ABSTRACT
OBJECTIVES: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections. METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality. RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; Pâ=â0.011]. In addition, with MICsâ≤â0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (Pâ=â0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin. CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs wereâ≤â0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.
Subject(s)
Anti-Bacterial Agents , Carbapenems , Drug Monitoring , Gram-Negative Bacteria , Gram-Negative Bacterial Infections , Polymyxin B , Humans , Male , Female , Middle Aged , Polymyxin B/therapeutic use , Polymyxin B/administration & dosage , Polymyxin B/pharmacokinetics , Anti-Bacterial Agents/cerebrospinal fluid , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Prospective Studies , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/cerebrospinal fluid , Gram-Negative Bacterial Infections/mortality , Gram-Negative Bacterial Infections/microbiology , Carbapenems/therapeutic use , Carbapenems/pharmacokinetics , Carbapenems/pharmacology , Aged , Gram-Negative Bacteria/drug effects , Adult , Central Nervous System Infections/drug therapy , Central Nervous System Infections/cerebrospinal fluid , Central Nervous System Infections/microbiology , Central Nervous System Infections/mortality , Injections, Spinal , Treatment Outcome , Microbial Sensitivity Tests , Cerebrospinal Fluid/microbiologyABSTRACT
BACKGROUND: Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited. METHODS: We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections. RESULTS: We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus , coagulase-negative Staphylococci and Streptococcus pneumoniae . Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics. CONCLUSIONS: We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.
Subject(s)
Anti-Bacterial Agents , Ceftaroline , Cephalosporins , Staphylococcal Infections , Humans , Cephalosporins/therapeutic use , Cephalosporins/adverse effects , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Infant , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/drug effects , Vancomycin/therapeutic use , Vancomycin/adverse effects , Male , Cerebral Ventriculitis/drug therapy , Cerebral Ventriculitis/microbiology , Central Nervous System Infections/drug therapy , Central Nervous System Infections/microbiology , Rifampin/therapeutic use , Rifampin/adverse effectsABSTRACT
OBJECTIVES: To describe the pharmacokinetics/pharmacodynamics (PK/PD) of ceftazidime/avibactam in critically ill patients with CNS infections. METHODS: A prospective study of critically ill patients with CNS infections who were treated with ceftazidime/avibactam and the steady-state concentration (Css) of ceftazidime/avibactam in serum and/or CSF was conducted between August 2020 and May 2023. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of ceftazidime/avibactam was evaluated. RESULTS: Seven patients were finally included. The ceftazidime/avibactam target attainment in plasma was optimal for three, quasi-optimal for one and suboptimal for three. In three patients with CSF drug concentrations measured, ceftazidime/avibactam target attainment in CSF was 100% (3/3), which was optimal. The AUCCSF/serum values were 0.59, 0.44 and 0.35 for ceftazidime and 0.57, 0.53 and 0.51 for avibactam. Of the seven patients, 100% (7/7) were treated effectively, 71.4% (5/7) achieved microbiological eradication, 85.7% (6/7) survived and 14.3% (1/7) did not survive. CONCLUSIONS: The limited clinical data suggest that ceftazidime/avibactam is effective in the treatment of CNS infections caused by MDR Gram-negative bacilli (MDR-GNB), can achieve the ideal drug concentration of CSF, and has good blood-brain barrier penetration.
