit lamp can determine if the conjunctivitis is progressing to corneal ulceration and can usually diagnose herpes simplex infection on examination alone. Although various factors in the neonatal intensive care unit may aeruginosa infection may indicate that the infant was colonized at influence conjunctival flora,35,36 P. aeruginosa does not constitute many sites, one of which served as the source of infection. the normal bacteria flora of the healthy eye, even in hospitalized Meningitis as a complication of neonatal bacterial conjunctivitis infants.35 Therefore, the presence of Gram-negative rods on a Gram- has been reported for other organisms, including group B streptococ- stained conjunctival specimen from a hospitalized infant with puru- ci,22 ,23 and Neisseria meningitidis.24,25 lent conjunctivitis, particularly a preterm, extremely low birth weight Meningitis may develop following intracranial invasion of organisms infant, should raise the suspicion for P. aeruginosa infection. In from a contiguous extracranial source or, more commonly, as a such cases, a complete sepsis evaluation, including blood cultures, result of hematogenous spread from a distant focus of infection.26,27 should be performed. Furthermore, since P. aeruginosa conjunctivi- Typically, brain abscesses arising from parameningeal foci are single tis has been associated with the rapid development of both ocular and and are located in the temporal or frontal lobes, whereas those arising systemic complications,6,8–16 treatment with topical and parenteral from distant foci are multiple and occur widely throughout the antipseudomonal therapy (usually an aminoglycoside or a third- brain.26 In our patient, there was no evidence of Pseudomonas inva- generation cephalosporin) should be considered until conjunctival sion into the or ; thus both the meningitis and brain ab- and blood culture results and susceptibility patterns are known. scesses were most likely secondary to bacteremia associated with P. The prognosis of P. aeruginosa conjunctivitis is variable. Rapid aeruginosa conjunctivitis rather than a direct extension of the infec- progression to endophthalmitis or bacteremia leading to loss of vision tion. or death may still occur despite early detection and treatment.8,9 It is impossible to make the diagnosis of neonatal P. aeruginosa In summary, P. aeruginosa is a relatively common but poten- conjunctivitis on clinical grounds alone. The clinical manifestations tially serious cause of conjunctivitis in hospitalized preterm and low

Table 2 Comparison of the Epidemiology of Neonatal Conjunctivitis due to Various Organisms Reference Organism Mean birth Mean gestational age Mean age at onset of weight (gm) (weeks) conjunctivitis (days)

6 Pseudomonas aeruginosa 1380 Ϯ 209 29.3 Ϯ 1.0 17.4 Ϯ 3.8 29 3290 40.0 — 30 Chlamydia trachomatis 2860 Ϯ 618 37.1 Ϯ 4.0 8.1 Ϯ 4.2 31 Chlamydia trachomatis 2900 Ϯ 400 — 13.7 Ϯ 1.1 30 2811 Ϯ 682 37.6 Ϯ 4.8 6.5 Ϯ 4.1 31 Neisseria gonorrhoeae 2900 Ϯ 400 — 11.9 Ϯ 0.8 32 Neisseria gonorrhoeae 2410 Ϯ 234 35.7 Ϯ 1.1 3.9 Ϯ 0.4 30 2831 Ϯ 858 38.8 Ϯ 3.7 — 33 Haemophilus influenzae 1864 Ϯ 345 32.8 Ϯ 1.7 2.8 Ϯ 0.9

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