Propensity of fluoroquinolones with different moieties at position 8 to cause resistance development in clinical isolates of Streptococcus pneumoniae.
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Anti-Infective Agents↗
Biomedical subjects
A C Fluit
Publications and source records attributed to A C Fluit.
Molecular detection of antimicrobial resistance.
The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art.
Bacterial Infections↗
Increased prevalence of class I integrons in Escherichia coli, Klebsiella species, and Enterobacter species isolates over a 7-year period in a German university hospital.
The prevalence of integrons in five enterobacterial species was analyzed in 900 blood culture isolates from 1993, 1996, and 1999. Remarkably, the prevalence increased from 4.7% in 1993 to 9.7% in 1996 and finally to 17.4% in 1999 (P < 0.01). Within 7 years the combined percentage of P1 strong promoters and P1 weak plus P2 active promoters with high transcription efficacies has increased from 23.1 to 33.3 and finally 60% (P < 0.05).
Blood↗
Epidemiology and susceptibility of 3,051 Staphylococcus aureus isolates from 25 university hospitals participating in the European SENTRY study.
A total of 3,051 methicillin-susceptible Staphylococcus aureus (MSSA) isolates and methicillin-resistant S. aureus (MRSA) isolates in Europe were compared. MRSA isolates constituted 25% of all isolates and were more prevalent in southern Europe. MRSA isolates appeared to be more prevalent in intensive care units than in outpatient departments. Only a small minority of MSSA isolates were multidrug resistant, whereas the majority of MRSA isolates were multidrug resistant.
Anti-Bacterial Agents↗
International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program.
A surveillance program (SENTRY) of bloodstream infections (BSI) in the United States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184 episodes of candidemia in 71 medical centers (32 in the United States, 23 in Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were due to Candida albicans, followed by Candida glabrata and Candida parapsilosis (15%), Candida tropicalis (9%), and miscellaneous Candida spp. (6%). In the United States, 45% of candidemias were due to non-C. albicans species. C. glabrata (21%) was the most common non-C. albicans species in the United States, and the proportion of non-C. albicans BSIs was highest in Latin America (55%). C. albicans accounted for 60% of BSI in Canada and 58% in Europe. C. parapsilosis was the most common non-C. albicans species in Latin America (25%), Canada (16%), and Europe (17%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (97 to 100% at < or =8 microg/ml). Likewise, 97 to 100% of these species were inhibited by < or =1 microg/ml of ravuconazole (concentration at which 50% were inhibited [MIC(50)], 0.007 to 0.03 microg/ml) or voriconazole (MIC(50), 0.007 to 0.06 microg/ml). Both ravuconazole and voriconazole were significantly more active than fluconazole against C. glabrata (MIC(90)s of 0.5 to 1.0 microg/ml versus 16 to 32 microg/ml, respectively). A trend of increased susceptibility of C. glabrata to fluconazole was noted over the three-year period. The percentage of C. glabrata isolates susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and MIC(50)s decreased from 16 to 4 microg/ml. A similar trend was documented in both the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some geographic differences in susceptibility to triazole were observed with Canadian isolates generally more susceptible than isolates from the United States and Europe. These observations suggest susceptibility patterns and trends among yeast isolates from BSI and raise additional questions that can be answered only by continued surveillance and clinical investigations of the type reported here (SENTRY Program).
Antifungal Agents↗
Bacterial resistance in urinary tract infections: how to stem the tide.
