Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter ephesus study.

BACKGROUND: Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). MATERIALS/METHODS: This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. RESULTS: Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). CONCLUSIONS: Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.

Healthcare-Associated Infections in the Neurocritical Care Unit.

PURPOSE OF REVIEW: This article summarizes updated data and knowledge on healthcare-associated infections in the neurocritical care unit, with a focus on central nervous system infections and systemic infectious complications in patients with acute brain disease. It also reviews the concept of brain injury-induced immune modulation, an underlying mechanism to explain why the neuro-ICU population is particularly susceptible to infections. RECENT FINDINGS: Healthcare-associated infections in the neuro-ICU are common: up to 40 % of meningitides in the developed world are now healthcare-associated. The number of gram-negative infections is rising. New diagnostic approaches attempt to aid in the diagnosis of healthcare-associated meningitis and ventriculitis. Healthcare-associated infections in the neurocritical care unit remain a challenge for diagnosis, treatment, and prevention. Gaining a better understanding of at-risk patients and development of preventative strategies will be the goal for future investigation.

Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis.

BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

A higher area under the concentration-time curve/minimum inhibitory concentration target as a potential prognostic factor for vancomycin treatment of methicillin-resistant Staphylococcus aureus meningitis: A case report.

The area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) - guided approach is recommended for vancomycin therapeutic drug monitoring in severe methicillin-resistant Staphylococcus aureus (MRSA) infection. However, evidence regarding the efficacy of vancomycin AUC-guided strategies for the treatment of systemic infections is limited. This case report describes the successful treatment of MRSA meningitis, with vancomycin using a higher AUC/MIC target. A 61-year-old woman who underwent ventriculoperitoneal (VP) shunt placement for subarachnoid hemorrhage, developed MRSA meningitis due to shunt infection. Vancomycin was administered intravenously, with concurrent monitoring of serum and cerebrospinal fluid (CSF) vancomycin concentrations and AUC/MIC. On post-operative day (POD) 24 of VP shunt placement, the vancomycin trough concentration and AUC/MIC were 12.0 µg/mL and 515, respectively, with persistently positive CSF culture. On POD 28, the trough concentration and AUC/MIC were 18.6 µg/mL and 610, respectively. There were no major adverse events, and CSF culture turned negative on POD 30. The vancomycin CSF-to-serum ratio was approximately 41 %. For patients with MRSA meningitis, we suggest an optimal therapeutic range with a vancomycin AUC/MIC target near the upper limit of the therapeutic window.

Spontaneous nosocomial Proteus mirabilis meningitis in a Human Immunodeficiency Virus (HIV)-infected adult patient: a case report.

BACKGROUND: Gram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease. CASE PRESENTATION: A 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis. CONCLUSIONS: This case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.

Etiology and Outcomes of Healthcare-Associated Meningitis and Ventriculitis-A Single Center Cohort Study.

Healthcare associated meningitis and ventriculitis (HCAMV) are serious complications of neurosurgical procedures. We conducted a retrospective cohort study of patients with HCAMV treated at the University Hospital for Infectious Diseases Zagreb during the 2013-2019 period. A total of 144 patients with 151 episodes of HCAMV were included. The most common indications for neurosurgical procedures were brain tumor, hemorrhage and hydrocephalus. Etiology was identified in 90 (59.6%) episodes (either positive CSF culture or positive PCR), and in other 61 (40.39%) the diagnosis of HCAMV was made based on clinical and CSF parameters, without microbiologic confirmation. Carbapenem-resistant Acinetobacter baumannii was the most common pathogen (15.89%), followed by Staphylococcus aureus (13.91%), Pseudomonas aeruginosa (13.25%) and Coagulase negative staphylococci (7.95%). Overall, 24 (16.3%) patients died, and the majority had adverse outcomes, persistent vegetative state (8, 5.56%) and severe disability (31, 21.53%). The worst clinical outcomes were observed in A. baumannii infections. High rate of complications, the need for external ventricular drainage (re)placement often complicated with nosocomial infections and prolonged stay in intensive care units were observed. Clinicians should be aware of local microbial epidemiology on guiding proper empirical antimicrobial treatment in patients with HCAMV.

Nosocomial meningitis in intensive care: a 10-year retrospective study and literature review.

