what are the various therapeutic effects of drugs used to treat urinary tract infections quizlet
Bacterial urinary tract infections (UTIs) typically issue from normal peel and GI tract flora ascending the urinary tract and overcoming the normal urinary tract defenses that prevent colonization. Bacterial UTI is the most common infectious disease of dogs, affecting 14% of all dogs during their lifetime. Although UTIs are uncommon in young cats, the incidence of UTI is much higher in older cats, which may be more susceptible to infection because of diminished host defenses secondary to crumbling or concomitant disease (such as diabetes mellitus, renal failure, or hyperthyroidism). Approximately two-thirds of those cats also have some degree of renal failure. Bacterial UTIs in ruminants are associated with catheterization or parturition in females and as both a cause and consequence of urolithiasis in males. In horses, UTIs are uncommon and typically associated with bladder paralysis, urolithiasis, or urethral harm.
Unlike man patients, veterinarian patients are often asymptomatic, and the UTI may exist an incidental finding. The consequences of untreated UTI include lower urinary tract dysfunction, urolithiasis, prostatitis, infertility, septicemia, and pyelonephritis with scarring and eventual kidney failure. Coagulase-positive staphylococci are involved in the formation of struvite (MgNH4POiv) calculi in dogs. In intact male dogs, UTI frequently extends to the prostate gland. Because of the claret-prostate barrier, it is difficult to eradicate leaner from the prostate, and the urinary tract may be reinfected afterwards advisable treatment, causing a systemic bacteremia, infecting the residue of the reproductive tract, or causing an abscess within the prostate.
Big, retrospective studies have documented the most common species of uropathogens in dogs and cats, with Escherichia coli being the single near common pathogen in both acute and recurrent UTIs. The other common pathogens include Staphylococcus, Proteus, Streptococcus, Klebsiella, and Pseudomonas spp. In UTIs in horses, E coli, Streptococcus, and Enterococcus spp predominate, whereas Corynebacterium renale and E coli are the most mutual pathogens in ruminants. In immunocompromised animals, funguria from Candida spp may occur.
Urine culture is the "gilt standard" for diagnosis of UTI. Indications to perform urine culture include visualization of bacteria during urine sediment examination, evidence of pyuria, dilute urine (<1.013 SG), immunosuppression, and diabetes mellitus or hyperadrenocorticism. Antimicrobial susceptibility testing should be done with complicated or recurrent cases of UTIs, immunosuppressed animals, animals recently catheterized, or animals treated with antimicrobials within the preceding three wk (because of selection for antimicrobial resistance). In improver, civilization and susceptibility testing should be performed in cases that do not respond within vii days of therapy for UTI or in cases associated with multiple pathogens.
High urine concentrations of antimicrobials are correlated with efficacy in handling of elementary cystitis. Only in complicated cases and in pyelonephritis, tissue concentrations may be every bit important. Most antimicrobials undergo renal elimination to a great extent, so urine concentrations may be up to 100 times peak plasma concentrations. Drug excretion through the kidney involves diverse processes such as secretion and/or reabsorption in dissimilar parts of the nephron, depending on the molecular construction of the drug, its pKa, the pH in the tubular fluid, and degree of poly peptide binding. The flow of urine through the urinary tract is office of the defense against invading pathogens, because the flow of fluid rinses the epithelial linings. High urine antimicrobial concentrations are of import for eradication of leaner in the urine, but for infection of the bladder wall or renal tissue it is necessary to use antimicrobials that take agile concentrations in the tissues. Serum or plasma concentrations are useful surrogate markers for antimicrobial concentrations in the renal or bladder tissues.
In add-on to having the appropriate antimicrobial action and achieving effective concentrations in urine, the selected antimicrobial should be piece of cake for owners to administer, accept few agin effects, and be relatively inexpensive. Once urine civilisation and sensitivity results are known, the bacterial minimum inhibitory concentration (MIC) tin be compared with the mean urinary concentration of the drug and an appropriate antimicrobial chosen.
