Penicillin meningitis

The natural and semi ynthetic penicillins are used in tire treatment of bacterial infections due to susceptible microorganisms. Fbnicillins may be used to treat infections such as urinary tract infections, septicemia, meningitis, intra-abdominal infection, gonorrhea, syphilis, pneumonia, and other respiratory infections. Examples of infectious microorganisms (bacteria) that may respond to penicillin therapy include gonococci, staphylococci,... 

Penicillin is the dmg of choice for the treatment of group B streptococcal, meningococcal and pneumococcal infections but, as discussed earlier, CSF concentrations of penicillin are significantly influenced by the intensity of the inflammatoiy response. To achieve therapeutic concentrations within the CSF, high dosages are required, and in the case of pneumococcal meningitis should be continued for 10-14 days. 

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... 

Aggressive, early intervention with high-dose IV crystalline penicillin G, 50,000 units/kg every 4 hours, is usually recommended for treatment of N. meningitidis meningitis. 

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. 

Do not treat severe pneumonia, empyema, bacteremia, pericarditis, meningitis, or purulent or septic arthritis with an oral penicillin during the acute stage. 

In most cases one week of i.v. penicillin is adequate for meningococal meningitis. Ten to 14 days is recommended for pneumococcal meningitis. Two to 3 weeks for Listeria and group B streptococcal meningitis and 3 weeks is necessary for gramnegative meningitis. 

When prescribing one of the penicillin G depot formulations, practitioners must individualize treatment to clinical and microbial conditions. Some long-acting formulations may not maintain adequate plasma and tissue concentrations to treat specific organisms or infections. For acute streptococcal meningitis, the goal is rapid... 

Mezlocillin, piperacillin, and ticarcillin are parenteral antibiotics formulated as sodium salts, so prescribers must consider the sodium content of these antibiotics when administering them to patients with congestive heart failure. During their distribution phase, antipseudomonal penicillins achieve orfly low concentrations in the cerebrospinal fluid. Consequently, antipseudomonal penicillins are not among the drugs of first choice for meningitis therapy. 

Mild, moderate, or severe prostate, urinary tract, and CNS infections (excluding meningitis)-, uncomplicated gonorrhea inflammatory acne Brucellosis skin granulomas cholera trachoma nocardiasis yaws and syphilis when penicillins are contraindicated PO... 

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. 

Among the semisynthetic derivatives, cephalothin (9.47) is the most widely used since it is a broad-spectrum antibiotic resistant to lactamase. Its main drawback is that it must be injected. Cefazolin (9.48) and cephaloridine (9.49) are metabolized to a lesser extent cephalexin (9.50, analogs to ampicillin) is orally active and has a much higher acid stability than the penicillins. Cefotaxime (9.51) and moxalactam (9.52) are highly active against meningitis. 

Streptococcal infections Pharyngitis, rheumatic fever, otitis media and even for subacute bacterial endocarditis. Staphylococcal infections Penicillinase resistant penicillin can be used. Meningococcal infections Meningitis other infections caused by meningococci. 

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. 

Penicillin concentrations in most tissues are equal to those in serum. Penicillin is also excreted into sputum and milk to levels 3-15% of those in the serum. Penetration into the eye, the prostate, and the central nervous system is poor. However, with active inflammation of the meninges, as in bacterial meningitis, penicillin concentrations of 1-5 mcg/mL can be achieved with a daily parenteral dose of 18-24 million units. These concentrations are sufficient to kill susceptible strains of pneumococci and meningococci. 

Cefazolin penetrates well into most tissues. It is a drug of choice for surgical prophylaxis. Cefazolin may be a choice in infections for which it is the least toxic drug (eg, penicillinase-producing E coli or pneumoniae) and in persons with staphylococcal or streptococcal infections who have a history of penicillin allergy other than immediate hypersensitivity. Cefazolin does not penetrate the central nervous system and cannot be used to treat meningitis. Cefazolin is an alternative to an antistaphylococcal penicillin for patients who are allergic to penicillin. 

Penicillin-allergic patients tolerate aztreonam without reaction. Occasional skin rashes and elevations of serum aminotransferases occur during administration of aztreonam, but major toxicity has not yet been reported. In patients with a history of penicillin anaphylaxis, aztreonam may be used to treat serious infections such as pneumonia, meningitis, and sepsis caused by susceptible gram-negative pathogens. 

Because of potential toxicity, bacterial resistance, and the availability of many other effective alternatives, chloramphenicol is rarely used. It may be considered for treatment of serious rickettsial infections such as typhus and Rocky Mountain spotted fever. 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. 

See footnote 3 in Table 51-2 for guidelines on the treatment of penicillin-resistant pneumococcal meningitis. 

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