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PubMed1999

Effect of subinhibitory concentrations of antimicrobial agents (quinolones and macrolide) on the production of verotoxin by enterohemorrhagic Escherichia coli O157:H7.

In Japan, antimicrobial agent therapy for patients with diarrhea due to enterovirulent organisms including enterohemorrhagic Escherichia coli (EHEC) is common, and norfloxacin (NFLX), fosfomycin, and kanamycin are recommended for EHEC treatment by the Japanese Ministry of Health and Welfare. The aim of this study was to analyze the effects of antimicrobial agents which have been used or recommended for the treatment of EHEC on the production of verotoxin (VT) in vitro. Subinhibitory concentrations of quinolones, NFLX, sparofloxacin (SPFX), and grepafloxacin (GPFX) markedly stimulated the productions of VT1 and VT2. The macrolide azithromycin (AZM), erythromycin (EM), and clarithromycin (CAM) did not stimulate the production of VT at a wide range of concentrations. These in vitro results indicate that when quinolones are prescribed for a patient infected with EHEC, the concentration of antimicrobial agents used in vivo and the susceptibility of the EHEC strains against quinolones should be taken into consideration.

Animals↗
PubMed1999

Pharmacokinetic principles during continuous renal replacement therapy: drugs and dosage.

Some drugs are removed significantly by continuous renal replacement therapies (CRRTs), and a substitutional dose is required to prevent underdosing of the substance. This review outlines the basic pharmacokinetic principles that determine whether a dose adjustment is required. Only the free non-protein-bound fraction of a drug can pass through the dialyzer membrane. In postdilution hemofiltration the drug clearance equals the ultrafiltration rate, while in predilution hemofiltration, the dilution of the blood prior to filtration needs to be considered when calculating clearance. In continuous hemodialysis, drugs are eliminated by diffusion. Drugs with a higher molecular weight will diffuse more slowly and show a lower clearance than smaller drugs. The clinical relevance of a given drug clearance caused by CRRT will mainly depend on the competing drug clearance by other elimination pathways. Even a high clearance for a drug may be irrelevant for overall drug removal if nonrenal clearance pathways provide a much higher clearance rate. The ideal drug to be removed by CRRT that requires a dose adjustment has: a low protein binding, a low volume of distribution, and a low nonrenal clearance. Examples include aminoglycosides, vancomycin, fosfomycin, and flucytosine. Even if there are no studies available on the pharmacokinetics of a particular drug during CRRT, knowledge of the basic concepts of drug elimination by continuous hemodialysis allows a prediction of whether or not a dose adjustment will be required during CRRT.

Anuria↗
PubMedDate not supplied

[Diffusion in bone tissue of antibiotics].

DIFFICULT ASSESSMENT: Bone and joint infections are difficult to treat. Therapeutic success depends greatly on the diffusion of antibiotics into bone tissue. Few studies have been devoted to this subject and the variable nature of those reported hinders interpretation. Bone biopsies are generally obtained during orthopedic procedures. Antibiotic administration routes vary although intravenous infusion predominates. Agar gel diffusion is generally used for antibiotic assays but methodology varies depending of the study. The most recent reports use high-performance liquid chromatography. DIFFUSION STUDIES: The different studies examining antibiotic diffusion in bone tissue describe three classes: good diffusion (greater than 30%), moderate diffusion (between 15% and 30%), and low diffusion (less than 15%). Antibiotics in the good diffusion class include fluoroquinolones, teicoplanin, macrolides, rifampicin and trimethoprime. Antibiotics with moderate bone diffusion are ureidopenicillins, second and third generation cephalosporins, aminoglycosides, clindamycin, fosfomycin and vancomycin. Those with low bone diffusion are aminopenicillins, penicillin M and first generation cephalosporins. No data is available on the bone diffusion of pristinamycin. DATA INTERPRETATION: The clinical impact of these classifications must be interpreted with precaution when considering bone and joint infections as they were established on the basis of pharmacokinetic studies and not clinical trials. They would however appear to be useful in guiding antibiotic prophylaxis for orthopedic surgery in protocols with administration conditions and concentration goals similar to the experimental conditions. PRACTICAL ATTITUDES: These laboratory results could be used in clinical practice by comparing the MIC50 of the germs regularly encountered in bone infections (staphylococci, streptococci including enterococci, Gram negative bacilli including P. aeruginosa and H. influenzae) with concentrations obtained in the different studies, i.e. by calculating the inhibitor coefficient (IQ) of each antibiotic for each susceptible germ. This gives a classification by efficacy (excellent IQ > 10, good 1 < IQ < 10, poor IQ < 1) useful for guiding antibiotic choice in the difficult situation of bone and joint infection.

