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J A Karlowsky

Publications and source records attributed to J A Karlowsky.

At least 19 recordsLinked to original sources
PubMed2004

Rates of antimicrobial resistance among common bacterial pathogens causing respiratory, blood, urine, and skin and soft tissue infections in pediatric patients.

Antimicrobial resistance patterns among the principal bacterial pathogens from infections of the respiratory tract, blood, skin and soft tissue, and urinary tract of pediatric patients from the USA, Canada, Germany, France, and Italy were studied using the The Surveillance Network (TSN) database. Among Streptococcus pneumoniae isolates from respiratory tract infections, the prevalence of high-level penicillin resistance (MIC>/=2 microg/ml) ranged from 1.1 (Italy) to 36.2% (USA); erythromycin resistance was higher, ranging from 13.4 (Germany) to 63.8% (France). The prevalence of beta-lactamase-positive Haemophilus influenzae among isolates from lower respiratory tract infections ranged from <10 (Italy and Germany) to 38.4% (USA). Among isolates from blood and skin and soft tissue infections, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) ranged from 7.2% (Canada and Germany) to 27.3% (Italy). The prevalence of Escherichia coli and Klebsiella pneumoniae with putative extended-spectrum beta-lactamases among isolates from blood, urinary tract, and skin and soft tissue infections ranged from 0 (Germany and France) to 29.6% (Italy). With the exception of pseudomonal infections or infections with MRSA, amoxicillin-clavulanate retained moderate activity, whilst ceftriaxone and cefepime were the most effective broad-spectrum injectable agents. Meropenem was the most effective agent against Pseudomonas aeruginosa with <5% resistance. Low levels of resistance, along with acceptable safety profiles and the availability of convenient oral formulations, continue to support the use of ceftriaxone, cefepime, amoxicillin-clavulanate, and meropenem as viable options for the treatment of infections in pediatric patients.

Anti-Bacterial Agents↗
PubMed2004

Antimicrobial susceptibility to levofloxacin and other antibacterial agents among common respiratory pathogens-a Brazilian perspective from the GLOBAL Surveillance Initiative 2001-2002.

The GLOBAL (Global Landscape On Bactericidal Activity of Levofloxacin) Surveillance programme monitored antimicrobial susceptibility patterns of the key respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected in Brazil during 1997-1998, 1999-2000 and 2001-2002. Penicillin and azithromycin resistance among S. pneumoniae strains increased from 1997-1998, reaching 7.9% and 9.5%, respectively, in 2001-2002. Although decreasing by 4.9% since the previous study, trimethoprim-sulphamethoxazole resistance remained high at 33.7%. Concurrent resistance to penicillin, azithromycin and trimethoprim-sulphamethoxazole was seen in 2.9% of the S. pneumoniae isolates collected. Levofloxacin remained extremely active against S. pneumoniae, with 0.3% resistance reported in 1997-1998 and 0% resistance in 1999-2000 and 2001-2002. beta-Lactamase production in H. influenzae was > 10% in all three studies, with correspondingly high rates of ampicillin resistance. Trimethoprim-sulphamethoxazole was the least active agent tested against H. influenzae, with resistance rates of > 40% recorded in all three studies. All H. influenzae isolates were susceptible to cefuroxime, ceftriaxone, azithromycin and levofloxacin. Of the M. catarrhalis isolates, 98.0% in 1997-1998, 98.0% in 1999-2000 and 81.8% in 2001-2002 were beta-lactamase-positive. The continued high prevalence of antimicrobial resistance in Brazil underscores the importance of current surveillance initiatives. Levofloxacin, a fluoroquinolone prescribed widely for respiratory tract infections, continued to show potent activity against key respiratory pathogens.

Anti-Bacterial Agents↗
PubMed2004

Optimal use of antibiotic resistance surveillance systems.

Increasing concern about the emergence of resistance in clinically important pathogens has led to the establishment of a number of surveillance programmes to monitor the true extent of resistance at the local, regional and national levels. Although some programmes have been operating for several years, their true usefulness is only now being realised. This review describes some of the major surveillance initiatives and the way in which the data have been used in a number of different settings. In the hospital, surveillance data have been used to monitor local antibiograms and determine infection control strategies and antibiotic usage policies. In the community, surveillance data have been used to monitor public health threats, such as infectious disease outbreaks involving resistant pathogens and the effects of bioterrorism countermeasures, by following the effects of prophylactic use of different antibiotics on resistance. Initially, the pharmaceutical industry sponsored surveillance programmes to monitor the susceptibility of clinical isolates to marketed products. However, in the era of burgeoning resistance, many developers of antimicrobial agents find surveillance data useful for defining new drug discovery and development strategies, in that they assist with the identification of new medical needs, allow modelling of future resistance trends, and identify high-profile isolates for screening the activity of new agents. Many companies now conduct pre-launch surveillance of new products to benchmark activity so that changes in resistance can be monitored following clinical use. Surveillance data also represent an integral component of regulatory submissions for new agents and, together with clinical trial data, are used to determine breakpoints. It is clear that antibiotic resistance surveillance systems will continue to provide valuable data to health care providers, university researchers, pharmaceutical companies, and government and regulatory agencies.

