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In vitro antimicrobial activity of GAR-936 tested against antibiotic-resistant gram-positive blood stream infection isolates and strains producing extended-spectrum beta-lactamases.

GAR-936, a new, semisynthetic glycylcycline, has shown good antibacterial activity against a wide range of clinically important Gram-positive and -negative aerobic bacteria including Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, most Enterobacteriaceae, Staphylococcus aureus and Enterococcus spp. The purpose of this study was to determine the activity of GAR-936 against a range of Gram-positive and -negative bloodstream isolates including many strains producing extended-spectrum beta-lactamases (ESBLs). Six hundred four bloodstream isolates of Gram-positive cocci collected as part of the SENTRY surveillance program were selected for their geographic diversity. GAR-936 was also tested against an additional 176 Gram-negative cocci isolates (Klebsiella pneumoniae, 98 strains; Escherichia coli, 78 strains), 96 of which were ESBL-producers. Broth microdilution testing was used to determine the susceptibility of the selected organisms and a range of comparator antimicrobial agents whose choice was based on their activities against the selected pathogens and included a mix of both newer and older agents. Presence of an ESBL-producing strain was confirmed using the clavulanate test. GAR-936 demonstrated impressive activity against all 604 strains of Gram-positive cocci, with an MIC range of <or=0.015-1 microg/mL, and MIC(90)s ranging from <or=0.05 microg/mL for S. pneumoniae to 0.25 for S. aureus and coagulase-negative staphylococci. MICs against the 176 Gram-negative isolates were higher (range 0.06-4 microg/mL), with MIC(90)s of 0.25-1 microg/mL. The activity of GAR-936 was relatively unaffected by the presence of ESBLs. The activity of GAR-936 was particularly impressive against Gram-positive cocci when compared against the test results for vancomycin and the newer antimicrobial agents, linezolid and quinupristin/dalfopristin. The MIC(90)s for GAR-936 were significantly lower than the comparator agents for all species tested with particularly impressive results against S. pneumoniae and enterococci.

Anti-Bacterial Agents↗

Antimicrobial resistance in recent fecal enterococci from healthy volunteers and food handlers in Spain: genes and phenotypes.

Susceptibility patterns to 15 different antibiotics and the presence of resistance genes were evaluated in recent fecal Enterococcus isolates recovered from 42 healthy volunteers (HV) and 43 food-handlers (FH). A total of 142 Enterococcus faecalis, 74 Enterococcus faecium, and 23 Enterococcus spp. with different antibiotic susceptibility patterns were studied. A higher percentage of resistance for moxifloxacin, erythromycin, glycopeptides and high-level resistance (HLR) to gentamicin were observed in the FH group. Ampicillin- or linezolid-resistant isolates were not recovered in any of the groups. The tet(M) gene was found in 96% and in 85% of tetracycline-resistant isolates from HV and FH, respectively. HLR-kanamycin was mediated by aph(3')-IIIa, or aac(6')-aph(2"), or both genes in all isolates from HV group and in 86% from FH group. The aac(6')-aph(2") gene was found in all HLR-gentamicin isolates. Ninety-one percent of HV and 71% of FH erythromycin-resistant isolates harbored the erm(B) gene (erythromycin MIC range of 8-128 microg/ml), whereas erm(A), erm(C), or mef(A) genes were not detected. Coexistence of erm(B), aph(3')-IIIa, and tet(M) genes was observed in 17% of the isolates of both groups. The HLR-gentamicin isolates presented unrelated PFGE patterns while 2 out of 3 vanA E. faecium isolates showed an indistinguishable SmaI-pulsed-field gel electrophoresis (PFGE) pattern. This study shows that despite 4 years of official banning of antibiotic growth promoters in animals, enterococci isolated from FH are more resistant than those from HV. This suggests the permanence of resistant clones or transferable resistance elements in farms and a possible exchange between food products and humans, or eventually the long-term permanence of certain clones in the FH intestinal tract.

Anti-Bacterial Agents↗

[The effect of a raffinose diet and cooked legumes on various processes in the large bowel in the rat].

Changes of pH, enzyme activity and microflora in the large bowel of the rat after feeding them various diets containing raffinose and leguminous seeds (soybean, peas and beans) have been studied. Feeding a 12% raffinose-containing diet as well as cooked leguminous seeds lowered pH. However, similar decrease of pH was observed after some other diets (for example, milk powder or raw pearl barley). Remarkable alpha-galactosidase activity in the large bowel of rats after legume diet has been observed whereas it was not noted in the small bowel. The source of alpha-galactosidase are probably bacteria of the large intestine content (Lactobacillus spp., Enterococcus, Escherichia coli). No relationship between the isolated microflora and kind of a diet was observed.