Subject(s)
Ceftazidime , Central Nervous System Infections , Humans , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Carbapenems , Critical Illness , Azabicyclo Compounds/pharmacology , Azabicyclo Compounds/therapeutic use , Drug Combinations , Central Nervous System Infections/drug therapy , Microbial Sensitivity TestsABSTRACT
BACKGROUND: Carbapenems are widely used for empiric treatment of healthcare-associated central nervous system (CNS) infections. We investigated the feasibility of a carbapenem-sparing strategy, utilising a third-generation cephalosporin (ceftriaxone or cefotaxime) (combined with vancomycin) for the empirical treatment of healthcare-associated CNS infections in Eastern Denmark. METHODS: The departments of neurosurgery and neuro-intensive care at Copenhagen University Hospital Rigshospitalet. First, we analysed local microbiological data (1st January 2020-31st August 2022) to identify microorganisms non-susceptible to third-generation cephalosporin. Subsequently, we assessed all carbapenem prescriptions over a three-month period for their indication and justification. RESULTS: In total, 25,247 bacterial cultures were identified, of which 2,563 CNS-related, were included in the analysis. The positivity rate was 10.5% (n = 257/2439) for cerebrospinal-fluid samples and 75.8% (n = 95/124) for brain parenchyma. CNS samples from five individual patients revealed bacteria non-susceptible to third generation cephalosporins (Enterobacter spp. (n = 3), Pseudomonas spp. (n = 2), Klebsiella spp. (n = 2), Citrobacter freundii (n = 1)). All five patients had been hospitalised for ≥10days at the time-point of antibiotic therapy. Out of 11,626 sets of blood cultures, a total of 10 individual patients had Gram-negative blood-stream infections with resistance to ceftriaxone and piperacillin/tazobactam. 140 days-of-therapy (32%) with carbapenem in 18 patients (36%) were definitively or possibly indicated according to guidelines, none were indicated for healthcare-associated CNS-infections. CONCLUSION: An empiric treatment strategy relying on a third-generation cephalosporin appears suitable for healthcare-associated CNS infections at our tertiary hospital, serving a population of 2.6 million. However, in patients with prolonged hospitalization (≥10 days), immunosuppression, prior broad-spectrum antibiotic use, or history of resistant Gram-negative bacteria, empirical prescription of carbapenem may be needed.
Subject(s)
Central Nervous System Infections , Cross Infection , Humans , Carbapenems/therapeutic use , Ceftriaxone , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Delivery of Health Care , Central Nervous System , Central Nervous System Infections/drug therapy , DenmarkABSTRACT
Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised. Individuals with systemic cryptococcosis (67-84%), candidiasis (3-64%), blastomycosis (40%), coccidioidomycosis (25%), histoplasmosis (5-20%), mucormycosis (12%), and aspergillosis (4-6%) are highly susceptible to develop CNS involvement, which often results in high mortality (15-100%) depending on the mycosis and the affected immunosuppressed population. Current antifungal drugs are limited, prone to resistance, present host toxicity, and show reduced brain penetration, making FI-CNS very difficult to treat. Given these limitations and the rise in FI-CNS, there is a need for innovative strategies for therapeutic development and treatments to manage FI-CNS in at-risk populations. Here, we discuss standards of care, antifungal drug candidates, and novel molecular targets in the blood-brain barrier, which is a protective structure that regulates movement of particles in and out of the brain, to prevent and combat FI-CNS.
Subject(s)
Central Nervous System Infections , Coccidioidomycosis , Cryptococcosis , Histoplasmosis , Mycoses , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Mycoses/microbiology , Histoplasmosis/microbiology , Coccidioidomycosis/drug therapy , Coccidioidomycosis/microbiology , Cryptococcosis/drug therapy , Central Nervous System Infections/drug therapyABSTRACT
OBJECTIVES: Postoperative central nervous system infections (PCNSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) frequently result in unfavourable outcomes. However, CRE PCNSIs have not been well described from a clinical and microbiological perspective. METHODS: A total of 254 PCNSIs cases were included (January 2017 through June 2020), and clinical features were compared based on pathogenic classification. Cox regression analysis was performed to assess risk factors for mortality. Antibiotic susceptibility testing and whole genome sequencing were conducted on CRE isolates preserved. MLST, cgMLST, resistance genes and virulence genes were further analysed. RESULTS: Among 254 PCNSI cases, 15.4% were caused by Enterobacteriaceae including 28 cases by CRE. The 28-day mortality rates for CRE, CSE and non-Enterobacteriaceae PCNSIs were 50.0%, 27.3%, and 7.4%, respectively. 