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Biomedical subjects

F W Goldstein

Publications and source records attributed to F W Goldstein.

At least 55 records · Page 3Linked to original sources

[Resistance of pneumococcus].

Resistance of S. pneumoniae to penicillin G and other useful antibiotics has sharply increase during the last years in many countries and especially in France. Resistance to penicillin G is due to an unpredictable qualitative and quantitative modification of several penicillin binding proteins. All the beta-lactams are affected but the level of cross-resistance depends upon the affinity of the beta-lactam for the modified penicillin binding proteins. As a consequence, the minimal inhibitory concentration of penicillin G and other useful beta-lactams have to be determined against S. pneumoniae isolated from serious infection, responsible for a clinical failure or resistant to penicillin G.

Drug Resistance, Microbial↗

Comparative activity of teicoplanin and vancomycin against 400 penicillin susceptible and resistant Streptococcus pneumoniae. The French Study Group.

The MICs of teicoplanin and vancomycin were determined for 400 penicillin-susceptible and -resistant strains of Streptococcus pneumoniae isolated during a multicenter study in 1992. Teicoplanin displayed a four-fold better activity than vancomycin, with modal MICs of these agents being 0.06 and 0.25 micrograms/ml, respectively. These data warrant further studies with teicoplanin in the treatment of pneumococcal infections.

Microbial Sensitivity Tests↗

N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci.

The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new generation of tetracyclines, were evaluated by an agar dilution method and were compared with those of tetracycline and minocycline against 224 tetracycline-resistant and 73 tetracycline-susceptible recent clinical isolates of gram-positive cocci, including multiple-antibiotic-resistant methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The MICs of DMG-MINO and DMG-DMDOT were up to 500- to 2,000-fold lower than those of tetracycline against methicillin-resistant S. aureus and Streptococcus pneumoniae (MIC for 50% of strains tested [MIC50], < 0.06 microgram/ml). Against Streptococcus groups A, B, C, and G and Enterococcus faecalis, the MIC50 was 0.5 microgram/ml. MIC50s were greater only for coagulase-negative staphylococci (2 micrograms/ml). These data indicate that DMG-MINO and DMG-DMDOT are very potent drugs, and further in vitro and in vivo studies are warranted.

Coagulase↗

Resistant pneumococci: a renewed threat in respiratory infections.

The emergence of penicillin-resistant Streptococcus pneumoniae (PRSP) is an international problem which has been compounded by the development of high-level, multiple resistance to other beta-lactam antibiotics. Resistance develops in a 'step-wise' but unpredictable manner due to the mutation of penicillin-binding proteins (PBP). This results in a high degree of heterogeneity between bacterial strains. Such mutations can result in the rapid emergence of antibiotic resistance, including extended-spectrum cephalosporins, with reported minimum inhibitory concentration (MIC) values of up to 32 mg/l. The effective treatment of diseases caused by such organisms is dependent upon rapid assessment of antibiotic sensitivities. Therefore, MIC values of a range of antibiotics must be determined in cases of treatment failure and in serious pneumococcal infections. However, pharmacokinetic properties, as determined by the inhibitory quotient, which reflect drug concentrations attainable in different tissues, should also be considered. Beta-lactam antibiotics with good inhibitory activity against pneumococci include: amoxycillin, cefotaxime, ceftriaxone, cefpirome and imipenem. Nevertheless, as the prevalence of PRSP strains is likely to increase, new therapeutic strategies may have to be adopted.

Anti-Bacterial Agents↗

Long-term follow-up of positive cultures in 500 abdominal aortic aneurysms.

