Urinary Tract Infections

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Chapter: Pharmaceutical Microbiology : Clinical Uses Of Antimicrobial Drugs

Urinary tract infection is a common problem in both community and hospital practice. Although occurring throughout life, infections are more common in preschool girls and women during their childbearing years, although in the elderly the sex distribution is similar.


URINARY TRACT INFECTIONS

 

Urinary tract infection is a common problem in both community and hospital practice. Although occurring throughout life, infections are more common in preschool girls and women during their childbearing years, although in the elderly the sex distribution is similar. Infection is predisposed by factors that impair urine flow. These include congenital abnormalities, reflux of urine from the bladder into the ureters, kidney stones and tumours and, in males, enlargement of the prostate gland. Bladder catheterization is an important cause of urinary tract infection in hospitalized patients.

 

a)     Pathogenesis

 

In those with structural or drainage problems the risk exists of ascending infection to involve the kidney and occasionally the bloodstream. Although structural abnormalities may be absent in women of childbearing years, infection can become recurrent, symptomatic and extremely distressing. Of greater concern is the occurrence of infection in the pre-school child, as normal maturation of the kidney may be impaired and may result in progressive damage which presents as renal failure in later life.

 

From a therapeutic point of view, it is essential to confirm the presence of bacteriuria (a condition in which there are bacteria in the urine), as symptoms alone are not a reliable method of documenting infection. This applies particularly to bladder infection, where the symptoms of burning micturition (dysuria) and frequency can be associated with a variety of non-bacteriuric conditions. Patients with symptomatic bacteriuria should always be treated. However, the necessity to treat asymptomatic bacteriuric patients varies with age and the presence or absence of underlying urinary tract abnormalities. In the preschool child it is essential to treat all urinary tract infections and maintain the urine in a sterile state so that normal kidney maturation can proceed. Likewise in pregnancy there is a risk of infection ascending from the bladder to involve the kidney. This is a serious complication and may result in premature labour. Other indications for treating asymptomatic bacteriuria include the presence of underlying renal abnormalities such as stones, which may be associated with repeated infections caused by Proteus spp.

 

b)     Drug therapy

 

The antimicrobial treatment of urinary tract infection presents a number of interesting challenges. Drugs must be selected for their ability to achieve high urinary concentrations and, if the kidney is involved, adequate tissue concentrations. Safety in childhood or pregnancy is important as repeated or prolonged medication may be necessary. The choice of agent will be dictated by the microbial aetiology and susceptibility findings, because the latter can vary widely among Gram-negative enteric bacilli, especially in patients who are hospitalized. Table 14.3 shows the distribution of bacteria causing urinary tract infection in the community and in hospitalized patients. The greater tendency towards infections caused by Klebsiella spp. and Ps. aeruginosa should be noted as antibiotic sensitivity is more variable for these pathogens. Drug resistance has increased substantially in recent years and has reduced the value of formerly widely prescribed agents such as the sulphonamides and ampicillin.

 


 

Uncomplicated community-acquired urinary tract infection presents few problems with management. Drugs such as trimethoprim, ciprofloxacin and ampicillin are widely used. Cure rates are close to 100% for ciprofloxacin, about 80% for trimethoprim and about 50% for ampicillin—to which resistance has been steadily increasing. Treatment for 3 days is generally satisfactory and is usually accompanied by prompt control of symptoms. Single-dose therapy with amoxicillin 3 g has also been shown to be effective in selected individuals. Alternative agents include nitrofurantoin, nalidixic acid and norfloxacin, although these are not as well tolerated. Oral cephalosporins and co-amoxiclav are also used.


It is important to demonstrate the cure of bacteriuria with a repeat urine sample collected 4–6 weeks after treatment, or sooner should symptoms fail to subside. Recurrent urinary tract infection is an indication for further investigation of the urinary tract to detect underlying pathology that may be surgically correctable. Under these circumstances it also is important to maintain the urine in a sterile state. This can be achieved with repeated courses of antibiotics, guided by laboratory sensitivity data. Alternatively, long-term chemoprophylaxis for periods of 6 months to control infection by either prevention or suppression is widely used. Trimethoprim is the most commonly prescribed chemoprophylactic agent and is given as a single nightly dose. This achieves high urinary concentrations throughout the night and generally ensures a sterile urine. Nitrofurantoin is an alternative agent.

 

Infection of the kidney demands the use of agents that achieve adequate tissue as well as urinary concentrations. As bacteraemia (a condition in which there are bacteria circulating in the blood) may complicate infection of the kidney, it is generally recommended that antibiotics be administered parenterally. Although ampicillin was formerly widely used, drug resistance is now common and agents such as cefotaxime, co-amoxiclav or ciprofloxacin are often preferred, because the aminoglycosides, although highly effective and preferentially concentrated within the renal cortex, carry the risk of nephrotoxicity.

 

Infections of the prostate tend to be persistent, recurrent and difficult to treat. This is in part due to the more acid environment of the prostate gland, which inhibits drug penetration by many of the antibiotics used to treat urinary tract infection. Agents that are basic in nature, such as erythromycin, achieve therapeutic concentrations within the gland but unfortunately are not active against the pathogens responsible for bacterial prostatitis. Trimethoprim, and quinolones, however, are useful agents as they are preferentially concentrated within the prostate and active against many of the causative pathogens. It is important that treatment be prolonged for several weeks, as relapse is common.

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