Anti-Bacterial Agents↗
PubMed1999

[The prevalence of methicillin-resistant Staphylococcus aureus phagotype 95 in the Hospitales Vall d'Hebron of Barcelona].

BACKGROUND: In our hospital endemic methicillin resistant Staphylococcus aureus (MRSA) has been documented since 1971, with epidemic and interepidemic periods. During these years phage groups I, I-III, and non-typable were found by the international set of phages Phage group 95 (F95) was unusual between 1986 (when phage typing was first available) and 1991, with prevalence of 5.2% (mean), and 100% of sensibility to methicillin. In November 1991 appeared the first MRSA F95 strain, and its prevalence has been increasing until 1997. MATERIAL AND METHODS: We have studied 133 strains of MRSA F95 isolated from 87 patients, 39 of them hospitalized in the General Hospital (HG), 38 in Traumatology Hospital (HT) and 8 in the Children's Hospital (HI). Two of these patients had successive stancies in HG and HT. Antimicrobial susceptibility was determined by the disk diffusion method and microdilution to check oxacillin resistance. Moreover these method we have maked: detection of mecA, phage typing with the international set of phages and study of the PGFE patterns by digestion of chromosomic DNA with Smal. RESULTS: The percentage of methicillin resistance in F95 strains was increased since the appear of the first strain between 8.3% in 1991 to a maximum of 76.9% in 1995, we had a descens to 13.7% in 1996 but 1997 can back to augment it to 72.5%. MICs for oxacillin of these strains were low (< or = 64 mg/l to 87.4% of strains), and all of them were mecA positive, 78.1% of them were resistant to macrolides, 96.5% to tobramycin and 84.9% to quinolones, but only 10.5% to gentamicin, 4.7% were resistant to cotrimoxazol, 1.2% to fosfomycin and 2.5% to rifampin. All of them were sensible to doxycycline, and vancomycin. The pulse field gel electrophoresis showed 7 restriction patterns in MRSA F95, 73.8% of strains correspond to one of them (B), spreading from the spinal cord injury unit and prevalent in HT; and 10.8% to another (C), the first that appear, spreading from the neurosurgical unit and with high prevalence in HG. 6.9% has pattern J a B subtype that appear in broth HG and HT. Pattern E is prevalent in HI it was spread from neonatology unit. CONCLUSIONS: The emergence in a Center with endemic resistance of new strains of MRSA, not all of them of the same clone, with characteristic resistance pattern to antibiotics and in convivence with other phage groups is one demonstration of genetic variability of SAMR in our entorn.

Bacteriophage Typing↗
PubMed2000

[Bioavailability of antibiotics].

To be effective, an antibiotic must achieve therapeutic concentrations at the site of infection. This article is a review on the bioavailability of local and systemic antibiotics. Amongst topical antibiotics, fluoroquinolones and fusidic acid have the best intra-corneal and intra-cameral penetration. Chloramphenicol penetrates the anterior chamber but not always at therepeutic levels. Serum levels are low from topical administration, and haematological toxicity of chloramphenicol eyedrops is still not proven. Amongst systemic antibiotics, the molecules capable of penetrating the eye at therapeutic levels are fosfomycin, imipenem, some of third generation cephalosporins, fluoroquinolones and ureidopenicillins. Intra-ocular penetration of antibiotics is increased by infection, corneal epithelium abrasion, increasing dose frequency or delivery using a biomaterial reservoir (soft contact lenses or collagen schields). Antibiotic-antiinflammatory associations can make infected sites more accessible to antibiotics. The choice of a treatment must take in consideration molecules, dosing and route, and be adapted to the germ to kill and the infected site to treat.

