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Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997-2000.

We report age-related trends in pathogen frequency and antimicrobial susceptibility from 25,745 bloodstream infections (BSI) due to bacterial pathogens reported from medical centres participating in the North American SENTRY Antimicrobial Surveillance Program between January 1997 and September 2000. Staphylococcus aureus, Escherichia coli and coagulase-negative staphylococci (CoNS) were the most common pathogens, together accounting for 55% of all BSI pathogens during this time period. Among nosocomial BSI, CoNS were the most frequently isolated pathogens in infants less than 1 year of age, but S. aureus increased in frequency with increasing age. Among community-onset BSI pathogens, Streptococcus pneumoniae was the most frequently reported pathogen causing BSI in patients aged 1-5, S. aureus among those aged 6-64, and E. coli predominated at the extremes of age (less than 1 year and > or = 65 years of age). Among key organism: antimicrobial agent combinations evaluated, oxacillin resistance in S. aureus increased with increasing age; conversely, oxacillin resistance among CoNS was highest among children 5 years of age or younger. Penicillin resistance among S. pneumoniae BSI was highest in children younger than 5 years, while vancomycin resistance among Enterococcus spp. predominated among nosocomial BSI in patients over 50 years of age. Important age-related differences exist in species distribution and antimicrobial susceptibility of pathogens causing BSI. This information should be helpful for clinicians as they consider empirical antimicrobial therapy for patients with suspected BSI across the age continuum.

Adolescent↗

Antibacterial activity of 2,4-diacetylphloroglucinol produced by Pseudomonas sp. AMSN isolated from a marine alga, against vancomycin-resistant Staphylococcus aureus.

Antibacterial activity of 2,4-diacetylphloroglucinol (DAPG) was evaluated against 23 vancomycin-resistant Staphylococcus aureus (VRSA) strains isolated from several Asian and European countries, Brazil, South Africa and USA, and against vancomycin-resistant Enterococcus spp (VRE) genotypes A, B and C. DAPG was active against a wide range of VRSA isolates as well as vancomycin hetero-resistant S. aureus (h-VRSA) at MIC 4 mg/l. This substance also had moderate activity against both VRE-A and -B at MIC 8 mg/l, but not against VRE-C at up to 16 mg/l. The activity of DAPG did not directly correlate with levels of vancomycin resistance in VRSA and VRE. These results suggest that DAPG might be useful in developing new antibiotics against VRSA.

Anti-Bacterial Agents↗

Infections in diabetic foot ulcers.

Foot ulcers and infections are common in diabetic patients. A 30-month-long descriptive study was conducted in our hospital in which we analyzed microbiological isolates of all patients admitted with diabetic foot infections. The predominant flora identified were Staphylococcus aureus and coagulase-negative Staphylococcus, followed by Enterococcus spp., Streptococcus spp., and enterobacteriaceaes. In 27 positive cultures (42%) polymicrobial flora were found. There were only 5% anaerobic bacteria. There appears to be a relationship between the sample collection system and microbiological isolates.

Journal Article↗

Combinatorial modification of natural products: synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A: A-ring modifications.

Thiazole peptide GE2270 A (1) possesses potent antimicrobial activity against many gram-positive pathogens, including methicillin resistant Staphylococcus aureus (S. aureus, MRSA; MIC(90)=0.06 microg/mL) and vancomycin resistant Enterococcus spp. (VRE; MIC(90)=0.03 microg/mL); however its poor aqueous solubility has prohibited its development for the clinical treatment of infections. An integrated combinatorial and medicinal chemistry program was employed to identify derivatives of 1 that retain activity but possess greatly enhanced aqueous solubility.

Anti-Bacterial Agents↗

The Bogorol family of antibiotics: template-based structure elucidation and a new approach to positioning enantiomeric pairs of amino acids.

