Marc Leone
Claude Martin
Objective
Intensive care units (ICUs) represent a meeting point between the most seriously ill patients receiving aggressive therapy and the most resistant pathogens that are selected by the use of broad-spectrum antimicrobial therapy. Most patients who are hospitalized in ICUs receive an indwelling urinary catheter to monitor urine output. Urinary tract infection (UTI) remains a leading cause of nosocomial infections with significant morbidity, mortality, and, hence, additional hospital costs (1).
Although UTI represents 30% to 40% of nosocomial infections (1,2), its prevalence in patients admitted to the ICU is approximately 20% (3). In a large European survey, UTI was the third most common cause of nosocomial infections in the ICU (3). Another study suggests that the incidence of urosepsis, defined as an inflammation of the upper urinary tract that causes sepsis, occurs in approximately 16% of the ICU patient population (4). The aim of this chapter is to focus on the prevention and management of UTI in patients hospitalized in the ICU.
Definitions
The Centers for Disease Control and Prevention (CDC) definitions of symptomatic UTIs and asymptomatic UTIs are collected in Tables 113.1, 113.2, and 113.3 (5). In the ICU, UTI is the consequence of placement of an indwelling catheter. This results in the concept of catheter-associated UTI, the definition of which is restricted to the presence of bacteria in the bladder of a patient with an indwelling catheter. Bacteriuria is defined as the detection of greater than or equal to 105 micro-organisms/mL of urine with no more than two species of organisms (5). It is of interest to note that, contrary to non–ICU-acquired urinary tract infections, this definition does not take into account the clinical symptoms.
Pathophysiology
With the exception of the distal urethra, the urinary tract is normally sterile. Resistance to UTI is influenced by exposure to uropathogenic bacteria, age, hormonal status, and urine flow (6). Insertion of a catheter allows organisms to gain access to the bladder. The catheter induces an inflammation of the urethra, allowing bacteria to ascend into the bladder in the space between the urethral mucosa and the catheter. Catheter-associated UTI usually follows the formation of biofilm, which consists of adherent micro-organisms, their extracellular products, and host components deposited on both the internal and external catheter surfaces. The biofilm protects the organisms from both antimicrobials and the host immune response (7). The ascending route of infection is predominant in women, owing to their short urethra and contamination with anal flora. An internal route of contamination (i.e., through the lumen of the catheter) is less frequent and related to reflux of pathogens from the drainage system into the bladder. This contamination occurs when the drainage system fails to close or contamination of urine in the collection bag.
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Table 113.1 Definitions for symptomatic urinary tract infections |
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Table 113.2 Definitions for asymptomatic urinary tract infections |
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Table 113.3 Other urinary tract infections |
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Microbiology
The isolated pathogens in ICU patients with bacteriuria are essentially relatively few: Escherichia coli, Pseudomonas aeruginosa, and Enterococcus species (Table 113.4) (8,9,10). Polymicrobial infections represent a relatively small percentage—5% to 12% (2,8,9)—of total infections. In a large report investigating nosocomial infections in ICU patients, Gram-negative bacteria caused 71% of UTIs, with stability over a 17-year period of surveillance (10). Resistance to antimicrobials increased during this period, with rates of resistance to third-generation cephalosporins up to 20% for E. coli (10,11). Although its role is demonstrated in a urologic ward, cross-transmission probably plays a much greater role than suggested up to the present (12).
Risk Factors
As stated, in ICU patients, UTIs are associated with the presence of indwelling catheters. The first step of prevention is to highlight the risk factors of catheter-associated UTI in this specific population. In a study assessing risk factors for bacteriuria in 553 patients with a urinary catheter for more than 48 hours and hospitalized in an ICU (8), female sex, length of ICU stay, prior use of antibiotics, severity score on admission, and duration of catheterization were independently associated with an increased risk of catheter-associated bacteriuria; these results mirrored those from a previous clinical study (13). Such results emphasize that reducing the duration of catheterization appears to be the most important clinical step that can be identified for prevention. One notable study showed that in 21% of 202 patients, the initial indication for the placement of a urinary catheter was unjustified. In a medical intensive care unit, excessive duration of urinary catheter use for monitoring urine output resulted in 64% of the total of unjustified patient-days (14).
