Open Forum Infectious Diseases MAJOR ARTICLE Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis Chanunya Srihawan,1 Rodrigo Lopez Castelblanco,1 Lucrecia Salazar,1 Susan H. Wootton,2 Elizabeth Aguilera,2 Luis Ostrosky-Zeichner,1 David I. Sandberg,3,4 HuiMahn A. Choi,3,5 Kiwon Lee,3,5 Ryan Kitigawa,3,5 Nitin Tandon,3,4,5 and Rodrigo Hasbun1 1Department of Internal Medicine, University of Texas Health Science Center at Houston; Departments of 2Pediatrics, 3Neurosurgery, 4Pediatric Surgery, University of Texas Health, and 5Mischer Neuroscience Institute, Memorial Hermann Hospital, Texas Medical Center, Houston Background. Healthcare-associated meningitis or ventriculitis is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Methods. We performed a retrospective study of adults and children with the diagnosis of healthcare-associated meningitis or ventriculitis, as defined by the 2015 Centers of Disease Control and Prevention case definition, at 2 large tertiary care hospitals in Houston, Texas from July 2003 to November 2014. Patients were identified by infection control practitioners and by screening ce- rebrospinal fluid samples sent to the central laboratory. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results. A total of 215 patients were included (166 adults and 49 children). A positive cerebrospinal fluid culture was seen in 106 (49%) patients, with the majority of the etiologies being Staphylococcus and Gram-negative rods. An adverse clinical outcome was seen in 167 patients (77.7%) and was defined as death in 20 patients (9.3%), persistent vegetative state in 31 patients (14.4%), severe disability in 77 patients (35.8%), or moderate disability in 39 patients (18.1%). On logistic regression analysis, age >45 years (adjusted odds ratio [OR], 6.47; 95% confidence interval [CI], 2.31–18.11; P ≤ .001), abnormal neurological exam (adjusted OR, 3.04; 95% CI, 1.27–7.29; P = .013), and mechanical ventilation (adjusted OR, 5.34; 95% CI, 1.51–18.92; P = .01) were associated with an adverse outcome. Conclusions. Healthcare-associated meningitis or ventriculitis is associated with significant morbidity and mortality. Keywords. healthcare-associated meningitis; prognosis; risk factors; ventriculitis. Healthcare-associated meningitis or ventriculitis are serious negative Staphylococcus, remain the most common cause [2–4], complications of invasive neurosurgical procedures (eg, craniot- the increasing incidence of Gram-negative organisms and other omy, placement of internal or external ventricular catheters, in- multidrug-resistant pathogens have complicated the management trathecal infusions, spinal anesthesia, or lumbar puncture) or of these infections. The goal of our study was to identify risk factors may occur after penetrating head trauma [1]. for adverse clinical outcomes among patients with healthcare- Early diagnosis of healthcare-associated meningitis remains associated meningitis or ventriculitis. challenging. Clinical symptoms may be nonspecific and are dif- ficult to distinguish from the underlying neurological disease or PATIENTS AND METHODS postsurgical-related condition, and no standard diagnostic guidelines are available. Although the incidence of meningitis Study Population and ventriculitis has been declining, morbidity and mortality The study was conducted at Memorial Hermann Texas Medical ’ rates in patients who do develop these infections patients remain Center and Children s Memorial Hermann Hospital, both ter- high. Although Gram-positive pathogens, such as coagulase tiary care hospitals and primary teaching sites for the University of Texas McGovern Medical School in Houston, Texas. From July 2003 to November 2014, all adult and pediatric patients Received 19 February 2016; accepted 11 April 2016. with possible healthcare-associated meningitis or ventriculitis Correspondence: R. Hasbun, University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 2.112, Houston, Texas 77030 ([email protected]). were screened by infection control practitioners; in addition, Open Forum Infectious Diseases® from February 2010 until November 2014, all cerebrospinal © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases fluid (CSF) samples sent to the laboratory were screened. Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ Those patients who met the 2015 Centers of Disease Control by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any and Prevention (CDC)’s National Healthcare Safety Network medium, provided the original work is not altered or transformed in any way, and that the work fi is properly cited. For commercial re-use, please contact [email protected]. (NHSN) surveillance de nition [5] were retrospectively DOI: 10.1093/ofid/ofw077 reviewed. Nosocomial Meningitis in Adults and Children • OFID • 1 Definition Table 1. Demographic, Clinical, and Laboratory Characteristics of 215 Adult In accordance with the 2015 CDC/NHSN definition, health- and Pediatric Patients With Healthcare-Associated Meningitis or Ventriculitis care-associated meningitis or ventriculitis was defined as either Characteristics No. (%) a patient with positive CSF culture or a patient with at least 2 Median age (years, range) 45 (0.17–87) signs and symptoms (fever >38.0 °C, headache, meningeal or Male sex 115 (53.5) cranial nerve signs) along with at least 1 of the following: abnor- Race mal CSF analysis (increased white cells, elevated protein, and White 97 (45.1) decreased glucose in CSF per reporting laboratory’s reference Hispanic 56 (26.1) range); organisms seen on CSF Gram stain; organisms cultured African American 42 (19.5) Other 20 (9.3) from blood; positive nonculture diagnostic laboratory test of Immunocompromised statea 15 (7.0) CSF, blood, or urine; or diagnostic single antibody titer (immu- Indication for neurosurgical procedure noglobulin [Ig]M) or 4-fold increase in paired sera (IgG) for or- Hemorrhageb 106 (49.3) ganism. Among patients ≤1 year of age, the definition is similar Subarachnoid 61 (28.4) Intraventricular 43 (20.0) except that signs include fever >38.0°C, hypothermia <36.0°C, Intracerebral 29 (13.5) apnea, bradycardia, or irritability [5]. Hydrocephalus 104 (48.4) Trauma 38 (17.7) Data Collection Brain tumor 24 (11.2) A predesigned, standard case report form was used. Inpatient Unknown 2 (0.9) electronic medical records were retrospectively reviewed to extract Fever (temperature >100.4oF) 87 (40.5) the following data: demographic information, comorbidities, im- Glasgow Coma Scale GCS ≤ 14c 148 of 212 (69.8) mune status, procedures before diagnosis of meningitis or ventri- GCS < 8d 33 of 212 (15.5) culitis, recent neurosurgical procedure(s), signs and symptoms at Neurological signs and symptomse presentation, Glasgow Coma Scale (GCS), laboratory tests, imag- Headache 63 of 130 (48.5) ing studies, treatments received during hospitalization, and clini- Changes in mental status 69 of 170 (40.6) cal outcomes at the time of discharge from hospital or death using Nausea/vomiting 62 of 157 (39.5) Focal neurological deficit 61 of 184 (33.2) the Glasgow outcome scale (GOS). The GOS categories were as Neck stiffness 23 of 123 (18.7) follows: 1 = death, 2 = persistent vegetative state, 3 = severe dis- Seizures 20 of 192 (10.4) ability (defined as partially or totally dependent on assistance Photophobia 6 of 93 (6.5) from others in daily living), 4 = moderate disability (defined as in- VP shunt placement 64 (29.8) CSF leakf 46 (21.4) dependent and can resume almost all activities in daily living, but Had EVD placement 175 (81.4) disabled to the extent that they cannot participate in a variety of Median duration (days, range) 8.5 (1–30) social and work activities), and 5 = good recovery. Adverse clinical ICU admission 153 (71.2) outcomes were defined as GOS of 1 to 4. Mechanical ventilation 93 (43.3) Median duration (days, range) 9 (1–35) Statistical Analysis Empirical antibiotics 200 (93.0) Bivariate analyses to identify variables associated with adverse Antibiotics initiated before CSF analysis 109 (50.7) Steroids 40 (18.6) clinical outcomes were conducted by Pearson χ2 or Fisher’s CSF analysis (median, range) fi P exact test. All signi cant variables ( < .05) were then evaluated Leukocytes (per mm3) 272 (0–34750) in multivariate logistic regression model to identify risk factors Glucose (mg/dL) 49 (1–121) related to adverse clinical outcomes. Bootstrapping was per- Protein (mg/dL) 131 (14–1774) – formed to validate the regression model. All statistical analyses Lactate (mmol/L) 4.65 (1 22.8) Peripheral leukocytes (per mm3, median, range) 12.8 (3.6–48.7) were conducted using IBM SPSS program, version 21. Positive CSF Gram stain 43 of 215 (20.0) Positive CSF culture 106 of 215 (49.3) RESULTS Positive blood cultures 7 of 176 (3.9) Demographic and Clinical Characteristics Abbreviations: AIDS, acquired immunodeficiency syndrome; CSF, cerebrospinal fluid; EVD, external ventricular drain; GCS, Glasgow Coma Scale; HIV, human immunodeficiency virus; Our study included 215 patients: 166 adults and 49 children. The ICU, intensive care unit, VP, ventriculoperitoneal. demographic, clinical, and laboratory