The sequence positions of d and l Leu and Lys residues in bogorol A (1) have been defined by a simple and novel approach that utilizes small amounts of sample and focuses on detecting the order in which amino acids are liberated from the parent peptide during acid-catalyzed hydrolysis. This technique builds on a previously established relationship between the steric and electronic features of amino acids and their predilection for acidic liberation from polypeptides via dipeptides. The results, which complete the structure of bogorol A, have been confirmed by traditional degradation experiments. Utilizing the knowledge of the structure of bogorol A (1) as a template, we rapidly elucidated the structures of bogorols B-E (2-5) via analysis of ESI-MS and ESI-MS/MS data and GC analysis of degradation products. The bogorol cationic peptide antibiotics contain a number of unusual structural features, which include the reduction of the C-terminal residue to valinol, an N-terminal residue of 2-hydroxy-3-methylpentanoic acid, the incorporation of four d amino acids, and the presence of a dehydroamino acid. Bogorols show selective and relatively potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp., as well as moderate activity against Escherichia coli.

Amino Acid Sequence↗

Comparative in vitro activities of five quinolone antibiotics, including gemifloxacin, against clinical isolates.

The in vitro activities of ciprofloxacin, ofloxacin, norfloxacin, levofloxacin and gemifloxacin against 343 clinical isolates were compared. Gemifloxacin showed the greatest activity, with MIC90 values as low as 0.03-0.25 mg/L against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus and Klebsiella pneumoniae, while methicillin-resistant Staphylococcus aureus, Enterococcus spp., Pseudomonas spp., Acinetobacter spp., Escherichia coli and Enterobacter spp. strains exhibited low rates of susceptibility to all five fluoroquinolones.

Anti-Infective Agents↗

Molecular and physiological characterization of dominant bacterial populations in traditional mozzarella cheese processing

The development of the dominant bacterial populations during traditional Mozzarella cheese production was investigated using physiological analyses and molecular techniques for strain typing and taxonomic identification. Analysis of RAPD fingerprints revealed that the dominant bacterial community was composed of 25 different biotypes, and the sequence analysis of 16S rDNA demonstrated that the isolated strains belonged to Leuconostoc mesenteroides subsp. mesenteroides, Leuc. lactis, Streptococcus thermophilus, Strep. bovis, Strep. uberis, Lactococcus lactis subsp. lactis, L. garviae, Carnobacterium divergens, C. piscicola, Aerococcus viridans, Staphylococcus carnosus, Staph. epidermidis, Enterococcus faecalis, Ent. sulphureus and Enterococcus spp. The bacterial populations were characterized for their physiological properties. Two strains, belonging to Strep. thermophilus and L. lactis subsp. lactis, were the most acidifying; theL. lactis subsp. lactis strain was also proteolytic and eight strains were positive to citrate fermentation. Moreover, the molecular techniques allowed the identification of potential pathogens in a non-ripened cheese produced from raw milk.

Journal Article↗

Antibiotic resistance in bacteria from magpies (Pica pica) and rabbits (Oryctolagus cuniculus) from west Wales.

The prevalence of antibiotic-resistant bacteria in wild animal and bird populations is largely unknown, with little consistency among the few published reports. We therefore examined intestinal bacteria from magpies (Pica pica) and rabbits (Oryctolagus cuniculus) collected in rural west Wales. Escherichia coli isolates resistant to multiple antibiotics were grown from eight of 20 magpies trapped in spring, 1999 and one of 17 in spring, 2000; the most prevalent resistance trait among these isolates was to tetracycline, but resistances to ampicillin, chloramphenicol, kanamycin, sulphonamide, tetracycline and trimethoprim were also found. Tetracycline-resistant Enterococcus spp. were found in one of 20 magpies in 1999 and three of 17 in 2000. Only one resistant E. coli isolate was detected among gut bacteria from 13 rabbits, and this strain was resistant only to tetracycline. Differences in the prevalence of resistance between bacteria from rabbits and magpies may reflect differences in diet: rabbits graze field edges, whereas magpies are omnivorous and opportunistic. The resistance genes found in E. coli isolates from magpies mostly corresponded to those common among human isolates, but those conferring tetracycline resistance were unique.

Animals↗

Optimizing antimicrobial therapy for gram-positive bloodstream infections in patients on hemodialysis.

