The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 ,g/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.

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The application of stringent inclusion criteria and the use of the PCR yielded a population of infants that better represents the noninfected neonate than earlier reports. These values can be used for reference in evaluating the febrile or ill neonate.

We describe a seven-year-old female with acute pericarditis presenting with pericardial tamponade, who screened positive for coronavirus disease 2019 (COVID-19 [SARS-CoV-2]) in the setting of cough, chest pain, and orthopnea. She required emergent pericardiocentesis. Due to continued chest pain and orthopnea, rising inflammatory markers, and worsening pericardial inflammation, she underwent surgical pericardial decortication and pericardiectomy. Her symptoms and pericardial effusion resolved, and she was discharged to home 3 days later on ibuprofen and colchicine with instruction to quarantine at home for 14 days from the date of her positive testing for COVID-19.

In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.

To assess the effects of antifungal therapy on the course of Candida albicans central nervous system infection and inflammation, we inoculated intracisternally 105 CFU of C. albicans into rabbits. Fluconazole (10 mg/kg of body weight) or amphotericin B (1 mg/kg) was infused intravenous daily for 14 days. Treatment was initiated 24 h or 5 days after infection. Cerebrospinal fluid (CSF) was repeatedly obtained to culture the organisms, assess the level of inflammation, and measure drug concentrations. Brain tissue was obtained at the end of therapy for culture, drug concentration determinations, and histopathology. The median number of days of treatment required to sterilize CSF cultures was 4 days for fluconazole therapy and 1 day for amphotericin B therapy (P = 0.037). There was a significant reduction in tumor necrosis factor alpha and leukocyte concentrations in the CSF of animals treated early versus those in untreated control animals (P < 0.05 and P < 0.001, respectively; analysis of variance). Compared with treated animals, a higher proportion of cultured CSF samples from untreated animals were positive for Candida (P < 0.001). A cultured brain sample from 1 of the 12 animals treated early with amphotericin B was positive for C. albicans (P < 0.01 versus controls); cultures of brain samples from 3 of 12 animals treated early with fluconazole were positive, whereas cultures of brain samples from 10 of 12 controls were positive (P < 0.05). The mean density of C. albicans was lower in the single culture-positive amphotericin B recipient (1 x 101 CFU/g of brain tissue) than in those treated with fluconazole (1 x 103 CFU/g) and in controls (8 x 104 CFU/g). In animals treated late, the density of C. albicans in the brain in relation to the number of days of therapy was significantly lower in amphotericin B recipients than in those treated with fluconazole (P < 0.01) and untreated controls (P < 0.01; analysis of covariance). By histopathology, a larger proportion of untreated animals compared with those treated early demonstrated features of severe infection such as perivasculitis, ventriculitis, and evidence of fungal organisms. Compared with amphotericin B-treated rabbits, those given fluconazole had a trend toward more severe pathologic lesions. Reduced susceptibility to both fluconazole and amphotericin B was observed in the C. albicans organisms isolated from the brain of one fluconazole-treated animal. These data suggest that amphotericin B is the preferred treatment for C. albicans infections of the central nervous system.

The role of cytokines in the regulation of articular inflammation and cartilage degradation was evaluated in the rabbit model of Haemophilus influenzae type b arthritis. At 6 and 12 h after intraarticular infection, treatment with IB4 monoclonal antibody to the CD18 leukocyte receptor alone or in combination with dexamethasone resulted in significant reduction of synovial fluid (SF) neutrophil concentration. Treatment with dexamethasone alone was associated with lower SF concentrations of interleukin-1 (IL-1), tumor necrosis factor-alpha, and stromelysin than in other groups. At 24 h after infection, increased cartilage degradation was detected in untreated controls and in animals treated with IB4 alone or in combination with dexamethasone compared with those treated with dexamethasone alone. Multiple regression analyses indicated SF concentration of IL-1 and stromelysin as the significant predictors of cartilage degradation. These data suggest that IL-1 mediates cartilage degradation by regulation of metalloproteinases, such as stromelysin, during acute experimental bacterial arthritis.

Intracisternal or intraarticular inoculation of rabbit recombinant interleukin (IL)-1 beta and rabbit tumor necrosis factor-alpha combined with IL-1 receptor antagonist (IL-1RA) and soluble tumor necrosis factor receptor (sTNFR), respectively, produced significantly less inflammation in rabbits than after inoculation of these cytokines alone. In contrast, when Haemophilus influenzae type b (Hib) or Hib lipooligosaccharide (LOS) was given intraarticularly with IL-1RA, sTNFR, or the combination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation. In the experimental meningitis model, IL-1RA and sTNFR did not significantly reduce the meningeal inflammatory response associated with intracisternal inoculation of Hib LOS. These data indicate that specific cytokine inhibitors (sTNFR and IL-1RA) may not be effective in modulating inflammation induced by a broad inflammatory stimulus such as gram-negative bacteria or their products and suggest caution in using them to treat these infectious conditions in humans.