Impact of Urinary Tract Infections in the Intensive Care Unit
Although adverse consequences of asymptomatic UTIs have been described during pregnancy or in nursing home patients (15), the real impact of ICU-acquired UTIs on outcome remains unclear. In a general hospital population, Platt et al. showed that nosocomial UTIs were associated with significant attributable mortality (16). The picture is probably different in a specific ICU population. Indeed, even after controlling for many risk factors, UTIs have a higher incidence in ICUs as compared to other wards (17), although the urinary tract is the source of sepsis in only 10% to 14% of the cases, which is far less than the lung (Table 113.5) (18,19). Development of ICU-acquired UTIs is associated with both an increase in the length of ICU stay and the crude rate of mortality (8,9). However, adequately powered studies demonstrate that UTIs are not dependent factors for mortality (9,17).
Urosepsis is defined as an inflammation of the upper urinary tract that causes seeding of the blood with bacteria, resulting in local and distant destruction of tissue. A retrospective study evaluated 126 trauma patients with a urinary catheter for sepsis. Twenty (16%) were diagnosed with urosepsis, which was correlated with age older than 60 years, extended length of stay in the ICU and/or hospital, and duration of catheterization. The mortality rates (15%) of the patients without urosepsis and with urosepsis did not differ (4). Similarly, in a prospective study, 6 out of 60 (10%) catheterized patients with asymptomatic bacteriuria developed urosepsis (20). Another prospective, cohort study of 235 catheter-acquired infections among 1,497 patients, 90% of whom were asymptomatic, reported only one (0.42%) secondary bloodstream infection (21).
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Table 113.4 Percentage of pathogens associated with nosocomial urinary tract infections |
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Table 113.5 Rates of sepsis according to each site |
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Finally, UTIs can incur significant additional cost. An episode of symptomatic nosocomial UTI in a hospitalized patient is expected to result in an average of $676 in additional cost (22). Interestingly, however, a Turkish study calculated the daily antibiotic costs per infected ICU patient. Among the sites of nosocomial infections, urinary tract infections had the lowest daily antibiotic cost per infected patient ($52) (23).
Diagnostic Tools in the Intensive Care Unit
Urosepsis should be suspected any time a patient has a febrile episode. Because of the prevalence of bacteriuria in patients with urinary catheters, some have advocated daily monitoring of urine in catheterized patients. Routine daily bacteriologic monitoring of the urine from all catheterized patients is not an effective way to decrease the incidence of symptomatic, catheter-associated UTI, and is not recommended (24).
Three clinical trials have assessed the effectiveness of urinary dipsticks (leukocyte esterase and nitrite) for screening patients instead of quantitative urine culture in the ICU (Table 113.6) (25,26,27). Leukocyte esterase activity is an indicator of pyuria, and urinary nitrite production is an indicator of bacteriuria. In the medical ICU, it has been demonstrated that the urinary dipstick strategy is a rapid and cost-effective test with which to screen asymptomatic catheterized patients. This effectiveness is observed only for a positive quantitative urine culture level of 105 micro-organisms/mL. The urinary dipstick strategy decreases the cost of diagnosis of nosocomial infection and the daily workload in the microbiology laboratory (25). One limitation of this study is that the incidence of asymptomatic bacteriuria was 31%, as compared with 6% to 9% in other studies (8,9).
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Table 113.6 Assessing urinary reagent strips in the intensive care unit |
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In a prior study, analysis of 102 urine samples determined a positive predictive value of 81%. Those authors did not recommend the use of urinary dipsticks (27). Our best sense of these data is that the use of dipsticks—instead of quantitative urine culture—cannot be recommended for symptomatic UTIs in ICU patients. The Infectious Disease Society of America (IDSA) guidelines recommend that asymptomatic bacteriuria or funguria not be screened in patients with an indwelling urethral catheter (28). Hence, in symptomatic patients, quantitative urine culture with Gram stain examination is recommended to obtain rapid identification of the pathogen.
Prevention
The best prevention of ICU-acquired UTIs is to simply reduce the use of indwelling urethral catheters. In a medical ICU, an independent observer determined that 64% of the total unjustified patient-days with urethral catheter resulted from its prolonged use for monitoring urine output (14). Hence, each member of the critical care medicine team should attempt to reduce the length of urethral catheterization and, whenever possible, this evaluation should occur during daily rounds. Other measures, described below, can be useful only in units with a restrictive policy of catheterization (Table 113.7).
