Neonatal sepsis with meningitis, ventriculitis and brain abscess caused by Edwardsiella tarda.

A case of neonatal sepsis caused by Edwardsiella tarda, an uncommon pathogen typically associated with aquatic lifeforms, is described. The infant presented in septic shock with seizures and respiratory failure and was found to have meningitis, ventriculitis and a brain abscess requiring drainage. Only a small number of case reports of neonatal E. tarda infection, several with sepsis with poor auditory or neurodevelopmental outcomes or meningitis, have been described in the literature. This case report suggests that E. tarda, while uncommon, can be a cause of serious central nervous system disease in the neonatal population and that an aggressive approach to pursuing and treating complications may lead to improved neurodevelopmental outcomes.

Streptococcus intermedius causing primary bacterial ventriculitis in a patient with severe periodontitis - a case report.

BACKGROUND: Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously. CASE PRESENTATION: A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient's condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month. CONCLUSIONS: Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.

Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Systematic review and meta-analysis of intraventricular antibiotics for neonatal meningitis and ventriculitis.

PURPOSE: We aimed to determine the safety and effectiveness of intraventricular antibiotics in neonates with meningitis and/or ventriculitis and analyze the quality of available evidence. METHODS: DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, LILACS, and SCOPUS up to 17 February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized experimental and observational studies were included. The Cochrane methodology was used for systematic reviews. RESULTS: Twenty-six observational studies and one randomized clinical trial involving 272 patients were included. The risk of bias in both pediatric and neurosurgical studies was high, and the quality of evidence was low (evidence level C). In the pediatric studies, no significant differences in mortality were found between intraventricular antibiotics and only systemic antibiotic [25.4% vs 16.1%, OR = 0.96 (0.42-2.24), P = 0.93]. However, when analyzing the minimum administered doses, we found a lower mortality when a minimum duration of 3 days for intraventricular antibiotics was used compared to only systemic antibiotic [4.3% vs 17%, OR = 0.22 (0.07-0.72), P = 0.01]. In the neurosurgical studies, the use of intraventricular antibiotics in ventriculitis generally results in a mortality of 5% and a morbidity of 25%, which is lower than that in cases where intraventricular antibiotics were not used, with an average mortality of 37.3% and a morbidity of 50%. CONCLUSION: Considering the low quality of evidence in pediatric and neurosurgical studies, we can conclude with a low level of certainty that intraventricular antibiotics may not significantly impact mortality in neonatal meningitis and ventriculitis. However, reduced mortality was observed in cases treated with a minimum duration of 3 days of intraventricular antibiotic, particularly the multidrug-resistant or treatment-refractory infections. Higher-quality studies are needed to improve the quality of evidence and certainty regarding the use of intraventricular antibiotics for treating neonatal meningitis and ventriculitis.

Population pharmacokinetics and dosing simulations of total and unbound temocillin in the plasma and CSF of neurocritically ill patients with external ventricular drain-related cerebral ventriculitis.

BACKGROUND: Cerebral ventriculitis might be caused by Gram-negative bacteria, including ESBL producers. Temocillin may be a useful treatment option in this scenario; however, no consistent data are available regarding its penetration into the CSF. OBJECTIVES: To describe the population pharmacokinetics of temocillin in plasma and CSF and to determine the probability for different simulated dosing regimens to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets in the CSF. METHODS: Ten post-neurosurgical critically ill adult patients requiring continuous drainage of CSF were included in this monocentric, prospective, open-label, non-randomized study. They received 2 g loading dose temocillin over 30 min IV infusion, followed by a 6 g continuous infusion over 24 h. Total and unbound concentrations were measured in plasma (n = 88 and 86) and CSF (n = 88 and 88) samples and used to build a population PK model. Monte Carlo simulations were performed to estimate the PTA at 100% Css>MIC (steady state concentration above the MIC) in CSF. RESULTS: All patients were infected with Enterobacterales with temocillin MICs ≤8 mg/L. The median (min-max) temocillin penetration in CSF was 12.1% (4.3-25.5) at steady state. Temocillin unbound plasma pharmacokinetics were best described by a one-compartment model. PTA for the applied dosing regimen was >90% for bacteria with MIC ≤ 4 mg/L. CONCLUSIONS: The currently approved dose of 6 g by continuous infusion may be adequate for the treatment of ventriculitis by Enterobacterales with MIC ≤ 4 mg/L if considering 100% Css>MIC as the PK/PD target to reach. Higher maintenance doses could help covering higher MICs, but their safety would need to be assessed.

Talaromyces rugulosus ventriculitis diagnosed by nanopore amplicon sequencing, 2022.

Ventriculitis has serious complications and a high mortality rate, so it is important to early identification of the pathogen for appropriate treatment. We report case of ventriculitis caused by Talaromyces rugulosus, a rare pathogen, in South Korea. Affected patient was immunocompromised. Repeated cerebrospinal fluid culture tests were negative, but the pathogen was identified by fungal internal transcribed spacer amplicon nanopore sequencing. The pathogen was detected outside the endemic area of talaromycosis.

Cerebrospinal fluid penetration of fosfomycin in patients with ventriculitis: an observational study.