Animals↗

Newly documented antimicrobial activity of quinolones.

The improved antimicrobial activity of newer fluoroquinolones and novel applications recently found for the drugs already marketed are reviewed. Several new compounds are more active against gram-positive bacteria than the presently marketed fluoroquinolones. WIN 57273, the most potent compound in vitro on a weight basis, is 16 to 128 times more active than ciprofloxacin against various staphylococci, streptococci, Enterococcus spp., Corynebacterium spp., Listeria monocytogenes and Bacillus spp. BMY 40062, PD 117558, PD 127391, sparfloxacin, temafloxacin and tosufloxacin also show enhanced in vitro efficacy against these species. These drugs also possess increased activity against various anaerobes, notably Clostridium perfringens, Clostridium difficile and the Bacteroides fragilis group. Mycobacterium tuberculosis, rapidly growing mycobacteria other than Mycobacterium chelonae, and Mycobacterium leprae are often susceptible to quinolones displaying bactericidal activity which is potentially useful for curing difficult-to-treat mycobacteriosis. In addition, a number of new products, notably those containing a cyclopropyl group, are more active than reference fluoroquinolones against Mycobacterium leprae. Sparfloxacin, BMY 40062 and WIN 57273 compare favorably with older fluoroquinolones in the killing of intracellular Legionella spp., and several of the newer compounds have greater antichlamydial potency. Improved antibacterial activity has also been found against Mycoplasma hominis, Ureaplasma urealyticum, Acinetobacter spp. and Pseudomonas maltophilia. By contrast, the newer quinolones have similar or less activity against Pseudomonas aeruginosa and Enterobacteriaceae. Recently, pefloxacin, ofloxacin and ciprofloxacin were found to be active against protozoa, including Plasmodium spp., Trypanosoma cruzi and Leishmania donovani, but not against Toxoplasma gondii. In the near future, more specific research testing unusual pathogens may lead to the identification of quinolones with more selective activity.

4-Quinolones↗

Does circumcision alter the periurethral bacterial flora?

A prospective study of 25 boys who underwent circumcision for medical reason was performed. Specimens of periurethral bacterial flora were taken before operation as well as 3 weeks after surgery, so that each boy acted as his own control. Before circumcision, 13 (52%) harboured uropathogenic organisms (Escherichia coli and other coliforms, Enterococcus spp, Proteus spp, Pseudomonas spp, and Klebsiella spp); after circumcision, none of the boys had uropathogens, the only organisms cultured from the periurethral region being skin commensals. We postulate that circumcision converts a 'cul-de-sac' that is a reservoir of organisms capable of causing ascending urinary tract infection into a surface colonised by natural skin organisms. This study provides circumstantial evidence supporting the idea that circumcision in well-selected patients may confer protection from urine infection.

Bacteria↗

Antibiotic prophylaxis by low-dose cefaclor in children with vesicoureteral reflux.

Sulfamethoxazole/trimethoprim (SMX/TMP) and nitrofurantoin are the most frequently used agents for prophylaxis to reduce the risk of recurrent urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR). Nitrofurantoin, however, is not available in Japan and increasing resistance of organisms to SMX/TMP has recently raised doubts about its effectiveness as a prophylactic agent. This study was conducted to investigate whether antibiotic prophylaxis using low-dose cefaclor can effectively reduce the risk of recurrent UTIs. Thirty-nine children (31 male, 8 female) with primary VUR were enrolled. Ages varied from 0.5 to 111 months (mean 10.6 months). A prophylactic dose of 5-10 mg cefaclor per kg per day was given 1-3 times daily depending on the patient's age. Mean duration of prophylactic treatment was 15.5 months. Eleven children (ten male, one female) developed breakthrough UTIs during a total of 606 months treatment (or about one further infection in 55 months). Resistance to cefaclor was noted in three organisms: Enterococcus spp., Morganella spp., and Pseudomonas spp. Evidence of antibacterial activity was present in the morning urine samples from all of seven children tested. Cefaclor was well accepted and tolerated by all subjects. None withdrew from the study because of side effects. These results suggest that cefaclor can be an alternative choice for prophylactic treatment because of its safety, good compliance and low rates of resistant Escherichia coli.

Anti-Bacterial Agents↗

Evaluation of a new chromogenic medium for isolation and identification of common urinary tract pathogens.

