Nosocomial Ventriculitis Research Articles

A pilot study for evaluating the feasibility of using alpha-defensin to support the diagnosis of ventriculitis

ObjectivesNosocomial ventriculitis is a difficult infectious condition to diagnose given that typical cerebral spinal fluid (CSF) parameters, commonly used in the diagnosis of meningitis, lack sensitivity and specificity in nosocomial ventriculitis. Consequently, novel diagnostics are needed to aid in diagnosing this condition. Herein a pilot study using alpha-defensins (α-defensins) to diagnose ventriculitis is discussed. MethodsFrom May 01, 2022, to December 30, 2022, ten patients with culture-proven external ventricular drain (EVD)-associated ventriculitis and ten patients without EVD-associated ventriculitis had CSF preserved. Levels of α-defensins were compared between the two cohorts with enzyme-linked immunosorbent assay. ResultsThere was a statistically significant (P ˂0.0001) higher level of CSF α-defensins in the ventriculitis cohort compared to the non-ventriculitis cohort. The levels of α-defensins were not affected by blood in CSF or bacterial virulence. Patients with other infectious conditions had increased levels of α-defensins but these levels were still statistically significantly (P ˂0.001) less than those seen in the ventriculitis cohort. ConclusionThis pilot study shows that α-defensins have promise as a biomarker to aid in the diagnosis of ventriculitis. If larger studies support the findings here, this biomarker can help improve diagnostic accuracy and decrease unwarranted empirical broad-spectrum antibiotic use in suspected EVD-associated ventriculitis.

Use of α-Defensins to Help Diagnose Nosocomial Ventriculitis.

Ventriculitis is a severe complication of indwelling neurosurgical devices that is associated with significant morbidity and mortality. The incidence rate of ventriculitis is approximately 10% with external ventricular drains. Obstinately, patients with these indwelling neurosurgical devices are prone to have traditional cerebral spinal fluid parameters that lack sensitivity and specificity in diagnosing nosocomial ventriculitis. In addition, diagnosis can be arduous given that indolent pathogens are commonly implicated. Therefore, diagnosis is difficult but paramount to thwart the morbidity and mortality associated with this infectious condition as well as to reduce the prolonged use of broad-spectrum antibiotics. As we extrapolate from prosthetic joint infections, for which diagnosis can also be challenging, we learn that the use of α-defensins as a diagnostic biomarker for nosocomial ventriculitis may hold promise. Herein, the viewpoint of using α-defensins as a diagnostic biomarker for nosocomial ventriculitis is discussed.

A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients

Understanding antibiotic concentration-time profiles in the central nervous system (CNS) is crucial to treat severe life-threatening CNS infections, such as nosocomial ventriculitis or meningitis. Yet CNS distribution is likely to be altered in patients with brain damage and infection/inflammation. Our objective was to develop a physiologically based pharmacokinetic (PBPK) model to predict brain concentration-time profiles of antibiotics and to simulate the impact of pathophysiological changes on CNS profiles. A minimal PBPK model consisting of three physiological brain compartments was developed from metronidazole concentrations previously measured in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF) of eight brain-injured patients. Volumes and blood flows were fixed to their physiological value obtained from the literature. Diffusion clearances characterizing transport across the blood–brain barrier and blood–CSF barrier were estimated from system- and drug-specific parameters and were confirmed from a Caco-2 model. The model described well unbound metronidazole pharmacokinetic profiles in plasma, ECF and CSF. Simulations showed that with metronidazole, an antibiotic with extensive CNS distribution simply governed by passive diffusion, pathophysiological alterations of membrane permeability, brain ECF volume or cerebral blood flow would have no effect on ECF or CSF pharmacokinetic profiles. This work will serve as a starting point for the development of a new PBPK model to describe the CNS distribution of antibiotics with more limited permeability for which pathophysiological conditions are expected to have a greater effect.