Anti-Bacterial Agents↗
PubMed2003

Antimicrobial resistance in respiratory pathogens isolated in Brazil during 1999-2000.

The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus Pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study. Of 448 isolates of S. Pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant). All S. Pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin and >90% were susceptible to the B-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (axithyromycin and clarithromycin), showing that susceptibility to these agents also remained unchanged since 1997-1998. The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin resistance correlated with resistance to B-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of B-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998). All H. influenzae isolates were susceptible to levofloxacine, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies. Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of B-lactamase-producing isolates was unchanged (97.9% in 1999-2000;98.0% in 1997-1998). The most active agents against M. catarrhalis were azithromycin (MIC(90),< or = 0.03 microg/ml) and levofloxacin (MIC(90),< or = 0.03 microg/ml). Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the susceptibility of respiratory pathogens to any of the commonly tested and prescribed agents with the exception of trimethoprim-sulfamethoxazole for S. Pneumoniae.

Anti-Bacterial Agents↗
PubMed2003

Antimicrobial susceptibility of 840 clinical isolates of Haemophilus influenzae collected in four European countries in 2000-2001.

In 2000-2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). Beta-Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients or=18 years (16.5%). All isolates were susceptible to amoxicillin-clavulanate, ciprofloxacin and levofloxacin; 99.6% and 98.9% of isolates were susceptible to azithromycin and cefuroxime, respectively. Among the macrolides tested, azithromycin (MIC90, 2 mg/L) was eight-fold more potent than clarithromycin (MIC90, 16 mg/L) and roxithromycin (MIC90, 16 mg/L). Despite variations in beta-lactamase production between different countries, > 99% of all isolates were susceptible to amoxicillin-clavulanate, ciprofloxacin, levofloxacin, and azithromycin.

Anti-Bacterial Agents↗
PubMed2003

In vitro susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: a European multicenter study during 2000-2001.

OBJECTIVE: To assess the current (2001) activity of respiratory fluoroquinolones and comparator agents against respiratory pathogens isolated in European countries. METHODS: During 2000-2001, we prospectively collected 1995 isolates of Haemophilus influenzae, 1870 isolates of Streptococcus pneumoniae and 649 isolates of Moraxella catarrhalis from hospital laboratories in France, Germany, Greece, Italy, Spain and the UK. National Committee for Clinical Laboratory Standards (NCCLS)-approved broth microdilution antimicrobial susceptibility testing methods and interpretive criteria were used throughout. RESULTS: Of the S. pneumoniae isolates, 99.6% were susceptible to moxifloxacin, gatifloxacin and levofloxacin; the corresponding figure for H. influenzae was 100%. All M. catarrhalis isolates had moxifloxacin MICs </= 0.12 mg/L. For all three pathogens, fluoroquinolone susceptibility remained unchanged from the previous 1997-98 study. The incidence of penicillin non-susceptibility in the S. pneumoniae isolates tested remained similar to or higher than that recorded in previous studies: France, 165/291 (56.7%); Germany, 46/506 (9.1%); Greece, 20/55 (36.4%); Italy, 45/364 (12.4%); Spain, 146/268 (54.5%); and the UK, 26/386 (6.7%). Significant levels of resistance to oral compounds (cefuroxime, cefaclor, cefdinir, clarithromycin, azithromycin, tetracycline, and trimethoprim-sulfamethoxazole) were detected among S. pneumoniae isolates. beta-Lactamase production among H. influenzae isolates ranged from 6.2% to 33.1% per country, and ampicillin, clarithromycin or trimethoprim-sulfamethoxazole resistance were the most common phenotypes detected. beta-Lactamase production among M. catarrhalis isolates ranged from 94.1% to 100% per country. CONCLUSIONS: With the exception of a few localized reports, resistance to moxifloxacin and other new fluoroquinolones in common respiratory pathogens is a rare occurrence, despite significant resistance to other compound classes. Surveillance will play a key role in tracking changes in fluoroquinolone susceptibility in European countries.

