Fred W. Goldstein

Single- versus triple-lumen central catheter-related sepsis: A prospective randomized study in a critically ill population☆

PURPOSE A prospective randomized study was conducted over a 23-month period in an adult medical-surgical intensive care unit to determine whether triple-lumen catheters reduce the need for peripheral vascular access and whether they are associated with a higher rate of infection than single-lumen catheters. PATIENTS AND METHODS After the insertion route, internal jugular or subclavian, was selected by the physician, patients were randomized either to single-lumen or triple-lumen catheter groups. Complementary peripheral vascular access was allowed in both groups. Catheters were removed according to preestablished defined reasons: suspicion of catheter-related sepsis, uselessness of central venous access, duration of catheterization of more than 21 days, discharge from the intensive care unit, or death. RESULTS Data on 129 central venous catheters were collected from 91 consecutive patients. Twenty-five of 68 patients from the single-lumen group and 1 of 61 patients from the triple-lumen group needed peripheral vascular access (p less than 0.001). Catheter-related sepsis rates, defined either by clinical signs and positive qualitative tip cultures (8.9% versus 11.5%) or by quantitative tip cultures (16.2% versus 11.5%), were identical in the single-lumen and triple-lumen groups (type II error: 8%). CONCLUSION In intensive care units, the use of triple-lumen catheters is associated with a dramatic decrease in the need for peripheral vascular access. The incidence of central venous catheter-related sepsis appears identical for single- and triple-lumen catheters.

SHV-5, a novel SHV-type beta-lactamase that hydrolyzes broad-spectrum cephalosporins and monobactams.

SHV-5 (pI 8.2), a novel broad-spectrum beta-lactamase encoded by a ca. 150-kilobase plasmid, was found in Klebsiella pneumoniae 160. SHV-5 beta-lactamase caused decreased susceptibility to most penicillins, cephalosporins, and monobactams, except imipenem and compounds which have a C6 or C7 alpha-methoxy substituent. beta-Lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) inhibited its activity and showed a synergistic effect when associated with different hydrolyzable beta-lactam compounds. Hybridization studies suggested that this enzyme may be related to, or derived from, the SHV enzyme. Increased MICs of cephamycins and temocillin associated with a decreased synergistic effect of the inhibitors on K. pneumoniae 160 might be linked to a decrease in two outer membrane proteins. Images

Dissemination of the novel plasmid-mediated beta-lactamase CTX-1, which confers resistance to broad-spectrum cephalosporins, and its inhibition by beta-lactamase inhibitors.

The novel beta-lactamase CTX-1 (pI 6.3) encoded on a transferable 84-kilobase plasmid was found in six different bacterial species. It was responsible for a significant decrease in susceptibility towards most penicillins and cephalosporins, except imipenem, temocillin, and cephalosporins which have a 7-alpha-methoxy substituent. Synergy between either ampicillin, piperacillin, cefotaxime, ceftazidime, or aztreonam and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and YTR 830) was generally found for different strains harboring CTX-1. This enzyme may be related to or derived from the TEM enzyme, since an intragenic probe of the TEM-1 gene hybridized with a fragment of the plasmid carrying CTX-1. Images

Synergistic effect of amoxicillin and cefotaxime against Enterococcus faecalis.

The antibacterial efficacy of the combination of amoxicillin and cefotaxime was assessed against 50 clinical strains of Enterococcus faecalis. For 48 of 50 strains, the MIC of amoxicillin that inhibited 50% of isolates tested decreased from 0.5 microgram/ml (range, 0.25 to 1 microgram/ml) to 0.06 microgram/ml (range, 0.01 to 0.25 microgram/ml) in the presence of only 4 micrograms of cefotaxime per ml. Alternatively, the MIC of cefotaxime that inhibited 50% of isolates tested decreased from 256 micrograms/ml (range, 8 to 512 micrograms/ml) to 1 micrograms/ml (range, 0.5 to 16 micrograms/ml) in the presence of only 0.06 microgram of amoxicillin per ml. For JH2-2, a reference strain of E. faecalis, the MICs of amoxicillin, cefotaxime, and amoxicillin in the presence of cefotaxime (4 micrograms/ml) were 0.5, 512, and 0.06 microgram/ml, respectively. By using a penicillin-binding protein (PBP) competition assay, it was shown that with cefotaxime, 50% saturation of PBPs 2 and 3 was obtained at very low concentrations (< 1 microgram/ml), while 50% saturation of PBPs 1, 4, and 5 was obtained with > or = 128 micrograms/ml. With amoxicillin, 50% saturation of PBPs 4 and 5 was obtained at 0.12 and 0.5 microgram/ml, respectively. Therefore, the partial saturation of PBPs 4 and 5 by amoxicillin combined with the total saturation of PBPs 2 and 3 by cefotaxime could be responsible for the observed synergy between these two compounds.

