The penetration of antibiotics into cerebrospinal fluid and brain tissue

Barling, R. W. A.; Selkont, J. B.

doi:10.1093/jac/4.3.203

Cited by 105 publications

(45 citation statements)

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“…TMP-SMZ has been used with success in many infections due to intracellular pathogens, including Pneumocystis carinii, Chlamydia trachomatis, Salmonella typhi, Nocardia asteroides, Brucella sp., Pseudomonas pseudomallei, Mycobacterium marinum, and Plasmodium falciparum (35). Both TMP and SMZ penetrate well into the central nervous system (2,23,29,33). This combination shows promise in the therapy of meningitis due to a variety of pathogens (8,10,13,25), and at least two patients with meningitis due to L. monocytogenes have been treated successfully with TMP-SMZ (16,18).…”

Section: Discussionmentioning

confidence: 99%

In vitro activities of trimethoprim and sulfamethoxazole against Listeria monocytogenes

Winslow¹,

Ga²

1982

Antimicrob Agents Chemother

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The in vitro activities of trimethoprim and sulfamethoxazole against clinical isolates of Listeria monocytogenes were examined separately and in combination with a microtiter broth dilution system. Sulfamethoxazole demonstrated variable activity and was generally bacteriostatic. Trimethoprim alone was bactericidal against 96% of isolates at c0.5 jig/ml. The bactericidal action of trimethoprim against L. monocytogenes was generally potentiated by sulfamethoxazole even when isolates were relatively resistant to sulfamethoxazole alone.

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Section: Discussionmentioning

confidence: 99%

In vitro activities of trimethoprim and sulfamethoxazole against Listeria monocytogenes

Winslow¹,

Ga²

1982

Antimicrob Agents Chemother

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“…In particular, CSF penetration of rifampicin, the key drug in TBM treatment, is poor, as is that of ethambutol and streptomycin [75][76][77]. Isoniazid and pyrazinamide penetrate more readily [78,79]. Sufficient activity of rifampicin is key to successful treatment, demonstrated by the fact that rifampicin resistance is associated with 100% mortality [72].…”

Section: Specific Antituberculous Treatmentmentioning

confidence: 99%

Tuberculous Meningitis in Adults: A Review of a Decade of Developments Focusing on Prognostic Factors for Outcome

2012

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Tuberculous meningitis (TBM) is the most severe form of TB. Despite treatment, mortality and long-term disability remain unacceptably high. Prevention, early recognition, diagnosis and treatment are fundamental to improving outcomes. However, an effective vaccine remains elusive, initial symptoms are nonspecific, and sensitive diagnostic tests are not available. There has been progress in our understanding of the immunopathology of TBM, and several factors have been found to be associated with susceptibility to infection, disease progression and clinical outcome. However, these have not yet impacted on treatment. Early treatment initiation and uninterrupted continuation, severity on presentation, seizures, stroke, cranial nerve involvement, cerebrospinal fluid cell count and lactate levels, hyponatreamia and coinfection with HIV are all found to be important prognostic factors for outcome. Pathogen lineage (Beijing genotype) and host genetics (polymorphisms in TLR2, TIRAP and LTA4H genes) can influence susceptibility to TBM. However, these findings have not yet impacted on treatment. Progress in vaccine development, opportunities for better diagnostic tests, novel insights into pathogenesis and an increasing evidence base for improving treatment should impact the current high mortality and morbidity, if translated to global and local guidelines.

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“…Standard and newer antibacterial agents used for meningitis and ventriculitis therapy were studied. The drug concentrations were chosen such as to represent peak values attained in ventricular CSF during intravenous therapy (19)(20)(21)(22), and their 5 and 10 times multiples that correspond to the concentration range reached by intraventricular antibiotic administration (23)(24)(25).…”

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confidence: 99%

Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

et al. 1988

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ABSTRACT. The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity ( p < 0.001 or < 0.01) and to a lesser extent ( p < 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections. (Pediatr Res 24: 367-372,1988) Abbreviations BCC, brain cell culture CSF, cerebrospinal fluid DIC, days in culture CST, cerebral sulfate transferase reviews of case reports (1, 2). CNS toxicity is a well-described complication of intraventricular antibiotic therapy for gramnegative bacillary ventriculitis and CSF shunt infections (l,2,4-7). Animal toxicity tests bear a relatively poor predictive value for neurotoxicity in man and require the use of a high number of animals (4,5,(8)(9)(10). Therefore, back-shifting of neurotoxicity tests from the human or animal situation to a relatively simple and reproducible system in vitro was the principal aim of the present research.There are many reports presenting evidence of dose-dependent antiproliferative effects of various antibiotics on cultured eucaryotic cells. The cell types studied include human fibroblasts (1 1), bone marrow cells (12), and dissociated brain cells (1 3). As in vitro correlative of dose-related marrow suppression by chloramphenicol it was found several decades ago that this drug inhibits mitochondria1 protein synthesis not only in bacteria but also in proliferating bone marrow cells (14, 15). More recently, the inhibition of cell proliferation has most often been studied for the @-lactam antibiotics on cultured human myeloid percursor and lymphoid cells, the clinical consequences being neutropenia and impairment of cellular and humoral immune responses induced by 6-lactams (12, 16-1 8).The purpose of our investigation was to monitor the effects of antibiotics on growth and differentiation in dissociated rat BCC which might help to pred...

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The penetration of antibiotics into cerebrospinal fluid and brain tissue

Cited by 105 publications

References 0 publications

In vitro activities of trimethoprim and sulfamethoxazole against Listeria monocytogenes

In vitro activities of trimethoprim and sulfamethoxazole against Listeria monocytogenes

Tuberculous Meningitis in Adults: A Review of a Decade of Developments Focusing on Prognostic Factors for Outcome

Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

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