A dosing nomograph for cerebrospinal fluid penetration of meropenem applied by continuous infusion in patients with nosocomial ventriculitis

ObjectivesIn difficult-to-treat infections such as nosocomial ventriculitis, meropenem exposure in the infected compartment is often uncertain but crucial for antibacterial effects. The aim of this study was to investigate the cerebrospinal fluid (CSF) penetration of meropenem in patients with nosocomial ventriculitis and to derive a nomograph to predict effective meropenem doses as a function of clinical parameters. MethodsRetrospective patient data including meropenem serum and CSF levels as well as CSF inflammation markers were analyzed using NONMEM to assess the general pharmacokinetics and CSF penetration. Monte Carlo simulations were used to evaluate different meropenem dosing regimens. Probability of target attainment (PTA) in CSF was assessed, and a nomograph to achieve a target twice the minimal inhibitory concentration (MIC) during the dosing interval (100 %fT > 2x MIC) was developed. ResultsA one-compartment model with meropenem clearance dependent on the estimated glomerular filtration rate (CKD-EPI eGFR, p < 0.001) best described meropenem serum pharmacokinetics of 51 critically ill patients. CSF penetration ratio was correlated with the amount of protein in CSF (p < 0.001), with higher CSF protein levels accounting for higher penetration ratios. Preserved renal function (CKD-EPI eGFR >50 mL/min/1.73 m2) and low CSF protein levels (<500 mg/L) resulted in 80% PTA 100 %fT >2xMIC) for a meropenem dose of 6 g/24 h. DiscussionHigh interindividual variability in meropenem CSF concentration was observed in patients with nosocomial ventriculitis. A nomograph to predict the daily meropenem dose required for target attainment for a given eGFR and CSF protein count was developed.

Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis.

This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis. This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose. Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5-0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6-138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC24h) was 838 mg*h/L (515-1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95-12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47-42.1), and median CSF/serum ratio was 18.6% (8.4-41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004). Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.

Clinical spectrum and factors impacting outcome of Candida auris: a single center study from Pakistan

BackgroundAn outbreak of Candida auris began globally in 2014 including Pakistan and since then it has emerged as a nosocomial multi-drug resistant pathogen. The aim of this study was to assess the clinical spectrum and outcome of patients, from a single center in Pakistan, in whom C. auris was isolated.MethodsA retrospective study was conducted on 92 patients; ≥16 years with at least one culture positive for C. auris, at the Aga Khan University Hospital Karachi, Pakistan from Sept 2014-Mar 2017.Demographics, clinical history, management and outcome were studied. A logistic regression model was used to identify the risk factors for mortality.ResultsWe identified 92 patients with C. auris (193 isolates), of whom 52.2% were males. Mean age was 54.14 ± 20.4 years. Positive cultures were obtained after a median hospital stay of 14 days. Most patients had a history of surgery (57.6%), antibiotic use (95.6%), ICU stay (44.6%), indwelling lines (88.04%) and isolation of another multi-resistant organism (52.2%).Most patients were symptomatic (70.7%). Amongst these, 38 had candidemia while 27 had non-candidemia infections. Sites of infection included central lines (35), urinary tract (19), peritonitis (4), nosocomial ventriculitis (1), empyema (1), fungal keratitis (1) otitis externa (1) and surgical site (1). Fluconazole resistance was 100% while 28.5 and 7.9% were Voriconazole and Amphotericin resistant respectively. Overall crude mortality was 42.4% while 14-day mortality was 31.5%. Both infected and colonized cases shared similar mortality (46.2% vs 33.3%; p-value = 0.25). Among infected cases mortality was high in candidemia compared to non-candidemia (60.5% vs 25.9%) in which deaths related to C. auris were 34.2% vs 22.2% respectively. On multivariate analysis candidemia (AOR 4.2, 95% CI: 1.09–16.49; p-value = 0.037) was associated with greater mortality with source control being the only protective factor for mortality (AOR 0.22, 95% CI: 0.05–0.92; p-value0.038] while ICU stay, rapidity of blood culture clearance, DM, malignancy and MDR co-infection had no impact.ConclusionPatients with C.auris from a single center in Pakistan have a wide clinical spectrum with line associated infection being the predominant site of infection. Candidemia leads to high mortality while source control improves outcome.