Animals↗
PubMedDate not supplied

[Antimicrobial resistance among species of Salmonella, Shigella, Escherichia, and aeromonas isolated from children with diarrhea in 7 Argentinian centers].

The increasing levels of resistance of enteropathogenic bacteria against antimicrobial agents present geographic variations. We have analysed the antimicrobial susceptibility of isolates obtained from 4,364 children under 5 years of age with acute diarrhea, in 7 cities of Argentina. Diarrheagenic E. coli exhibited 74.5% of resistance against ampicillin, 64.2% against sulfametoxazole-trimethoprim, and Shigella spp., 62% and 75.6% respectively. Salmonella sp. showed 35%, 14%, 41.8%, 65.4%, 14.5%, and 13.6% of resistance against ampicillin, chloranfenicol, sulfametoxazole-trimetoprim, sulfadiazin, gentamycin, and fosfomycin respectively. These values are higher than the ones observed in developed countries. Aeromonas showed significantly lower resistance percentage. Important differences in our country were observed, consequently, local trials should be carried out in order to apply corrective measures.

Acute Disease↗
PubMed2000

[Surveillance of Pseudomonas aeruginosa sensitivity to antibiotics in France and distribution of beta-lactam resistance mechanisms: 1998 GERPB study].

In a prospective study carried out during a three-week period in October 1998 in 13 teaching hospitals, 735 non-repetitive isolates of Pseudomonas aeruginosa were collected. In patients presenting cystic fibrosis (70 strains), the main serotypes isolated were O:6 (14.3%) and O:1 (14.3%). Serotypes O:11 and O:12 were exceptional. In other patients (665 strains), the most frequent serotypes were O:6 (15.9%), O:11 (15.6%), O:1 (10.7%) and O:12 (9.2%). The antibiotic susceptibility rates were as follows (respectively, non-cystic fibrosis and cystic fibrosis strains): ticarcillin, 55 and 59%, piperacillin, 71 and 67%, ceftazidime, 75 and 67%, cefepime, 56 and 43%, cefpirome, 37 and 21%, aztreonam, 57 and 56%, imipenem, 83 and 70%, amikacin, 69 and 33%, ciprofloxacin, 56 and 61% and fosfomycin, 33 and 43%. Serotype O:12 was the least susceptible to antibiotics. Forty-five percent of the non-cystic fibrosis strains presented intermediate susceptibility or resistance to ticarcillin. The most frequent mechanisms of resistance were: non-enzymatic resistance (14.3%), overproduction of the constitutive cephalosporinase (13.8%), production of transferable beta-lactamase (8.6%) and a combination of these mechanisms (4.2%). Among cystic fibrosis strains, resistance to beta-lactam antibiotics was mainly due to overproduction of the constitutive cephalosporinase (18.6%), whereas production of a transferable beta-lactamase was rare (1.4%). Susceptibility to aminoglycosides and fluoroquinolones was less frequent in isolates producing transferable beta-lactamases and/or overproducing cephalosporinase. Decreased susceptibility to imipenem was more frequent in strains presenting a high level of cephalosporinase production. Among the cephalosporins, cefepime was the least affected by the overproduction of constitutive cephalosporinase. Ceftazidime remained the most efficient antibiotic against both susceptible isolates and strains presenting a non-enzymatic or PSE-1 penicillinase-producing mechanism.

Anti-Bacterial Agents↗
PubMed2000

The ECO*SENS Project: a prospective, multinational, multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens-interim report.

