Use Of Extended-spectrum Cephalosporins Research Articles

Antimicrobial Pressure and the Emergence and Spread of Multiresistant Enterococci

Multiresistant enterococci persist as important pathogens, particularly in US tertiary care hospitals. The emergence of vancomycin and ampicillin resistance in clinical Enterococcus faecium strains and the ascension of this species as an important nosocomial pathogen are among the more remarkable developments in the past decade. This emergence and spread is due to both the failure to adhere to well-established infection control measures and the persistent selective antibiotic pressure exerted in tertiary care institutions. Accumulating data specifically implicate the use of extended-spectrum cephalosporins and drugs with potent activity against anaerobic bacteria in the spread of vancomycin-resistant enterococci (VRE). These antibiotics appear to exert different effects on the initial establishment or the persistence of high levels of VRE colonization. Successful strategies to control the spread of multiresistant enterococci will require a more detailed understanding of the specific impacts of antimicrobial pressures as well as renewed commitment to adherence to well-established infection control measures.

Emerging bacterial pathogens: a consensus of the scientific data and the risk for development of multiple organ dysfunction syndrome.

Antibiotic resistance in the hospital setting is continuing to increase, particularly in intensive care units (ICUs) and other areas of the hospital such as oncology units, where the use of empiric broad-spectrum antibiotics is common. The problem of antibiotic resistance is also compounded in the immunocompromised patient. Multi-drug resistance is common among both Gram-positive and -negative bacteria, and becoming more prevalent among fungi (yeast). Two major antibiotic-resistant pathogens include extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) and vancomycin-resistant enterococci (VRE). When infections occur with ESBL-KP, a carbapenem antibiotic is usually the drug of choice. When infection occurs with VRE, specific therapy is bacteriostatic, and the clinician may have to rely on empirically selected antibiotics or combinations of antibiotics to achieve a positive outcome. Two newly-approved agents, linezolid and quinupristin/dalfopristin can be used to treat infections caused by resistant gram-positive cocci, but the latter is approved for use against VR-E. faecium. Risk factors for the development of ESBL-KP include the use of extended-spectrum cephalosporins such as ceftazidime. Risk factors for the development of VRE include inappropriate use of vancomycin, extended-spectrum cephalosporins, and antianaerobic drug therapy such as clindamycin. Several institutions have documented a reduction in one or both of these resistant pathogens following a decrease in the use of extended-spectrum cephalosporins combined with the increased use of extended-spectrum penicillins/beta-lactamase inhibitor combinations, such as piperacillin/tazobactam, for the empiric therapy of infections. For VRE, a reduction in the inappropriate use of vancomycin is also an important interventional strategy along with improved infection control practice.

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

The incidence of penicillin resistance amongst Streptococcus pneumoniae is increasing on a world-wide basis. Penicillinresistant 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 2x and 4x 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).