Anti-Infective Agents↗
PubMed2003

Antibiotic susceptibility of isolates of Bacillus anthracis, a bacterial pathogen with the potential to be used in biowarfare.

Bacillus anthracis is a bacterial species that could be used in a bioterrorist attack. We tested a collection of isolates with a range of relevant antimicrobial compounds. All isolates tested were susceptible to ciprofloxacin and doxycycline. Penicillin and amoxicillin, with or without clavulanate, showed in vitro activity against all B. anthracis isolates. Ceftriaxone demonstrated lower-level in vitro activity compared to penicillin-related compounds against B. anthracis. In vitro data from this study are in keeping with available guidelines.

Anthrax↗
PubMed2002

Ceftriaxone activity against Gram-positive and Gram-negative pathogens isolated in US clinical microbiology laboratories from 1996 to 2000: results from The Surveillance Network (TSN) Database-USA.

Ceftriaxone was introduced into clinical practice in the USA in 1985 and was the first extended-spectrum (third-generation) cephalosporin approved for once-daily treatment of patients with Gram-positive or Gram-negative infections. Review of ceftriaxone activity is important given its continued use since the mid-1980s and reports of emerging resistance among all antimicrobial agent classes. We reviewed the activity of ceftriaxone and relevant comparative agents against five Gram-positive and 11 Gram-negative species for a 5-year period, 1996-2000, using data from The Surveillance Network (TSN) Database-USA. All MIC results were interpreted using NCCLS breakpoint criteria. Ceftriaxone resistance among isolates of Streptococcus pneumoniae (n=17219) remained essentially unchanged over the 5 years studied and in fact was lower from 1998 to 2000 (5.0-5.1%) than in 1996 (6.3%) and 1997 (6.6%). Ceftriaxone resistance (range, 5.1-6.9%) among viridans group streptococci (n=6621) varied by <2% from 1997 to 2000. Beta-lactam-resistant Streptococcus pyogenes (n=935) and group B beta-haemolytic streptococci (n=2267) were not identified in any year. Among methicillin-susceptible Staphylococcus aureus (n=39 284) ceftriaxone resistance was 0.1-0.3% per year from 1996 to 2000. Ceftriaxone resistance among Escherichia coli (n=472407; range, 0.2-0.4%), Klebsiella oxytoca (n=16231; range, 3.5-4.8%), Klebsiella pneumoniae (n=117754; range, 1.9-2.6%), Proteus mirabilis (n=67692; range, 0.2-0.3%), Morganella morganii (n=11251; range, 0.3-2.1%) and Serratia marcescens (n=26519; range, 1.6-3.8%) was low and consistent from 1996 to 2000. Resistance to ceftriaxone among Enterobacter cloacae (n=48114; range, 21.7-23.9%) was relatively high, compared with other Enterobacteriaceae, but unchanged from 1996 to 2000. Rates of resistance to ceftriaxone among Acinetobacter spp. (n=20813) increased from 24.8% in 1996 to 45.1% in 2000. All Haemophilus influenzae (n=7911) and Neisseria gonorrhoeae (n=218) were susceptible to ceftriaxone, as were 99.7% of Moraxella catarrhalis (n=312) tested in 1996 and 1997. In summary, ceftriaxone has retained its potent activity against the most commonly encountered Gram-positive and Gram-negative human pathogens despite widespread and ongoing clinical use for more than 15 years.

Anti-Bacterial Agents↗
PubMed2002

In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe.

OBJECTIVE: To assess the activities of levofloxacin and the comparator agents erythromycin, clarithromycin, azithromycin and doxycycline against atypical respiratory pathogens. METHODS: One hundred and forty-six Legionella pneumophila, 41 Mycoplasma pneumoniae and nine Chlamydia pneumoniae isolates were procured from various culture collections in North America and Europe and tested for susceptibility to the above agents by broth microdilution. The isolates came primarily from clinical sources and were collected from patients between 1995 and 1999. RESULTS: Against L. pneumophila, levofloxacin was the most active agent, with an MIC(90) of 0.03 mg/L, twofold more active than clarithromycin (0.06 mg/L), 16-fold more active than erythromycin and azithromycin (0.5 mg/L) and 64-fold more active than doxycycline. Against M. pneumoniae, azithromycin (MIC(90) < or = 0.0005 mg/L) was the most active agent. However, two isolates of M. pneumoniae, one from the USA and one from Finland, were macrolide resistant (MIC > or = 4 mg/L), but levofloxacin susceptible (MIC 0.25 mg/L). The geographic origin of L. pneumophila and M. pneumoniae did not affect the MIC range for any antimicrobial agent tested. Against C. pneumoniae, clarithromycin was the most active agent, with an MIC range of < or =0.008-0.03 mg/L. CONCLUSIONS: Levofloxacin had comparable activity to the other agents tested against the atypical respiratory pathogens, confirming its potential as an alternative for empirical therapy of community-acquired pneumonia.