The ECO*SENS Project is the first international survey to investigate the prevalence and susceptibility of pathogens causing community-acquired, uncomplicated urinary tract infections (UTIs) in women. At 240 centres in 17 countries, female patients presenting with symptoms of uncomplicated UTIs were asked to provide a urine sample for testing for the presence of leucocytes and bacteria. The bacteria were identified and their susceptibility to 12 antibiotics commonly used in the treatment of UTIs was determined. The objective of the survey was to collect 5000 urine samples to obtain approximately 3500 isolates of defined uropathogens. This interim report includes the results from 1960 urine samples, 75% of which contained a uropathogen. Escherichia coli accounted for the majority (80%) of uropathogens isolated in all 17 countries. The rates of resistance among E. coli strains were: ampicillin and sulphamethoxazole, 30%; trimethoprim alone or with sulphamethoxazole, 15%; nalidixic acid, 6%; ciprofloxacin, 3%; amoxycillin-clavulanic acid, mecillinam, cefadroxil, nitrofurantoin and fosfomycin, 2%. The use of ampicillin, sulphonamides and trimethoprim alone or with sulphamethoxazole needs to be reconsidered. The seemingly rapid increase in quinolone resistance among community-acquired E. coli in some of the countries gives cause for concern.

Journal Article↗
PubMed2000

Treatment options for acute uncomplicated cystitis in adults.

Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of </=10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosprins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coli strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis.

Journal Article↗
PubMed2000

Epidemiological analysis of methicillin resistant Staphylococcus aureus in Thailand.

The geographical distribution of 65 clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) recovered from 7 hospitals in Thailand was investigated. The presence of mecA gene in MRSA was determined by specific PCR with the use of primers 5'-GTAGTTGTCGGGTTTGGT-3' and 5'-GGTATCATCTTGTACCCA-3'. Chromosomal DNA restriction analysis with SmaI was resolved by pulsed-field gel electrophoresis (PFGE) compared with antibiotype analysis and phage type analysis. All 65 strains carried mecA gene. They all were resistant to penicillin, tetracycline, erythromycin, amoxicillin/clavulanic acid and variably resistant to gentamicin, ofloxacin, trimethoprim-sulfamethoxazole, chloramphenicol, fosfomycin and clindamycin; and all isolates were susceptible to vancomycin. A total of 19 PFGE patterns designated as type A, A1, A2, A3, A4, B, B1, C, D, E, E1, E2, F, F1, F2, G, H, I and J was identified. Type A4 and E were commonly found in every studied areas. Phage typing showed even greater variability that 52 (80%) isolates belonged to 25 different phage types; 13 (20%) isolates were non-typable. The clarity and polymorphism of the PFGE patterns enable us to discriminate between isolates which could not be differentiated by antibiogram or phage type analysis. The findings demonstrate the existence of a common epidemic MRSA clone in Thailand.

Bacterial Typing Techniques↗
PubMed2000

The ECO.SENS Project: a prospective, multinational, multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens--interim report.

The ECO.SENS Project is the first international survey to investigate the prevalence and susceptibility of pathogens causing community-acquired, uncomplicated urinary tract infections (UTIs) in women. At 240 centres in 17 countries, female patients presenting with symptoms of uncomplicated UTIs were asked to provide a urine sample for testing for the presence of leucocytes and bacteria. The bacteria were identified and their susceptibility to 12 antibiotics commonly used in the treatment of UTIs was determined. The objective of the survey was to collect 5000 urine samples to obtain approximately 3500 isolates of defined uropathogens. This interim report includes the results from 1960 urine samples, 75% of which contained a uropathogen. Escherichia coli accounted for the majority (80%) of uropathogens isolated in all 17 countries. The rates of resistance among E. coli strains were: ampicillin and sulphamethoxazole, 30%; trimethoprim alone or with sulphamethoxazole, 15%; nalidixic acid, 6%; ciprofloxacin, 3%; amoxycillin-clavulanic acid, mecillinam, cefadroxil, nitrofurantoin and fosfomycin, < or =2%. The use of ampicillin, sulphonamides and trimethoprim alone or with sulphamethoxazole needs to be reconsidered. The seemingly rapid increase in quinolone resistance among community-acquired E. coli in some of the countries gives cause for concern.