Nosocomial ventriculitis caused by a meticillin- and linezolid-resistant clone of Staphylococcus epidermidis in neurosurgical patients

Postneurosurgical ventriculitis is mainly caused by coagulase-negative staphylococci. The rate of linezolid-resistant Staphylococcusepidermidis (LRSE) is increasing worldwide. To report clinical, epidemiological and microbiological data from a series of ventriculitis cases caused by LRSE in a Spanish hospital between 2013 and 2016. Cases of LRSE ventriculitis were reviewed retrospectively in a Spanish hospital over a four-year period. Clinical/epidemiological data of the infected patients were reviewed, the isolates involved were typed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing, and the molecular bases of linezolid resistance were determined. Five cases of LRSE ventriculitis were detected. The patients suffered from cerebral haemorrhage or head trauma that required the placement of an external ventricular drain; spent a relatively long time in the intensive care unit (ICU) (10-26 days); and three out of the five patients had previously been treated with linezolid. All LRSE had the same PFGE pattern, belonged to ST2, and shared an identical mechanism of linezolid resistance. Specifically, all had the G2576T mutation in the V domain of each of the six copies of the 23S rRNA gene, together with the Q136L and M156T mutations and the 71GGR72 insertion in the L3 and L4 ribosomal proteins, respectively. The high ratio of linezolid consumption in the ICU (7.72-8.10 defined daily dose/100 patient-days) could have selected this resistant clone, which has probably become endemic in the ICU where it could have colonized admitted patients. Infection control and antimicrobial stewardship interventions are essential to prevent the dissemination of this difficult-to-treat pathogen, and to preserve the therapeutic efficacy of linezolid.

Management of Nosocomial External Ventricular Drain-Related Ventriculomeningitis

Neurocritical care patients requiring external ventricular drainage are at risk for the development of a device-related infection. Infection rate of external ventriculostomy catheters is high with reported incidences ranging from 5% up to more than 20%. Nosocomial ventriculitis or ventriculomeningitis are potential life-threatening conditions which may contribute to a permanent adverse outcome of the patient. Reducing morbidity and mortality is strongly dependent on prompt diagnosis and on the initiation of appropriate antiinfective therapy. Management of nosocomial ventriculitis is challenging and needs to consider the most likely pathogens involved, local resistance patterns, the nature of the underlying disease, patient factors such as age, comorbidity, and immune status. Further, decisions on catheter exchange and the type and duration of systemic or local antimicrobial therapy have to be made. Because so many factors have to be taken into account, it is evident that the diagnostic and therapeutic approach to nosocomial ventriculitis is difficult to standardize. Staphylococci are the pathogens most frequently identified in nosocomial ventriculitis. Therefore, initial treatment with an antistaphylococcal agent with adequate cerebrospinal fluid penetration may be considered as first-line therapy for this infection. In the review of a contemporary case we will discuss important issues in the management of device-related ventriculitis.

Nosocomial ventriculitis and meningitis in neurocritical care patients

External ventricular drainage (EVD) is frequently necessary in neurological and neurosurgical intensive care patients. A major complication of this procedure is an EVD-related venticulitis or meningitis. The purpose of this review is (1) to address the magnitude of the problem in the neurocritical care patient population, (2) to discuss the difficulties in providing an appropriate and timely diagnosis of this disease entity and (3) to propose an algorithm for both rapid diagnosis and appropriate therapy. A MEDLINE literature search was carried out for studies from January 1990 through March 2008 reporting on ventriculostomy, EVD-related central nervous system infections, in particular ventriculitis and meningitis. EVD-related ventriculitis is a serious nosocomial complication in the neurocritical care setting where EVD catheters are frequently used for the management of elevated ICP secondary to acute hydrocephalus primarily caused by subarachnoid and intraventricular hemorrhage or traumatic brain injury. Infection rate is high with reported incidences in the range of 5 % up to more than 20 %. Predisposing factors for infection are non-adherence to rigid insertion and maintenance protocols, leakage of cerebrospinal fluid (CSF), catheter irrigation and the frequency of EVD manipulation. Diagnosis is frequently impaired either by the presence of systemic inflammation due to the primary disease or because the hemorrhagic CSF itself may cause an inflammatory reaction. Furthermore, the most common pathogens involved in EVD-related infections, i. e., staphylococci, initially provoke only a mild inflammatory response in the CSF and therefore patients rarely present with clear-cut clinical signs indicating severe central nervous system infection, in particular, ventriculitis. Nosocomial EVD-related ventriculitis is a significant cause of morbidity and mortality in critically ill neurological patients. Rapid diagnosis and prompt initiation of appropriate antimicrobial therapy is needed. A stepwise algorithm for the management of EVD-related ventriculitis is proposed.