Meningitis vancomycin

High-dose penicillin G traditionally has been the drug of choice for the treatment of pneumococcal meningitis. However, due to increases in pneumococcal resistance, the preferred empirical treatment now includes a third-generation cephalosporin in combination with vancomycin.13 All CSF isolates should be tested for penicillin and cephalosporin resistance by methods endorsed by the CLSI. Once in vitro sensitivity results are known, therapy may be tailored (Table 67-3). Patients with a history of type I penicillin allergy or cephalosporin allergy may be treated with vancomycin. Treatment should be continued for 10 to 14 days, after which no further maintenance therapy is required. Antimicrobial prophylaxis is not indicated for close contacts. 

Empirical therapy for postoperative infections in neurosurgical patients (including patients with CSF shunts) should include vancomycin in combination with either cefepime, ceftazidime, or meropenem. Linezolid has been reported to reach adequate CSF concentrations and resolve cases of meningitis refractory to vancomycin.35 However, data with linezolid are limited. The addition of rifampin should be considered for treatment of shunt infections. When culture and sensitivity data are available, pathogen-directed antibiotic therapy should be administered. Removal of infected devices is desirable aggressive antibiotic therapy (including high-dose intravenous antibiotic therapy plus intraventricular vancomycin and/or tobramycin) may be effective for patients in whom hardware removal is not possible.36... 

There is concern regarding administration of dexamethasone to patients with pneumococcal meningitis caused by penicillin- or cephalosporin-resistant strains, for which vancomycin would be required. Animal models indicate that concurrent steroid use reduces vancomycin penetration into the CSF by 42% to 77% and delays CSF sterilization due to reduction in the inflammatory response.23 Treatment failures have been reported in adults with resistant pneumococcal meningitis who were treated with dexamethasone, but the risk-benefit of using dexamethasone in these patients cannot be defined at this time. Animal models indicate a benefit of adding rifampin in patients with resistant pneumococcal meningitis whenever dexamethasone is used.21,23... 

Chloramphenicol, isolated in 1947, is a broad spectiarm antibiotic. It is rapidly absorbed from the gastrointestinal tract and hence can be given orally in case of typhoid, dysentery, acute fever, certain form of urinary infections, meningitis and pneumonia. Vancomycin and ofloxacin are the other important broad spectr-um antibiotics. The antibiotic dysidazirine is supposed to be toxic towards certain strains of cancer cells. 

After IV administration, vancomycin diffuses into serous cavities and across inflamed but not normal meninges. It can be used in the treatment of meningitis with susceptible organisms. It is also given via ventriculoatrial or ventriculoperitoneal shunts when these become infected. 

A clinical diagnosis of bacterial meningitis was made. Therapy was started immediately because of the life-threatening nature of the illness. He was empirically treated with ceftriaxone and vancomycin, intravenously. A short time later, a Gram stain of his CSF revealed that the bacteria were Gram-positive cocci. Accordingly, the empiric... 

Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of antibiotic-associated enterocolitis caused by C difficile. Parenteral doses must be administered intravenously. A 1-hour intravenous infusion of 1 g produces blood levels of 15-30 mcg/mL for 1-2 hours. The drug is widely distributed in the body. Cerebrospinal fluid levels 7-30% of simultaneous serum concentrations are achieved if there is meningeal... 

Rifampin is used in a variety of other clinical situations. An oral dosage of 600 mg twice daily for 2 days can eliminate meningococcal carriage. Rifampin, 20 mg/kg/d for 4 days, is used as prophylaxis in contacts of children with Haemophilus influenzae type b disease. Rifampin combined with a second agent is used to eradicate staphylococcal carriage. Rifampin combination therapy is also indicated for treatment of serious staphylococcal infections such as osteomyelitis and prosthetic valve endocarditis. Rifampin has been recommended also for use in combination with ceftriaxone or vancomycin in treatment of meningitis caused by highly penicillin-resistant strains of pneumococci. 

Pharmacokinetics Slow intravenous infusion is employed for treatment of systemic infections or for prophylaxis. Because vancomycin is not absorbed after oral administration, this route is only employed for the treatment of antibiotic-induced colitis due to Q difficile. Inflammation allows penetration into the meninges. Metabolism is minimal 90-100 % is excreted by glomerular filtration. [Note Dosage must be adjusted in renal failure since the drug will accumulate. Normal half-life is 6-10 hours compared to over 200 hours in end-stage renal disease.]... 

Daptomycin has proven efficacy in a number of in vivo animal models, including soft tissue infections by MRSA, bacteraemia caused by S. aureus or vancomycin-resistant enterococci (VRE), Enterococcus faecalis pyelonephritis, MRSA osteomyelitis, MRSA and Bacillus anthracis pulmonary infections, Gram-positive endocarditis, Clostridium difficile colitis and S. pneumoniae and S. aureus meningitis.9,64 66... 

It acts by inhibiting RNA synthesis, bacteria being sensitive to this effect at much lower concentrations than mammalian cells it is particularly effective against mycobacteria that lie semidormant within cells. Rifampicin has a wide range of antimicrobial activity. Other uses include leprosy, severe Legionnaires disease (with erythromycin or ciprofloxacin), the chemoprophylaxis of meningococcal meningitis, and severe staphylococcal infection (with flucloxacillin or vancomycin). 

When selecting antibiotics, the clinician must consider the antibiotic concentration at the site of infection, as well as the spectrum of antibacterial activity. Empirical choices should be based on age and predisposing conditions, (a) Ceftriaxone or cefotaxime and vancomycin are reasonable initial choices for empirical coverage of community-acquired meningitis in adult patients, (b) Listeria monocytogenes... 

