Cephalosporins meningitis

Development of resistance to P -lactam antibiotics, including penicillins and cephalosporins, has significantly impacted the management of bacterial meningitis. Approximately 17% of United States pneumococcal CSF isolates are resistant to penicillin, and 3.5% of CSF isolates are resistant to cephalosporins.26 The Clinical and Laboratory Standards Institute (CLSI) has set a lower ceftriaxone susceptibility breakpoint for pneumococcal CSF isolates (1 mg/L) than for isolates from non-CNS sites (2 mg/L). Increasing pneumococcal resistance to penicillin G... 

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. 

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 may be used in place of penicillin G. Several third-generation cephalosporins (e.g., cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime) approved for the treatment of meningitis are acceptable alternatives to penicillin G (Table 36-5). Meropenem and fluoroquinolones are suitable alternatives for treatment ofpenidUin-nonsusceptible meningococci. 

Cephalexin, cefaclor, cefprozil, cefadroxil, ceftibuten, and loracarbef are well absorbed from the Gl tract. Cephalosporins are widely distributed to most tissues and fluids. First and second generation agents do not readily enter cerebrospinal fluid (CSF), except cefuroxime, even when meninges are inflamed. Third generation compounds readily diffuse into the CSF of patients with inflamed meninges. However, CSF levels of cefoperazone are relatively low. Most cephalosporins and metabolites are primarily excreted renally. 

Cefotaxime (Claforan) [Antibiotic/Cephalosporin-3rd Generation] Uses Rx Infxns of resp tract, skin, bone, urinary tract, meningitis, s is Action 3rd-gen cephalosporin X cell wall synth Dose Adults. 1-2 g IV... 

The cephalosporins distribute in satisfactory concentrations to most tissues except the central nervous system. Only cefepime, cefuroxime (Zinacef), cefotaxime (Claforan), ceftriaxone Rocephin), and ceftazidime (Eortaz) achieve therapeutic concentrations in cerebrospinal fluid. Cefotaxime and ceftriaxone are antibiotics of first choice for the empirical treatment of brain abscess and meningitis. 

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli. 

Chloramphenicol remains a major treatment of typhoid and paratyphoid fever in developing countries. However, with increasing resistance to ampicillin, trimethoprim-sulfamethoxazole and, to some extent, chloramphenicol, fluoroquinolones and some third-generation cephalosporins (e.g., ceftriaxone) have become the drugs of choice. Salmonella infections, such as osteomyelitis, meningitis and septicemia, have also been indications for chloramphenicol use. Nevertheless, antibiotic resistance patterns can be a problem. As noted previously, nonty-phoidal salmonella enteritis is not benefited by treatment with chloramphenicol or other antibiotics. 

The answer is e. (Hardman, pp 1094—1095.) Penicillins were used in the treatment of meningitis because of their ability to pass across an inflamed blood-brain barrier. The third-generation cephalosporin, ceftriaxone, is preferred because it is effective against P-lactamase producing strains of H. influenzae that may cause meningitis in children. 

Cephalosporins are important bactericidal broad spectrum (3-lactam antibiotics used for the treatment of septicaemia, pneumonia, meningitis, urinary tract infections, peritonitis and biliary tract infections. They are obtained from fungus Cephalosporium acremonium and are chemically related to penicillin. It consists of beta lactam ring fused to a dihydrothiazine ring. 

It is a broad spectrum cephalosporin having anti-pseudomonal activity. Used in serious infections of respiratory tract, ENT and soft tissue infection, septicaemia, meningitis, GI and biliary tract infections. 

It is a broad spectrum cephalosporin having a long half life and administered once daily and indicated in meningitis, septicaemia, typhoid, urinary tract infections, prophylaxis in surgical infections, pneumonia, STD, bacteremia and pelvic inflammatory disease. 

It is broad spectrum cephalosporin with anti-pseudomonal activity. It is more susceptible to (3-lactamases and is primarily excreted in bile. Used in severe susceptible infections of respiratory, urinary, GIT, skin and soft tissues, meningitis, septicaemia, gonorrhoea, bacteremia and peritonitis. 

Escherichia coli Meningitis 3rd-generation cephalosporin or meropenem -... 

Pasteurella multocida Abscesses bacteremia meningitis wound infections (animal bites] Penicillin G A cephalosporin doxycycline amoxicillin/ clavulanate trimethoprim-sulfamethoxazole... 

Neisseria meningitidis (meningococcus) Meningitis Penicillin G 3rd-generation cephalosporin... 

Because of potential toxicity, bacterial resistance, and the availability of other effective drugs (eg, cephalosporins), chloramphenicol is all but obsolete as a systemic drug. It may be considered for treatment of serious rickettsial infections, such as typhus or Rocky Mountain spotted fever, in children for whom tetracyclines are contraindicated, ie, those under 8 years of age. It is an alternative to a b-lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci. The dosage is 50-100 mg/kg/d in four divided doses. 

Distribution All of these antibiotics distribute very well into body fluids. However, adequate therapeutic levels in the cerebrospinal fluid (CSF), regardless of inflammation, are achieved only with the third generation cephalosporins (for example, ceftriaxone or cefotaxime are effective in the treatment of neonatal and childhood meningitis caused by Haemophilus influenzae). Cefazolin (se FA zo lin) finds application in orthopedic surgery because of its activity against penicillinase-producing Staphylococcus aureus, its half-life and its ability to penetrate bone. 

Uses. The decision to use chloramphenicol for systemic infection is influenced by its rare but serious toxic effects (see below). Its role in meningitis and brain abscess has largely been superseded by broad-spectrum cephalosporins such as cefotaxime and ceftriaxone, but it is a second-line agent for these indications, and for haemophilus epiglottitis in children. Chloramphenicol may be used for salmonella infections (t) hoid fever, salmonella septicaemia) but ciprofloxacin is now preferred. Topical administration is effective for bacterial conjunctivitis. 

---