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There are several classifications of UTI: Uncomplicated UTI is a sporadic bacterial cystitis found in a healthy patient with normal urinary tract anatomy and function.

Complicated UTI occurs in a patient with functional or anatomic abnormalities of the urinary tract, or in patients with risk factors for persistent or recurrent infection as well as treatment failure.

Such conditions include immunosuppression (due to natural disease or prescribed therapy), diabetes mellitus, hyperadrenocorticism, kidney disease, prostatitis, pregnancy, urinary incontinence, and altered neurogenic function of the bladder.

Recurrent UTI requires investigation to determine whether it is reinfection, relapsing, or refractory. Reinfection is the return of a UTI—caused by a different organism—within 6 months of discontinuation of antibiotic therapy. Relapsing UTI occurs when the same organism is cultured again within 6 months of discontinuation of antibiotic therapy. This suggests that the patient has a condition that allows recolonization or one that prevents total eradication of infection; additional diagnostics are warranted in these patients ( Table 1 ). Refractory UTI occurs when a positive urine culture is obtained during appropriate antibiotic therapy (based on in vitro susceptibility testing). There are several possible causes for refractory UTI, including: Decreased renal drug elimination (results in lower than expected urine drug concentration) Inappropriate drug dose or administration schedule Low drug bioavailability (eg, due to drug compounding or gastrointestinal disease) Poor drug compliance.

Additionally, some drugs may show efficacy in vitro , but, for unknown reasons, the same effect is not present in vivo .

PK is the movement of a drug throughout the body and includes absorption, distribution, metabolism, and excretion.

PD is the effect of the drug on the body ; in the case of antibiotics, this also includes the effect on the microorganism. These relationships, often referred to as PK/PD, help predict the outcome of any drug prescription. Alterations in PK may happen with abnormal absorption (eg, severe gastrointestinal disease), drug metabolism (eg, synthetic liver dysfunction), altered protein binding (eg, uremia, hypoproteinemia), and diminished drug excretion (hepatic or kidney failure). An antibiotic’s PD is assessed clinically through in vitro culture and susceptibility testing. Ideally, all patients with a suspected UTI should have a urine sample collected

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Urine culture is considered the gold standard in the diagnosis of UTI.

The 2 techniques for determining antibiotic susceptibility are the disk diffusion and serial dilution methods. Disk diffusion testing is considered less reliable and does not provide the minimum inhibitory concentration (MIC) of the antibiotic, whereas antimicrobial dilution does provide the MIC and is the preferred method of antibiotic susceptibility testing. With antimicrobial dilution, a concentration of an antibiotic is added to a liquid medium inoculated with the bacterial isolate.

The concentration of antibiotic is doubled in each subsequent well.

The MIC is the concentration of antibiotic found in the first tube that exhibits no detectable growth, 5 and this concentration is used to categorize the isolate as susceptible , intermediate , or resistant (see CLSI Classification ).

Rarely, false-negative findings may result from inappropriate urine storage or slow organism growth (as seen with Corynebacterium species).

Urine processing for quantitative culture should be performed immediately after urine is obtained because bacterial colony count dramatically drops after 24 hours of refrigerated storage when urine is stored in a silicone clot tube.

6 If urine cannot be processed for quantitative culture immediately, use of a urine transport tube is recommended to help prevent false-negative or underestimated colony count results.

Isolate classifications— susceptible, intermediate , or resistant —are established by the Clinical Laboratory Standards Institute (CLSI) on the basis of drug PK and PD data. Several factors are considered in the establishment of CLSI breakpoint classifications. The peak drug concentration (C max ) obtained by a standard dose and normal route of administration must be higher than the isolate’s minimum inhibitory concentration (MIC) for the isolate to be labeled susceptible .

The C max is not always based on the drug concentration in urine. Some drugs have established CLSI breakpoints for UTI in some bacterial species (see CLSI publication VET01S); other breakpoints are based on infection in other organ systems or are even extrapolated from human use.

Drugs for which no breakpoint has been determined for UTI may still be effective against “intermediate” organisms because the concentration of the drug in urine may be higher than in plasma. When urine culture and susceptibility results are used to choose appropriate therapy for pyelonephritis, the plasma breakpoints should be used, rather than urine breakpoints. All of the preceding factors should be considered in selecting the most appropriate drug, as well as dosage and frequency of administration. Many antibiotics are excreted primarily in urine and achieve concentrations substantially higher than those in plasma.

The urine drug concentration should be evaluated with respect to the isolate’s MIC to determine the likelihood of eliminating the organism. Table 2 lists observed urine concentration of antibiotics at the specified dosages in healthy animals.

Urine antibiotic concentrations in veterinary patients with kidney disease have yet to be investigated. Reduced glomerular filtration rate (GFR) may decrease the excretion of the drug into urine, resulting in decreased urine concentrations. Additionally, polyuric patients may experience further reduction of urine drug concentration because of increased daily urine volume and subsequent dilution of filtered antibiotic. Decreased urine excretion caused by diminished GFR can result in plasma drug concentrations exceeding those normally observed and may cause adverse effects. This is most true for drugs with significant kidney elimination.

Drugs with mostly hepatic elimination may have minimal alteration in drug excretion in patients with decreased GFR.

However, the accumulated uremic toxins and hypoproteinemia present in many patients with kidney disease can lead to altered drug protein binding and abnormal drug PK/PD. The protein binding and lipid solubility of an antibiotic help determine its volume of distribution. Highly lipophilic drugs cross

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Such drugs are most effective in treating prostatitis, in which the blood–prostate barrier prevents passage of many water-soluble antibiotics (such as beta-lactams). In early stages of prostatitis, the blood–prostate barrier may be compromised, allowing delivery of water-soluble antibiotics to the site of infection.

However, after the initial inflammation resolves (1–2 weeks, based on my clinical experience), this barrier is restored and these antibiotics may no longer reach effective tissue concentration within the prostate, preventing bacterial cure. The lipophilic drugs that achieve effective concentrations within the prostate include fluoroquinolones, sulfonamides, and macrolides; however, choice of antibiotic should be based on urine culture and susceptibility results. The pill 3109 emergence of antimicrobial resistance and multidrug resistance has increased, making empiric antibiotic selection very difficult, particularly when previous antibiotic therapy has been administered to the patient.

Recommended drugs for uncomplicated UTI include

amoxicillin

Rational initial drug choices for complicated UTI include amoxicillin, fluoroquinolones, or trimethoprim-sulfonamide. To best use antibiotic urine data, an important consideration is whether a drug is time- or concentration-dependent.

Time-dependent drugs include beta-lactams, cephalosporins, sulfa drugs, tetracyclines, and chloramphenicol.