Each year, approximately 10% of the population is diagnosed with a urinary tract infection (UTI). Escherichia coli is the most prevalent pathogen in UTIs but other species make significant contributions. UTIs are commonly treated with antibiotics and, therefore, a potential source for the emergence and/or selection of resistant bacteria. Although susceptibility to some antibiotics for a number of species is still high, resistance is an issue both for community- and hospital-acquired UTI. However, often treatment is empiric, especially in the community setting. This empiric treatment is often guided by inadequate information about the (local) rates of resistance, selection and emergence of resistance, although there is a general consensus that there is a relationship between antibiotic use and resistance. It is well known that some antibiotics, e.g., some fluoroquinolones, are able to induce mutations leading to resistance but the antibiotics prescribed also affect the commensal flora, potentially selecting resistant organisms. However, antibiotics meant to treat other infections may select uropathogens and, thereby, the risk for UTIs increases. The duration of treatment of any infection is an important factor to consider in this respect, as well as subinhibitory concentrations of the antibiotic prescribed. Prudent use of new and still effective antibiotics is required. Although prudent use of these antibiotics may help to reduce the prevalence of antibiotic-resistant uropathogens, elimination will be hard to achieve. Therefore, we believe, that we can reduce the tide but we will still have to deal with the resistance problem in the future.
Anti-Bacterial Agents↗
Molecular analyses of possible mechanisms coding for low-level mupirocin resistance in clinical Staphylococcus aureus isolates.
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Anti-Bacterial Agents↗
Epidemiology of quinolone resistance of Klebsiella pneumoniae and Klebsiella oxytoca in Europe.
The epidemiology of quinolone resistance and the concomitant resistance to other antibiotic classes was investigated in 445 Klebsiella pneumoniae and 238 Klebsiella oxytoca isolates. Decreased susceptibility to ciprofloxacin was found in 7.2% and 3.4% of these two species, respectively. Ciprofloxacin resistance was significantly linked to ceftazidime resistance, the hallmark of extended-spectrum beta-lactamase production, as well as to resistance to all antibiotic classes tested. Using automated ribotyping, seven intrahospital- and interhospital-transmitted clones of ciprofloxacin-resistant isolates were found. The newer fluoroquinolones sitafloxacin and clinafloxacin may become increasingly valuable, since they proved to be active also against ciprofloxacin-resistant isolates.
Anti-Bacterial Agents↗
Antimicrobial resistance in European isolates of Pseudomonas aeruginosa. European SENTRY Participants.
Pseudomonas aeruginosa is responsible for a substantial fraction of hospital infections. Twenty-five European university hospitals submitted a total of 1411 Pseudomonas aeruginosa isolates for susceptibility testing during 1997 and 1998. The isolates showed highest susceptibility to amikacin (87.5%), meropenem (87.3%) and piperacillin/tazobactam (86.8%). Susceptibility to ciprofloxacin was 73.2%. There was no clear geographical distribution of resistance, although isolates from northwestern Europe tended to be more susceptible than those from southeastern Europe. Isolates that were resistant to one class of antibiotics were also often resistant to at least one other class of antibiotics. Imipenem-resistant isolates were generally not clonally related.
Anti-Bacterial Agents↗
Distribution of macrolide-resistance genes in Staphylococcus aureus blood-culture isolates from fifteen German university hospitals. M.A.R.S. Study Group. Multicentre Study on Antibiotic Resistance in Staphylococci.
The purpose of the study was to analyze the distribution of the macrolide-resistance genes in 134 erythromycin-resistant Staphylococcus aureus blood-culture isolates collected at 15 German university hospitals. The most prevalent resistance gene was ermC (68/134; 50.7%), followed by ermA (52/134; 38.8%), ereB (10/134; 7.5%), and mrsA/msrB (4/134; 6%). The least common genes were ermB (3/134; 2.2%) and ereA (1/134; 0.7%). Overall, resistance to erythromycin was predominantly due to the presence of two erm genes, although with different distributions, depending on the methicillin-resistance pattern.
Anti-Bacterial Agents↗
Antimicrobial resistance among urinary tract infection (UTI) isolates in Europe: results from the SENTRY Antimicrobial Surveillance Program 1997.