Adolescent↗
PubMed2000

Treatment options for acute uncomplicated cystitis in adults.

Urinary tract infection (UTI) is classified as uncomplicated if it occurs in a patient with a structurally and functionally normal urinary tract. Acute uncomplicated cystitis is observed chiefly in women. It needs, however, to be differentiated depending on whether it occurs in premenopausal, postmenopausal or pregnant women. Only a small number of 15-50 year old, otherwise healthy men suffer acute uncomplicated cystitis. In premenopausal, non-pregnant women, single-dose antimicrobial therapy is generally less effective than the same antibiotic used for longer duration. However, most antimicrobial agents given for 3 days are as effective as those given for longer duration, and adverse events tend to be found more often with longer treatment. Trimethoprim (or co-trimoxazole) can be recommended as first-line empirical therapy only in communities with resistance rates of uropathogens to trimethoprim of < or =10-20%. Otherwise fluoroquinolones are recommended. Alternatives are fosfomycin trometamol or beta-lactams, such as second- or third-generation oral cephalosporins or pivmecillinam, especially when fluoroquinolones are contraindicated or a high proportion (>10%) of Escherichia coil strains in the community are already resistant to fluoroquinolones, as in Spain, for example. Recurrent UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. The following prophylactic antimicrobial regimens are recommended: (i) the use of long-term, low-dose prophylactic antimicrobials taken at bedtime; (ii) post-coital prophylaxis for women in whom episodes of infection are associated with sexual intercourse. Other prophylactic methods are not as yet as effective as antimicrobial prophylaxis.

Adolescent↗
PubMed2001

[Glycopeptides].

Glycopeptides(Vancomycin(VCM), Teicoplanin(TEIC)) are effective against Gram positive cocci(GPC) and mainly prescribing for Methicillin Resistant Staphylococcus aureus(MRSA) infection in Japan. Mode of actions are little bit difference between VCM and TEIC, for example the rate of protein binding, post antibiotic effect and half-life time. Effect of glycopeptide depend on the above MIC. To keep the effective serum concentrations of the drug, recommended the method of loading dose for TEIC and the method of continuous drip infusions for VCM. Also keep the effective serum concentrations shows to shorten the duration of treatment and to protect for development of resistant strains. Biofilm diseases caused by P. aeruginosa, MRSA and MRSE are treated by combination therapy with Fosfomycin(FOM). The most powerful intensive chemotherapy (FOM + Sulbactam/Cefoperazon + Glycopeptides) shows superior effects against multiple infections caused by P. aeruginosa and MRSA.

Anti-Bacterial Agents↗
PubMed2001

[Pattern of antimicrobial susceptibility in uropathogen isolates from children].

The bacteriological profile in children with culture-positive bacteriuria was analyzed during a 5-year period. Escherichia coli was the most common cause of urinary tract infections (57%), followed by Streptococcus faecalis (11%), Pseudomonas aeruginosa (8%), and Proteus mirabilis (6%). Results of antimicrobial susceptibility testing indicated that cephalosporins (first, second and third generation) and nitrofurantoin are the best empirical oral treatment for urinary infections in children. Fosfomycin is a valid option in some cases. In hospitalized children treatment must be initiated with a third-generation cephalosporin, and gentamicin can be added in severely ill inpatients. These treatments can be modified when microbiological results become available.

Adolescent↗
PubMed2000

[Evolution of antimicrobial susceptibility of Acinetobacter baumannii clinical isolates].

