30 years of penicillin-resistant S pneumoniae: myth or reality?
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Drug Resistance, Multiple↗
Biomedical subjects
F W Goldstein
Publications and source records attributed to F W Goldstein.
[Stability of the ceftriaxone spectrum].
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Bacterial Infections↗
Trends in bacterial resistance to fluoroquinolones.
The emergence of resistance to fluoroquinolones in virtually all species of bacteria was recognized soon after the introduction of these compounds for clinical use more than 10 years ago. Various resistance mechanisms, often interdependent, may explain different levels of resistance. Epidemiological factors, local antibiotic policies, patients' characteristics, origin of the strains, and geographic location are among the factors contributing to highly variable resistance rates. During the last several years, resistance to fluoroquinolones has remained very high among methicillin-resistant Staphylococcus aureus strains and in intensive care unit patients, and it has increased among nosocomial isolates of Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa. More worrisome are recent reports of an overall increase in resistance to fluoroquinolones among bacteria responsible for community-acquired infections, such as Escherichia coli, Salmonella species, Campylobacter species and Neisseria gonorrhoeae.
Anti-Infective Agents↗
Choice of an oral beta-lactam antibiotic for infections due to penicillin-resistant Streptococcus pneumoniae.
The activity, pharmacokinetic and pharmacodynamic parameters of 5 oral beta-lactams have been compared against 400 penicillin-resistant Streptococcus pneumoniae (PRSP) isolated in 9 European countries. All the data have been calculated for the highest recommended oral dosage in France. Amoxicillin was by far the most effective antibiotic when considering its intrinsic activity (96% of the PRSP inhibited at 2 mg/l), the inhibitory quotient (100% of the PRSP > 1 vs 69.2% for cefuroxime) or a time above MIC > 40% which best correlates with clinical results (96% for amoxicillin vs < 25% for the cephalosporins).
Administration, Oral↗
Highlights of the French Antimicrobial Resistance Surveillance Project. French Study Group.
Thirty-three French laboratories took part in a study to determine the frequency of antibiotic resistance to S. pneumoniae, H. influenzae and M. catarrhalis in different regions of the country. A total of 1317 bacterial isolates were studied. The level of resistance to penicillin among isolates of S. pneumoniae was high particularly in children with otitis media or upper respiratory tract infections. In H. influenzae isolates the level of beta-lactamase production was over 30% in all groups of patients and specimen types and in M. catarrhalis the level of beta-lactamase production was in excess of 90%. Multidrug resistance was found often among the macrolides, tetracyclines, and trimethoprim/sulfamethoxazole, and these antimicrobials should not be regarded as therapeutic alternatives to the beta-lactams.
Adult↗
Relevance of the Alexander Project: pharmacodynamic considerations.
Application of pharmacodynamic principles for interpretation of data generated by the Alexander Project is possible for beta-lactam, quinolone and macrolide antibiotics. For beta-lactams, the time that serum concentrations remain above the MIC of the pathogen (T > MIC) is the parameter most closely linked with outcome. It has been shown that T > MIC need be only 50-60% of a dose interval. Since the MIC has the greatest influence on this parameter, a conservative estimate of activity would use the MIC90. The only beta-lactam antibiotics in the Alexander Project for which T > MIC90 for the four major pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus) exceeded 50% of the dose interval were amoxycillin/clavulanate (500/125 mg) and ceftriaxone. For macrolides, T > MIC is relevant for erythromycin and clarithromycin, but not azithromycin, for which AUC is the parameter most closely linked to outcome. Erythromycin, clarithromycin and azithromycin showed efficacy against M. catarrhalis only at MIC90. Quinolones (ciprofloxacin and ofloxacin), for which AUC is also the relevant pharmacodynamic parameter, had the greatest activity against H. influenzae and M. catarrhalis at MIC90, but were less effective against S. pneumoniae and S. aureus. Susceptibility data such as those provided by the Alexander Project can aid clinicians in choosing appropriate treatment for LRTI based on pharmacodynamic principles.
4-Quinolones↗
Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.
One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains, collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested for susceptibility to 16 antibiotics. The overall resistance to penicillin was 23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse and Cleveland. Seven centres reported low-level penicillin resistance only. Amoxycillin was more active than ceftriaxone against strains with intermediate resistance to penicillin, and at least four-fold more active than cefuroxime; cefaclor and cefixime had poor activity. Against penicillin-resistant strains, ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited borderline activity and cefixime and cefaclor were inactive. Ten strains fully susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may represent a first step towards the development of cephalosporin resistance. With the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and azithromycin) was considerably higher in penicillin-resistant strains compared with penicillin-susceptible isolates. Erythromycin-resistant isolates were also resistant to the other macrolides tested.
Anti-Bacterial Agents↗
Mortality of nosocomial pneumonia in ventilated patients: influence of diagnostic tools.