Infections with gram-positive organisms are highly prevalent in hemodialysis patients and are a major cause of morbidity and mortality in this population. Antimicrobial therapy is widely used to treat these infections, and prolonged therapy with these agents is often necessary. Extensive use of antimicrobials in hemodialysis patients has resulted in a growing threat of resistance, especially among gram-positive bacteria such as Enterococcus spp and Staphylococcus aureus. Vancomycin-resistant enterococci and S. aureus isolates with reduced susceptibility to vancomycin are increasingly being reported in hemodialysis patients. Additionally, resistance of these organisms to newer agents, such as linezolid and daptomycin, has been documented. Appropriate utilization of antimicrobial therapy to treat these organisms requires an understanding of the pharmacokinetic and pharmacodynamic principles to optimize therapy and avoid adverse drug events. The pharmacokinetic and pharmacodynamic profile of antimicrobial agents can be significantly altered in patients with chronic kidney disease. This review will describe mechanisms of antimicrobial resistance among common gram-positive organisms. The pharmacokinetic and pharmacodynamic principles of cephalosporins, vancomycin, aminoglycosides, linezolid, and daptomycin and applications for use of these agents in the treatment of patients with bloodstream infections on hemodialysis are discussed.

Anti-Bacterial Agents↗

Incidence and risk factors for acquiring nosocomial urinary tract infection in the critically ill.

PURPOSE: A urinary tract infection (UTI) is the most common hospital-acquired infection. However, the epidemiology of intensive care unit (ICU)-acquired UTIs is not well defined. The objective of this study was to describe the incidence, risk factors, and clinical outcomes of ICU-acquired UTIs. MATERIALS AND METHODS: All patients admitted to adult multidisciplinary ICUs in the Calgary Health Region (CHR, population approximately 1 million) during May 1, 1999 to April 30, 2000 were studied using a cohort design. RESULTS: A total of 1,158 admissions to a CHR ICU were 48 hours in duration or more. A total of 111 episodes of ICU-acquired UTI (defined as >10(5) CFU/mL of 1 or 2 organisms >48 hours after ICU admission) occurred in 105 (9%) patients and 5 (0.4%) had ICU-acquired bacteremic/fungemic UTIs for incidences of 11.3 and 0.5 UTIs per 1,000 ICU days, respectively. Significant independent risk factors for developing an ICU-acquired UTI as determined by a logistic regression model were female gender (adjusted odds ratio [OR(adj)], 2.31; 95% confidence interval [CI], 1.48-3.59) and natural logarithmic transformation of ICU length of stay (OR(adj), 3.96; 95% CI, 3.02-5.17). No differences in admitting vital signs, routine blood tests, APACHE II and TISS scores, or overall hospital mortality rate were observed among patients who developed an ICU-acquired UTI as compared with those who did not. The most common UTI etiologies were Enterococcus spp. (24%), Candida albicans (21%), and Escherichia coli (15%). Only 4 (3%) of the organisms were highly antibiotic resistant. CONCLUSIONS: Nosocomial UTIs develop commonly in the critically ill and women and those with an extended ICU stay are at increased risk. Although ICU-acquired UTIs are markers of morbidity, they do not significantly increase mortality.

APACHE↗

Outcome analysis of intraabdominal infection with resistant gram-positive organisms.

BACKGROUND: Although the microbiology of intraabdominal infection has been well described, the role of resistant organisms remains unclear. To evaluate the hypothesis that intraabdominal infections from resistant gram-positive cocci (rGPC) have worse outcomes compared to those with susceptible organisms, patient characteristics and outcomes were compared between these groups. METHODS: Analysis of peritoneal infections was performed on prospectively collected data of all consecutive surgical infections from December 1996 to June 1999 at a university hospital. Intraabdominal infection was defined either by a positive peritoneal cavity culture or on clinical grounds (e.g., abscess), which prompted antimicrobial or surgical therapy. Resistant Staphylococcus and Enterococcus spp. were defined as those strains resistant to oxacillin, gentamicin, or vancomycin. RESULTS: Compared to episodes of intraabdominal infection from susceptible organisms (n = 365), infections due to rGPC (n = 52) were associated with an increased severity of illness (p < 0.0001), longer time from admission to treatment (p < 0.0001), longer duration of therapy (p = 0.008), greater proportion of nosocomial infection (p < 0.0001), increased length of stay (p < 0.0001), and an increased mortality rate (9% versus 23%; p = 0.003). However, comparison of intraabdominal infection with rGPC to a group controlled for severity of illness demonstrated a prolonged time from admission until treatment and longer duration of hospitalization but a similar mortality rate between groups (17% versus 23%; p = 0.46). CONCLUSION: Intraabdominal infection with rGPC is an indicator of poor prognosis and severe illness. Although not an independent predictor of mortality, the significantly increased duration of therapy and prolonged duration of hospitalization may have considerable economic impact.

