Third generation cephalosporins as a risk factor for Clostridium difficile-associated disease: a four-year survey in a general hospital

Abstract

The main clinical features of patients who developed pseudomembranous colitis (PMC) or Clostridium difficile-associated diarrhoea (CDAD) during their stay at the S. Anna General Hospital, Como, over the period February 1984 to May 1988, are reported. Forty patients developed either CDAD (ten cases) or PMC (30 cases). Twenty-seven (65.7%) had undergone surgery and 32 (80.0%) had received prolonged antibiotic treatment. Three patients (7.5%) were given three doses only of ceftriaxone. Five patients (12.5%) had not received any antibiotic treatment; but three were nursed in a bed next to a patient with PMC-CDAD. The number of cases diagnosed were correlated retrospectively with the cumulative consumption of different groups of antibiotics on wards in which PMC or CDAD occurred. A significant difference (P less than 0.01) between third generation cephalosporins (16 cases) and ureidopenicillins (one case), was found. Twenty-five patients were treated with oral vancomycin. Two died of the underlying disease and 23 were cured. The disease recurred clinically in three, and follow-up cultures were positive in another asymptomatic case. Fifteen patients (all PMC cases) were treated with oral teicoplanin. All were clinically cured and remained asymptomatic and all but one were also cleared of C. difficile. No adverse reactions were observed in patients given either drug. Third generation cephalosporins, even when administered as short-term perioperative prophylaxis, but not ureidopenicillins, are significantly associated with C. difficile-related diseases. Teicoplanin proved to be very effective and safe in the treatment of PMC, and should be further evaluated there.

Detection ofClostridium difficile toxin by enzyme immunoassay, tissue culture test and culture

“…Cephalosporins were the most frequently used antibiotics in toxin-positive and -negative patients, but significantly more patients with C. difficile toxin in their stools had been administered cephalosporins. The finding, that cephalosporins are more likely to be associated with CDAD, is in agreement with previous reports [3,8,21]. We believe C. difficile toxin to be underestimated as a cause of AAD, mainly in departments with a lower degree of specialisation (data not shown), whereas routine stool samples are often inappropriately submitted for the detection of enteropathogenic bacteria in inpatients [22,23].…”

Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery

“…The incidence of C. difficile-associated disease and asymptomatic intestinal colonization has been shown to dramatically increase in patients who are given antimicrobial agents. Apart from clindamycin, which is the first agent that was clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly implicated as inciting factors of both C. difficile intestinal colonization and disease are cephalosporins and ampicillin (1,2,4,9,11,15,16,28). C. difficile colonization and disease develop more commonly after prolonged antibiotic treatment, but they have also been reported after short-term (usually three doses) perioperative prophylaxis with some antimicrobial agents (3,6,11,18,25,29).…”

“…The observations that (i) the emergence of C. difficile is not necessarily dependent upon long-term antibiotic treatment and (ii) cephalosporins are more likely to be associated with C. difficile intestinal disease (1,2,11,18) and to have a significant effect on the colonization resistance of the lower gastrointestinal tract (7,24) prompted us to perform a prospective study of the influence of single-dose perioperative prophylaxis with different antimicrobial agents on acquisition of the C. difficile carrier state during hospitalization.…”

“…Informed consent was obtained from each patient. To minimize the influence of colonization by endemic strains on the results of the study, only patients admitted to the two surgical wards of a single hospital (S. Anna Hospital) subjected to a strict surveillance program for C. difficile infection and environmental contamination (11) were enrolled and the length of the study was restricted to 3 months. Throughout this period cefazolin, cefoxitin, cefotetan, ceftriaxone, and cefoperazone were each randomly assigned to one of the surgical teams on the wards as the unique agent for perioperative prophylaxis and mezlocillin was assigned to two surgeons in order to include more treated patients, allowing comparison not only with each single cephalosporin but also with cephalosporins as a group.…”

Effects of Closed-SystemDrain in Surgery:Focus on Methicillin-Resistant<i>Staphylococcus aureus</i>

“…Recently, broad-spectrum cephalosporins, particularly the second- and third-generation ones, have frequently been used in gastrointestinal surgery because of their selective effects against gram-negative aerobes. Careless use of them, however, may be detrimental, since they have a potential risk of increasing drug-resistant gram-positive bacteria [11, 12] and are less effective in decreasing the positive rate of both gram-negative and gram-positive cocci in the sputum [13]. Ratto et al [14], in their study of antimicrobial prophylaxis in lung cancer surgery, pointed out that antibiotic prophylaxis, while effective in preventing postoperative empyema, might induce colonization of the respiratory tract with highly resistant bacteria.…”