The overmortality induced by nosocomial infections, especially pneumonia in ventilated patients (VNP), is still a matter of controversy because it is difficult to know precisely the respective effects of VNP per se and both the underlying illness and the severity of the disease that indicates ICU stay. During a 3-yr period, for each patient mechanically ventilated for more than 48 h we recorded underlying illness, reason for mechanical ventilation, clinical and therapeutic data collected during the first 48 h of ventilation, and death in the ICU. Patients with suspicion of VNP (S-VNP) according to clinical, radiologic, and biologic criteria underwent bronchoscopy with protected specimen brush (PSB) and bronchoalveolar lavage culture (BAL-C). VNP was confirmed (C-VNP) if PSB > or = 10(3) cfu/ml and/or BAL-C > or = 10(4) cfu/ml. Prognostic multivariate analysis was performed introducing S-VNP and C-VNP as time-dependent covariates. Of the 387 studied patients, 112 S-VNP and 56 C-VNP were observed with overall mortality of 43% (168 patients). MacCabe, APACHE II score, shock, use of sedatives and absence of enteral nutrition were additively associated with an increased mortality as well as C-VNP (relative risk [RR]: 1.8, p = 0.007). Nevertheless, when S-VNP and C-VNP were simultaneously introduced in the Cox model, only S-VNP remained associated with increased mortality. In patients suspected of VNP, confirmation of VNP using PSB and/or BAL-C adds no prognostic information. Whether this could be explained by the lack of sensitivity of protected distal samples or the severity of underlying conditions of S-VNP patients is still an open issue. A multivariate analysis based on follow-up data during the ICU course of ventilated patients will be initiated in the near future.
Aged↗
Native valve endocarditis due to nutritionally variant Streptococcus adjacens associated with Enterococcus faecium.
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Aged↗
Epidemiology of antibiotic resistance in Haemophilus influenzae.
During the last 10 years, a continuous increase in the incidence of beta-lactamase-producing Haemophilus influenzae has been observed; in addition, beta-lactamase-negative ampicillin-resistant strains are better identified and more frequently isolated. During the same period, resistance to tetracyclines and chloramphenicol decreased to a very low level. The incidence of resistant bacteria is highly variable according to the site of infection, patient's age, type of Haemophilus, and country or region, according to local epidemiological factors. Follow-up multicenter studies are needed to monitor the evolution of resistance to these antibiotics and also emergence and spread of resistance to other antibiotics, such as new fluoroquinolones, new beta-lactams, and new macrolides.
Anti-Bacterial Agents↗
Decreased teicoplanin susceptibility of methicillin-resistant strains of Staphylococcus aureus.
Between February 1992 and February 1993, 12 patients were seen who were infected or colonized with methicillin-resistant strains of Staphylococcus aureus. The strains had decreased susceptibility to teicoplanin (MICs, 8-16 micrograms/mL). Field inversion gel electrophoresis showed the strains belonged to three related clones (A1, A2, and A3). The patients were though to have acquired the strains nosocomially. Consistent with results of laboratory studies of teicoplanin-resistant S. aureus, all but 1 strain expressed a 35-kDa membrane protein, and 9 strains expressed increased levels of penicillin-binding protein 2 complex. Six strains were isolated from patients treated with glycopeptides. These data suggest that nosocomial transmission of S. aureus with decreased teicoplanin susceptibility may occur during glycopeptide use and that such strains develop resistance by a mechanism associated with the appearance of a 35-kDa membrane protein. Surveillance is necessary to monitor for the potential selection of resistant clones that may be capable of dissemination.
Adult↗
SYN987, SYN1193, and SYN1253, new quinolones highly active against gram-positive cocci.
SYN987, 1193 and 1253 are new fluorinated quinolones with enhanced activity against Gram-positive bacteria. The MICs of SYN 987, 1193 or 1253 were studied by an agar dilution method against 88 streptococci (including penicillin resistant Streptococcus pneumoniae), 30 enterococci and 62 Staphylococcus aureus. SYN 987, 1193 and 1253 were 2 to 4 times more active than sparfloxacin and 16-64 times more active than older fluoroquinolones against all streptococci and ciprofloxacin-resistant S. aureus. This study demonstrates that SYN 987, 1193 and 1253 are extremely potent antibacterial agents which deserve further evaluation.
Anti-Infective Agents↗
Resistance to ceftriaxone and other beta-lactams in bacteria isolated in the community. The Vigil'Roc Study Group.
The incidence of bacterial species and their susceptibilities to ceftriaxone and other beta-lactams from patients with community-acquired infections were evaluated in a multicenter study over a 4-month period. A total of 5,768 bacterial isolates were classified according to whether the patient had been previously hospitalized or had received antibiotic treatment. The most relevant findings were the presence of 33.8% penicillin-resistant Streptococcus pneumoniae isolates, 25% beta-lactamase-producing Haemophilus influenzae isolates, and 36.4% amoxicillin-resistant Escherichia coli isolates. All of these bacteria were fully susceptible to ceftriaxone. Nosocomial multiply-resistant bacteria, and particularly methicillin-resistant S. aureus, were found, as expected, at a higher frequency among previously hospitalized patients. However, such bacteria may be present in the community; their incidence is high in particular clinical settings, and such bacteria should be considered when one is choosing a first-line therapy for the treatment of severe infections.