In the study presented here, a new chromogenic medium (CPS ID 3; bioMérieux, Marcy l'Etoile, France) was compared to routine media for the isolation, identification and antimicrobial susceptibility testing of bacteria recovered from urine specimens, and a cost analysis was performed. Escherichia coli, Proteeae tribe, Pseudomonas aeruginosa, Enterococcus spp. and Streptococcus agalactiae grew on the chromogenic medium as typical differentiated colonies and were accurately identified even in mixed cultures. Although the similarity of colors produced by isolates belonging to the Klebsiella, Enterobacter, Serratia and Citrobacter (KESC) group prevents differentiation among them, members of KESC were easily identified as coliforms. No substantial difference was observed when comparing the results of antimicrobial susceptibility testing performed on colonies selected from reference media versus CPS ID 3. Use of the new medium was associated with a savings of 75% over the conventional methods and the API system. Furthermore, this medium facilitated a remarkable reduction in the laboratory workload and consequently resulted in additional time and cost savings.

Anti-Bacterial Agents↗

Comparison of antimicrobial use and resistance of bacterial isolates in a haematology ward and an intensive care unit.

The objective of the study presented here was to compare antimicrobial use and resistance of bacterial isolates in the haematology ward and the intensive care unit of Bolzano General Hospital. The bacterial organisms isolated most frequently from patients in the two wards (coagulase-negative staphylococci, Enterococcus spp., and Pseudomonas aeruginosa) were investigated for antimicrobial resistance. Isolates obtained from patients in the haematology ward were more often resistant to antimicrobial agents than isolates obtained from patients in the intensive care unit, and the agents against which the highest rates of resistance were found were third- and fourth-generation cephalosporins, carbapenems and monobactams, quinolones, aminoglycosides, and trimethoprim-sulfamethoxazole. These classes of antimicrobial agents were also used more frequently in the haematology ward than in the intensive care unit. Conversely, penicillinic beta-lactam antibiotics, rifamycins, macrolides and lincosamides were used less frequently in the haematology ward than in the intensive care unit, and the rates of resistance against these classes of antimicrobial agents were significantly lower in the haematology ward than in the intensive care unit. The results support the hypothesis that a causal relationship exists between antimicrobial use and the development of resistance and indicate that careful monitoring of antimicrobial use in hospitals is required to identify situations in which prescription patterns are contributing to the development of resistance.

Anti-Bacterial Agents↗

Leucocin F10, a bacteriocin from Leuconostoc carnosum.

Leucocin F10 is a bacteriocin produced by a strain of Leuconostoc carnosum isolated from fermented meat. It is sensitive to proteolytic enzymes and alpha-amylase, heat resistant up to 121 degrees C for 10 min at pH 3.0 and is inhibitory to Listeria spp., Leuconostoc spp., Enterococcus faecalis and Lactobacillus sake. Bactericidal activity against L. innocua in potassium phosphate buffer was strongly dependent of the growth phase of the indicator cells. A rapid sub-lethal damage, followed by slow death was observed for log-phase cells of L. innocua. The bacteriocin induced a rapid release of K+ from energized L. innocua cells. Leucocin F10 production occurred at temperatures between 4 and 30 degrees C and followed a primary metabolite kinetics in batch fermentations at controlled pH. Maximum bacteriocin activity was obtained at pH 6.0.

Bacteriocins↗

Antibiotic resistance of urinary pathogens isolated from patients attending the Toronto Hospital between 1986 and 1990.

A study was carried out on 1523 urinary isolates obtained at The Toronto Hospital, Canada's largest tertiary care establishment, over three 1-month periods in 1986, 1987 and 1990. Escherichia coli was the most frequently isolated organism, with Enterococcus spp. the second most common isolate in 1986 and 1987, and Streptococcus spp. in 1990. Pseudomonas aeruginosa isolates were found to be resistant to many of the antimicrobial agents tested. Resistance patterns were found to commonly prescribed ampicillin, co-trimoxazole and, to some extent, the new fluoroquinolones, ciprofloxacin and norfloxacin. These results are relevant to the treatment and management of urinary tract infections in patients attending a tertiary care hospital.

Cross Infection↗

Evolution of bacterial susceptibility to antibiotics during a six-year period in a haematology unit.

A knowledge of the bacterial ecology of a haematology unit should help in the management of the febrile patient with or without neutropenia. We studied the prevalence and the susceptibility profiles of bacteria isolated during a six-year period among patients hospitalized in a 44-bed haematology unit. Antibiotic use over this period was also studied. The most prevalent bacteria were coagulase-negative staphylococci (CNS) (35.1%), Escherichia coli (11.4%), Staphylococcus aureus (9.9%), Enterococcus spp. (8.2%), and Pseudomonas aeruginosa (7.5%). The susceptibility of CNS to oxacillin decreased from 67-44% over six years, while that of enterobacteriaceae to amoxycillin and piperacillin was reduced by about 50%. P. aeruginosa susceptibility to ceftazidime remained remarkably stable at around 90%, despite extensive empirical use. Imipenem and ciprofloxacin were used restrictively and ceftazidime-resistant P. aeruginosa remained susceptible to these two agents in most cases. Our antibiotic policy was found to be compatible with the frequency of the bacterial strains isolated in our department and with their susceptibility profiles.