Anti-Bacterial Agents↗
PubMed2002

Antimicrobial resistance among respiratory pathogens collected in Thailand during 1999-2000.

A multi-center surveillance study was conducted in Thailand during 1999-2000 to determine antimicrobial susceptibilities among the respiratory pathogens Streptococcus pneumoniae (n = 206), Haemophilus influenzae (n = 305), and Moraxella catarrhalis (n = 39). Of the S. pneumoniae isolates collected, 33.5% were penicillin-susceptible, 27.2% intermediate and 39.3% resistant. Expectedly, resistance rates to beta-lactams were higher among penicillin-resistant (ceftriaxone, 14.8%; amoxicillin-clavulanate, 42.0%; cefuroxime, 100%) than penicillin-susceptible (ceftriaxone, 0%; amoxicillin-clavulanate, 0%; cefuroxime, 0%) isolates. Likewise, azithromycin and clarithromycin resistances were 4.3% and 5.8% among penicillin-susceptible isolates, and 77.8% and 95.1% among penicillin-resistant isolates. All S. pneumoniae remained susceptible to vancomycin and 99.5% were susceptible to levofloxacin. Multidrug resistance (resistance to >3 antimicrobial classes) was present in 25.2% of pneumococcal isolates (n = 52), with resistance to azithromycin, penicillin and trimethoprim-sulfamethoxazole the most common phenotype (40/52 isolates; 77.0%). Among the isolates of H. influenzae, the prevalence of beta-lactamase production was 45.2%. All isolates of H. influenzae were susceptible to amoxicillin-clavulanate, azithromycin, ceftriaxone, cefuroxime and levofloxacin while 49.5% were resistant to trimethoprim-sulfamethoxazole. All 39 isolates of M. catarrhalis produced beta-lactamase. Azithromycin (MIC90, < or = 0.03 microg/ml) and levofloxacin (MIC90, 0.03 microg/ml) were the most active agents tested against M. catarrhalis. The results of this study may serve as a baseline for future studies to monitor antimicrobial susceptibilities among respiratory pathogens in Thailand.

Anti-Bacterial Agents↗
PubMed2001

Prevalence of antimicrobial resistance among urinary tract pathogens isolated from female outpatients across the US in 1999.

In the United States, trimethoprim-sulphamethoxazole (TMP-SMX) is the recommended first-line treatment for uncomplicated urinary tract infections (UTIs) in females, in regions with resistance rates of <10-20%. Unfortunately, current data on regional resistance is often not readily available to physicians and regional variability in resistance remains largely unknown. This report presents antimicrobial susceptibility data for TMP-SMX and three other commonly tested antimicrobials organized by state and region to demonstrate current regional variability in resistance in the US. In the last quarter of 1999, 5739 fresh clinical isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Staphylococcus saprophyticus were collected from 202 laboratories throughout the US. Susceptibility testing was performed against TMP-SMX, cephalothin, nitrofurantoin and ciprofloxacin using broth microdilution. Data were analyzed by patient age and specimen source, and by state and region. In the US as a whole, resistance to TMP-SMX was 16.8% for E. coli, 7.8% for K. pneumoniae, 12.1% for P. mirabilis and 3.0% for S. saprophyticus, but these rates showed considerable regional variation. By state, E. coli resistance ranged from 7.4% in Pennsylvania to 33.3% in Iowa (among states with > or =50 isolates tested). Regionally, resistance for all uropathogens taken together ranged from 8.5% in East South-Central to 22.8% in West South-Central. Ciprofloxacin demonstrated the broadest activity of the antimicrobials tested and was more active than TMP-SMX against all pathogens. Resistance to TMP-SMX among E. coli now approaches or exceeds 20% in some areas. As resistance among uropathogens reaches clinically significant levels in many areas, continued regional surveillance is essential to ensure the provision of effective empiric therapy for urinary tract infections.

Adolescent↗
PubMed2001

Evaluation of current activities of fluoroquinolones against gram-negative bacilli using centralized in vitro testing and electronic surveillance.