Anti-Bacterial Agents↗
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.
Amoxicillin↗
Effect of previous antimicrobial therapy on the accuracy of the main procedures used to diagnose nosocomial pneumonia in patients who are using ventilation.
We evaluated the effect of antibiotic treatment received before the suspicion of pneumonia on the diagnostic yield of protected specimen brush (PSB), direct examination (BAL D) and culture (BAL C) of lavage fluid on consecutive mechanically ventilated patients with suspected nosocomial pneumonia. Bronchoscopy was always performed before any treatment for suspected pneumonia. One hundred and sixty-one patients with suspected pneumonia underwent PSB and BAL before any institution or change in antibiotic therapy (AB). Sixty-five patients received AB for an earlier septic episode (ON AB group) and 96 patients did not (OFF AB group). All but two strains recovered were highly resistant to previous AB. Sensitivity and specificity of each test were not different between the ON AB and OFF AB groups as well as the percentage of complete agreement between the 3 procedures, 74 and 67% respectively. We conclude that previous AB received to treat an earlier septic episode unrelated to suspected pneumonia do not affect the diagnostic yield of PSB and BAL.
Aged↗
Reappraisal of distal diagnostic testing in the diagnosis of ICU-acquired pneumonia.
BACKGROUND: The thresholds of the diagnostic procedures performed to diagnose ICU-acquired pneumonia (IAP) are either speculated or incompletely tested. PURPOSE: To evaluate the best threshold of protected specimen brush (PSB), plugged telescoping catheter (PTC), BAL culture (BAL C), and direct examination of cytocentrifugated lavage fluid (BAL D) to diagnose IAP. Each mechanically ventilated patient with suspected IAP underwent bronchoscopy successively with PSB, PTC, and BAL in the lung segment identified radiographically. POPULATION: One hundred twenty-two episodes of suspected IAP (occurring in 26% of all mechanically ventilated patients) were studied. Forty-five patients had definite IAP, and 58 had no IAP. Diagnosis was uncertain in 19 cases. RESULTS: Using the classic thresholds, sensitivity was 67% for PSB, 54% for PTC, 59% for BAL D, and 77% for BAL C. Specificity was 88% for PSB, 77% for PTC, 98% for BAL D, and 77% for BAL C. We used receiver operating characteristics methods to reappraise thresholds. Decreasing the thresholds to 500 cfu/mL for PSB, 10(2) cfu/mL for PTC, 2% cells containing bacteria for BAL D, 4 x 10(3) cfu/mL for BAL C increased the sensitivities (plus 14%, 23%, 25%, 10%, respectively) and moderately decreased the specificities (minus 4%, 9%, 2%, 4%, respectively) of the four examinations. The association of PSB with a 500 cfu/mL threshold and BAL D with a 2% threshold recovered all but one episode of pneumonia (SE 96 +/- 4%) with a 84 +/- 10% specificity. For a similar ICU population, these "best" thresholds increased negative predictive value with a minimal decrease of positive predictive value. They need to be confirmed in multiple ICU settings in prospective fashion.
Aged↗
Epidemiology of quinolone resistance: Europe and North and South America.
After nearly 10 years of fluoroquinolone usage for a wide range of bacterial infections, a striking difference has been observed in the incidence of bacterial resistance to fluoroquinolones between bacteria responsible for community- and hospital-acquired infections, respectively. Resistance is only rarely encountered among common pathogens. In most studies, 97 to 100% of all pathogens are fully susceptible to fluoroquinolones. In contrast, resistance to fluoroquinolones has emerged and increased among bacteria responsible for nosocomial infections. The incidence of resistance to fluoroquinolones varies between bacterial species, clinical settings and countries, and is related to local epidemic spread of a few clones. The highest incidence of resistance is observed in Pseudomonas aeruginosa, Acinetobacter spp., Serratia marcescens and, particularly, methicillin-resistant Staphylococcus aureus (MRSA): some investigators have reported 95 to 100% fluoroquinolone resistance among MRSA. Follow-up of trends in the resistance to fluoroquinolones based upon surveillance programmes are needed.
4-Quinolones↗
Usefulness of pulsed-field gel electrophoresis in the epidemiological analysis of Staphylococcus aureus isolates with decreased susceptibility to teicoplanin.
Pulsed-field gel electrophoresis for analysis of comparatively mega-base sized chromosomal restriction fragments is an important molecular technique in the epidemiological study of a variety of nosocomial pathogens. The usefulness of this approach is demonstrated in the evaluation of Staphylococcus aureus isolates exhibiting decreased susceptibility to teicoplanin in two clinical settings: multiple cultures from a single patient and isolates from different patients within the same hospital.
Cross Infection↗