Abdomen↗

Bacteriology of urinary tract infection associated with indwelling J ureteral stents.

PURPOSE: To investigate the microorganisms responsible for urinary tract infection (UTI) and stent colonization in patients with indwelling J ureteral stents and to compare the antimicrobial susceptibility pattern of the isolates from urine and J stents in order to establish the etiologic agents of bacteriuria and colonized stents in such patients and provide baseline data on an antibiotic policy for the urology unit. PATIENTS AND METHODS: Midstream urine from 250 patients requiring J stent insertion was investigated microbiologically prior to stent insertion and on the day of stent removal. After stent removal, 3 to 5 cm of the tip located in the bladder was also sent for culture. Patients' bio-data and underlying diseases were documented. Those with no known systemic diseases ("normal patients") were also studied as controls. Of the 250 patients studied, 152 (61%) were normal, while 27 (11%), 53 (21%), and 18 (7%) had diabetes mellitus (DM), chronic renal failure (CRF), and diabetic nephropathy (DN), respectively. The mean duration of stent retention was 27 days. All microbial isolates were tested for their susceptibility to a panel of 10 antibiotics. RESULTS: Twelve patients (5%) before stent insertion and 42 patients (17%; P < 0.001) on the day of stent removal had positive urine cultures. One hundred four stents (42%) were culture positive. Of the 104 patients with positive stent cultures, in 62 patients (60%), urine culture was sterile. The commonest isolates were Escherichia coli, Enterococcus spp., Staphylococcus spp., Pseudomonas, and Candida spp. On the day of stent removal, urine culture was positive in 28% of the normal patients compared with 57% (P = 0.11), 78% (P < 0.001), and 62% (P < 0.001) of patients with CRF, DM, and DN, respectively. Stent isolates were more resistant to antibiotics than the organism isolated before stent insertion. CONCLUSION: An indwelling J ureteral stent carries a significant risk of bacteriuria and stent colonization. The sensitivity of urine culture to stent colonization is low, and therefore, a negative culture does not rule out a colonized stent. Bacteria cultured from urine after stent insertion and from the stents are more resistant to antibiotics than are those cultured from urine before stent insertion. Norfloxacin or ciprofloxacin is recommended as prophylaxis prior to stent insertion, and an aminoglycoside can be added to treat symptomatic patients with severe infections.

Adult↗

An assessment of temafloxacin in the treatment of chronic bacterial prostatitis.

Based on its in-vitro activity against the majority of organisms associated with bacterial prostatitis and its excellent penetration into prostatic tissue, prostatic secretions and seminal fluid, temafloxacin appears to be a suitable agent for the treatment of prostatic infections. The efficacy and safety of temafloxacin 400 mg bd for 28 days were assessed in 61 patients from ten centres in Germany with symptomatic bacterial prostatitis diagnosed by segmented localizing cultures. Urine and prostatic secretions were obtained for culture. Clinical signs and symptoms were evaluated at two weeks during treatment, and at 5 to 9 days and 26 to 30 days after treatment. Safety was monitored during and at the end of treatment. Escherichia coli and Enterococcus spp. were the most frequent pathogens. In 41 clinically and bacteriologically evaluable patients, 37 (90%) were successfully treated at 5 to 9 days; four of these patients did not return for follow-up at the final visit and the remaining patients (33) continued to be clinically cured or improved. Thirty-seven patients (90.2%) had eradication of pre-treatment pathogens at 5 to 9 days after treatment; three of these patients did not return for this final follow-up visit. There were six patients with persistent or recurrent pathogens isolated and six patients with reinfecting pathogens. Thus, 26 of 38 (68%) evaluable patients at visit 5 were free from infection (from either a pre-treatment pathogen or any subsequent new infecting pathogen) up to 26 to 30 days after treatment. One clinically evaluable but bacteriologically non-evaluable patient was classified as a therapeutic failure after nine days of treatment and was not included in the final assessment. Improvement in the severity of specific signs and symptoms was observed in greater than 90% of cases. Mild to moderate adverse events, mostly occurring during the first or second weeks of long-term therapy, were reported in 11.5% of patients. Temafloxacin 400 mg bd, for four weeks was very effective and well tolerated by the majority of patients with documented bacterial prostatitis.

