Failure of cefonicid prophylaxis for infectious complications related to endoscopic retrograde cholangiopancreatography.

We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis.

[Excretion of cefonicid and ceftriaxone into the saliva]. / Cefonicid és ceftriaxon nyálba történö kiválasztódásának vizsgálata.

The serum and saliva levels of cefonicid (Monocid) and ceftriaxon (Rocephin) were studied after iv. administration on mice. It was found that both of the antibiotics were secreted well into saliva and their therapeutic values remained for 4-5 hours.

Development of revised quality control limits for disk diffusion susceptibility tests of selected cephem antibiotics with Haemophilus influenzae and description of a new control strain.

Inconsistent quality control results in disk diffusion testing of cefaclor, cefamandole, cefonicid, and cefuroxime with Haemophilus influenzae ATCC 49247 and Haemophilus test medium (HTM) prompted a search for an alternative control strain that would provide more reliable results. A five-laboratory study was conducted to evaluate two candidate H. influenzae strains as possible alternatives to the aforementioned strain. Repetitive testing of the candidate strains and H. influenzae ATCC 49247 over several days with a total of six different lots of HTM documented consistent performance of the two candidate strains and confirmed inconsistent results for some of the antibiotics with H. influenzae ATCC 49247. In particular, certain lots of HTM failed to yield cefaclor and cefamandole zone sizes within the quality control range advocated by the National Committee for Clinical Laboratory Standards. Because of the greater consistency offered by the new strains, one was selected (now designated H. influenzae ATCC 49766) to be recommended for routine quality control testing of cefaclor, cefamandole, cefonicid, cefuroxime, and the related carbacephem loracarbef. The new control strain and zone size ranges proposed here have been approved by the National Committee for Clinical Laboratory Standards in place of the previously recommended strain and zone size limits for testing of these five cephem antibiotics.

Cefonicid potentiation of human macrophage activity.

This study was undertaken to evaluate the in vitro effects of cefonicid on phagocyte functions such as phagocytosis and intracellular killing of phagocytosed bacteria. At concentrations of half the MIC cefonicid caused human macrophages to ingest and kill Klebsiella pneumoniae at a greater rate than did drug-free macrophages. Bacteria pretreated with subinhibitory concentrations of cefonicid became more susceptible to the phagocytic and bactericidal activity of macrophages than untreated microorganisms. Sub-MIC cefonicid pretreatment of macrophages did not reduce phagocytosis and killing, confirming the inability of beta-lactam antibiotics to cross biological membranes.

Cefonicid versus cefuroxime: an in vitro study of 1,000 Enterobacteriaceae.

Cefuroxime and cefonicid, two common representatives of the second-generation cephalosporins, were compared for their spectrum of activity against 1,000 isolates of gram-negative Enterobacteriaceae. Cefuroxime had an overall advantage of 6.3% over cefonicid. Upon investigation, we found that this was mainly due to Escherichia coli: 11.2% of the E. coli strains proved resistant to cefonicid whilst only 0.4% were cefuroxime resistant.

Effects of cefonicid on platelet aggregation.

Beta-lactam antibiotics may interfere with platelet aggregation by inhibiting the binding of agonists of platelet aggregation, such as ADP and collagen, to specific receptor sites. The aim of this study was to evaluate in vitro the effects of cefonicid, a semi-synthetic cephalosporin, on platelet aggregation. Spontaneous platelet aggregation and platelet aggregation induced by ADP and collagen were assessed. Platelets from healthy subjects were incubated with cefonicid at final concentrations of 0.1 mg/ml, 1 mg/ml and 10 mg/ml (0.1 mg/ml is the concentration of cefonicid achieved in humans at therapeutic doses). When compared with saline, cefonicid at a concentration of 0.1 mg/ml had no effect on platelet aggregation, but at 1 mg/ml it inhibited ADP-induced aggregation and at 10 mg/ml it also inhibited aggregation induced by collagen. These findings suggest that therapeutic doses of cefonicid do not affect platelet aggregation.

In-vitro interaction of cephalosporin and the immune system.

In this study we have evaluated the effects of an antibiotic, such as cefonicid, on some immune reactivities in vitro. The following immune parameters have been analyzed: i) interferon-gamma and interleukin-2 production and ii) lymphocyte proliferation following mitogen stimulation in the presence of cefonicid concentrations ranging from 50 to 500 microg/ml. No. decrease in lymphokine production in the presence of cefonicid concentrations up to 250 microg/ml was observed between untreated or antibiotic-treated lymphocyte cultures. When lymphocyte proliferation upon Con A stimulation, as evaluated by 3H-dHtd incorporation, was measured in the presence of cefonicid, no differences were observed with untreated controls. These results demonstrate that the in vitro interaction of cefonicid with the immune system does not lead to a decrease of the immune response.

Therapeutic efficacy and renal effects of cefonicid in the treatment of difficult urinary tract infections.

UNLABELLED: EFFICACY, renal effects and nephrotoxicity of the cephalosporin cefonicid (CEF) were evaluated in 11 adult patients with urinary tract infection and varying renal function (creatinine cl 19-161 ml/min, mean 75). CEF was administered i.m. for 7 days at a daily dose adjusted to renal function of the patients. EFFICACY: At the 4th day and at the end of the treatment urine cultures were negative in all cases; a recurrence of the infection was observed in 4 patients 10 days after completion of therapy. Renal effects and nephrotoxicity: CEF neither modified plasma creatinine, urea, uric acid and their renal clearances nor glomerular filtration rate. Only the urinary enzyme activity of alanine aminopeptidase increased slightly at the end of the therapy. It returned to basal values in the post-treatment period. Urinary enzyme activities of gamma-glutamyltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and lysozyme were unmodified during and after treatment with CEF. These results indicate that CEF is an effective antimicrobial agent which does not influence renal function, nor cause nephrotoxic effects.