Urinary Drainage System
In order to prevent infection, the maintenance of a closed sterile drainage system is recommended as the most successful method (29). A closed drainage system was described for the first time in 1928 (30), and its benefit has been subsequently re-enforced (16). A subgroup analysis of a randomized study, in which analyzed patients did not receive antibiotic treatment, showed a reduction in mortality in the group using the closed system (16). Historically, “open systems” were large, uncapped glass bottles. The drainage catheters were inserted into the glass bottles, often below the level of urine. Urine was stagnant, and bacteria could easily grow and ascend through the drainage catheter. The introduction of closed drainage systems was a major improvement, and their use has greatly reduced the rate of bacteriuria. However, in the modern era, several studies have failed to confirm the benefit of complex closed systems compared with simple devices (31,32,33).
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Table 113.7 Comparative studies performed in the intensive care unit on the prevention of catheter-associated urinary tract infection |
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There are only two studies in the literature specifically focused on ICU patients (34,35) and comparing a two-chamber, open drainage system with a complex closed drainage system. Both of them, which were performed by the same team of investigators, found similar results, although one of these studies was not randomized (34). In the randomized and prospective trial, 311 patients requiring an indwelling urinary catheter for longer than 48 hours were assigned to the two-chamber drainage system group or to the complex closed drainage system group to compare the rates of bacteriuria. The rates of UTIs were 12.1 and 12.8 episodes per 1,000 days of catheterization, respectively (35). The data extracted from the recent literature do not support the use of complex closed drainage systems in ICU patients in view of the increased cost.
Owing to the lack of specific ICU studies, the guidelines for the management of drainage systems should be viewed as recommendations at best.
The following are reasonable suggestions:
1. Only people who know the proper technique of aseptic insertion and maintenance of the catheter should handle catheters.
2. Hospital personnel should be given periodic in-service training stressing the proper techniques and potential complications of urinary catheterization.
3. Hand washing should be performed immediately before and after any manipulation of the catheter site or apparatus.
4. If small volumes of fresh urine are needed for examination, the distal end of the catheter, or preferably the sampling port if present, should be cleansed with a disinfectant, and urine then aspirated with a sterile needle and syringe.
5. Larger volumes of urine for special analyses should be obtained aseptically from the drainage bag.
6. Unobstructed flow should be maintained.
7. In order to achieve free flow of urine, (a) the catheter and collection tube should be kept from kinking; (b) the collection bag should be emptied regularly using a separate collecting container for each patient (the draining spigot and nonsterile collection container should never come into contact); (c) poorly functioning or obstructed catheters should be irrigated or, if necessary, replaced; (d) collection bags should always be kept below the level of the bladder; and (e) indwelling catheters should not be changed at arbitrary fixed intervals (36).
Types of Urethral Catheters
There are a large number of articles in the literature that stress the efficacy of antiseptic-impregnated catheters, including silver oxide or silver alloy, and antibiotic-impregnated catheters in hospitalized patients (37,38,39). The results of two meta-analyses clarify some points (38,39) related to these devices.
Silver oxide catheters are not associated with a reduction in bacteriuria in short-term catheterized adults, whereas silver alloy catheters reduce the incidence of asymptomatic bacteriuria and the risk of symptomatic UTI in catheterized adults. Further, economic evaluation is required to confirm that the reduction of infection compensates for their increased cost. Catheters coated with a combination of minocycline and rifampin or nitrofurazone may also be beneficial in reducing bacteriuria in hospitalized men catheterized less than 1 week, but this requires further testing (38,39). No trials directly compare nitrofurazone-coated and silver alloy–coated catheters.
In a specific ICU patient population, a randomized, prospective, double-blind multicenter trial compared catheters coated with hydrogel and silver salt with classic urinary tract catheters in 199 patients requiring urethral catheterization for more than 3 days (40). The cumulative incidence of UTIs associated with catheterization was 11.1% overall, 11.9% for the control group, and 10% for the coated catheter group. The odds ratio was 0.82 (95% confidence interval [CI] 0.3–2.2). The differences between the two groups were not significant, although the power of the study was more than 90% (40). A prior trial, which included five hospitals selected to participate in a blinded prospective study, exchanged the standard latex Foley catheter for a hydrogel latex Foley catheter with a monolayer of silver metal applied to the inner and outer surfaces of the device. The adjusted catheter-associated infection rate during the baseline and intervention periods was 8.1 and 4.9 infections per 1,000 catheter-days (p = 0.13), respectively (41).
