The role of fourth-generation cephalosporins in the treatment of infections caused by penicillin-resistant streptococci

Abstract

The incidence of penicillin resistance amongst Streptococcus pneumoniae is increasing on a world-wide basis. Penicillin-resistant strains of viridans streptococci have also been reported, associated with serious clinical infections, particularly in neutropenic patients. Although there are fewer data on the epidemiology of viridans streptococci, it is known that penicillin resistance determinants can be transferred between these organisms and S. pneumoniae. Paradoxically, the increased incidence of multiresistant pneumococci has led to a re-evaluation of β-lactam antibiotics for the treatment of streptococcal infections. Cefotaxime, ceftriaxone, cefpirome, cefepime, imipenem, meropenem and amoxicillin remain the most potent β-lactam antibiotics, with at least 95% of penicillin-resistant strains of S. pneumoniae being inhibited by 2 mg/L and 95% of penicillin-resistant viridans streptococci by 8 mg/L. Cefpirome is two-fold more active than cefotaxime, ceftriaxone or cefepime and, like penicillin and cefotaxime, is bactericidal at 2× and 4× the MIC value against penicillin-resistant strains of S. pneumoniae and viridans streptococci. Synergistic interactions have been demonstrated between penicillin or cefpirome and vancomycin, fosfomycin or gentamicin. Studies have shown that the clinical outcome of pneumonia is not related to in vitro MIC data below 4 mg/L, since infections caused by penicillin-resistant pneumococci responded as well to β-lactam therapy as those caused by penicillin-susceptible strains. This is most likely to be due to high antibiotic concentrations achieved at the site of infection following intravenous dosage, which are sufficient to cover strains with reduced susceptibility. Any degree of penicillin resistance rules out the use of penicillin for pneumococcal meningitis, necessitating the use of extended-spectrum cephalosporins, such as cefotaxime or ceftriaxone. An alternative could be the use of the fourth-generation cephalosporins or the carbapenems. Overall, when predicting the clinical outcome of infections caused by penicillin-resistant streptococci, it is important to consider the relationship between a number of factors, namely, the specific susceptibility of the infecting strain to the chosen agent, the type of infection (i.e. pneumonia, bacteremia or meningitis) and the relevant antibiotic concentrations achieved over time at the site of infection (i.e. those in serum or cerebrospinal fluid).