Culture-negative Bacterial Meningitis Research Articles

446: DISSEMINATED STRONGYLOIODES INFECTION AFTER CORTICOSTEROID USE

Introduction: While there are endemic foci of Strongyloides in the southeastern United States, strongyloidiasis in the US is most commonly found in immigrants and military veterans who have lived in endemic regions. We report a case of reactivated disseminated strongyloidiasis in a critically ill COVID-19 patient. Description: A 46 year old undomiciled man with a medical history of hypertension was found down by a friend and brought to the hospital for evaluation of altered mental status. The patient immigrated from Mexico in 1991 and lived in Florida for several years working as a gardener. On presentation he complained of headaches, with tremors and tongue fasciculations noted on physical exam. He underwent treatment for alcohol withdrawal. His hospital course was complicated by COVID-19 pneumonia requiring intubation, and a subarachnoid hemorrhage that did not require acute neurosurgical intervention. Several days after completion of remdesivir and dexamethasone treatment for COVID-19, the patient’s absolute eosinophil count increased from 20/uL on admission to 340/uL with a peak at 1500/uL. The patient was found to have Strongyloides and ESBL Klebsiella in a bronchoalveolar lavage after a bedside bronchoscopy. Ivermectin 200ug/kg/day and meropenem 2g every 8 hours were started. The patient remained persistently comatose despite being off sedation and a relatively benign brain MRI that demonstrated resolving subarachnoid hemorrhages. Strongyloides were confirmed in the CSF nine days after initial discovery in the BAL. Albendazole 400mg BID was added to the regimen and meropenem was continued for possible culture negative bacterial meningitis in the setting of disseminated strongyloidiasis. HIV and HTLV-1 serology was negative. The patient remained in the ICU with poor neurological status and ongoing goals of care discussions with the family. Discussion: Strongyloides hyperinfection is an uncommon complication with a high mortality rate, with meningeal involvement often described post-mortem. Prophylactic anti-parasitic agents can be considered for patients identified as high risk for chronic strongyloidiasis who are about to undergo corticosteroid treatments, including COVID-19 associated regimens.

An autopsy case of Nocardia meningitis patient presenting with multiple folliculitis

Abstract Rationale: Nocardia is widespread in the soil and causes life-threatening infections in the central nervous system, such as meningitis. Nocardia infection can develop in immunocompetent individuals, not just in immunocompromised persons. Nocardia is a slow-growing bacterium, which makes its detection difficult during routine microbial examinations, resulting in a delayed diagnosis and poor prognosis. Patient concerns: A 64-year-old Japanese man was admitted with fever, headache with meningeal irritation, and multiple folliculitis on his face and neck. Cerebrospinal fluid revealed neutrophilic pleocytosis. All cultures, including cerebrospinal fluid examination, were negative, and serum procalcitonin levels were normal. Diagnoses: The tentative diagnosis was culture-negative bacterial meningitis or meningeal neuro-Behçet disease. Intervention: Meropenem was administered for 12 days, along with corticosteroids. His symptoms were temporarily relieved but worsened again, and finally, he died suddenly on the 37th day of hospitalization. An autopsy revealed extensive infiltration of inflammatory cells in the subarachnoid space, especially the brain stem, cerebellum, whole spinal cord, and cerebral base, where Nocardia species were detected. The final diagnosis was Nocardia meningitis. Lessons: Given the very close timing of the onset of signs of meningitis and multiple folliculitis, the most reasonable and probable idea is that the patient had disseminated nocardiosis. In patients with meningitis with multiple skin infection lesions, such as folliculitis, nocardiosis should be considered a differential diagnosis.

Evaluation of FilmArray ME panel for the rapid diagnosis of meningitis-encephalitis in emergency departments.

To assess the impact of a rapid diagnostic system based on nucleic acid amplification techniques (FilmArray ME) on the diagnosis and treatment of patients with meningitis or encephalitis admitted to our emergency department. Between November 2016, and June 2019 we studied 79 samples of cerebrospinal fluid from patients admitted to our emergency department with suspected diagnoses of meningitis or encephalitis. FilmArray ME panel was used routinely in addition to conventional laboratory methods for the identification of microorganisms in cerebrospinal fluid samples (CSF). A total of 46 (58%) patients had clinical and CSF results suggestive of meningitis or encephalitis, and 24 (30%) had a confirmed microbiological diagnosis. Patients' mean age was 41years (range 2months to 90years) and 56% were male. Four patients had been partially treated with antibiotics. FilmArray ME identified 23 cases (1 fungal, 11 bacterial, and 11 viral). Gram staining showed microorganisms in 5 cases (1 fungal, 4 bacterial), and conventional microbiology cultures identified 8 cases (1 fungal and 7 bacterial). The time difference (95% confidence interval) between FilmArray ME and cerebrospinal fluid culture results was 3.2days (95% CI 2.7-3.7; P < 0.001). FilmArray ME results induced modifications in antimicrobial treatment in 27 (59%) patients. The FilmArray ME panel provided a fast and reliable result in a large proportion of patients, even in those patients with culture-negative bacterial meningitis. Use of FilmArray ME can contribute to antimicrobial stewardship.

