Concomitant Aseptic Meningitis and Bacterial Urinary Tract Infection in Young Febrile Infants

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We evaluated the incidence and implications of coexistent bacterial urinary tract infection and aseptic meningitis in 1629 young febrile infants (age 1 to 60 days) who underwent sepsis work-up. Urinary tract infection was diagnosed in 13.2% and aseptic meningitis in 8.8%. Eleven patients (0.7%) had both infections. In view of possible coinfection initial laboratory results may be insufficient for decision-making regarding treatment in young febrile infants. Fever in young infants (age 1 to 60 days) is a threatening symptom because of the likelihood of severe bacterial infection. Most patients undergo sepsis workup, and empiric antibiotic treatment is often initiated until culture results are received. If a thorough investigation is done (including viral and bacterial cultures and serologic tests), an etiologic agent can be found in 36 to 67% of infants. 1, 2 Although the agent responsible is almost always a sole pathogen, 1–3 there have been some reports of mixed viral and bacterial infections in this age group. The present study was prompted by two cases of concomitant aseptic meningitis and bacterial urinary tract infection (UTI) in young febrile infants that were identified on routine sepsis workup in our pediatric department. The aim of this study was to evaluate the incidence and implications of coexistent viral and bacterial infections in young infants. UTI and aseptic meningitis, the most common bacterial and viral infections in this patient population, were selected as the representative diagnoses for the study. Patients and methods. The database of the Department of Pediatrics B at Schneider Children’s Medical Center of Israel was reviewed for all febrile infants (age 1 to 60 days) who underwent sepsis workup from January, 1995, to January, 1999. Sepsis workup of febrile infants routinely includes complete blood cell count and differential, blood chemistry and blood culture; urinalysis and urine culture (urine is obtained either by suprapubic aspiration or bladder catheterization); and lumbar puncture for cerebrospinal fluid (CSF) protein, glucose, cell count, bacterial and viral cultures and CSF bacterial antigens (Bactigen; Wampole Laboratories, Cranbury, NJ). Results. During the study period 1629 febrile infants (age 1 to 60 days) were hospitalized in our department for sepsis workup. Of these 143 (8.8%) had aseptic meningitis and 215 (13.2%) had bacterial UTI. In 11 of the patients (0.7%) concomitant aseptic meningitis and bacterial UTI was diagnosed. Table 1 shows the clinical and laboratory data of the 11 infants (8 boys) with concomitant infections. Mean age at diagnosis was 5.0 weeks (range, 1 to 8 weeks), mean temperature at presentation was 38.6 ± 0.6°C and mean white blood cell count was 11 606 ± 3297 cells/μl. Pyuria (≥5 white blood cells (WBC)/high power field in a centrifuged urine sample) was detected on urinalysis in only 6 of the infants (55%); in the remainder urinalysis was normal. In all 11 infants bacterial pathogens were isolated from urinary cultures (≥100 000 colony-forming units/ml), including Escherichia coli (n = 6), Klebsiella pneumoniae (n = 4), Enterococcus faecalis (n = 1) and Proteus mirabilis (n = 1). In one patient urinary culture grew both Klebsiella pneumoniae and Enterococcus sp. Blood cultures were negative in all 11 infants, as were CSF bacterial cultures and bacterial antigen tests (including E. coli). Mean CSF WBC count was 525 ± 480; CSF chemistry was compatible with aseptic meningitis. Enteroviruses were isolated from the CSF in 3 infants (27%). Ultrasonographic examination of the urinary system of the 11 infants revealed mild unilateral dilatation of the kidney, pelvis and ureter in 1 case.Table 1: Clinical and laboratory features of 11 infants with concomitant bacterial UTI and aseptic meningitisTreatment with iv ampicillin (200 mg/kg/day) and cefotaxime (200 mg/kg/day) was initiated in all cases because of the initial CSF laboratory results. On receipt of the positive urine but negative bacterial CSF and blood cultures, the antibiotic regimen was switched to either iv cefotaxime (100 mg/kg/day) (n = 6), iv cefuroxime (100 mg/kg/day) (n = 3), iv gentamicin (7.5 mg/kg/day) (n = 1) or oral cephalexin (50 mg/kg/day) (n = 1), according to bacterial susceptibility. Discussion. Sepsis workup in febrile infants <2 months old yields evidence of serious bacterial infection in 8 to 14.8% of cases. 1–3 Of these UTI is the most common, occurring in up to 11% of cases. This number is close to the 13.2% rate of UTI found in the present study. Our finding of pyuria in only 6 of the 11 infants (55%) is of interest. 3–7 In two large studies the absence of pyuria (≥10 WBC/ml) was almost invariably associated with sterile urine culture. This may eliminate the need for urine culture. 4–6 However, in a recent metaanalysis evaluating several screening tests for UTI, 7 microscopic analysis for pyuria had a sensitivity of only 67% and a specificity of 79%, a result that supports our findings. UTI is followed in frequency by pneumonia, bacterial meningitis and sepsis at varying rates. 1, 2 Aseptic meningitis is the most common nonbacterial diagnosis on sepsis workup, with rates of 11 to 22% in different series, 2, 3 not far from the 8.8% found in our study. Enterovirus is the most common pathogen causing neonatal meningitis (up to 34% of cases). 1, 8 Concomitant isolation of viral and bacterial pathogens is well-documented in infants and children. In a retrospective analysis of 276 children with culture-positive viral or bacterial meningitis, Sferra and Pacini 9 found that 5 had mixed viral and bacterial infections. These 5 children accounted for 2.8% of the positive CSF viral cultures and 4.8% of the positive CSF bacterial cultures. Enteroviruses were isolated in all 5. In a recent study conducted in the Philippines, 608 febrile infants age 90 days or less, underwent sepsis workup; 35 (5.8%) had a positive blood and/or CSF bacterial culture, and 10 (1.6%) had a concomitant viral infection, including 7 with enteroviruses. 2 These high frequencies of mixed viral-bacterial meningitis or bacteremia raise doubts about the usefulness of rapid CSF diagnostic tests for viruses, regarding the management and treatment of this patient population. Mixed viral bacterial etiology is more common and more well-known in respiratory infections. 10, 11 In the present study coinfection involved the central nervous system and urinary tract, indicating that viral and bacterial infections may coexist also in different anatomic sites, without obvious cause and effect phenomenon. A MEDLINE search yielded no studies specifying the presence of concomitant aseptic meningitis and bacterial UTI in febrile infants. This is surprising considering the 0.7% rate found in the present study and the large number of neonatal sepsis workups conducted worldwide. We believe that rather than being a new observation, this combined infection may simply be overlooked or disregarded and go unreported. The present study has several clinical implications. First clinicians tend to attribute all symptoms and signs to a single etiologic agent, but this is not always the case. Second the initial results of sepsis workup in young infants may be insufficient for decision-making regarding withdrawal of antibiotic treatment. For example the characteristic findings of aseptic meningitis (e.g. mild to moderate CSF pleocytosis with almost normal glucose and protein values) do not rule out serious bacterial infection in another site. Furthermore normal urinalysis, as found in 45% of the infants in our study, caused delay in the diagnosis of UTI which was made by positive bacterial urine culture. Third the finding of a bacterial infection in one site (e.g. urinary tract) does not necessarily imply that the infection in another site (e.g. meninges) is also bacterial. Acknowledgments. We thank Charlotte Sachs and Gloria Ginzach of the Editorial Board, Rabin Medical Center, Beilinson Campus, for their assistance.