Meatal Care
Twice-daily cleansing of the urethral meatus with povidone-iodine solution and daily cleansing with soap and water have failed to reduce catheter-associated UTIs. Thus, at this time, daily meatal care with either of these two regimens cannot be endorsed.
A randomized, controlled, prospective clinical trial involving 696 patients hospitalized in medical and surgical units was undertaken to determine the effectiveness of 1% silver sulfadiazine cream applied twice daily to the urethral meatus in preventing transurethral catheter-associated bacteriuria. The overall incidence of bacteriuria was approximately 13% in both groups (p = 0.56) (42). In the absence of data from an ICU-specific patient population, the current guidelines should be followed.
There are no data available on the level of sterility required to insert a urinary catheter. Experts recommend that catheters should be inserted using an aseptic technique and sterile equipment, including gloves, drapes, and sponges. However, in a prospective study conducted in the operating room, 156 patients underwent preoperative urethral catheterization, randomly allocated to “sterile” or “clean/nonsterile” technique groups. There was no statistical difference between the two groups with respect to the incidence of UTI, but the cost differed considerably between the two groups (43).
Vesical Irrigation and Antiseptic in the Drainage System
The objective of antibiotic irrigation is to clear bacteria from the urinary tract. A randomized study compared 89 patients receiving a neomycin-polymyxin irrigation administered through a closed urinary catheter to 98 patients not so irrigated. Although the number of ICU patients was not specified in this clinical study, 19 of the 98 (18%) patients not irrigated became infected as compared with 14 out of the 89 (16%) of those who were irrigated; the organisms from the irrigated patients were more resistant (44). Another study was conducted in 264 urology patients, evaluating the effect of povidone-iodine bladder irrigation prior to catheter removal on subsequent bacteriuria. Of 264 patients, 138 received irrigation and 126 were controls. Urine cultures were positive in 22% in the control group and 18% in the study group (45). Thus, irrigation methods failed to demonstrate efficacy in surgical patients, and its use is not recommended in ICU patients.
The addition of antimicrobial agents to the drainage device has not been studied in the ICU. The largest reported clinical trial evaluating the effect of H2O2 insertion into the drainage device of 353 patients, and comparing this to 315 control patients, failed to show a benefit in the treatment group. It is of interest to note that 68% of these patients required an indwelling catheter for hemodynamic monitoring, with antimicrobial therapy prescribed in 75% of the patients, suggesting that these results may apply to ICU patients (46). Expert opinion recommends that we not use irrigation unless obstruction is anticipated, as might occur with bleeding after prostatic or bladder surgery.
Alternatives to a Urinary Catheter
For selected patients, other methods of urinary drainage, such as condom catheters, suprapubic catheterization, and intermittent urethral catheterization, should be considered as alternatives to indwelling urethral catheterization. There are limited ICU data available to assess these alternative devices. There is evidence, however, that suprapubic catheterization is advantageous, as compared to indwelling catheters, with respect to bacteriuria, recatheterization, and discomfort (47,48). The use of a condom connected to a collection bag has been evaluated in a study comparing 167 patients over two periods of 6 months. The occurrence of bacteriuria was significantly decreased for the period using the condom catheters (26.7 vs. 2.4%) (49). However, this issue merits further study to determine whether or not this alternative method may actually reduce bacteriuria rates. The use of intermittent catheterization is also associated with a lower risk of bacteriuria than indwelling urethral catheter, although such a procedure has never been investigated in ICU patients (48,50,51).
Miscellaneous Measures
While there is a low risk of bacteremia during urinary catheterization (52), the administration of antimicrobial therapy at the time the device is placed leads to a reduction in bacteriuria (53,54,55). The efficacy of antibiotic treatment has been assessed as optimal for catheterization lasting less than 14 days (54). However, the prophylactic use of antibiotic in the ICU can be detrimental to the bacterial ecology by increasing the pressure for antimicrobial resistance among bacteria. The practice of administration of prophylactic antimicrobials in this manner must be discouraged in our ICUs. It should be noted that in most ICU studies, 75% of the patients with an indwelling catheter require antibiotics for reasons unrelated to the urinary catheter (8). Further, all measures aimed at reducing the burden of nosocomial infections can reduce the rate of UTIs (56,57,58).