Bacterial contamination of hospital physicians' stethoscopes.

Because stethoscopes might be potential vectors of nosocomial infections, this study, conducted in a 450-bed general hospital, was devised to evaluate the bacterial contamination of stethoscopes; bacterial survival on stethoscope membranes; the kinetics of the bacterial load on stethoscope membranes during clinical use; and the efficacy of 70% alcohol or liquid soap for membrane disinfection. Among the 355 stethoscopes tested, 234 carried > or =2 different bacterial species; 31 carried potentially pathogenic bacteria. Although some bacteria deposited onto membranes could survive 6 to 18 hours, none survived after disinfection.

Mutation of Salmonella paratyphi A conferring cross-resistance to several groups of antibiotics by decreased permeability and loss of invasiveness.

A spontaneous one-step mutant of Salmonella paratyphi A selected on ampicillin showed cross-resistance to all beta-lactam antibiotics except imipenem and to aminoglycosides, chloramphenicol, tetracycline, trimethoprim, and quinolones. It also grew as small colonies. Examination of the cell envelope of the mutant showed a quantitative decrease in three major outer membrane proteins of 40.6, 39.6 (presumably porins), and 24 kilodaltons and quantitative as well as qualitative modifications in the ladder pattern of lipopolysaccharide. Direct evidence for decreased permeability in the mutant included reduced uptake of [3H]glucose and norfloxacin, reduced accessibility of aztreonam and benzylpenicillin to penicillin-binding proteins in whole cells, and decreased diffusion of lactose and cephaloridine into proteoliposomes that were reconstituted with outer membrane proteins from the mutant. There was also loss of invasiveness of the mutant into HeLa cells. We assume that a pleiotropic mutation was responsible for multiple alterations in the outer membrane components of the resistant mutant of S. paratyphi A. Images

Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 beta-lactams.

Twelve Nocardia asteroides isolates were tested for their susceptibility to 46 antibiotics by the agar dilution method. N-Formimidoyl thienamycin was the most active of 22 beta-lactam antibiotics, inhibiting 11 of the 12 strains at 1 microgram/ml. Penicillins, including ureidopenicillins, showed poor activity. Cefotaxime, ceftriaxone, and especially cefuroxime had the best activities of the cephalosporins tested. Among the other antibiotics, amikacin and minocycline, respectively, inhibited all of the strains tested at 0.5 and 4 micrograms/ml.

In vitro activities of 15 oral beta-lactams against Klebsiella pneumoniae harboring new extended-spectrum beta-lactamases.

The activities of 15 oral beta-lactams against Klebsiella pneumoniae harboring new extended-spectrum beta-lactamases were studied. All compounds were affected by these enzymes, especially by the SHV derivatives. Except for ceftibuten, the compounds with the greatest intrinsic activity were more affected by the presence of these enzymes than were older compounds with moderate intrinsic activity.

In vitro activities of tigecycline (GAR-936) against multidrug-resistant Staphylococcus aureus and streptococcus pneumoniae

During recent years, a dramatic increase in bacterial resistance to antibiotics has been observed worldwide, both in community and nosocomial isolates, curtailing the use of many valuable antibiotics. In France, more than 50% of Streptococcus pneumoniae strains isolated in the community are resistant to penicillin and macrolides (8), and more than 40% of Staphylococcus aureus strains isolated in hospitals are resistant to β-lactams, aminoglycosides, macrolides, and fluoroquinolones, including the newer compounds (≈100% of the methicillin-resistant S. aureus [MRSA] strains) (5). S. aureus strains with low-level resistance to glycopeptides have been isolated in our hospital for more than 10 years (6), and resistance to quinupristin-dalfopristin (Synercid) is not uncommon due to the frequent use of oral pristinamycin in France. Most of these multidrug-resistant (MDR) bacteria are resistant to tetracyclines, emphasizing the need for new compounds. Tigecycline (GAR-936) is the 9-t-butylglycylamino derivative of minocycline, a new generation of tetracyclines called glycylcyclines. These glycylcyclines overcome tetracycline resistance due to both ribosomal protection and efflux determinants (1-3, 7). The aim of this study was to assess the in vitro activity of GAR-936 against MDR S. pneumoniae and S. aureus in comparison with tetracycline, minocycline, telithromycin, linezolid, and quinupristin-dalfopristin.

Molecular Detection and Identification of Agents of Eumycetoma: Detailed Report of Two Cases

ABSTRACT We describe two cases of eumycetoma in the legs. The infections could not be adequately diagnosed by classical mycology, but the causative agents were successfully identified as Madurella mycetomatis by species-specific PCR and DNA sequencing.