***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Plasma and salivary amoxicillin ( AMO ) concentrations were quantified following a single oral dose ( 875 mg ) of two formulations of AMO ( Amoxicillin-EMS Sigma Pharma and Amoxil BD 875 mg ) . In addition , the effect of amoxicillin against oral microorganisms was accessed . The open , r and omized , two-period crossover study was carried out in 20 volunteers . Saliva and blood sample s were collected at 0 , 0.5 , 1 , 2 , 4 , 8 and 12 h after drug administration , and quantified using HPLC-ESI-MS and HPLC , respectively . Streptococci counts , anaerobe counts and total microorganism counts were obtained . No differences were observed between formulations ( p > 0.05 ) in the plasma and salivary AMO concentrations and the pharmacokinetic parameters ( C(max ) , t(max ) , AUC(0 - 8 ) , and AUC(0-infinity ) ) also showed no statistically significant differences between formulations ( p > 0.05 ) . Microorganism counts for the two formulations at all sampling times did not differ ( p > 0.05 ) but all microorganism counts at 60 min post-dose showed a significant decrease ( p < 0.05 ) . Amoxicillin was effective in reducing oral microorganism levels up to 12 h post-dose ABSTRACT To characterize the penetration of moxifloxacin ( BAY 12 - 8039 ) into peripheral target sites , the present study aim ed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis , an innovative clinical sampling technique . In addition , moxifloxacin concentrations were measured in cantharides-induced skin blisters , saliva , and capillary plasma and compared to total- and free-drug concentrations in venous plasma . For this purpose , 12 healthy volunteers received moxifloxacin in an open r and omized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min . An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed , with mean area under the concentration-time curve (AUC)interstitial fluid/AUCtotal-plasma ratios ranging from 0.38 to 0.55 and mean AUCinterstitial fluid/AUCfree-plasma ratios ranging from 0.81 to 0.86 . The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h , indicating a preferential penetration of moxifloxacin into inflamed lesions . The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma . Our data show that  moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90 % of isolates are inhibited for most clinical ly relevant bacterial strains , notably including penicillin-resistant Streptococcus pneumoniae . These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans The pharmacokinetics of AM-1155 , a new 6-fluoro-8-methoxy quinolone , was examined in healthy male volunteers after the oral administration of a single dose of 100 , 200 , 400 , or 600 mg and multiple doses of 300 mg twice daily for 6.5 days ( 13 total doses ) . Throughout the whole study period , AM-1155 was well tolerated in every subject . In the single-dose study , the concentrations in serum reached a peak between 1 and 2 h , and the peak concentrations were 0.873 , 1.71 , 3.35 , and 5.41 micrograms/ml at the doses of 100 , 200 , 400 , and 600 mg , respectively . The elimination half-life was 7 to 8 h , independently of the doses . The unchanged drug was excreted mainly in the urine , with 82 to 88 % of the doses appearing for 72 h. The fecal recovery of the unchanged drug amounted to 5.7 % for 72 h after a single oral administration of a 400-mg dose . Urinary excretion of metabolites was minimal . The serum protein binding was 20 % , independently of the concentrations in serum . The concentrations in saliva were approximately 80 % of those in serum . The intake of food had no effect on the pharmacokinetic parameters and urinary excretion of AM-1155 except the slight decrease in area under the concentration-time curve . The concurrent administration of probenecid prolonged the elimination half-life , increased the area under the concentration-time curve , and decreased the apparent total body clearance , renal clearance , urinary recovery of unchanged drug , and the excretion ratio ( intrinsic renal clearance of AM-1155/creatinine clearance ) . This indicated that the tubular secretion contributed to the renal excretion of AM-1155 . In the multiple-dose study , the concentrations of AM-1155 in serum and urine reached a steady state within 2 to 3 days . The measured concentrations in serum fitted well the simulation curve , which reflected the persistence of linear pharmacokinetics of AM-1155 . In conclusion , AM-1155 is expected to be clinical ly useful because of its potent antibacterial activity and favorable pharmacokinetics BACKGROUND The occurrence of acquired rifamycin resistance despite use of directly observed therapy for tuberculosis is associated with advanced human immunodeficiency virus ( HIV ) disease and highly intermittent administration of antituberculosis drugs . Beyond these associations , the pathogenesis of acquired rifamycin resistance is unknown . METHODS We performed a pharmacokinetic sub study of patients in a trial of treatment with twice-weekly rifabutin and isoniazid .  