BACKGROUND: Nosocomial meningitis is a medical emergency that requires early diagnosis, prompt initiation of therapy, and frequent admission to the intensive care unit (ICU). METHODS: A retrospective study was conducted in adult patients diagnosed with nosocomial meningitis who required admission to the ICU between April 2010 and March 2020. Meningitis/ventriculitis and intracranial infection were defined according to Centers for Disease Control and Prevention guidelines. RESULTS: An incidence of 0.75% of nosocomial meningitis was observed among 70 patients. The mean patient age was 59 years and 34% were ≥65 years. Twenty-two percent of patients were in an immunocompromised state. A clear predisposing factor for nosocomial meningitis (traumatic brain injury, basal skull fracture, brain hemorrhage, central nervous system [CNS] invasive procedure or device) was present in 93% of patients. Fever was the most frequent clinical feature. A microbiological agent was identified in 30% of cases, of which 27% were bacteria, with a predominance of Gram-negative over Gram-positive. Complications developed in 47% of cases, 24% of patients were discharged with a Glasgow coma scale <14, and 37% died. There were no clear clinical predictors of complications. Advanced age (≥65 years old) and the presence of complications were associated with higher hospital mortality. CONCLUSIONS: Nosocomial meningitis in critical care has a low incidence rate but high mortality and morbidity. In critical care patients with CNS-related risk factors, a high level of suspicion for meningitis is warranted, but diagnosis can be hindered by several confounding factors.

Corrected white blood cell count, cell index, and validation of a clinical model for the diagnosis of health care-associated ventriculitis and meningitis in adults with intracranial hemorrhage.

OBJECTIVES: To evaluate the utility of the corrected CSF white blood cell (WBC) count, cell index, CSF lactate, CSF glucose and a newly developed diagnostic model for the diagnosis of healthcare-associated ventriculitis or meningitis (HCAVM) in the setting of intracranial hemorrhage (ICH). PATIENTS AND METHODS: A case-control study of 111 adult patients with ICH with HCAVM (cases) or without HCAVM (controls) matched 1:2 by age, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II (APACHE II) score enrolled in a large tertiary care center from 2003 to 2016. RESULTS: Subjects were appropriately matched by age, GCS, and APACHE II score (P > 0.2). Cases had significantly higher CSF WBC count (uncorrected and corrected), cell index, and CSF lactate, but lower CSF glucose levels than controls (P < 0.05). There were no differences between CSF protein, CSF neutrophilic pleocytosis, and serum C-reactive protein between cases and controls (P > 0.1). The diagnostic accuracy as analyzed by the area under the receiver operating characteristic curve (AUC of ROC) was found to be good for the cell index (0.825), fair for the corrected CSF WBC count (0.770), and poor for the diagnostic model and uncorrected CSF WBC count (0.652 and 0.653, respectively). CONCLUSION: The diagnosis of HCAVM in patients with ICH remains challenging and although no single parameter is sufficient for diagnosis the cell index proved to be an important indicator of infection in our study.

Healthcare-Associated Meningitis or Ventriculitis in Older Adults.

BACKGROUND/OBJECTIVES: Healthcare-associated meningitis or ventriculitis (HCAMV) is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Older adults are at higher risk of adverse outcomes in community-acquired meningitis but studies of HCAMV are lacking. Therefore, we perform the study to define the differences in clinical outcomes between older and younger adults with HCAMV. DESIGN: Retrospective study. SETTING: A large tertiary care hospital in Houston, Texas, from July 2003 to November 2014. PARTICIPANTS: Adults with a diagnosis of HCAMV (N = 160) aged ≥65 (n = 35), aged 18-64 (n = 125). MEASUREMENTS: Demographic characteristics, clinical presentation, laboratory results, treatments, and outcomes (Glasgow Outcome Scale). RESULTS: Older adults had more comorbidities and CSF abnormalities [pleocytosis, high cerebrospinal fluid (CSF) protein, low CSF glucose) and were more likely to have altered mental status than younger adults (P < .05). An adverse clinical outcome was seen in 142 participants (89%) (death (n = 18, 11%), persistent vegetative state (n = 26, 16%), severe disability (n = 68, 43%), moderate disability (n = 30, 19%). There was no difference in adverse outcomes between older (97%) and younger (86%) adults (P = .13). On logistic regression analysis, abnormal neurological examination (adjusted odds ratio (aOR) = 7.13, 95% confidence interval (CI) = 2.15-23.63, P = .001) and mechanical ventilation (aOR = 11.03, 95% CI = 1.35-90.51, P = .02) were associated with adverse clinical outcomes. CONCLUSION: Older adults with HCAMV have more comorbidities and CSF abnormalities and are more likely to have altered mental status than younger adults but have similar high rates of adverse clinical outcomes.

Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis.

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 cerebrospinal 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.