Treatment and Management
The management of catheter-associated UTI has not been evaluated in ICU patients. Several nonspecific measures, including hydration, have been advocated in the therapy of UTI. Adequate hydration would appear to be important, although there is no evidence that it improves the effectiveness of an appropriate antimicrobial therapy (59). The management of complicated UTIs in the ICU may include mechanical intervention. Consequently, appropriate diagnostic tests and urologic consultation should be included in the algorithm of the management of these patients (Fig. 113.1).
Management of Asymptomatic Bacteriuria
According to leaders in our field, asymptomatic catheter-associated UTI does not require treatment (28). However, antimicrobial treatment may be considered for asymptomatic women with a catheter-acquired UTI that persists 48 hours after catheter removal (60). In a specific ICU patient population, 60 patients with an indwelling urethral catheter for longer than 48 hours who developed an asymptomatic positive urine culture were randomized to receive either a 3-day course of antibiotics associated with the replacement of the indwelling urethral catheter 4 hours after the first antibiotic administration or no antibiotics and no catheter replacement. Six patients equally distributed in the two groups developed urosepsis. The profile of bacterial resistance was similar in the two groups. Hence, treating a positive urine culture in an asymptomatic patient with an indwelling urethral catheter does not reduce the occurrence of urosepsis (20).
Management of Symptomatic Urinary Tract Infections
Choice of Antimicrobial Agents
The optimal characteristics of agents to treat urinary tract infection must include activity against the major pathogens involved in these infections, good tissue penetration, and minimal side effects. High urinary levels should be present for an adequate period to eliminate the organisms, since disappearance of bacteriuria correlates with the sensitivity of the pathogen to the concentration of the antimicrobial agent achieved in the urine (61). Inhibitory urinary concentrations are achieved after administration of essentially all commonly used antibiotics. However, an antibiotic that achieves active concentrations in the renal tissue is required for infection of the renal tissue. The antibiotic concentration in the serum or plasma can be used as surrogate markers for the antibiotic concentrations in the renal tissue (62). For drugs with concentration-dependent time-kill activity such as the aminoglycosides or the fluoroquinolones, the peak antibiotic concentration is the most important parameter for the in vivo effect. Experimentally, gentamicin and fluoroquinolone treatment are both more effective than the β-lactam antibiotics in rapid bacterial killing (62).
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Figure 113.1. Suggested algorithm for the management of urinary tract infections related to an indwelling catheter in the intensive care unit. CT, computed tomography. *Discuss the need for antipseudomonal coverage according to the duration of hospitalization, prior medical history, and local ecology. #Discuss if renal failure. |
Most clinical studies have shown that the renal concentrations of the cephalosporins remained higher than the minimal inhibitory concentration for the most common bacteria during the time interval between the administration of two doses (63,64,65). By contrast, β-lactam antibiotics, which have a low pKa and poor lipid solubility, penetrate poorly into the prostate, except for some cephalosporins. Good to excellent penetration into the prostatic tissue has been demonstrated with many antimicrobial agents, such as aminoglycosides, fluoroquinolones, sulfonamides, and nitrofurantoin (66).
In ICU patients, the side effects of treatment should be minimized at both the individual and the community level. Many patients develop renal failure, associated with the inability to concentrate antimicrobial agents in the urine. Additionally, administration of drugs with potential renal toxicity may worsen renal insufficiency. This may be an important limiting factor for using aminoglycosides in patients with renal failure. Otherwise, antimicrobial treatment must produce a minimal effect on the bacterial flora of the community (67). From this standpoint, there is significant literature demonstrating that the use of fluoroquinolone is associated with the emergence of resistant pathogens (68,69,70). This implies that an indication for antibacterial therapy should be weighed thoroughly and fluoroquinolones should be used in accordance with sensitivity testing (70). Hence, it is of importance to stress that UTI should not be treated before the results of sensitivity testing, except in patients with pyelonephritis and those with severe sepsis or septic shock who require empirical antimicrobial therapy.
Cystitis
As acute uncomplicated cystitis is infrequent in ICU patients, most recommendations focus on the treatment of nonhospitalized women, which makes their relevance in ICU patients questionable; E. coli is the evident target pathogen. The 1999 IDSA guidelines recommend treatment with trimethoprim-sulfamethoxazole for 3 days as standard therapy for acute uncomplicated cystitis. Single-dose therapy is less effective in eradicating initial bacteriuria than longer durations of treatment with trimethoprim-sulfamethoxazole, trimethoprim, norfloxacin, ciprofloxacin, fleroxacin, and, as a group, β-lactam antibiotics (71). In contrast, a meta-analysis determined that 3 days of antibiotic therapy is similar to 5 to 10 days in achieving symptomatic cure during uncomplicated UTI treatment, while the longer treatment is more effective in obtaining bacteriologic cure. Consequently, such durations should be considered for treatment of women in whom eradication is critical (72). Quinolones are recommended for acute cystitis in regions where the level of resistance to trimethoprim-sulfamethoxazole is high. There were no significant differences in clinical or microbiologic efficacy between quinolones. The rate of adverse events causing antimicrobial withdrawal tends to be lower with norfloxacin and ciprofloxacin than with other quinolones (73).