The SENTRY Antimicrobial Surveillance Program was established to monitor the occurrence and antimicrobial susceptibility of bacterial pathogens via an international network of sentinel hospitals. Twenty European hospitals referred a total of 887 urinary tract infection (UTI) isolates to the European SENTRY reference laboratory during the period October-December 1997. Ninety percent of the referred species were represented by Escherichia coli (52%), Enterococcus spp. (12%), Klebsiella spp. (7%), Proteus spp. (7%), Pseudomonas aeruginosa (7%), and Enterobacter spp. (5%). The susceptibility of E. coli isolates to penicillins was less than 60%, while almost all of the isolates were susceptible to piperacillin/tazobactam (98% susceptibility), cephalosporins (98%), and carbapenems (100%). Amikacin was the best aminoglycoside (99.8% susceptibility). The susceptibility to quinolones was only 88-89%, with highest levels of resistance observed for isolates from Portugal, Italy, England, The Netherlands, and some centers in France, Spain, and Poland. The susceptibility of Klebsiella spp. to the newer generations of cephalosporins was 82-95% and to the carbapenems 100%. Amikacin was again the best aminoglycoside (94% susceptibility). The susceptibility of Enterobacter spp. to any beta-lactam antibiotic was poor, except for the carbapenems (100% susceptibility) and cefepime (90% susceptibility), while the susceptibility to aminoglycosides was 80-89%. Proteus spp. showed complete susceptibility to cefepime, ceftriaxone, the carbapenems, and piperacillin/tazobactam, while the susceptibility of P. aeruginosa isolates was poor, with best results for the carbapenems (susceptibility 89%), piperacillin/tazobactam (susceptibility 84%), and amikacin and ticarcillin (susceptibility to both 80%). Enterococcus spp. showed the highest susceptibility to vancomycin (98%), teicoplanin (98%), and ampicillin (94%).
Candida↗
Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998.
As part of the European arm of the SENTRY Antimicrobial Surveillance Program, 25 European university hospitals referred 9613 blood isolates for in vitro testing against >20 antimicrobial agents. Escherichia coli, Staphylococcus aureus, coagulase-negative Staphylococcus, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the 5 most frequent isolates and accounted for two-thirds of all referrals, with minor regional variation. Of these, approximately 0.36% of E. coli and 16.7% of K. pneumoniae isolates proved to be potential extended-spectrum beta-lactamase producers, and their incidence clearly varied regionally. Quinolone resistance was detected among gram-negative species; in particular, P. aeruginosa and Acinetobacter species. Considerable regional variation was observed in the incidences of methicillin resistance in S. aureus and penicillin resistance in Streptococcus pneumoniae. The incidence of vancomycin resistance in enterococci was relatively low overall and primarily associated with Enterococcus faecium. However, extrapolation of these data to smaller and nonteaching hospitals should be undertaken with caution, since resistance rates may be lower in these facilities.
Anti-Bacterial Agents↗
Genetic relatedness of multidrug-resistant, methicillin (oxacillin)-resistant Staphylococcus aureus bloodstream isolates from SENTRY Antimicrobial Resistance Surveillance Centers worldwide, 1998.
We reviewed Staphylococcus aureus bloodstream infection isolates from SENTRY centers worldwide during 1998 to evaluate the molecular epidemiology of multiply drug-resistant methicillin (oxacillin)-resistant S. aureus (MDR-MRSA). MDR-MRSA was defined as a S. aureus isolate with a MIC for oxacillin at >2 microg/ml and with four or more additional resistances. A total of 325 unique patient isolates of MDR-MRSA from five continents were analyzed using ribotyping and pulsed-field gel electrophoresis (PFGE). The frequency of MDR-MRSA among all S. aureus BSI isolates ranged from only 2.2% in Canada to 35.6% in the Asia-Pacific region. Forty-eight ribotypes (RT) were distinguished, but over 80% of the isolates were contained within the 10 most prevalent RTs. The most common RT, RT 184.5, which included 30% of all MDR-MRSA, was found on four of five continents. PFGE provided superior discrimination and identified numerous clusters of possible clonal dissemination of MDR-MRSA within individual medical centers and between institutions that are in geographic proximity. In four instances, strains with indistinguishable PFGE patterns were found on more than one continent. The predominant PFGE subtype in South America (RT 893.5/Ia) was isolated from patients at centers in Brazil, Argentina, and Portugal, and closely related subtypes were isolated in Chile and Italy. There is great geographic variation in rates of methicillin- and multidrug-resistance among S. aureus bloodstream isolates worldwide. Although many MDR-MRSA strains group geographically, a few closely related epidemic strains have wide regional and even global range.