Routine aneurysm culture is frequently performed as it is thought that a positive culture could be a risk factor for secondary graft infection. Five hundred aneurysms, in a series of 796 patients, had microbiologic examination of the thrombus and/or aneurysm wall. Cultures were positive in 185 cases (37%), mostly due to normal skin flora microorganisms (80%), whereas 16 patients (3.2%) had infectious aortitis. Gram-stained smears were positive in nine of these 16 patients compared with two of the other 169. Of the 185 patients with positive culture, after a mean length of follow-up of 35 months, only one had a graft infection that occurred 6 years later and was not due to the same microorganism. Graft sepsis was diagnosed in six of the 296 patients who did not have a positive culture, and was related to clinically obvious locoregional or systemic foci. In this series, positive cultures from aneurysm without rupture or signs of infection were not a risk factor for secondary graft sepsis. Therefore, in cases of asymptomatic unruptured aneurysm, routine culturing is not necessary as a positive result has no pathogenic significance or therapeutic implication.

Aged↗

Susceptibility survey of piperacillin alone and in the presence of tazobactam.

Among 325 fresh isolates of bacteria from 153 hospital patients with serious infections, 142 were susceptible to piperacillin, 129 were resistant and a further 54 exhibited a marked inoculum effect. Tazobactam restored the susceptibility of resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis (except methicillin-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter spp. and Bacteroides fragilis. Among 87 Enterobacteriaceae that were resistant to piperacillin, or showed an inoculum effect, 78 (89%) were restored to susceptibility by tazobactam. Pseudomonas spp. resistant to piperacillin were mostly resistant to the combination.

Bacteria↗

Characterization of ceftriaxone-resistant Enterobacteriaceae: a multicentre study in 26 French hospitals. Vigil'Roc Study Group.

During a multicentre study performed in 26 French hospitals, 287 (3.2%) of 9038 Enterobacteriaceae isolated, mainly Enterobacter spp., Serratia spp., Citrobacter spp. and Klebsiella spp. were classified as ceftriaxone resistant on the basis of an MIC > 4 mg/L or the presence of an extended-spectrum beta-lactamase. Extended-spectrum beta-lactamase was present mainly in Klebsiella pneumoniae (65 strains, 10.2%) and very rarely in Escherichia coli, Proteus mirabilis, Klebsiella oxytoca, Citrobacter spp. and Enterobacter spp. The extended-spectrum beta-lactamases conferred low-level resistance to ceftriaxone in nearly 60% of the strains harbouring them, emphasizing the need for routine testing for the presence of these enzymes. Among transconjugants three types of extended-spectrum beta-lactamase were identified. Those resembling TEM-3 were the most common, but TEM-21, and SHV-4 were also found. Clavulanate and to a lesser extent sulbactam inhibited all the extended-spectrum beta-lactamases encountered in this study.

Ceftriaxone↗

Is protected specimen brush a reproducible method to diagnose ICU-acquired pneumonia?

UNLABELLED: Protected specimen brush (PSB) is considered to be one of the standard methods for the diagnosis of ventilator-associated pneumonia, but to our knowledge, intraindividual variability in results has not been reported previously. PURPOSE: To compare the results of two PSB performed in the same subsegment on patients with suspected ICU-acquired pneumonia (IAP). STUDY DESIGN: Between October 1991 and April 1992, each mechanically ventilated patient with suspected IAP underwent bronchoscopy with two successive PSB in the lung segment identified as abnormal on radiographs. Results of the two PSB cultures were compared using 10(3) cfu/ml cutoff for a positive result. Four definite diagnoses were established during the follow up: definite pneumonia, probable pneumonia, excluded pneumonia, and uncertain pneumonia. POPULATION: Forty-two episodes in 26 patients were studied; 60 percent of patients received prior antibiotic therapy. Thirty-two microorganisms were isolated from 24 pairs of PSB. Definite diagnosis was definite pneumonia in 7, probable pneumonia in 8, excluded pneumonia in 17, and uncertain pneumonia in 10 cases. RESULTS: The PSB recovered the same microorganisms and argued for a good qualitative reproducibility. The distinction of positive and negative results on the basis of the 10(3) cfu/ml classic threshold was less reproducible. For 24 percent of the microorganisms recovered and in 16.7 percent of episodes of suspected IAP, the two consecutive samples gave results spread out on each side of the 10(3) cfu/ml cutoff. Discordance was higher when definite diagnosis was certain or probable than when diagnosis was excluded (p = 0.015). There was no statistical effect of the order of samples between the two specimens for bacterial index and microorganism concentrations. CONCLUSION: These findings argue for the poor repeatability of PSB in suspected IAP and question the yield of the 10(3) cfu/ml threshold. In attempting to diagnose IAP, the results of PSB must be interpreted with caution considering the intraindividual variability.