Amoxicillin and ampicillin are bactericidal and relatively nontoxic, with a spectrum of antibacterial activity greater than that of penicillin G. They accept fantabulous activity against staphylococci, streptococci, enterococci, and Proteus, and may accomplish urinary concentrations loftier plenty to be effective confronting Eastward coli and Klebsiella. Pseudomonas and Enterobacter are resistant. Amoxicillin is more bioavailable in dogs and cats (better absorbed from the GI tract) than ampicillin, hence the lower dosage. Assimilation of ampicillin is also affected by feeding, so therapeutic success may be easier to achieve with amoxicillin. Equally penicillins, they are weak acids with a low volume of distribution, then they exercise not achieve therapeutic concentrations in prostatic fluid.
Amoxicillin-clavulanic acrid has an increased spectrum of activity against gram-negative leaner because of the presence of clavulanic acrid. Clavulanic acid irreversibly binds to β-lactamases, allowing the amoxicillin fraction to collaborate with the bacterial pathogen. This combination usually has excellent bactericidal activity confronting β-lactamase–producing staphylococci, E coli, and Klebsiella. Pseudomonas and Enterobacter remain resistant. However, clavulanic acid undergoes some hepatic metabolism and excretion, so much of the antimicrobial activity in the float may be due to the high concentrations of amoxicillin achieved in urine. Thus, despite an unfavorable susceptibility report for amoxicillin, clinically amoxicillin lonely may be as effective as amoxicillin-clavulanic acid to treat UTIs.
Cefadroxil and cephalexin are beginning-generation cephalosporins. Cefadroxil is a veterinary-labeled suspension production, whereas cephalexin is bachelor in both human and veterinary formulations every bit tablets, paste, or suspension products. Like the penicillins, they are bactericidal, acidic drugs with a low volume of distribution and are relatively nontoxic. Vomiting and other GI signs may occur in dogs and cats treated with cephalosporins. Cephalosporins have greater stability to β-lactamases than penicillins, and then they take greater activeness against staphylococci and gram-negative bacteria. They have excellent activity against Staphylococcus spp, Streptococcus spp, Eastward coli, Proteus, and Klebsiella. Pseudomonas, enterococci, and Enterobacter are resistant.
Cefovecin is an injectable, tertiary-generation cephalosporin approved for treatment of dogs with a UTI due to Due east coli or Proteus. In cats, it is only approved for skin infections but may be used in an extra-characterization fashion for UTIs. With SC dosing, therapeutic concentrations are accomplished for fourteen days, making this an attractive treatment choice for fractious animals.
Cefpodoxime is an oral, third-generation cephalosporin canonical for utilize in dogs for peel infections (wounds and abscesses), only information technology is used actress-label for treatment of canine UTI. Cefpodoxime has a relatively long half-life in dogs, so it is dosed once daily.
Ceftiofur is an injectable cephalosporin approved for respiratory illness in horses, swine, and cattle and for handling of canine UTI caused by Due east coli and Proteus. Ceftiofur has pharmacokinetic backdrop very dissimilar from those of other cephalosporins. Later on injection, ceftiofur is immediately metabolized to desfuroylceftiofur, which has different antimicrobial action than the parent compound. Desfuroylceftiofur has equivalent activity to ceftiofur confronting E coli (MIC 4 mcg/mL) only is much less agile against Staphylococcus spp and has variable activity against Proteus (MIC 0.5–16 mcg/mL). Considering of the instability of desfuroylceftiofur, microbiology services use a ceftiofur disk when performing susceptibility testing, and then a false expectation of therapeutic efficacy may event for some pathogens. Pseudomonas, enterococci, and Enterobacter spp are resistant to ceftiofur and desfuroylceftiofur. Ceftiofur is associated with a duration- and dose-related thrombocytopenia and anemia in dogs, which would not be expected with the recommended dosage regimen.