42.9% (12/28) of the CRE PCNSIs patients achieved clinical cure, with 25.0% achieved microbiological clearance. ST11-KL64 carrying blaKPC-2 was dominant in CRE (17/23, 73.9%), and the 28-day mortality rate of its infection was 58.5%. Most CRKP carried rampA/rampA2 genes (17/23, 73.9%). CONCLUSION: ST11-KL64 CRKP carrying blaKPC-2 dominated among CRE PCNSIs. Targeted anti-infective combination therapy based on ceftazidime/avibactam or amikacin, combined with intrathecal administration of amikacin, was found to be effective. These findings render a new insight into the clinical and microbiological landscape of CRE PCNSIs.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Central Nervous System Infections , Enterobacteriaceae Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenem-Resistant Enterobacteriaceae/genetics , Amikacin/therapeutic use , Multilocus Sequence Typing , Enterobacteriaceae Infections/microbiology , Central Nervous System Infections/drug therapyABSTRACT
Vancomycin is a commonly used antibacterial agent in patients with primary central nervous system (CNS) infection. This study aims to examine predictors of vancomycin penetration into cerebrospinal fluid (CSF) in patients with external ventricular drainage and the feasibility of CSF sampling from the distal drainage port for therapeutic drug monitoring. Fourteen adult patients (9 with primary CNS infection) were treated with vancomycin intravenously. The vancomycin concentrations in blood and CSF (from proximal [CSF_P] and distal [CSF_D] drainage ports) were evaluated by population pharmacokinetics. Model-based simulations were conducted to compare various infusion modes. A three-compartment model with first-order elimination best described the vancomycin data. Estimated parameters included clearance (CL, 4.53 L/h), central compartment volume (Vc, 24.0 L), apparent CSF compartment volume (VCSF, 0.445 L), and clearance between central and CSF compartments (QCSF, 0.00322 L/h and 0.00135 L/h for patients with and without primary CNS infection, respectively). Creatinine clearance was a significant covariate on vancomycin CL. CSF protein was the primary covariate to explain the variability of QCSF. There was no detectable difference between the data for sampling from the proximal and the distal port. Intermittent infusion and continuous infusion with a loading dose reached the CSF target concentration faster than continuous infusion only. All infusion schedules reached similar CSF trough concentrations. Beyond adjusting doses according to renal function, starting treatment with a loading dose in patients with primary CSF infection is recommended. Occasionally, very high and possibly toxic doses would be required to achieve adequate CSF concentrations, which calls for more investigation of direct intraventricular administration of vancomycin. (This study has been registered at ClinicalTrials.gov under registration no. NCT04426383).
Subject(s)
Central Nervous System Infections , Vancomycin , Adult , Humans , Anti-Bacterial Agents/pharmacokinetics , Central Nervous System Infections/drug therapy , Drainage , Plasma , Vancomycin/pharmacokineticsABSTRACT
BACKGROUND: Consensus guidelines for antibiotic prophylaxis in endoscopic endonasal surgery (EES) have not been developed. The study objective was to define the microbiologic and clinical characteristics of post-EES central nervous system (CNS) infections. METHODS: This was a single-center retrospective study of patients >18 years of age who underwent EES between January 2010 and July 2021 at a high-volume skull base center. Patients with confirmed CNS infection within 30 days of EES were included. During the study period, the standard prophylaxis regimen was ceftriaxone 2 g every 12 hours for 48 hours. For patients with a documented penicillin allergy, vancomycin plus aztreonam was recommended. RESULTS: In total, 2440 EES procedures were performed on 2005 patients; the CNS infection rate was 1.8% (37/2005). CNS infections were more common among patients with a history of previous EES (6.5%; 20/307) compared with those who did not (1%; 17/1698; P < 0.001). The median time from EES to CNS infection was 12 (6-19) days. Thirty-two percent (12/37) of CNS infections were polymicrobic, which was more common among patients without previous EES (52.9%; 9/17) compared with those with previous EES (15%; 3/20; P = 0.03). Across all cases, Staphylococcus aureus (n = 10) and Pseudomonas aeruginosa (n = 8) were commonly isolated pathogens. Among those with confirmed methicillin-resistant Staphylococcus aureus (MRSA) nares colonization before EES, 75% (3/4) developed MRSA CNS infections compared with 6.1% (2/33) of noncolonized patients (P = 0.005). CONCLUSIONS: CNS infection after EES is rare and causative pathogens vary. Further studies are needed to identify the impact of MRSA nares screening on antimicrobial prophylaxis before EES.