Administration, Oral↗

The in-vitro activity of faropenem, a novel oral penem.

The in-vitro activity of faropenem, a novel oral penem, was studied in comparison with other beta-lactam antimicrobials against 711 recent clinical isolates including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that faropenem was active against most members of the Enterobacteriaceae (MICs < or = 4 mg/L), with reduced activity against Serratia spp. (MIC90 = 32 mg/L). In common with its comparators, faropenem had weak activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia (MIC > 128 mg/L). Faropenem was active against staphylococci, although for MRSA MICs were raised (MIC90 = 2 mg/L) compared with those for MSSA (MIC90 = 0.12 mg/L). Faropenem was also found to be active against streptococci, Neisseria spp., Enterococcus faecalis and beta-lactamase-producing and non-producing strains of Haemophilus influenzae and Moraxella catarrhalis. Of the anaerobic bacteria studied, faropenem was most active against peptostreptococci and Clostridium perfringens (MIC90 < or = 1 mg/L) and Bacteroides fragilis (MIC90 = 4 mg/L). An increase in inoculum from 10(4) to 10(6) cfu raised faropenem MICs for Morganella morganii from 0.06-1 mg/L to 2-4 mg/L and for MRSA from 0.25-2 mg/L to 8 mg/L (a similar increase was not observed for MSSA). The MICs of faropenem were not affected by the presence of either 20% or 70% (v/v) serum. MICs for faropenem to 11 well characterized beta-lactamase producers were similar to those of non-producers. In hydrolysis studies, faropenem was shown to be highly stable to a number of beta-lactamases, including TEM-1, SHV-1, the extended spectrum beta-lactamases, TEM-3 and TEM-9, and the beta-lactamase produced by Staphylococcus aureus (NCTC 11561).

Anti-Bacterial Agents↗

Comparative in-vitro activity of cefpirome against isolates from intensive care and haematology/oncology units. Belgian Multicentre Study Group.

The susceptibility of 389 Enterobacteriaceae, 231 other Gram-negative bacilli (including 150 Pseudomonas aeruginosa) and 233 Gram-positive organisms was determined by the NCCLS reference microdilution technique against cefpirome and other antibiotics. Cefpirome and cefepime were the most active compounds against Enterobacteriaceae, including potentially beta-lactamase-inducible species. The MIC90 of cefpirome against potentially inducible and non-inducible species of Enterobacteriaceae was 2 mg/L and 0.5 mg/L, respectively. Ceftazidime, cefpirome and cefepime had similar activity against P. aeruginosa, with MIC90s of 64 mg/L, 64 mg/L and 32 mg/L, respectively. Cefpirome and cefepime had similar activity against Gram-positive cocci, with MIC90s of 1 mg/L and 2 mg/L, respectively, against oxacillin-susceptible Staphylococcus aureus and 64 mg/L and 128 mg/L, respectively, against Enterococcus spp.; both had an MIC90 of 1 mg/L against Streptococcus pneumoniae. This study shows that fourth-generation cephalosporins, such as cefpirome, could be useful in haematology/oncology units and, in particular, ICUs where high resistance rates are observed.

Cefepime↗

Comparative effects of omeprazole, amoxycillin plus metronidazole versus omeprazole, clarithromycin plus metronidazole on the oral, gastric and intestinal microflora in Helicobacter pylori-infected patients.