Anti-Bacterial Agents↗
Prevalence of macrolide-resistance genes in Staphylococcus aureus and Enterococcus faecium isolates from 24 European university hospitals.
The polymerase chain reaction (PCR) was used to study the prevalence of the macrolide resistance genes ermA, ermB, ermC, msrA/msrB, ereA and ereB, in 851 clinical isolates of Staphylococcus aureus and 75 clinical isolates of Enterococcus faecium that were erythromycin resistant. The isolates were from 24 European university hospitals. In S. aureus, the ermA gene was more common in methicillin-resistant S. aureus (MRSA) isolates (88%) than in methicillin-susceptible S. aureus (MSSA) isolates (38%), and occurred mainly in strains with constitutive MLS(B) expression. In contrast, ermC was more common in MSSA (47%) than in MRSA (5%), occurring mainly in strains with inducible expression. The ereB gene was only found in MRSA isolates expressing a constitutive MLS(B) phenotype (1%). The ereA gene was not detected. Macrolide resistance by efflux due to the msrA/msrB gene was only detected in MSSA isolates (13%). In contrast to S. aureus, erythromycin resistance in E. faecium was almost exclusively due to the presence of the ermB gene (93%).
Anti-Bacterial Agents↗
Typing of 154 clinical isolates of Stenotrophomonas maltophilia by pulsed-field gel electrophoresis and determination of the in vitro susceptibilities of these strains to 28 antibiotics.
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Anti-Bacterial Agents↗
In vitro potency of moxifloxacin, clinafloxacin and sitafloxacin against 248 genetically defined clinical isolates of Staphylococcus aureus.
The in vitro potency of three newer fluoroquinolones, moxifloxacin, clinafloxacin and sitafloxacin was tested against 248 genetically defined Staphylococcus aureus isolates, comprising 116 unrelated S. aureus, seven heterogeneous intermediate vancomycin-resistant S. aureus strains as well as 125 clonally related methicillin-resistant S. aureus. All strains were susceptible to clinafloxacin and sitafloxacin based on an investigational breakpoint of 1 mg/L and were less influenced by mutations within the grl and gyr gene loci. In one-quarter to one-third of the strains tested, reserpine decreased slightly the MICs of moxifloxacin, clinafloxacin and sitafloxacin. Compared with moxifloxacin, clinafloxacin and sitafloxacin showed a significantly increased anti-staphylococcal potency.
Anti-Infective Agents↗
Development of resistance to ciprofloxacin, rifampin, and mupirocin in methicillin-susceptible and -resistant Staphylococcus aureus isolates.
A relationship between resistance to methicillin and resistance to fluoroquinolones, rifampin, and mupirocin has been described for Staphylococcus aureus. Differences in resistance rates may be explainable by a higher spontaneous mutation rate (MR) or a faster development of resistance (DIFF) in methicillin-resistant S. aureus (MRSA). No differences in MR, DIFF, and mutations in grlA and gyrA were detected between methicillin-susceptible S. aureus and MRSA. The higher resistance rates in MRSA are not the result of hypermutability of target genes or a faster emergence of different mutations and may be the consequence of clonal spread of multiresistant MRSA.
Anti-Bacterial Agents↗
In vitro activities of sitafloxacin (DU-6859a) and six other fluoroquinolones against 8,796 clinical bacterial isolates.
The in vitro activities of sitafloxacin, ciprofloxacin, trovafloxacin, levofloxacin, clinafloxacin, gatifloxacin, and moxifloxacin against 5,046 gram-negative bacteria, 3,344 gram-positive cocci, and 406 anaerobes were determined. Sitafloxacin was the most active agent against gram-positive cocci and anaerobes. Against Enterobacteriaceae and nonfermenters, its activity was either equivalent to or better than that of clinafloxacin.
Anti-Infective Agents↗