Anti-Bacterial Agents↗

National survey of the in vitro spectrum of piperacillin-tazobactam tested against more than 40,000 aerobic clinical isolates from 236 medical centers.

Hospital microbiology laboratories from 41 states participated in a bacterial antimicrobial susceptibility study comparing in vitro results generated by the standardized disk diffusion method. Over 41,000 freshly isolated aerobic and facultative strains, representing all specimen types (except stools and urines), were tested for their susceptibility to piperacillin-tazobactam and 21 other antimicrobial agents. Enterococcus spp. was the second or third most common isolate from intraabdominal, gynecologic, and cutaneous infections, confirming its growing importance as a nosocomial pathogen. Escherichia coli was the most frequent isolate overall, despite the exclusion of urinary tract specimens from the study. Pseudomonas aeruginosa was the second most prevalent species, ranking first in frequency of recovery from lower-respiratory-tract specimens. Piperacillin-tazobactam was the most active beta-lactamase inhibitor combination tested against Gram-negative bacteria. Its activity against Gram-positive bacteria and Haemophilus influenzae was similar to that of ampicillin-sulbactam (95-97% susceptible). Imipenem and piperacillin-tazobactam displayed similar spectrums of activity against Gram-positive organisms and Haemophilus influenzae. Against Enterobacteriaceae, piperacillin-tazobactam and ceftazidime exhibited similarly wide spectrums of activity, but with some gaps, particularly among Enterobacter spp. and Citrobacter freundii. In this large-scale in vitro study, piperacillin-tazobactam and imipenem displayed the widest antimicrobial spectrums, inhibiting > 90% of all isolates tested.

Bacteria↗

Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002).

The empiric treatment of patients with bloodstream infections (BSI) has become more complicated in an era of increasing antimicrobial resistance. The SENTRY Antimicrobial Surveillance Program has monitored BSI from patients in medical centers worldwide since 1997. During 1997-2002, a total of 81,213 BSI pathogens from North America, Latin America, and Europe were tested for antimicrobial susceptibility. S. aureus, E. coli, and coagulase-negative staphylococci were the three most common BSI pathogens in all three regions each year. Prevalence variability was noted in regions for some species, including higher rates of isolation of E. coli in Europe, Enterococcus spp. in North America, and Gram-negative enteric and nonenteric species in Latin America. Patient age analysis showed the most common BSI pathogen among neonates was coagulase-negative staphylococci and among elderly patients, E. coli. Resistance among BSI pathogens was much more prevalent in nosocomial infections and in patients in intensive care units (ICUs); age differences were also noted. Geographically, oxacillin-resistant S. aureus (39.1%, 2002) and vancomycin-resistant enterococci (17.7%, 2002) were highest in North America, and extended-spectrum beta-lactamase-producing Klebsiella spp. (35.8-46.7%) and multidrug-resistant P. aeruginosa (18.7%, 2002) were highest in Latin America. Activity of commonly used antimicrobial agents remained relatively stable in North America, except in the case of vancomycin-resistant enterococci (20% decline between 1997 and 2002). An epidemiologic investigation of oxacillin-resistant S. aureus in North America identified 10 significant clones (ribotypes) and the common resistance patterns associated with them. Surveillance of BSI pathogens is needed to determine trends of resistance and provide useful information regarding patient risk factors and geographic differences.

Adolescent↗

Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit.

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.

Anti-Bacterial Agents↗

Potency and spectrum of tigecycline tested against an international collection of bacterial pathogens associated with skin and soft tissue infections (2000-2004).

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.

Anti-Bacterial Agents↗

Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents.

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

Anti-Bacterial Agents↗

Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA).

