COMBINATION ANTIMICROBIAL THERAPYAlthough international Paper

Published: 2021-08-31 09:45:13
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COMBINATION ANTIMICROBIAL THERAPY
Although international guidelines [131,132] suggest combination empirical therapy in the management of HA-MEN, there is no controlled clinical trial that proves the efficacy of the combination therapy over monotherapy. Another unknown issue is the cutoff for methicillin-resistant rate in which empirical vancomycin should be added.
Moreover, while vancomycin is the primarily recommended option in MRSA meningitis under IDSA guidelines [133,134] and adding rifampin is considered as an alternative, there are no controlled data regarding this issue except one animal model study .
Combination therapy as ampicillin + gentamicin or vancomycin + gentamicin is also the recommended regimen in the treatment of enterococcal meningitis while there is a lack of controlled data regarding this issue. [135]
For carbapenem-resistant Gram-negative meningitis in the case of tigecycline usage, a combination therapy with another available option may be rational, since tigecycline monotherapy may be associated with higher mortality. [136]
SPECIAL PROBLEMS WITH MULTIDRUG RESISTANT BACTERIA
The introduction of linezolid and daptomycin into our therapeutic armamentarium have increased the options to treat CNS infections by multi-resistant S. aureus and coagulase – negative staphylococci. Severe problems to find an adequate antibacterial,however, can arise in rare cases of meningitis & ventriculitis caused by vancomycin resistant enterococci .
Baumannii is a very rare cause of community acquired meningitis, but is an increasingly important pathogen in meningitis after neurosurgery. Multidrug resistant carbapenemase producing Acinetobacter spp. are resistant against all antibacterials routinely used to treat CNS infections. [137] Here, intravenous combined with intrathecal colistin has arisen as the ultimate treatment option.
Tigecycline, although also active against carbapenem resistant Acinetobacter spp. in vitro, is not recommended because the CSF concentrations after intravenous administration do not reliably exceed the MICs of most A. baumannii strains.
A variety of antibacterials have been used for intrathecal therapy (Table 5). [138] Because of the direction of CSF flow, intraventricular administration via external ventriculostomy or via a Rickham reservoir is more effective than injection into the lumbar CSF to reach adequate concentrations in all parts of the CSF compartment.
DURATION OF THERAPY
European Federation of Neurological Societies guidelines suggest 21-28 days of therapy in Gram negative bacillary or Pseudomonas meningitis. There is no recommendation for the treatment of staphylococcal or enterococcal meningitis in either guidelines as well as in IDSA guidelines related to S. aureus. 7 days is commonly recommended for Antimicrobial therapy before the placement of a new shunt. [139]
CORTICOSTEROIDS
Corticosteroids ar historically used as connected treatment in infectious disease to cut back the inflammatory response.
The proof for corticosteroids is heterogeneous and restricted to specific microorganism pathogens,but the organism is not usually known at the time of the initial presentation.
The best proof supports the utilization of Dexamethasone Intensol ten to twenty minutes before or concomitantly with antibiotic administration within the following groups: infants and youngsters with H.
influenzae type B, adults with S. pneumoniae, or patients with Mycobacterium tuberculosis without concomitant human immunodeficiency virus infection. [140]
Despite antibiotic medical aid, patients with infectious disease square measure in danger for semipermanent medicine complications.
There is some evidence that the use of anti-inflammatory agents such as corticosteroids may reduce brain injury.[141,142]
Corticosteroids decrease inflammation and the release of cytokines, including tumor necrosis factor-alpha. Dexamethasone is the most common corticosteroid used to prevent or minimize the neurologic complications of meningitis.
A 2015 Cochrane review found restricted proof from 2 trials that instructed reductions in death and deafness with use of adjuvant corticosteroids, and there was no advantage for
reducing neurologic sequelae.[143]
Currently, the IDSA guideline recommends that connected corticosteroids be utilized in infants and kids with Hib infections, with initiation 10 to 20 minutes prior to the first antibiotic.
Corticosteroids shouldn’t run to patients WHO have already received antimicrobial medical aid, owing to a lack of benefit.
Although the IDSA guideline does not provide recommendations for pneumococcal meningitis, the AAP suggests that dexamethasone be considered in patients aged 6 weeks and older after weighing the risks and benefits.
There is no proof supporting the routine use of connected corticosteroids in meningococcal infectious disease.
IMMUNOMODULATORY THERAPY
i.DEXAMETHASONE
Corticosteroids reduce the permeability of the blood-CSF and blood-brain barrier and thereby lower the CSF concentrations of hydrophilic antibiotics by approximately 30% (methylprednisolone, entamicin; dexamethasone, vancomycin), 40% (dexamethasone, ceftriaxone) & 50% (methylprednisolone, ampicillin). [144,145]
The CSF concentrations of rifampicin and the antibacterial activity of the combination ceftriaxone plus rifampicin were not diminished by adjunctive dexamethasone .Streptococcus group B and S. pneumoniae meningitis, dexamethasone as an adjunct to antibiotic treatment aggravated apoptotic neuronal injury in the hippocampal dentate gyrus. [146-148] A recent pediatric review concluded that in high-income countries dexamethasone has shown good results to prevent hearing loss in H. influenzae meningitis if administered before or at the same time as the first dose of antibiotics. Both in children and adults, there is no evidence to recommend the use of corticosteroids in meningococcal meningitis. [149-150]
Since dexamethasone therapy must start, when the causative pathogen has not been determined yet, several authors recommend to stop dexamethasone, once Neisseria meningitidis was isolated. Fortunately, there is no evidence of a detrimental effect of adjuvant dexamethasone in meningococcal meningitis. [151] Corticosteroids are not effective for community-acquired meningitis in low-income countries.
ii.TOLL-LIKE RECEPTOR ANTAGONISTS
Toll-like receptors (TLR) belong to the pathogen-recognition receptors. TLR2 recognizing lipoteichoic acids, TLR4 detecting endotoxin and pneumolysin and TLR9 sensing unmethylated cytosine-guanosine epitopes of bacterial DNA play an established role in the pathophysiology of bacterial meningitis. [152]
TLR do not only recognize pathogen structures, but also host proteins related to tissue injury, for example, oxidized host phospholipids , or increased permeability of the Blood-CSF and blood-brain barrier, for example, the blood derived protein fibrinogen . Eritoran has recently been shown to prevent lung injury, decrease clinical symptoms, cytokine and oxidized phospholipid expression, and viral titers and increase survival in a murine model of influenza. [153]

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