Subject(s)
Central Nervous System Infections , Methicillin-Resistant Staphylococcus aureus , Nervous System Malformations , Staphylococcal Infections , Humans , Retrospective Studies , Endoscopy/methods , Nose , Staphylococcal Infections/drug therapy , Central Nervous System Infections/epidemiology , Central Nervous System Infections/etiology , Central Nervous System Infections/drug therapy , Anti-Bacterial Agents/therapeutic useABSTRACT
OBJECTIVES: Klebsiella pneumoniae (K. pneumoniae) is one of the most common bacteria in the hospital-acquired central nervous system (CNS) infections. Central nervous system infections caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with significant mortality rates and high hospital costs due to limited antibiotic treatment options. This retrospective study aimed to evaluate the clinical efficacy of ceftazidime-avibactam (CZA) for the treatment of CNS infections caused by CRKP. METHODS: Twenty-one patients with hospital-acquired CNS infections caused by CRKP who received treatment with CZA for ≥ 72 hours were enrolled. The primary outcome was to assess the clinical and microbiology efficacy of CZA for the treatment of CNS infections caused by CRKP. RESULTS: A high burden of comorbidity was discovered in 20 of 21 patients (95.2%). Most patients had a history of craniocerebral surgery and 17 (81.0%) of the patients were in the intensive care unit with a median APACHE II score of 16 (IQR 9-20) and SOFA score of 6 (IQR 3-7). Eighteen cases were treated by CZA-based combination therapies, while the remaining three cases were treated with CZA alone. At the end of the treatment, the overall clinical efficacy was 76.2% (16 of 21) with a bacterial clearance rate of 81.0% (17 of 21) and all-cause mortality of 23.8% (five of 21). CONCLUSION: This study showed that CZA-based combination therapy is an effective treatment option for CNS infections caused by CRKP.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Central Nervous System Infections , Klebsiella Infections , Humans , Klebsiella pneumoniae , Retrospective Studies , Klebsiella Infections/microbiology , Ceftazidime/therapeutic use , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/therapeutic use , Drug Combinations , Carbapenems/therapeutic use , Central Nervous System Infections/drug therapy , Hospitals , Microbial Sensitivity TestsABSTRACT
BACKGROUND: Central nervous system (CNS) infection is one of the most serious complications after neurosurgery. This study aimed to analyze the effect of penicillin allergy (PA) and alternative prophylactic antibiotics on risk of postoperative CNS infection in patients undergoing neurosurgery. METHODS: Data of patients who underwent neurosurgical procedures from January 2015 to December 2021 were analyzed retrospectively. Patients with PA were compared with patients without PA in a 1:1 ratio. A multivariate logistic regression model was used to examine whether PA was a risk factor for postoperative CNS infection. RESULTS: Overall, 15,049 eligible neurosurgical records were reviewed, from which 578 surgical records of 556 patients with PA were matched to 578 records of 570 patients without PA. Patients with PA showed significantly lower probability to receive prophylactic cephalosporins (55.9% vs. 98.8%, P < 0.01), but significantly higher probability to receive clindamycin (41.86% vs. 1.03%, P < 0.01), than patients without PA. Multivariate analysis revealed that patients with PA were more likely to experience postoperative CNS infection than patients without PA (odds ratio = 2.03; 95% confidence interval, 1.15-3.56; P = 0.014). The incidence of postoperative CNS infection returned to a level comparable to that in general population when patients with suspected PA received prophylactic cephalosporins. CONCLUSIONS: PA is associated with higher risk of postoperative CNS infection in patients undergoing neurosurgery. This may be attributed to the use of alternative prophylactic antibiotics other than cephalosporins, especially clindamycin.
Subject(s)
Central Nervous System Infections , Drug Hypersensitivity , Hypersensitivity , Humans , Anti-Bacterial Agents/therapeutic use , Penicillins/adverse effects , Clindamycin/adverse effects , Retrospective Studies , Antibiotic Prophylaxis , Surgical Wound Infection/etiology , Cephalosporins , Hypersensitivity/etiology , Central Nervous System Infections/drug therapyABSTRACT
Infections of the central nervous system (CNS) are complex to treat and associated with significant morbidity and mortality. Historically, antistaphylococcal penicillins such as nafcillin were recommended for the treatment of methicillin-susceptible staphylococcal CNS infections. However, the use of antistaphylococcal penicillins presents challenges, such as frequent dosing administration and adverse events with protracted use. This narrative reviews available clinical and pharmacokinetic/pharmacodynamic (PK/PD) data for cefazolin in CNS infections and produces a recommendation for use. Based on the limited available evidence analyzed, dose optimized cefazolin is likely a safe and effective alternative to antistaphylococcal penicillins for a variety of CNS infections due to methicillin-susceptible Staphylococcus aureus. Given the site of infection and wide therapeutic index of cefazolin, practitioners may consider dosing cefazolin regimens of 2 g IV every 6 h or a continuous infusion of 8-10 g daily instead of 2 g IV every 8 h to optimize PK/PD properties.
