Urine antimicrobial concentrations

The ability to eradicate bacteria from the urinary tract is directly related to the sensitivity of the organism and the achievable concentration of the antimicrobial agent in the urine. 

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. Apart from the bloodstream, other body fluids where drug concentration data are clinically relevant include urine, synovial fluid, and peritoneal fluid. Pharmacokinetic parameters such as area under the concentration-time curve (AUC) and maximal plasma concentration can be predictive of treatment outcome when specific ratios of AUC or maximal plasma concentration to the minimum inhibitory concentration (MIC) are achieved. For... 

These are adapted from the ampicillin molecule, with a side-chain derived from urea. Their major advantages over the carboxypenicillins are higher efficacy against Pseudomonas aeruginosa and the fact that as monosodium salts they deliver on average about 2 mmol of sodium per gram of antimicrobial (see above) and are thus safer where sodium overload should particularly be avoided. They are degraded by many p-lactamases. Ureidopenicillins must be administered parenterally and are eliminated mainly in the urine. Accumulation in patients with poor renal function is less than with other penicillins as 25% is excreted in the bile. An unusual feature of their kinetics is that, as the dose is increased, the plasma concentration rises disproportionately, i.e. they exhibit saturation (zero-order) kinetics. 

For infection of the lower urinary tract a low dose may be effective, as many antimicrobials are concentrated in the urine. Infections of the substance of the kidney require the doses needed for any systemic infection. Elimination of infection is hastened by a large urine volume (over 1.51/d) and by frequent micturition. 

Susceptibility designations are based on achievable plasma concentrations and do not take preferential drug accumulation at specific sites into account most antimicrobial agents are eliminated by the kidneys, achieving concentraflons in urine that are hundreds of times higher than those in plasma tetracyclines accumulate in pneumonic limg tissue. 

It warrants mention that resistance to a particular antimicrobial agent in vitro may not preclude successful treatment with the drug as long as high concentrations are achieved in urine. Similarly, demonstrable susceptibility in vitro does not always guarantee a successful response to treatment. For example. Enterococcus spp. is often found to be susceptible to the potentiated sulfonamide combinations in vitro however, this pathogen is inherently resistant to these combinations in vivo (Jose-Cunilleras Hinchcliff 1999, Schott 1998). Antimicrobial therapy should be continued for at least 1 week for the treatment of lower UTIs and for 2-6 weeks for upper UTls in horses. Ideally, a voided, midstream urine sample should be submitted for bacterial culture 2-4 days after the initiation of therapy and again 1-2 weeks after treatment has been discontinued. 

Ciprofloxacin is well absorbed in the gastrointestinal tract. Serum concentration peaks in 1.5-2 h postingestion. The elimination half-life with normal renal function is 4h. Ciprofloxacin is 20-40% bound to serum proteins and distributed widely throughout the body. Four metabolites in human urine have been identified, which account for 15% of an oral dose. The metabolites have antimicrobial activity, which are less active than the parent compound of ciprofloxacin. Ciprofloxacin inhibits CYP3A4 enzyme system. 

Caution must be excercised when selecting an antimicrobial agent for clinical use on the basis of tissue or fluid penetration. Body fluids where drug concentration data are clinically relevant include CSF, urine, synovial fluid, and peritoneal fluid. Apart from these areas, more attention should be paid to clinical efficacy, antimicrobial spectrum, toxicity, and cost than to comparative data on penetration into a given body site. 

The ahUity to eradicate bacteria from the urine is related directly to the sensitivity of the microorganism and the achievable concentrations of the antimicrobial agent in the urine. Unfortunately, most susceptibifity testing is directed at achievable concentrations in the blood. There is a poor correlation between achievable blood levels of antimicrobial agents and the eradication of bacteria from the urine. In the treatment of lower tract infections, plasma concentrations of antibacterial agents may not be important, but achieving appropriate plasma concentrations appears critical in patients with bacteremia and renal abscesses. 

A number of nonspecific therapies have been advocated in the treatment and prevention of UTIs. Fluid hydration has been used to produce rapid dilution of bacteria and removal of infected urine by increased voiding. A critical factor appears to be the amount of residual volume remaining after voiding. As little as 10 mL of residual urine can alter the eradication of infection significantly. Paradoxically, increased dimesis also may promote susceptibifity to infection by diluting the normal antibacterial properties of the urine. Often in clinical practice the concentrations of antimicrobial agents in the mine are so high that dilution has little effect on efficacy. 

Nitrofurantoin is absorbed rapidly and completely from the GI tract. Antibacterial concentrations are not achieved in plasma at recommended doses because the drug is eliminated rapidly. The plasma tj 2 hour 40% is excreted unchanged in the urine. The urine should not be alka-linized because this reduces antimicrobial activity. Nitrofurantoin colors the urine brown. 

Trisulfa -pyrimidines (Triple Sulfas) Therapeutic doses of sulfadiazine, sulfamerazine or sulfamethazine alone are likely to precipitate in the urine due to poor solubility. When the three drugs are combined (each at 1/3 of its therapeutic dose) the antimicrobial effects are additive but the urine solubility is independent. Thus a full" therapeutic dose of combined sulfonamides is delivered but the concentration of each is below the threshold required for precipitation. 

Urine concentration may be affected by silver sulfadiazine (Silvadene), a topical antimicrobial that is used to treat burns, but Sulfamylon does not affect urine concentration. 

The range of kits currently available for the Charm II system and their applications are given in Table 5.5. The test manufacturer claims that the Charm II tests are capable of detecting compounds belonging to the antimicrobial class at or below their defined MRLs (or USFDA tolerances, as indicated) within the relevant matrix, including, milk, urine, serum, animal tissue, honey, and other substances at concentrations of interest to regulatory agencies. 

The USDA/FSIS have a number of rapid tests for determining the presence of antimicrobial substances in carcasses or in live animals. The swab test on premises and the live animal swab test are developed for kidney (or liver) and urine samples, respectively, using an inhibition agar plate assay. The sulfa on site test is used on farm or at slaughter plant to screen samples of serum, urine, or feed for sulfadimidine residues. The test is based on TLC and uses well-defined ratios between concentrations of sulfadimidine in serum or urine and in edible tissues... 

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