The goal of the North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study was to determine antibiotic susceptibility to commonly used agents for urinary tract infections against outpatient urinary isolates obtained in various geographic regions in the USA and Canada. Forty-one medical centres (30 from the USA and 11 from Canada) participated, with each centre submitting up to 50 consecutive outpatient midstream urine isolates. Isolates were identified to species level by the standard protocol of each laboratory. Susceptibility testing was determined using the National Committee for Clinical Laboratory Standards (NCCLS) microdilution method. Resistance breakpoints used were those published by the NCCLS, including: ampicillin (resistant > or = 32 microg/mL), sulphamethoxazole/trimethoprim (SMX/TMP) (resistant > or = 4 microg/mL), nitrofurantoin (resistant > or = 128 microg/mL), ciprofloxacin (resistant > or = 4 microg/mL) and levofloxacin (resistant > or = 8 microg/mL). Of the 1990 isolates collected, 75.1% (1494) were collected from the USA and 24.9% (496) were collected from Canada. The mean age of the patients was 48.3 years (range 1 month to 99 years), and 79.5% and 20.5% of isolates were obtained from women and men, respectively. The most common organisms were Escherichia coli (57.5%), Klebsiella pneumoniae (12.4%), Enterococcus spp. (6.6%), Proteus mirabilis (5.4%), Pseudomonas aeruginosa (2.9%), Citrobacter spp. (2.7%), Staphylococcus aureus (2.2%), Enterobacter cloacae (1.9%), coagulase-negative staphylococci (1.3%), Staphylococcus saprophyticus (1.2%), Klebsiella spp. (1.2%), Enterobacter aerogenes (1.1%) and Streptococcus agalactiae (1.0%). Among all 1990 isolates, 45.9% were resistant to ampicillin, 20.4% to SMX/TMP, 14.3% to nitrofurantoin, 9.7% to ciprofloxacin and 8.1% to levofloxacin. Fluoroquinolone resistance was highest in patients > or = 65 years of age. For the 1142 E. coli isolates, resistance rates were: ampicillin 37.7%, SMX/TMP 21.3%, ciprofloxacin 5.5%, levofloxacin 5.1% and nitrofurantoin 1.1%. For all 1990 isolates and for the 1142 E. coli only, resistance rates were significantly higher in US compared with Canadian medical centres. This study reports higher rates of antibiotic resistance in US versus Canadian outpatient urinary isolates and demonstrates the continuing evolution of resistance to antimicrobial agents.

Adolescent↗

Assessment of the microbial integrity, sensu G.S. Wilson, of piped and bottled drinking water in the condition as ingested.

The second half of the 20th century witnessed substantial progress in the assurance and verification of microbiological integrity, i.e., safety and sensory quality, of drinking water. Enteropathogenic agents, such as particular viruses and protozoa, not previously identified as transmitted by industrially provided water supplies, were demonstrated to cause disease outbreaks, when ingested with piped water. The potential harm posed by carry-over of orally toxic metabolites of organisms, producing 'algal' (cyanophytic) blooms, was considered. In addition, earlier observations on the colonization of attenuated drinking water bodies by a variety of oligotrophic Gram-negative bacteria were confirmed and extended. This new evidence called for updating both water purification technologies and analytical methodology, serving to verify that goals had been attained. For the former purpose, the hazard analysis empowering control of critical practices (HACCP) strategy, introduced about 1960 in industrial food processing, was successfully adopted. Elimination, devitalization or barrier technologies for the more recently identified water-borne pathogens were elaborated, taking account of the hazard of production of chlorinated compounds with alleged adverse health effects. Biofilm formation throughout water distribution networks was brought under control by strict limitation of concentrations of compounds, assimilable by oligotrophic bacteria. Upon acknowledging that direct detection tests for pathogens were futile, because of their most sporadic and erratic distribution, Schardinger's marker organism concept was anew embraced, rigorously revised and substantially enlarged. Misleading designations, like searches for 'faecal coliforms' were replaced by boundary testing for Escherichia coli and appropriate Enterococcus spp. In addition, though still to be perfected, detection protocols for relevant bacteriophages or index viruses and, to a certain extent, also for spores of aerobic and anaerobic sporing rods were also elaborated. In all monitoring account was taken of sublethally injured target organisms, surviving purification technologies, though not deprived of their ecological significance. A need remains for a rigorously standardized operating procedure (SOP) for colony counts of psychrotrophic, oligotrophic Gram-negative rod-shaped bacteria ('heterotrophic plate count'), which constitute a useful criterion of indicator value. As in the contemporary HACCP approach to food safety, guidelines for assessing success or failure in control of integrity (Water Safety Objectives) were empirically elaborated. These rely on surveys on water samples, originating from drinking water supplies, previously verified as complying with longitudinally integrated HACCP-based purification technologies. Structured Academic dissemination of these innovations, through professional microbiologists to operator and executive levels, is recommended. Web based Distance Learning MSc Programmes, like the one, since the academic year 2003-2004, offered by the University of Hertfordshire, Hatfield, UK, may contribute to such endeavours. Though the complete Course is centered around Food Safety, the Modules in-Residence Practicals and Science and Technology of Drinking Water can be studied as an entity while being employed.

Bacteria↗