Subject(s)
Bacteremia , Central Nervous System Infections , Staphylococcal Infections , Humans , Cefazolin/adverse effects , Anti-Bacterial Agents/adverse effects , Methicillin/pharmacology , Staphylococcal Infections/drug therapy , Penicillins/adverse effects , Central Nervous System Infections/chemically induced , Central Nervous System Infections/drug therapy , Bacteremia/drug therapyABSTRACT
BACKGROUND: Bacterial central nervous system (CNS) infection is challenging to treat and carries high risk of recurrence, morbidity, and mortality. Low CNS penetration of antibiotics may contribute to poor clinical outcomes from bacterial CNS infections. The current application of therapeutic drug monitoring (TDM) to management of bacterial CNS infection was reviewed. METHODS: Studies were included if they described adults treated for a suspected/confirmed bacterial CNS infection and had antibiotic drug concentration(s) determined that affected individual treatment. RESULTS: One-hundred-and-thirty-six citations were retrieved. Seventeen manuscripts were included describing management of 68 patients. TDM for vancomycin (58/68) and the beta-lactams (29/68) was most common. Timing of clinical sampling varied widely between studies and across different antibiotics. Methods for setting individual PK-PD targets, determining parameters and making treatment changes varied widely and were sometimes unclear. DISCUSSION: Despite increasing observational data showing low CNS penetration of various antibiotics, there are few clinical studies describing practical implementation of TDM in management of CNS infection. Lack of consensus around clinically relevant CSF PK-PD targets and protocols for dose-adjustment may contribute. Standardised investigation of TDM as a tool to improve treatment is required, especially as innovative drug concentration-sensing and PK-PD modelling technologies are emerging. Data generated at different centres offering TDM should be open access and aggregated to enrich understanding and optimize application.
Subject(s)
Central Nervous System Infections , Drug Monitoring , Adult , Humans , beta-Lactams/therapeutic use , Anti-Bacterial Agents/therapeutic use , Vancomycin/therapeutic use , Central Nervous System Infections/drug therapyABSTRACT
The development of targeted therapies has revolutionized the approach to immunosuppression in several medical specialties. While the prescriber of these therapies is familiar with these agents, both the general internist and the infectious disease specialist must deal with the consequences of these products. Encephalitis, for which prompt and appropriate management is paramount, is a challenge in the patient undergoing immunomodulatory therapies because of its atypical presentation, the involvement of particular germs and the potential brain toxicity of some immunomodulatory treatments. This article outlines the mechanisms of action of some targeted therapies and reviews the associated brain infections.
Le développement des thérapies ciblées a révolutionné l'approche de l'immunosuppression dans plusieurs spécialités médicales. Si le prescripteur de ces thérapies est familiarisé avec ces agents, l'interniste généraliste et l'infectiologue doivent tous deux faire face aux conséquences de ces produits. Les encéphalites, dont la prise en charge rapide et adéquate est primordiale, représentent un défi chez le patient soumis aux thérapies immunomodulatrices, en raison de leur présentation atypique, de l'implication de germes particuliers et de la toxicité cérébrale potentielle de certains traitements immunomodulateurs. Cet article expose les mécanismes d'action de certaines thérapies ciblées et passe en revue les infections de l'encéphale qui y sont associées.
Subject(s)
Central Nervous System Infections , Central Nervous System Infections/complications , Central Nervous System Infections/drug therapy , Humans , Immunosuppression TherapyABSTRACT
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.
Subject(s)
Central Nervous System Infections , Cerebral Ventriculitis , Phaeohyphomycosis , Amphotericin B , Antifungal Agents/therapeutic use , Ascomycota , Central Nervous System , Central Nervous System Infections/drug therapy , Cerebral Ventriculitis/drug therapy , Child , Female , Humans , Phaeohyphomycosis/diagnosis , Phaeohyphomycosis/drug therapy , Phaeohyphomycosis/microbiologyABSTRACT
Infection of the central nervous system (CNS) is a global healthcare concern with high rates of death and disease. CNS infections mainly include meningitis, encephalitis, and brain abscesses. Bacteria, viruses, fungi, protozoa, and parasites are the most common causes of neuroinfections. There are many types of medications used in the treatment of CNS infections, but drug delivery through the blood-brain barrier (BBB) is a major challenge to overcome. The BBB is a specialized multicellular barrier separating the neural tissue from the peripheral blood circulation. Unique characteristics of the BBB allow it to tightly control the movement of ions and molecules. Thus, there is a critical need to deal with these conditions with the aim of improving novel antimicrobial agents. Researchers are still struggling to find effective drugs to treat CNS infections. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem because NPs can be tailored to facilitate drug transport across the BBB. NPs are colloidal systems with a size range of 1-1000 nm, which can be used to encapsulate therapeutics, improve drug transport across the BBB, and target specific brain areas in CNS infections. A wide variety of NPs has been displayed for the CNS delivery of therapeutics, especially when their surfaces are coated with targeting moieties. This study aimed to review the available literature on the application of NPs in CNS infections.