Antibiotic treatment of UTI depends on the ability of the antibiotic to inhibit the growth or kill the bacteria present in the urinary tract. This is related to the concentration of antibiotics at the site of infection. Very high concentrations of antibiotics with renal clearance are obtained in urine. Consequently, even in the presence of pathogens exhibiting in vitro resistance, the high concentrations of antibiotics in urine inhibit the growth of pathogens, rendering them effective to treat a UTI.
Prostatitis
For outpatients, bacterial prostatitis is a common diagnosis and a frequent indication for antibiotics. Although urethral instrumentation and prostatic surgery are known causes of prostatitis, the incidence of prostatitis among ICU patients has never been assessed, and there is only a weak relation between acute and chronic prostatitis.
Acute prostatitis is an acute infection producing local heat, tenderness, and fever, with the presence of IgA and IgG bacteria-specific immunoglobulins in the prostatic secretions. Few symptoms, usually perineal discomfort, are exhibited with prostatitis. Most patients with chronic prostatitis have no history of positive urine or urethral cultures (74).
In ICU patients, acute bacterial prostatitis is probably a common infection. The patient presents septic, but without an evident source of infection. There may be a history of urine retention due to bladder outlet obstruction. Rectal examination, a crucial step in the diagnosis, reveals a warm, swollen, and tender prostate. The prostatic fluid contains leukocytes and the pathogen responsible for the infection. However, massage of the prostate is proscribed to avoid bacteremia. Fluoroquinolones are the drugs of choice to treat acute prostatitis because of their excellent penetration in the tissue and excretions (75,76). The targeted pathogens are E. coli, Proteus sp., Klebsiella sp., Enterococcus sp., Staphylococcus aureus, Neisseria gonorrhoeae, and Chlamydia trachomatis. For acute prostatitis occurring without bacteremia, antimicrobial treatment consists of oral ofloxacin 200 mg twice per day for 28 days; ceftriaxone 2 g/day has good prostatic tissue penetration and represents an alternative to ofloxacin (77). Gentamicin 3 mg/kg/day is added in the presence of positive blood cultures (Table 113.8). Of importance, urethral instrumentation should be discouraged, and if acute retention occurs, suprapubic drainage of urine is required. Treatment of chronic prostatitis is based on the oral administration of ofloxacin 200 mg twice per day, or trimethoprim 160 mg–sulfamethoxazole 800 mg twice per day for at least 28 days. The indications for this treatment should be discussed with specialists.
Acute Pyelonephritis
There are no specific data available in the literature on the management of acute pyelonephritis in the ICU. The urine of all patients with suspicion of complicated pyelonephritis should be cultured and a Gram stain of the spun urine performed. Blood cultures, which are positive in 36% of women not admitted to the ICU, are also required (78). All patients with acute pyelonephritis should have an ultrasound examination or a renal computed tomography scan to evaluate for obstruction and stones.
For uncomplicated acute pyelonephritis, the IDSA, in 1999, derived two conclusions from the analysis of randomized clinical trials. The first is that trimethoprim-sulfamethoxazole is preferred over ampicillin. Indeed, there is a relatively high prevalence of organisms causing acute pyelonephritis that are resistant to ampicillin, and even for susceptible organisms, there is a significantly increased recurrence rate in patients given ampicillin compared with those given trimethoprim-sulfamethiazole. The second conclusion is that 10 to 14 days of therapy appears to be adequate for the majority of women (71). There has been little additional information since the publication of these recommendations. However, 255 outpatients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days, followed by placebo for 7 days versus trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days. In this study, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen (79)
(Table 113.8). Gatifloxacin appears to be equivalent to ciprofloxacin for this indication (80).