Chloramphenicol has a loftier volume of distribution, and high tissue concentrations tin can be achieved, including in the prostate of male person dogs and cats. It is active against a broad range of gram-positive and many gram-negative bacteria, confronting which it is unremarkably bacteriostatic. Chloramphenicol is typically active against enterococci, staphylococci, streptococci, E coli, Klebsiella, and Proteus. Pseudomonas are resistant. North American isolates of methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius are typically susceptible. Well known for causing idiosyncratic (non-dose-dependent) anemia in people and dose-dependent bone marrow suppression in animals, its utilise in both human being and veterinary medicine is increasing because of resistance to other antimicrobial drugs.
Enrofloxacin, orbifloxacin, and marbofloxacin are all fluoroquinolones canonical to treat UTIs in dogs; although all are used in cats, only some are approved for this apply. Pradofloxacin is only canonical for skin infections in cats in Due north America, but it is approved for treatment of UTI in dogs in Europe and is used to care for feline UTI. The fluoroquinolones are bactericidal, amphoteric drugs. They possess acidic and basic properties but are very lipid soluble at physiologic pH (pH half-dozen–eight) and thus accept a high book of distribution. All fluoroquinolones usually accept first-class activeness against staphylococci and gram-negative bacteria, only they may take variable activity against streptococci and enterococci. The therapeutic advantages of these drugs are their gram-negative antimicrobial activity and high degree of lipid solubility. They are the simply orally administered antimicrobials effective against Pseudomonas. Therefore, fluoroquinolones should be reserved for UTIs that involve gram-negative leaner, especially Pseudomonas, and for UTIs in intact male dogs and cats because of their splendid penetration into the prostate gland and action in abscesses. They are concentration-dependent killers with a long postadministration consequence, and then once daily, high-dose therapy for a relatively brusk duration of handling is effective.
Fluoroquinolones should be avoided for chronic, low-dose therapy, because this encourages emergence of resistant bacteria that are cross-resistant to other antimicrobial drugs besides. Cases that involve Pseudomonas should be carefully investigated for underlying pathology, which must corrected if at all possible. Once Pseudomonas spp become resistant to the fluoroquinolones, at that place are no other convenient therapeutic options.
Gentamicin and the other aminoglycosides are very large, polar (h2o-soluble) molecules, and so they take a low book of distribution and do not penetrate the blood-prostate barrier. They are not absorbed orally and must exist given by SC, IM, or IV injection. The aminoglycosides take a similar spectrum of activity to that of the fluoroquinolones, merely their use for UTI is limited because of the necessity of parenteral injections and the adventure of toxicity with annihilation but short-term utilize. Like the fluoroquinolones, the aminoglycosides are concentration dependent, bactericidal killers with a long postadministration effect, then once-daily therapy of brusk duration is effective and minimizes the risk of nephrotoxicity. They tin be considered for in-hospital or outpatient treatment of UTI due to fluoroquinolone-resistant pathogens; even so, the importance of identifying and correcting underlying pathology must be emphasized.
Nitrofurantoin is a human product bachelor as tablets, capsules, and a pediatric suspension. It is not normally used in veterinary medicine. It is typically used just for treatment of UTI in people, because it has a very depression volume of distribution, and therapeutic concentrations are attained only in urine. It is considered a carcinogen, so it is banned for use in food-producing animals, but its use in small animals is increasing with the rise rates of antimicrobial resistance to veterinary antimicrobials. Nitrofurantoin is used for infections caused by E coli, enterococci, staphylococci, Klebsiella spp, and Enterobacter spp. It is increasingly indicated for treatment of UTIs caused past multidrug-resistant bacteria, which are otherwise difficult to treat using conventional veterinary antimicrobial agents. The pharmacokinetics and adverse effect profile of nitrofurantoin accept not been investigated in dogs, cats, or horses, and the need for multiple daily dosing makes it inconvenient for owners.