Subject(s)
Anti-Infective Agents , Central Nervous System Infections , Communicable Diseases , Anti-Infective Agents/pharmacology , Blood-Brain Barrier , Brain , Central Nervous System Infections/drug therapy , Drug Delivery Systems , Humans , Pharmaceutical PreparationsABSTRACT
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.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Central Nervous System Infections , Cerebral Ventriculitis , Encephalitis , Klebsiella Infections , Amikacin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Central Nervous System Infections/drug therapy , Cerebral Ventriculitis/drug therapy , Encephalitis/drug therapy , Humans , Klebsiella Infections/drug therapy , Klebsiella pneumoniae , Male , Microbial Sensitivity Tests , Middle Aged , Tigecycline/therapeutic useABSTRACT
Listeria monocytogenes is a Gram-positive food-borne pathogen that causes gastrointestinal symptoms and CNS infection in susceptible hosts. Two lineages of Listeria cause the majority of neurolisteriosis in humans. In this report, we discuss a case of a 23-year-old previously healthy woman who presented with acute-onset rapidly progressive altered mental status after eating undercooked meats at a local restaurant. Given her age and lack of comorbidities, bacterial meningitis was suspected, and she was treated with ceftriaxone, vancomycin, and steroids. MRI of the brain was consistent with meningitis and ventriculitis; CSF analysis also suggested bacterial meningitis. Despite mechanical ventilation, pressors, and ventricular drain placement, she quickly decompensated and died 12 hours after arrival. CSF culture later returned positive for Listeria monocytogenes We used whole-genome sequencing and near-source comparison to identify the Listeria subtype that led to her unexpected presentation. The results suggest that her CSF isolate was consistent with a lineage II Listeria serotype, which is known to exhibit greater genetic variation than the more commonly isolated lineage I serotypes. We conclude the discussion with diagnostic and treatment approaches to neurolisteriosis. In susceptible hosts, namely immunocompromised, pregnant, neonatal, or elderly patients, Listeria infection may result in CNS invasion, causing meningoencephalitis and, rarely, ventriculitis and rhombencephalitis. Although neurolisteriosis most commonly affects individuals with known risk factors, CNS infection is nevertheless possible in otherwise healthy young patients. Suspicion should be raised in patients with an exposure history who do not improve with empiric antibiotics.
Subject(s)
Central Nervous System Infections , Cerebral Ventriculitis , Encephalitis , Gastritis , Listeria monocytogenes , Listeria , Meningitis, Listeria , Myelitis , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Central Nervous System Infections/drug therapy , Cerebral Ventriculitis/diagnosis , Encephalitis/drug therapy , Female , Humans , Infant, Newborn , Meningitis, Listeria/diagnosis , Myelitis/drug therapy , Pregnancy , Young AdultABSTRACT
Among central nervous system (CNS) infections (e.g., meningitis, brain abscess, ventriculitis, transverse myelitis), those caused by Staphylococcus aureus (SA) are particularly challenging both in management and treatment, with poor clinical outcomes and long hospital stay. It has been estimated that SA is responsible for around 1%-7% of meningitis (up to 19% in healthcare-associated meningitis). Recent neurosurgical procedures and immunocompromisation are major risk factors for SA CNS infections. Hand hygiene, surveillance nasal swabs and perioperative prophylaxis are crucial points for effective SA infections prevention. In case of SA-CNS infections, pending microbiological results, anti-methicillin-resistant SA (MRSA) antibiotic, with good CNS penetration, should be included, with prompt de-escalation as soon as MRSA is ruled out. Consultation with an expert in antimicrobial therapy is recommended as well as prompt source control when feasible. In this narrative review, we reviewed current literature to provide practical suggestions on diagnosis, prevention, management, and treatment of SA CNS infections.