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Table 113.8 Antimicrobial treatment of urinary tract infectionsa |
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Patients with complicated acute pyelonephritis should be hospitalized and initial administration of broad-spectrum intravenous antibiotics begun. The targeted bacteria are Enterobacter sp., E. coli, Proteus sp., and Enterococcus sp. Ciprofloxacin, 500 mg twice daily, is administered orally for 14 to 21 days. Gentamicin, 3 mg/kg/day intravenously, is added during the first 3 days. Interestingly, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of complicated pyelonephritis (81), and gatifloxacin is as effective as ciprofloxacin (80). If needed, ceftriaxone, 2 g/day intravenously, is an alternative choice to ciprofloxacin. Further, the success rates are similar in patients given ceftriaxone or ertapenem (82).
The drainage of urine must be urgently performed using bladder catheterization, percutaneous nephrostomy drainage, or definitive surgery. Antimicrobial treatment is administered after urine and blood specimen collection. The antibiotic selection is based on the result of the Gram stain of the urine and the knowledge of the local ecology. Antimicrobial treatment should be adapted to the susceptibility testing results as soon as possible, and de-escalation should be performed in favor of a narrow-spectrum antibiotic.
Specificities of Complicated Urinary Tract Infections in the Intensive Care Unit
Although there is little in the literature on the treatment of UTIs in the ICU, one presumes the need for intravenous antibiotics for these patients because of the possibility of bacteremia or sepsis. The guidelines from the Surviving Sepsis Campaign state that (a) antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained; (b) initial empirical anti-infective therapy should include one or more drugs that have activity against the likely pathogens and that penetrate the presumed source of sepsis; and (c) monotherapy is as effective as combination therapy with a β-lactam and an aminoglycoside as empiric therapy of patients with severe sepsis or septic shock (83). Hence, empirical antimicrobial therapy should include drugs with good penetration in the urinary tract, and the choice is guided by the susceptibility patterns of micro-organisms in the hospital. For the septic shock patients whose presumed source is urine, we recommend, empirically, a combination of a β-lactam antibiotic with antipseudomonal activity and a fluoroquinolone. This broad-spectrum treatment is narrowed as soon as the results of the susceptibility testing are known. The durations of treatment should be tailored to the source of infection.
Management of Candiduria
Candiduria represents from 3% to 15% of catheter-associated UTI in the ICU (8,9,13). Candida albicans and Candida (Torulopsis) glabrata are found in 46% and 31% of cases, respectively (84). According to the International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections, colonized patients without evidence of infection do not require treatment, but the contributing cause should be addressed, such as changing or removing the indwelling catheter and discontinuing inappropriate antibiotic therapy. Fluconazole may be the best option for treating a candiduria (85), but only if the species is C. albicans. Voriconazole may be more effective against non-albicans species.
Clinician reaction to isolating Candida organisms in urine was assessed in a retrospective review of 133 consecutive patients. The average patient age was 68.8 years old, most (78%) had an indwelling catheter, and many (35%) were in the ICU. In response to culture results, clinicians initiated antifungal therapy in 80 instances (60%). Treatment was often based on a single culture result without evidence of infection (66%) and in the absence of risk of invasive disease. Removal of the indwelling catheter was never attempted and antibiotics were rarely discontinued or modified (1.3%). Fluconazole was most frequently utilized (52%), followed by amphotericin B bladder irrigation (32%) and combined fluconazole/amphotericin B bladder irrigation (15%). Therapy was more frequently initiated in ICU cases (77 vs. 56%; p = 0.02) (86). These results show the poor adherence to guidelines.
A prospective, randomized trial compared fungal eradication rates among 316 hospitalized patients with candiduria treated with fluconazole (200 mg) or placebo daily for 14 days. Candiduria cleared by day 14 in 50% of the patients receiving fluconazole and 29% of those receiving placebo, with higher eradication rates among patients completing 14 days of therapy. Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients. In 41% of the catheterized subjects, candiduria was resolved as the result of catheter removal only. The outcomes of patients were not provided in the results (87).
Bladder irrigation using amphotericin B has been proposed as an alternative technique to clear Candida from the urine. A comparative and randomized study of 109 elderly patients showed that funguria was eradicated in 96% of the patients treated with amphotericin B and 73% of those treated with fluconazole (p <0.05). One month after study enrollment, the mortality rate associated with all causes was greater among patients who were treated with amphotericin B bladder irrigation than among those who received oral fluconazole therapy (41% vs. 22%, respectively; p <0.05). This finding suggests that irrigation therapy could be associated with poorer survival (88).