Given the propensity for Enterobacteriaceae and clinically significant nonfermentative gram-negative bacilli to acquire antimicrobial resistance, consistent surveillance of the activities of agents commonly prescribed to treat infections arising from these organisms is imperative. This study determined the activities of two fluoroquinolones, levofloxacin and ciprofloxacin, and seven comparative agents against recent clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia using two surveillance strategies: 1) centralized in vitro susceptibility testing of isolates collected from 27 hospital laboratories across the United States and 2) analysis of data from The Surveillance Network Database-USA, an electronic surveillance network comprising more than 200 laboratories nationwide. Regardless of the surveillance method, Enterobacteriaceae, P. aeruginosa, and A. baumannii demonstrated similar rates of susceptibility to levofloxacin and ciprofloxacin. Susceptibilities to the fluoroquinolones approached or exceeded 90% for all Enterobacteriaceae except Providencia spp. (</=65%). Approximately 70% of P. aeruginosa and 50% of A. baumanii isolates were susceptible to both fluoroquinolones. Among S. maltophilia isolates, 50% more isolates were susceptible to levofloxacin than to ciprofloxacin. Overall, the rate of ceftazidime nonsusceptibility among Enterobacteriaceae was 8.7%, with fluoroquinolone resistance rates notably higher among ceftazidime-nonsusceptible isolates than ceftazidime-susceptible ones. Multidrug-resistant isolates were present among all species tested but were most prevalent for Klebsiella pneumoniae and Enterobacter cloacae. No gram-negative isolates resistant only to a fluoroquinolone were encountered, regardless of species. Thus, while levofloxacin and ciprofloxacin have maintained potent activity against Enterobacteriaceae, the potential for fluoroquinolone resistance, the apparent association between fluoroquinolone and cephalosporin resistance, and the presence of multidrug resistance in every species examined emphasize the need to maintain active surveillance of resistance patterns among gram-negative bacilli.

Anti-Infective Agents↗
PubMed2001

Nitrofurantoin is active against vancomycin-resistant enterococci.

The activity of nitrofurantoin was tested against 300 isolates of Enterococcus faecium, Enterococcus faecalis, and Enterococcus gallinarum. No isolates tested were resistant to nitrofurantoin (MIC, >/=128 microg/ml), including vancomycin-resistant E. faecium isolates with vanA- and vanB-positive genotypes and vancomycin-resistant E. gallinarum isolates. We conclude that nitrofurantoin may provide effective treatment of urinary tract infections caused by vancomycin-resistant enterococci.

Anti-Bacterial Agents↗
PubMed2001

Need for annual surveillance of antimicrobial resistance in Streptococcus pneumoniae in the United States: 2-year longitudinal analysis.

Although changing patterns in antimicrobial resistance in Streptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniae antimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997-1998 and 1998-1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997-1998 were encountered in 1998-1999. This longitudinal surveillance study of resistance in S. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

Anti-Bacterial Agents↗
PubMed2001

Multidrug-resistant urinary tract isolates of Escherichia coli: prevalence and patient demographics in the United States in 2000.

Concurrent resistance to antimicrobials of different structural classes has arisen in a multitude of bacterial species and may complicate the therapeutic management of infections, including those of the urinary tract. To assess the current breadth of multidrug resistance among urinary isolates of Escherichia coli, the most prevalent pathogen contributing to these infections, all pertinent results in The Surveillance Network Database-USA from 1 January to 30 September 2000 were analyzed. Results were available for 38,835 urinary isolates of E. coli that had been tested against ampicillin, cephalothin, ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Of these isolates, 7.1% (2,763 of 38,835) were resistant to three or more agents and considered multidrug resistant. Among the multidrug-resistant isolates, 97.8% were resistant to ampicillin, 92.8% were resistant to trimethoprim-sulfamethoxazole, 86.6% were resistant to cephalothin, 38.8% were resistant to ciprofloxacin, and 7.7% were resistant to nitrofurantoin. The predominant phenotype among multidrug-resistant isolates (57.9%; 1,600 of 2,793) included resistance to ampicillin, cephalothin, and trimethoprim-sulfamethoxazole. This was the most common phenotype regardless of patient age, gender, or inpatient-outpatient status and in eight of the nine U.S. Bureau of the Census regions. Rates of multidrug resistance were demonstrated to be higher among males (10.4%) than females (6.6%), among patients > 65 years of age (8.7%) than patients < or = 17 (6.8%) and 18 to 65 (6.1%) years of age, and among inpatients (7.6%) than outpatients (6.9%). Regionally, the rates ranged from 4.3% in the West North Central region to 9.2% in the West South Central region. Given the current prevalence of multidrug resistance among urinary tract isolates of E. coli in the United States (7.1%), continued local, regional, and national surveillance is warranted.

Adolescent↗
PubMed2001

Influence of human serum on antifungal pharmacodynamics with Candida albicans.

Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum-20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (> or = 4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding.

Antifungal Agents↗