BACKGROUND: For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis. METHODS: Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated. RESULTS: Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159-289] mg/L and the CSF concentration 99 [66-144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163-438] mg/L and 104 [65-269] mg/L. Median CSF penetration was 46 [36-59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L. CONCLUSION: Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.

Management of Extensive Central Nervous System Cladophialophora bantiana Infection in a 9-Year-Old Child.

BACKGROUND: Pediatric central nervous system (CNS) phaeohyphomycosis is a rare invasive fungal infection associated with high mortality. METHODS: We describe a child with progressive neurologic symptoms whose ultimate diagnosis was Cladophialophora bantiana -associated CNS phaeohyphomycosis. We discuss her clinical presentation, medical and surgical management and review the current literature. RESULTS: A 9-year-old female presented with acute onset of headaches, ophthalmoplegia and ataxia. Initial infectious work-up was negative, including serial fungal cerebrospinal fluid cultures. Over 2 months, she experienced progressive cognitive and motor declines, and imaging revealed worsening meningitis, ventriculitis and cerebritis. Ultimately, Cladophialophora was detected by plasma metagenomic next-generation sequencing (mNGS). Fourth ventricle fluid sampling confirmed the diagnosis of C. bantiana infection. Given the extent of her disease, complete surgical resection was not feasible. She required multiple surgical debridement procedures and prolonged antifungal therapy, including the instillation of intraventricular amphotericin B. With aggressive surgical and medical management, despite her continued neurologic deficits, she remains alive 3 years after her initial diagnosis. To our knowledge, this is one of a few published pediatric cases of CNS phaeohyphomycosis and the first with the causative pathogen identified by plasma mNGS. CONCLUSION: CNS phaeohyphomycosis is a serious, life-threatening infection. The preferred management includes a combination of surgical resection and antifungal therapy. In cases complicated by refractory ventriculitis, intraventricular antifungal therapy can be considered as adjuvant therapy. Direct sampling of the CNS for pathogen identification and susceptibility testing is the gold standard for diagnosis; however, the use of plasma mNGS may expedite the diagnosis.

Intravenous plus intraventricular tigecycline-amikacin therapy for the treatment of carbapenem-resistant Klebsiella pneumoniae ventriculitis: A case report.

RATIONALE: Central nervous system infections (CNSIs) are one of the most serious complications after neurosurgery, especially carbapenem-resistant bacterial meningitis. Owing to the poor blood-brain barrier permeability of most antibiotics, the treatment of CNSIs by intraventricular (IVT) administration is becoming a hot topic in clinical research. Currently, the treatment of CNSIs caused by carbapenem-resistant Klebsiella pneumoniae is mainly based on intraventricular injection of an antibiotic combined with one or more other systemic intravenous (IV) antibiotics, whereas there are few case reports of intraventricular injection of 2 antibiotics. PATIENT CONCERNS: A 57-year-old man with an open craniocerebral injury presented with dyspnea, high fever, and seizures associated with surgery. DIAGNOSIS: Intracranial infection caused by carbapenem-resistant K. pneumoniae was diagnosed. INTERVENTIONS: On the advice of a clinical pharmacist, the patient was given tigecycline (100 mg IV + 3 mg IVT q12h) combined with amikacin (0.8 g IV + 30 mg IVT qd) antiinfective therapy. Ultimately, the pathogens in the cerebrospinal fluid were eradicated after 7 days, and the CNSIs were completely cured after 14 days. OUTCOMES: The patient recovered and was discharged from the hospital without adverse reactions. LESSONS: A series of in vitro and in vivo synergy tests of carbapenem-resistant K. pneumoniae showed that tigecycline combined with aminoglycosides had good synergistic effects and effectively suppressed bacterial resistance selection. Intravenous plus intraventricular tigecycline-amikacin seems to be a safe and effective treatment option for carbapenem-resistant K. pneumoniae CNSIs.

Norvancomycin for the treatment of central nervous system MRSA infections: A randomized controlled trial.

Combined intravenous and intrathecal administration of norvancomycin (NVCM) is routinely employed in treating methicillin-resistant Staphylococcus aureus (MRSA) ventriculitis in patients following craniotomy. However, the optimal dosing regimen, the pharmacokinetics (PK) of NVCM in cerebrospinal fluid (CSF), and the clinical outcome are yet to be elucidated. Herein, a single-center randomized controlled trial was conducted in the Neurosurgery Department of the Second Hospital of Hebei Medical University (Shijiazhuang, China). Patients with MRSA ventriculitis after craniotomy were randomly assigned to two groups. The control group received 800 mg NVCM intravenously every 12 h, and the experimental group received 800 mg NVCM intravenously every 12 h and 16 mg NVCM intrathecal administration every 24 h. The primary outcome was the length of therapy, while the secondary outcomes included the area under the concentration-time curve in 0-24 h/minimum inhibitory concentration ratio (AUC0-24h/MIC) of NVCM in CSF. A total of 29 patients (14 in the experimental group and 15 in the control group) were included in this study. Of these, 24 constituted the final analysis population, with 12 in each group. The average length of therapy in the experimental group was markedly shorter than that of the control group (11.2 ± 2.6 days vs. 16.6 ± 5.2 days, P = 0.005), while the AUC0-24h/MIC in the experimental group was significantly higher than that in the control group (2306.57 ± 928.58 vs. 46.83 ± 27.48, P < 0.001) with no increase in adverse reactions. Combined intravenous and intrathecal administration can shorten the treatment time of intracranial infection without higher adverse reaction risks in our research. Further studies with larger sample size are warranted to verify its safety and efficacy.