Ceftriaxone and vancomycin are the agents of choice to treat presumed pneumococcal meningitis empirically until the susceptibility is known. Penicillin may be used for drug-susceptible isolates with MICs of 0.06 mg/L or less, but for intermediate isolates, ceftriaxone is used, and for highly drug resistant isolates, a combination of ceftriaxone and vancomycin should be used. Vancomycin should not be used as monotherapy. In especially severe cases, therapeutic drug monitoring of the CSF and possibly even direct antibiotic instillation may be necessary. 

B. anthracis typically is susceptible to penicillin, amoxicillin, erythromycin, doxycycline, ciprofloxacin, and chloramphenicol. The bioterrorism-related strain was susceptible to the fluoroquinolones, rifampin, tetracycline, vancomycin, imipenem, meropenem, chloramphenicol, clindamycin, and the aminoglycosides. However, the strain was resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole. Ciprofloxacin or doxycycline plus one or two of the aforementioned antibiotics is the currently recommended regimen for the treatment of inhalational anthrax, but doxycycline is not recommended for the treatment of anthrax meningitis owing to poor CNS penetration and recent in vitro resistance. ... 

Routine use of dexamethasone in meningitis is not without controversy. A potential concern is that adjunctive dexamethasone therapy might reduce the penetration of antibiotics into the CSF by inhibiting meningeal inflammation. In experimental models of meningitis, steroids decreased the CSF concentrations of ampiciUin, rifampin, vancomycin, and gentamicin. Ceftriaxone penetration into CSF was unaffected by concurrent dexamethasone administration in pediatric patients. ... 

Williamson JC, Glazier SS, Peacock JE. Successful treatment of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus with intravenous and intraventricular quinupristin/ dalfopristin. CUn Neurol Neurosurg 2002 104 54-56. 

Pathogens from the Staphylococcus genus are found in both the hospital and the community, and the most prevalent species, aureus,. causes illnesses that range from minor skin abscesses to severe pneumonia, meningitis, and infections of the heart, bloodstream, bone, and joint. Multiple strains of S. aureus are now antibiotic resistant, including a few strains that are partially resistant to vancomycin (18), the last effective antibiotic against... 

Penicillin G IV (12 million units/day for adults) ceftriaxone or cefotaxime Meningitis vancomycin + ceftriaxone or cefotaxime rifampin Other infections vancomycin + ceftriaxone or cefotaxime or levofloxacin, gatifloxacin, or moxifloxacin... 

For parenteral therapy of sensitive isolates, penicillin G or penicillin G procaine is favored. Therapy should be continued for 7—10 days, including 3—5 days after the patient is afebrile. Similarly, pneumococcal meningitis initially should be treated with a combination of vancomycin and a third-generation cephalosporin until it is established that the infecting pneumococcus is penicillin-sensitive. Recommended therapy is 20—24 million units of penicillin G daily by constant intravenous infusion or divided into boluses given every 2—3 hours for 14 days. 

ABSORPTION, DISTRIBUTION, AND EXCRETION Vancomycin is poorly absorbed after oral administration. For parenteral therapy, the drug should be administered intravenously. The drug has a serum elimination t, of 6 hours. Approximately 30% of vancomycin is bound to plasma protein. Vancomycin appears in various body fluids, including the CSF when the meninges are inflamed, bile, and pleural, pericardial, synovial, and ascitic fluids. About 90% of an injected dose is excreted by glomerular filtration. 

THERAPEUTIC USES Vancomycin (vancocin, others) is marketed for intravenous use as a sterile powder. It should be diluted and infused over at least 60 minutes to avoid infusion-related adverse reactions. The usual dose of vancomycin for adults is 30 mg/kg/day in 2-3 divided doses. A trough serum concentration of 5-15 (Xg/mL (10-20 (Xg/mL for serious infections such as endocarditis or meningitis) is recommended. Doses above 30 mg/kg/day may be required to achieve these trough concentrations, and up to 60 mg/kg/day has been suggested for meningitis. The peak concentration is not monitored routinely but should generally remain below 60 (Xg/mL to avoid ototoxicity. 

Rifampin also is indicated for the prophylaxis of meningococcal disease and Haemophilus influenzae meningitis. To prevent meningococcal disease, adults may be treated with 600 mg twice daily for 2 days or 600 mg once daily for 4 days children should receive 10-15 mg/kg, to a maximum cf600 mg. Combined with a f-lactam antibiotic or vancomycin, rifampin is used in selected cases of staphylococcal endocarditis or osteomyelitis. Rifampin may be used to eradicate nasal staphylococci in patients with chronic furunculosis. 

Pneumococcal isolates with a minimal inhibitory concentration for penicillin G of greater than 2 pg/mL are highly resistant. Such strains are not killed by the concentrations of penicillin G or ampicillin that can be achieved in the cerebrospinal fluid. Nafcillin would be of value in a purulent meningitis suspected to be due to staphylococci but has minimal activity against penicillin-resistant pneumococci. Cefotaxime and ceftriaxone (not listed) are the most active cephalosporins against penicillin-resistant pneumococci, and the addition of vancomycin or rifampin is recommended in the case of highly resistant strains. As mentioned above, cefopera-zone does not readily cross the blood-brain barrier. The answer is (C). 

The third-generation cephalosporins cefotaxime and ceftriaxone are effective in the empiric treatment of bacterial meningitis caused by most strains of meningococci, pneumococci, and H influenzae. However, the prevalence of drug-resistant S pneumoniae ctin influence empiric therapy and may necessitate the addition of vancomycin. Note that some isolates of H influenzae are now resistant to both ampicillin and chloramphenicol. 

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