Ceftriaxone resistance

Fey P.D., T.J. Safranek, M.E. Rupp, E.F. Duime, E. RiboL P.C. Iwen, P.A. Bradford, F.J. Angulo, and S.H. Hinrichs (2000). Ceftriaxone-resistant Salmonella infection acquired by a child from cattle. New England Journal of Medicine 342 1242-1249. 

Resistance of H. influenzae to ampicillin has increased in the past decade and varies geographically. Thus, it can no longer be prescribed with confidence as initial therapy, and cetotaxime or ceftriaxone are the preferred alternatives. However, once laboratoiy evidence for /3-lactamase activity is excluded, ampicillin can be safely substituted. 

Complicated exacerbation FEV, less than 50% predicted Comorbid cardiac disease Greater than or equal to 3 exacerbations per year Antibiotic therapy in the previous 3 months Above organisms plus drug-resistant pneumococci, P-lactamase-producing H. influenzae and M. catarrhalis, Escherichia coli, Proteus spp., Enterobacter spp., Klebsiella pneumoniae Oral P-Lactam/P-Iactamase inhibitor (amoxicil 1 i n-clavulanate) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin) Intravenous P-Iactam/P-Iactamase inhibitor (ampicillin-sulbactam) Second- or third-generation cephalosporin (cefuroxime, ceftriaxone) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, moxifloxacin)... 

Broad-spectrum antibiotic cefotaxime or ceftriaxone (clindamycin for cephalosporin allergy) vancomycin for staphylococcal and resistant pneumococcal organisms... 

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... 

Most isolates are highly susceptible to penicillin therefore, penicillin G remains the regimen of choice. However, ceftriaxone may be used as an alternative agent if the patient is allergic or resistance is suspected to penicillin. Typically, the length of treatment is 4 weeks and remains the most common regimen. However, a shorter course (i.e., 2 weeks) maybe employed for a patient with uncomplicated IE due to highly penicillin-susceptible strains... 

If the isolate is determined to be vancomycin-resistant, it is most important to know the exact species because some of the treatment options, such as quinupristin/dalfopristin, are not active against E. faecalis. Currently, the treatment options for vancomycin-resistant enterococci (VRE) are not well established by clinical studies or patient experience. The treatment recommendations for vancomycin-resistant E. faecium include linezolid or quinupristin/dalfopristin for a minimum of 8 weeks. However, newer agents, such as daptomycin, may provide another option for treatment for either enterococci species (E. faecium and E. faecalis). Additionally, guidelines suggest the use of imipenem-cilistatin plus ampicillin or ceftriaxone plus ampicillin for the treatment of E. faecalis with a minimum of 8 weeks of therapy. Consultation with an infectious diseases specialist is recommended. 

Vancomycin use should be based on local incidence of penicillin-resistant S. pneumoniae and until cefotaxime or ceftriaxone minimum inhibitory concentration results are available. 

Penicillin resistant Cefotaxime or ceftriaxone (A-lll) Chloramphenicol (A-lll), meropenem (A-lll), fluoroquinolone (A-lll) ... 

The treatment of choice until susceptibility of the organism is known as the combination of vancomycin plus ceftriaxone. Penicillin may be used for drug-susceptible isolates with minimum inhibitory concentrations of 0.06 mcg/mL or less, but for intermediate isolates ceftriaxone is used, and for highly drug-resistant isolates a combination of ceftriaxone and vancomycin should be used. A high percent of S. pneumoniae is either intermediately or highly resistant to penicillin. 

Approximately 30% to 40% of H. influenzae are ampicillin resistant. For this reason, many clinicians use a third-generation cephalosporin (cefotaxime or ceftriaxone) for initial antimicrobial therapy. Once bacterial susceptibilities are available, ampicillin may be used if the isolate proves ampicillin sensitive. Cefepime and fluoroquinolones are suitable alternatives regardless of /1-lactamase activity. 

For patients with complicated infection (e.g., extracardiac foci) or when the organism is relatively resistant (MIC = 0.12 to 0.5 mcg/mL), combination therapy with an aminoglycoside and penicillin (higher dose) or ceftriaxone for the first 2 weeks is recommended (Table 37-4). 

If treatment failure occurs with amoxicillin, an agent should be chosen with activity against /1-lactamase-producing H. influenzae and M. catar-rhalis as well as drug-resistant S. pneumoniae (such as high-dose amoxicil-lin-clavulanate (recommended), or, cefuroxime, cefdinir, cefpodoxime, cefprozil, or intramuscular ceftriaxone). 

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. 

One of the prindpal deficiencies of the older cephalosponns was the lack of resistance to -lactamases. Compounds with improved jS-lactamase resistance have one or more of tire following characteristics a second, monovalent substiluenl on the a-carbon of the C-7 acyl group such as is found in cefamandole and cefoperazone a jy -oxime substiluenl, e.g., cefuroxime and ceftriaxone a methoxy, or formamido, substituent on the fl-laclam ring at tire 7 a-position such as in cefoxitin. However, these various substituents have different effects, and increased resistance to one enzyme does not indicate resistance to all (3-lactamases. 

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. 

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