Clinically based surveillance of invasive meningococcal disease in young children admitted to selected US hospitals between January 2000 and June 2009

Invasive meningococcal disease (IMD) is under-reported in countries that do not employ polymerase-chain reaction for surveillance because culture-negative cases are omitted. To evaluate a clinically based, case-finding method, we developed case definitions for “probable,” “compatible with,” and “possible, but unlikely” IMD, respectively, based on supportive documentation (e.g., discharge diagnosis of meningococcal infection, culture-negative bacterial meningitis, petechiae/purpura, Gram-negative diplococci on Gram stain) and weight of clinical evidence, which we then applied to electronic health records for all children aged ≤5 y who were admitted to approximately 100 US hospitals between January 2000 and June 2009. Among 47,863 qualifying admissions, 16 children had culture-positive IMD, 5 had “probable” IMD, and 5 had illness “compatible with” IMD. Five additional children had disease considered “possible but unlikely” IMD. Our case-finding methods suggest that culture-based ascertainment may underestimate the number of IMD cases by 31–63%, supporting findings in other nations that culture-based reporting provides incomplete information on disease incidence and therefore underestimates the potential benefits of routine vaccination of young children against meningococcal disease.

Ribosomal DNA Assay of Culture-Negative Streptococcus pneumoniae Meningitis

Culture-negative bacterial meningitis with secondary complications remains a significant challenge. Optimal treatment requires identification of the infecting organism. While the gold standard for diagnosis remains cerebrospinal fluid culturing, a significant number of cultures remain negative despite clinical evidence of meningitis. This patient illustrates the usefulness of polymerase chain reaction technology in identifying a specific organism, in an otherwise culture-negative bacterial meningitis with spinal cord abscess.

Diagnosis of partially treated culture-negative bacterial meningitis using 16S rRNA universal primers and restriction endonuclease digestion

Cerebrospinal fluid (CSF) obtained from patients with partially treated and culture-negative meningitis was subjected to PCR using 16S rDNA universal primers followed by restriction endonuclease digestion. In all, 43 patients and 7 controls were enrolled in this study. Twenty-one meningitic samples were positive by PCR. Mycobacterium tuberculosis was the causative agent in seven cases followed by Haemophilus influenzae (four), Streptococcus pneumoniae (two), Listeria monocytogenes (one), Escherichia coli (one), Pseudomonas aeruginosa (one) and Staphylococcus aureus (one). Only two meningitic CSF samples were culture-positive. In this study, PCR using bacterial 16S rDNA specific universal primers was found to be superior to conventional methods in the diagnosis of partially treated meningitis.

Diagnostic value of cytokine assays in cerebrospinal fluid in culture-negative, polymerase chain reaction-positive bacterial meningitis.

Analysis of bacterial DNA using a polymerase chain reaction performed with broad-range eubacterial 16S rDNA primers may yield a diagnosis of bacterial meningitis in cases where Gram staining of cerebrospinal fluid (CFS), antigen detection techniques or culture fail. Since this PCR technique occasionally gives false-positive results due to contamination of samples or laboratory reagents, a study was performed to establish the diagnostic value of assaying concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 90 CSF samples. A high correlation was found between a positive PCR result and the concentrations of TNF-alpha and IL-10, indicating that cytokine assays may be used as a confirmatory test. The findings suggested that a combination of the PCR technique, amplicon sequencing and assay of TNF-alpha and IL-10 concentrations in CSF is a reliable and cost-effective procedure for diagnosis of culture-negative bacterial meningitis.

Polymerase chain reaction, with sequencing, as a diagnostic tool in culture-negative bacterial meningitis

OBJECTIVE: To evaluate the feasibility of using 16S rDNA universal primer PCR (followed by sequencing) and 65-kDa heat shock Mycobacterium tuberculosis protein gene PCR as a method to determine a bacterial etiology in culture---negative cerebrospinal fluid (CSF) samples. METHODS: One hundred and forty-nine CSF samples from 128 patients were processed. DNA was extracted from the CSF samples and amplified with the eubacterial 16S rDNA primers P11E and P13B, and with the 65-kDa heat shock protein gene mycobacterial primers. The amplicons were identified by sequencing and specific oligoprobe hybridization. RESULTS: Overall, a microbiological diagnosis was made in 11 of 125 ultimately culture-negative cases. The use of 65-kDa heat shock protein gene PCR was needed to improve the diagnosis of tuberculous meningitis; in four patients, prospectively studied, the outcome of antituberculous therapy could also be followed. CONCLUSIONS: In culture-negative bacterial meningitis it is possible to improve the microbiological diagnosis by use of 16S rDNA amplification and sequencing, together with amplification of a more specific gene in mycobacteria.