Tetracyclines are bacteriostatic, amphoteric drugs with a high volume of distribution. Tetracyclines are broad-spectrum antimicrobials, but because of plasmid-mediated resistance, susceptibility is variable in staphylococci, enterococci, Enterobacter, E coli, Klebsiella, and Proteus. In virtually tissues, Pseudomonas spp are resistant. All the same, the tetracyclines are excreted unchanged in urine, so high urinary concentrations may result in therapeutic efficacy. Doxycycline is a very lipid-soluble tetracycline better tolerated in cats and reaches therapeutic concentrations in the prostate, and so it may be useful for some UTIs. Doxycycline may as well be constructive to care for methicillin-resistant staphylococcal UTIs. If capsules are administered, it is critical to take the animate being drink afterward to ensure passage into the stomach. If capsules remain in the esophagus, astringent local necrosis with subsequent esophageal stricture tin can occur.
Trimethoprim-sulfonamides (TMP-sulfas) are combinations of ii very different drugs that deed synergistically on unlike steps in the bacterial folic acid pathway. Trimethoprim is a bacteriostatic, basic drug with a high volume of distribution and a brusk elimination half-life, whereas the sulfonamides are bacteriostatic, acidic drugs with a medium volume of distribution and long half-lives (ranging from 6 to >24 hr). These drugs are formulated in a ane:five ratio of TMP to sulfa, although the optimal bactericidal concentration is a ratio of 1:twenty TMP:sulfa. Microbiology services use the 1:twenty ratio in susceptibility testing; however, the widely varying pharmacokinetic properties of this drug combination make it difficult to determine a therapeutic regimen that achieves the 1:20 ratio at the infection site. Although the combination does penetrate the blood-prostate bulwark, sulfa drugs are ineffective in purulent cloth considering of freely available para-aminobenzoic acid from expressionless neutrophils. The combination of TMP-sulfa is synergistic and bactericidal against staphylococci, streptococci, E coli, and Proteus. Activity against enterococci and Klebsiella is variable, and Pseudomonas is resistant. TMP-sulfas are associated with a number of agin effects, and chronic low-dose therapy may consequence in os marrow suppression and keratoconjunctivitis sicca in dogs.
Currently, the duration of therapy for UTI is controversial. Although animals are routinely treated with antimicrobial drugs for 10–xiv days, shorter elapsing antimicrobial regimens are routinely prescribed in homo patients, including unmarried-dose fluoroquinolone therapy. A clinical comparison of 3 days of therapy with a one time-daily high dose of enrofloxacin with 2 wk of twice daily amoxicillin-clavulanic acid showed equivalence in the treatment of elementary UTI in dogs. However, further studies are needed to determine the optimal dosage regimens for unlike classes of antimicrobials, and it is inappropriate to employ fluoroquinolones every bit starting time-line therapy for simple UTIs. Animals with complicated UTI may require longer courses of therapy, and underlying pathology must be addressed. Chronic complicated cases of UTI, pyelonephritis, and prostatitis may require antimicrobial treatment for 4–half-dozen wk, with the risk of selecting for antimicrobial resistance. A follow-up urine culture should be performed after iv–7 days of therapy to determine efficacy. If the aforementioned or a different pathogen is seen, and so an alternative therapy should exist called and the culture repeated again after iv–vii days. Urine should too be cultured seven–x days after completing antimicrobial therapy to determine whether the UTI has resolved or recurred.
In dogs and cats, if UTI occurs only once or twice yearly, each episode may be treated every bit an astute, uncomplicated UTI. If episodes occur more oft, and predisposing causes of UTI cannot be identified or corrected, chronic depression-dose therapy may exist necessary. Low antimicrobial concentrations in the urine may interfere with fimbriae production past some pathogens and prevent their adhesion to the uroepithelium. In dogs, recurrent UTIs are due to a different strain or species of bacteria ~eighty% of the fourth dimension; therefore, antimicrobial culture and susceptibility is still indicated. Antimicrobial therapy should be started every bit previously described and when urine culture is negative, continued daily at ⅓ the total daily dose. The antimicrobial should be administered last thing at night to ensure that the bladder contains urine with a high antimicrobial concentration for as long as possible.