Fourteen patients with Helicobacter pylori infection were treated with 20 mg omeprazole, 1 g amoxycillin and 400 mg metronidazole bd for 7 days (OAM), and 16 patients were treated with 20 mg omeprazole, 250 mg clarithromycin and 400 mg metronidazole bd for 7 days (OCM). Saliva, gastric biopsies and faecal samples were collected before, during (day 7) and 4 weeks after treatment in order to analyse alterations of the normal microflora and to determine antimicrobial susceptibility. Both treatment regimens resulted in marked quantitative and qualitative alterations. A selection of resistant streptococcal strains were noticed in both treatment groups, most apparent in the OCM group where a shift from susceptible to resistant strains was recorded. In the OAM group, six patients had overgrowth of resistant enterobacteriaceae during treatment compared with none in the OCM group, in the gastric microflora. The MICs for Enterococcus spp. and Enterobacteriaceae in faeces increased significantly during treatment in both groups. Nine patients in the OAM group became intestinally colonized by yeasts during treatment. The total anaerobic microflora was strongly suppressed in both treatment groups, although most pronounced in the OCM group, where the frequency of clarithromycin-resistant bacteroides strains increased from 2 to 76% during treatment, and remained at 59% 4 weeks post-treatment. Even if the treatment outcome was better in the OCM group (100%) than in the OAM group (71%), the amoxycillin-based treatment might be preferable from an ecological point of view, since the qualitative alterations in terms of emergence and persistence of resistant strains seemed to be most pronounced in the clarithromycin-treated group.

Adult↗

Susceptibility of a variety of clinical isolates to linezolid: a European inter-country comparison.

Using standardized in vitro susceptibility tests, 3382 bacteria recently isolated from skin, blood or respiratory tract infections were analysed for their susceptibility to linezolid, a new oxazolidinone, and a number of comparator antibacterial agents. Isolates originated in France, Italy, Germany, Spain, Sweden, The Netherlands and the UK. Laboratories in each country independently conducted broth microdilution susceptibility tests using NCCLS methods and epsilonometry (Etest). Isolates of Gram-positive cocci tested in each laboratory included methicillin-susceptible and -resistant Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae and Enterococcus spp. Isolates of Moraxella catarrhalis and Haemophilus influenzae were also included. Where appropriate, comparator drugs (oxacillin, vancomycin, gentamicin, co-amoxiclav, ciprofloxacin, erythromycin, penicillin G, clindamycin and ampicillin) were also tested. Linezolid demonstrated excellent activity against all of the Gram-positive cocci with MIC50s ranging from 0.5 to 4 mg/L. The drug demonstrated only modest activity against M. catarrhalis and H. influenzae with MIC50s ranging from 4 to 16 mg/L.

Acetamides↗

In vitro action of carboxyfullerene.

Fullerene compounds have avid reactivity with free radicals and are regarded as 'radical sponges'. The trimalonic acid derivative of fullerene is one of the water-soluble compounds that has been synthesized and found to be an effective antioxidant both in vivo and in vitro. Carboxyfullerene has been shown to be effective in the treatment of both Gram-positive and -negative infections, although its mode of action is poorly understood. We determined the MIC and minimal bactericidal concentration of carboxyfullerene for 20 isolates, including Staphylococcus spp., Streptococcus spp., Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumoniae. We further investigated the action of carboxyfullerene using transmission electron microscopy (TEM), anticarboxyfullerene antibody binding assay and a membrane perturbation assay. All Gram-positive species were inhibited by < or = 50 mg/L of carboxyfullerene, whereas Gram-negative species were not inhibited, even at 500 mg/L carboxyfullerene. Bactericidal activity was demonstrated only for Gram-positive species, particularly for Streptococcus pyogenes A-20, which was killed rapidly. Intercalation of carboxyfullerene into the cell wall of staphylococci and streptococci was demonstrated by TEM and anti-carboxyfullerene binding assay. Damage to the cell membrane in Gram-positive, but not Gram-negative, bacteria was confirmed by the membrane perturbation assay. These findings indicate that the action of carboxyfullerene on Gram-positive bacteria is achieved by insertion into the cell wall and destruction of membrane integrity.

Anti-Bacterial Agents↗