Bacteriological Techniques↗

The epidemiology of bacterial resistance to quinolones.

The new fluoroquinolones have been in use for nearly 10 years in the treatment of community- and nosocomially-acquired infections. Resistant clones may be selected during therapy and disseminate if favourable epidemiological conditions prevail. Resistance to the fluoroquinolones is still rare in common pathogens with 97 to 100% of strains remaining susceptible. Resistance has been reported in methicillin-susceptible Staphylococcus aureus, Campylobacter jejuni/coli, Salmonella, Shigella and Escherichia coli. Among nosocomial pathogens, the incidence of fluoroquinolone resistance varies between bacterial species, countries and periods of study, and is dependent on local epidemiological factors and antibiotic policies. The highest incidence of resistance is observed in Serratia and Acinetobacter spp., and particularly in methicillin-resistant S. aureus. Surveillance programmes are needed to follow up trends in resistance to the fluoroquinolones and their possible association with clinical failures.

Anti-Infective Agents↗

Epidemiology of resistance to diaminopyrimidines.

Resistance to trimethoprim emerged in Enterobacteriaceae and later in other Gram-negative and Gram-positive bacteria within two years of the clinical introduction of the drug. Resistance is borne in many different replicons often present in multiply-resistant epidemic bacteria. The incidence of trimethoprim resistance is highly variable, depending upon methodology, type of patients, local epidemiology: this can be illustrated by the high variation of trimethoprim resistance among Salmonella, Shigella or MRSA in various countries and by the incidence of resistance in penicillin-resistant Streptococcus pneumoniae.

Cross Infection↗

[Resistance of Salmonella].

The emergence and the increase of antibiotic resistant Salmonella particularly in non-typhi species has occurred in recent years. Beside plasmid mediated resistance, new resistance mechanisms like alterations of permeability have been identified. Factors associated with resistance are the use of antibiotics in human and animals. These findings have important public health implications. It seems necessary to define a more adapted policy in human and veterinary use in order to avoid the rapid emergence of drug-resistance among regularly active antibiotics like fluoroquinolones.

Animals↗

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.

Adult↗

Resistance to cefotaxime and seven other beta-lactams in members of the family Enterobacteriaceae: a 3-year survey in France.

During the second quarter each of 1988, 1989, and 1990, a French collaborative study group, including 12 university hospital laboratories, surveyed the resistance to beta-lactams of clinical isolates from hospitalized patients: consecutively, 10,641, 10,692, and 9,382 isolates were tested. The distribution of bacterial species over time was similar in each laboratory. The susceptibilities of microorganisms to amoxicillin, ticarcillin, cephalothin, cefoxitin, cefotaxime (CTX), ceftazidime (CAZ), aztreonam (ATM), and imipenem (IPM) were measured by the disk diffusion method in accordance with the recommendations of the Antibiogram Committee of the French Society for Microbiology. Five reference strains were included for quality control. Extended-spectrum beta-lactamases were detected by the synergistic effect of the combination of clavulanic acid-amoxicillin with CTX, CAZ, and ATM in the double-diffusion test. A synergistic effect with CTX, CAZ, and ATM was detected for 1.5% of all strains, mainly those of Klebsiella pneumoniae (13.3%). For this species, the synergy test enabled the detection of roughly 50% of the resistant strains misclassified as susceptible on the basis of interpretative standards. Extended-spectrum beta-lactamases disseminated in 1990 in most enterobacterial species but at a low frequency. Important variations in the percentages of resistant strains were observed in terms of bacterial species, hospitals, and wards. However, when the total number of strains was considered, the percentages of resistance to newer beta-lactams remained low.

Anti-Bacterial Agents↗