Interference of cephalosporins with immune response: effects of cefonicid on human T-helper cells.

To determine the immunosuppressive effect(s) of cephalosporin cefonicid (CEFO) on human T-helper cells (Th), we exposed human peripheral blood mononuclear cells (PBMC) to various concentrations of CEFO during in vitro stimulation with a panel of T-lymphocyte stimulators that activate different Th/antigen presenting cell (APC) pathways. We evaluated the proliferation and IL-2 production induced by influenza virus (FLU), allogeneic lymphocytes (ALLO), xenogeneic mouse splenocytes (XENO) or phytohemagglutinin (PHA). The proliferative responses to FLU and XENO were much more depressed by CEFO than those to ALLO or PHA. After 7 days of culture with the highest dose of CEFO tested (200 mg/l) the stimulation index (stimulated/unstimulated culture) was near to 0 in FLU and XENO treated cultures, indicating that the response against these antigens was completely abrogated. The responses to ALLO and PHA were also impaired, but not abrogated (stimulation index greater than 1). Since FLU and XENO utilize the CD4+ Th/self-APC pathway our data suggested that this pathway was extremely sensitive to CEFO-induced inhibition both when the response requires memory Th cells (FLU) and virgin Th cells (XENO). The incubation with CEFO (200 mg/l) reduced the IL-2 production by XENO, FLU and ALLO to less than 20% of control cultures, while paradoxically increases to 120% the production by PHA.

Antibacterial activity of combined cefotaxime and desacetyl-cefotaxime against aerobic and anaerobic gram-negative bacilli.

Synergy between cefotaxime and desacetyl-cefotaxime was evaluated against 12 strains (9 Enterobacteriaceae and 3 Bacteroides fragilis) by the chequerboard technique. A 1:1 combination of cefotaxime and desacetyl-cefotaxime was synergistic against two-thirds of the 12 strains tested. The in vitro activity of the combination was compared with that of four other beta-lactam antibiotics against 96 recent clinical isolates: 78 Enterobacteriaceae, 8 Haemophilus influenzae, 10 B. fragilis. The MICs of the combination for Gram-negative bacilli were similar to those of ceftazidime. Cefotaxime/desacetyl-cefotaxime was more active than cefotetan, cefonicid and piperacillin against Enterobacteriaceae and H. influenzae.

In vitro activity of cefonicid compared to other antibiotics against clinical bacterial isolates.

The in vitro activity of cefonicid compared to that of other antibiotics has been evaluated against 401 Enterobacteriaceae, 20 H. influenzae, 17 Branhamella catarrhalis and 71 staphylococci. Cefonicid was always more active than cefazolin, and usually more active than cefamandole and cefuroxime against susceptible gram-negative organisms (E. coli, P. mirabilis, Klebsiella, Shigella, Salmonella, H. influenzae). Cefonicid was ineffective against most strains of Enterobacter, Citrobacter, S. marcescens and M. morganii. Staphylococci were 6 to 8 times less susceptible to cefonicid than to the other cephalosporins.

[Pulmonary and tonsillar distribution of ceftriaxone and cefonicid and the resultant bactericidal activity of the organ]. / Distribuzione polmonare e tonsillare di ceftriaxone e cefonicid e risultante attività battericida d'organo.

The therapeutic efficacy of Ceftriaxone and Cefonicid 1 g I.M. single-dose against S. Pneumoniae, H. Influenzae and K. Pneumoniae in tonsil and lung infections was studied using bactericidal quotient (BQ). Samples of lung tissue and serum were obtained from two groups of surgical patients, treated with Ceftriaxone or Cefonicid 1 g I.M., 2-8-16 and 24 hours before surgery. From two other groups of 10 surgical patients, treated as above, samples of tonsil tissue and serum were obtained. In lung tissue the higher levels of Ceftriaxone and Cefonicid appeared at the second hour (11.54 +/- 1.59 mcg/g and 11.4 +/- 2.49 mcg/g respectively); the lower values were observed at the 24th hour (2.18 +/- 0.47 mcg/g for Ceftriaxone and 0.64 +/- 0.21 mcg/g for Cefonicid). Higher Ceftriaxone and Cefonicid levels also appeared in tonsil tissue at the 2nd hour (11.12 +/- 2.42 mcg/g and 9.22 +/- 3.12 mcg/g respectively); the lower values were observed at the 24th hour (1.54 +/- 0.46 mcg/g for Ceftriaxone and 0.42 +/- 0.23 mcg/g for Cefonicid). BQ values were estimated using the ratio between the mean concentrations of Ceftriaxone and Cefonicid in tissue samples and the MBC mean values determined for the above mentioned pathogens, isolated in hospital. Ceftriaxone always showed BQ values greater than 1 during 24 hours versus levels observed for the three reported pathogens. Cefonicid showed BQ values greater than 1 during 24 hours against S. Pneumoniae and BQ values less than 1 for 6-8 hours against H. Influenzae and for 1-4 hours against K. Pneumoniae.