Ventriculitis and meningitis: by methicillin-resistant S. epidermidis: comparison of serum and CSF vancomycin concentrations and possible effect on MIC.

A case of HCAMV due to methicillin-resistant S. epidermidis (MRSE) in a new-born treated with vancomycin is described. Despite adequate vancomycin serum concentrations, an increase in vancomycin MIC (from 1 to 2 mg/L) in presence of persistently low CSF concentrations were observed. The eGFR during the treatment period was normal (no evidence of hyperfiltration). This report confirms the observation of a relationship among antibiotic PK/PD, cure of localized infections and resistance selection and specifically suggests the need for a first-line alternative to vancomycin in case of HCAMV due to CoNS with MIC ≥ 1 mg/L.

Carbapenem-Resistant Gram-Negative Bacteria-Related Healthcare-Associated Ventriculitis and Meningitis: Antimicrobial Resistance of the Pathogens, Treatment, and Outcome.

Carbapenem-resistant Gram-negative bacteria (CRGNB)-related health care-associated ventriculitis and meningitis (HCAVM) is dangerous. We aimed to report the antimicrobial resistance of the pathogens, treatment, and outcome. All cases with CRGNB-related HCAVM in2012-2020 were recruited. Antimicrobial agents were classified as active, untested, or inactive using antimicrobial susceptibility tests. The treatment stage was classified as empirical or targeted according to the report of pathogens. The treatment effect was classified as ineffective or effective according to HCAVM-related parameters. Overall, 92 cases were recruited. For most antimicrobial agents, the resistance rate was higher than 70.0%. The polymyxin resistance rate was the lowest at 11.6%. The chloramphenicol, trimethoprim-sulfamethoxazole, amikacin, levofloxacin, and tetracycline resistance rates were relatively low, ranging from 21.1% to 64.1%. The meropenem resistance rate was 81.9%. There was no significant trend for any antimicrobial agent tested. Meropenem was the most common antimicrobial agent used in empirical treatment; trimethoprim-sulfamethoxazole and polymyxin were the most used active antimicrobial agents, and meropenem/sulbactam and polymyxin were the most used untested antimicrobial agents in targeted treatment. In total, 42 (45.7%) cases received ineffective treatments. The ineffective treatment rate of cases that received active antimicrobial agents was lower than that of cases that received untested antimicrobial agents and cases that received inactive antimicrobial agents (29.3% [12/41] versus 46.2% [18/39] versus 100.0% [12/12], P < 0.001). Antimicrobial resistance was prevalent but without increasing trends. Active antimicrobial agents are necessary. Additionally, untested antimicrobial agents, including meropenem/sulbactam and polymyxin, might be optional. Inactive antimicrobial agents must be replaced. IMPORTANCE Carbapenem-resistant Gram-negative bacteria-related health care-associated ventriculitis and meningitis is a clinical threat because of the poor outcome and challenges in treatment. We reached several conclusions: (i) the antimicrobial resistance of pathogens is severe, and some antimicrobial agents represented by polymyxin are optional according to the antimicrobial susceptibility tests; (ii) in the background that the portion of carbapenems resistance in Gram-negative bacteria is increasing, there is no increasing trend for the antimicrobial resistance of carbapenem-resistant Gram-negative bacteria in the 9-year study; (iii) meropenem is the main antimicrobial agent in treatment, and trimethoprim-sulfamethoxazole, tigecycline, polymyxin, and meropenem/sulbactam are commonly used in the targeted treatment; (iv) the treatment effect was poor and affected by the treatment: timely active antimicrobial agents should be given. And untested antimicrobial agents represented by polymyxin and meropenem/sulbactam might be optional. Inactive antimicrobial agents must be replaced.

Unusual case of spinal subdural empyema with ventriculitis managed conservatively with lumbar drain.

It has long been believed that spinal subdural empyemas (SDEs) with neurological symptoms result in death if operative intervention is not performed. We present a case of addressing an extensive spinal SDE with a minimally invasive procedure: a bedside lumbar drain. Our patient is a 67-year-old man with medical history significant for type I diabetes who presented 2 weeks after a right shoulder steroid injection with septic arthritis. An MRI was obtained for back pain which revealed spinal SDE from the cervical to lumbosacral spine. Given patient's acute sepsis, haemodynamic instability, and extent of empyema, we placed a lumbar drain for decompression. The patient had a prolonged complicated hospital course. Imaging 2 months later revealed interval decrease in the spinal SDE. Although this severe septic event left the patient with significant deficits, he was able to return to ambulation without surgical intervention.

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

OBJECTIVES: In 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. METHODS: Retrospective 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. RESULTS: A 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. DISCUSSION: High 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.

Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.