RESULTS A total of 102 ( 60 % ) of 169 patients in the treatment trial participated in the pharmacokinetic sub study , including 7 of 8 patients in whom tuberculosis treatment failure or relapse occurred in association with acquired rifamycin-resistant mycobacteria ( hereafter , " ARR failure or relapse " ) . The median rifabutin area under the concentration-time curve ( AUC(0 - 24 ) ) was lower for patients with than for patients without ARR failure or relapse ( 3.3 vs. 5.2 microg*h/mL ; P = .06 , by the Mann-Whitney exact test ) . In a multivariate analysis adjusted for CD4 + T cell count , the mean rifabutin AUC(0 - 24 ) was significantly lower for patients with ARR failure or relapse than for other patients ( 3.0 microg*h/mL [ 95 % confidence interval { CI } , 1.9 - 4.5 ] vs. 5.2 microg*h/mL [ 95 % CI , 4.6 - 5.8 ] ; P = .02 , by analysis of covariance ) . The median isoniazid AUC(0 - 12 ) was not significantly associated with ARR failure or relapse ( 20.6 vs. 28.0 microg*h/mL ; P = .24 , by the Mann-Whitney exact test ) . However , in a multivariate logistic regression model that adjusted for the rifabutin AUC(0 - 24 ) , a lower isoniazid AUC(0 - 12 ) was associated with ARR failure or relapse ( OR , 10.5 ; 95 % CI , 1.1 - 100 ; P = .04 ) . CONCLUSIONS Lower plasma concentrations of rifabutin and , perhaps , isoniazid were associated with ARR failure or relapse in patients with tuberculosis and HIV infection treated with twice-weekly therapy The fluoroquinolone , ofloxacin , has been reported to be mainly excreted unchanged in urine , with only minimal hepatic metabolism of the drug . Previous studies have shown that 70 to 80 % is excreted in the urine over 24 hours , and if the collection duration increases so , too , does the recovery of the drug}ll With such a high renal excretion , any change in renal function may affect the dosage of ofloxacin that should be administered . This becomes particularly relevant in the elderly , as a 50 % reduction in renal function is normal in those aged over 70 years . In fact , some research ers recommend that the dose of ofloxacin should be reduced by as much as a half in elderly patients , while others do not consider such a reduction necessaryPl In addition , pharmacokinetic studies have shown that most of a dose of ofloxacin penetrates into saliva , and its concentration in this site correlates well with serum levelsPl This makes it easy and convenient to estimate ofloxacin levels by measuring concentration in saliva rather than serum . The purpose of this study was to determine the optimal dose of ofloxacin in patients with impaired renal function by measuring the drug concentration in the saliva .  80 patients ( 53 males , 27 females ; mean age 62.7 + 19.7 years ) were divided into 5 groups according to their creatinine clearance ( CLCR ) : group A , CLcR > 70 ml/min ; group B , 50 to 69 ml/min ; group C , 30 to 49 ml/min ; group D , 20 to 29 ml/min ; and group E , < 20 mllmin . Serum concentration was measured at the beginning of , and 2 hours after , administration , and saliva concentration was measured 2 and 4 hours after the drug was administered . The paper disk method was used , with Bacillus subtilis ATCC 6051 , and Escherichia coli KP as the test bacteria . 41 patients were diagnosed as having urinary tract infections ( UTIs ) , 2 had other infections , 6 required ofloxacin as prophylaxis for postoperative infection , and there were 31 volunteers .  Ofloxacin dosage schedules depended on CLCR and ranged from 600 mg/day administered as 200 mg 3 times daily , to 100 mg administered for 5 days as a single daily dose to patients with severe renal impairment ( CLCR < 30 ml/min ) . The smallest dosage was 100 mg once a day or once The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children .  Mean peak serum concentrations of 5.4 micrograms/ml in fasting and 3.2 micrograms/ml in nonfasting patients were observed after 15 mg/kg amoxicillin doses . Area under the curve values and serum half-life values were similar in fasting and nonfasting patients . The pharmacokinetics of amoxicillin ( 15 mg/kg ) were compared to those of ampicillin ( 25 mg/kg ) . Peak serum concentrations , area under the curve values and half-life times were comparable for the two drugs . Amoxicillin ( 25 mg/kg ) and ampicillin ( 25 mg/kg ) were compared in cross-over fashion in 11 children .  Serum concentrations of  amoxicillin were consistently larger than those of ampicillin ; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage . The bioavailability of amoxicillin was twice that of ampicillin .  Amoxicillin  was detected in approximately half of the saliva sample s studied . Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-beta lactamase-producing Haemophilus influenzae type b strains , the clinical relevance of these observations is unknown Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND Based on a hollow-fiber system model of tuberculosis , we hypothesize that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic variability . METHODS Clinical and pharmacokinetic data were prospect ively collected from 142 tuberculosis patients in Western Cape , South Africa . Compartmental pharmacokinetic parameters of isoniazid , rifampin , and pyrazinamide were identified for each patient . Patients were then followed for up to 2 years . Classification and regression tree analysis was used to identify and rank clinical predictors of poor long-term outcome such as microbiologic failure or death , or relapse . RESULTS Drug concentrations and pharmacokinetics varied widely between patients . Poor long-term outcomes were encountered in 35 ( 25 % ) patients . The 3 top predictors of poor long-term outcome , by rank of 
    Output:
    
Conclusions : For gatifloxacin and linezolid , salivary therapeutic drug monitoring is likely possible due to a narrow range of saliva – plasma and saliva – serum ratios .
For isoniazid , rifampicin , moxifloxacin , ofloxacin , and clarithromycin , salivary therapeutic drug monitoring might be possible ; however , a large variability in saliva – plasma and saliva – serum ratios was observed .
Unfortunately , salivary therapeutic drug monitoring is probably not possible for doripenem and amoxicillin/clavulanate , as a result of very low salivary drug concentrations