Appropriate antimicrobials for chronic, low-dose therapy include amoxicillin, ampicillin, amoxicillin-clavulanic acid, doxycycline, cephalexin, cefadroxil, and nitrofurantoin. A trimethoprim-sulfonamide can be used, but folate supplementation should be provided (15 mg/kg, bid) to prevent bone marrow suppression; there is also the risk of keratoconjunctivitis sicca developing with longterm use. Although bonny for owner convenience, third-generation cephalosporins such every bit cefpodoxime and cefovecin and fluoroquinolones should not exist used for longterm therapy. During longterm therapy, urine civilization should be repeated every 4–vi wk. Every bit long every bit the culture is negative, therapy is connected for 6 mo. If bacteriuria occurs, the infection is treated every bit an acute episode with an appropriate antimicrobial. After 6 mo of bacteria-free urine, the longterm, low-dose antimicrobial therapy may be discontinued, and many animals volition not have boosted recurrences. In some cases, longterm therapy may be continued for years in animals that continue to have recurrent UTIs.
Treatment failures may be due to poor owner compliance, inappropriate choice of antimicrobials, inappropriate dose or duration of treatment, antimicrobial resistance, superinfection, or an underlying predisposing crusade (eg, urolithiasis, neoplasia, urachal diverticula). If handling for a simple or complicated UTI fails, a thorough evaluation should be performed to decide and, when possible, address the cause of failure. When faced with a therapeutic failure, the practitioner must consider whether the UTI is due to a relapse or a reinfection. Relapses due to infection by uropathogens with enhanced intrinsic virulence occur with what should be effective antimicrobial therapy. Strains of uropathogenic Eastward coli have a number of virulence mechanisms that enable them to invade, survive, and multiply within the uroepithelium. The sequestration of uropathogenic E coli within the bladder uroepithelium presents a bully therapeutic challenge in both human and veterinarian patients. In that location is no clear consensus in the man medical literature nigh how to approach these recurrent and persistent UTIs.
Acquired resistance to antimicrobials by uropathogens is of great concern in both human being and veterinary medicine. The prevalence of multidrug resistance in uropathogens is increasing, peculiarly in infections in dogs and cats. Extended-spectrum β-lactamase genes are increasingly identified in Due east coli isolates from companion animals. Increases in the occurrence of fluoroquionolone-resistant E coli in dogs have been widely reported. Because the mechanism of resistance to fluoroquinolones frequently involves efflux pumps, it also conveys multidrug resistance. Fluoroquinolone resistance is also increasing in other uropathogens, including enterococci, Proteus mirabilis, and Staphylococcus pseudintermedius isolates. Methicillin-resistant staphylococci have been identified in cases of canine UTI. There is increasing testify that animals are an of import reservoir of antimicrobial-resistant bacteria causing infections in people. Enterococci isolated from canine UTIs have been associated with several different resistant phenotypes, with most exhibiting resistance to three or more antimicrobials. One Enterococcus faecium isolate displayed high-level resistance to vancomycin and gentamicin. Sequence assay suggested that resistance was due to cistron exchange betwixt human and canine enterococci. The use of "final resort" human antimicrobials in veterinary patients with resistant infections is controversial. Vancomycin, imipenem-cilastatin, meropenem, fosfomycin, quinupristin-dalfopristin, and tigecycline should not be used routinely in treatment of UTI in animals. Nonantimicrobial control of infection should be considered whenever viable. Custom-made vaccines, cranberry juice/extract, probiotics and adherence/colonization inhibitors, and establishment of asymptomatic bacteriuria may assist preserve the efficacy of antimicrobials.
Source: https://www.msdvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-urinary-system/bacterial-urinary-tract-infections
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