Acinetobacter baumannii is a microorganism frequently implicated in colonization and infection in hospitalized patients. An increase of resistance has been observed in recent years making these infections difficult to treat. The in vitro activity of 24 antibiotics, 15 betalactam agents and nine nonbetalactams, was studied in 156 A. baumannii clinical isolates. The strains were collected from different clinical samples obtained from inpatients (92%) and 8% were from outpatients. Evolution of susceptibility from January 1995 to December 1997 was studied. MIC of the following antibiotics was determined by the agar dilution method: ampicillin, ticarcillin, piperacillin, ampicillin-sulbactam, amoxicillin- clavulanic acid, ticarcillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, clavulanic acid, sulbactam, tazobactam, amikacin, gentamicin, tobramycin, ofloxacin, doxycycline, fosfomycin, rifampin, azithromycin and colistin. Low antimicrobial susceptibility was observed in most A. baumannii strains. Colistin, imipenem, meropenem and ampicillin-sulbactam showed the greatest susceptibility (100, 88.4, 88.4 and 84.6%, respectively). A. baumannii strains from inpatients showed a lower antimicrobial susceptibility than strains from outpatients, who showed a high percentage of susceptibility to most antibiotics. Rifampin and azithromycin showed certain in vitro activity against the most susceptible A. baumannii strains. A progressive decrease in susceptibility to most antibiotics was observed during the period studied. Carbapenem-resistant A. baumannii emerged in 1996 and increased in 1997.

Acinetobacter↗
PubMed2001

[Mycoplasma pneumonia complicated by acute renal failure].

A 17-year-old woman presented with cough and fever. Treatment with cefteram pivoxil and fosfomycin calcium was not effective. Chest radiography showed infiltration with an air bronchogram in the left upper lung field. The case was initially treated as atypical pneumonia by administering minocycline hydrochloride and piperacillin sodium. Since acute renal failure progressed rapidly, we introduced hemodialysis, and renal function improved. The mycoplasma polymerase chain reaction (PCR) in the pharynx smear was positive, and the mycoplasma serum titer was 1280 on admission. On the basis of these findings, mycoplasma pneumonia was diagnosed. Only one other case of mycoplasma pneumonia with hemodialysis has been reported in Japan. We report and assess the pathogenesis of mycoplasma pneumonia complicated by renal dysfunction.

Acute Kidney Injury↗
PubMed2002

[Acute bacterial cystitis].

It is now important to differentiate lower urinary tract infection also known as classical acute cystitis (because it involves a healthy genitourinary system) from complicated or potentially complicated urinary tract infection. The bacteriology of lower urinary tract infection is dominated by enterobacteria and Escherichia coli in particular. Since E. coli are now commonly resistant to amoxicillin and cotrimoxazole, those antibiotics cannot be used as first-intention. Fluoroquinolones, fosfomycin trometamol or furans must be preferred instead. The clinical problem here is trying to avoid overzealous diagnoses and remembering that symptom-free bacteriuria is very frequent, particularly in elderly patients. The management of uncomplicated lower urinary tract infection should remain simple (urinalysis with reagent strips and more cell bacteriology tests); the treatment should be simple too [single-dose or short treatment (3 days)]. The management of complicated lower urinary tract infection is very different however and requires a more extensive workup followed by a dual therapy, namely antibiotics and eradication of the complicating factor, if possible.

Acute Disease↗
PubMed2002

Antibiotics as anti-inflammatory agents.

Although the empirical use of some antibacterial agents in various inflammatory diseases has proved beneficial in the past, it is only recently that the therapeutic anti-inflammatory potential of cyclines and macrolides has received attention worldwide. Other drugs like fosfomycin and some quinolones are also contenders for this role. Owing to the complexity of the inflammatory process, which involves many redundant cellular effectors and soluble mediators, and the obscure etiopathogenesis of many inflammatory diseases (some of which may be secondary to persistent infections), the precise mechanisms underlying the therapeutic benefit of anti-inflammatory antibiotics remain to be elucidated. Structure-activity relationships are the key to developing new anti-inflammatory agents derived from antibacterial drugs.

Animals↗