There has only been one study performed in ICU patients developing candiduria, which reached the same conclusions; unfortunately, methodologic issues restrict the interest of this study. The authors retrospectively compared three means to manage candiduria in ICU patients: successful bladder irrigation with amphotericin B (10 of 27 patients), failure of bladder irrigation requiring the use of parenteral amphotericin B (17 of 27), and patients treated with parenteral fluconazole (n = 20). Severity score on admission day was significantly lower in the first group than in the two others. However, the mortality rate was 53% and 5% in patients experiencing a failure of bladder irrigation and in patients receiving fluconazole, respectively (89). These results must be considered with caution because of serious methodologic limitations. However, these data indicate that bladder irrigation of critically ill patients has a negative survival advantage.
Summary
Bacteria in the bladder constitute a reservoir for the development of multiresistant bacterial strains, and the rate of bacteriuria may be used as a marker of the level of care in the ICU. Prevention of UTIs in the ICU is not improved by the use of expensive devices, but can reflect the level of general unit hygiene. While management of UTIs in the ICU is poorly described in the literature, it is reasonably clear that there is no need to treat asymptomatic bacteriuria. However, although infrequent, severe sepsis with a urine source requires empirical broad-spectrum antimicrobial treatment based on the local bacterial ecology. Treatment is de-escalated after identification of the pathogen and reporting of the susceptibility testing.
References
1. Richards MJ, Edwards JR, Culver DH, et al. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med. 1999;27:887.
2. Bagshaw SM, Laupland KB. Epidemiology of intensive care unit-acquired urinary tract infections. Curr Opin Infect Dis. 2006;19:67.
3. Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995;274:639.
4. Rosser CJ, Bare RL, Meredith JW. Urinary tract infections in the critical ill patient with a urinary catheter. Am J Surg. 1999;177:287.
5. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128.
6. Agace W, Connell H, Svanborg C. Host resistance to urinary tract infection. In: Mobley HLT, Warren JW, eds. Urinary Tract Infections. Molecular Pathogenesis and Clinical Management. Washington, DC: ASM Press; 1996:221.
7. Trautner BW, Darouiche RO. Role of biofilm in catheter-associated urinary tract infection. Am J Infect Control. 2004;32:177.
8. Leone M, Albanese J, Garnier F, et al. Risk factors of nosocomial catheter-associated urinary tract infection in a polyvalent intensive care unit. Intensive Care Med. 2003;29:1077.
9. Laupland KB, Bagshaw SM, Gregson DB, et al. Intensive care unit-acquired urinary tract infections in a regional critical care system. Crit Care. 2005;9:R60.
10. Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41:848.
11. Wagenlehner FME, Naber KG. Emergence of antibiotic resistance and prudent use of antibiotic therapy in nosocomially acquired urinary tract infection. Int J Antimicrobial Agents. 2004;23(Suppl 1):24.
12. Wagenlehner FME, Krcmery S, Held C, et al. Epidemiological analysis of the spread of pathogens from a urological ward using genotypic, phenotypic and clinical parameters. Int J Antimicrobial Agents. 2002;19:583.
13. Tissot E, Limat S, Cornette C, et al. Risk factors for catheter-associated bacteriuria in a medical intensive care unit. Eur J Clin Microbiol Infect Dis. 2001;20:260.
14. Jain P, Parada JP, David A, et al. Overuse of the indwelling urinary tract catheter in hospitalized medical patients. Arch Intern Med. 1995;155:1425.
15. Platt R. Adverse consequences of asymptomatic urinary tract infections in adults. Am J Med. 1987;82(Suppl 6B):47.
16. Platt R, Polk BF, Murdock B, et al. Mortality associated with nosocomial urinary-tract infection. N Engl J Med. 1982;307:637.
17. Mnatzaganian G, Galai N, Sprung CL, et al. Increased risk of bloodstream and urinary infections in intensive care unit (ICU) patients compared with patients fitting ICU admission criteria treated in regular wards. J Hosp Infect. 2005;59:331.
18. Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344.
19. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303.
20. Leone M, Perrin AS, Granier I, et al. A randomized trial of catheter change and short course of antibiotics for asymptomatic bacteriuria in catheterized ICU patients. Intensive Care Med. 2007;33:726.
21. Tambyah PA, Maki DG. Catheter associated urinary tract infection is rarely symptomatic: a prospective study of 1497 catheterized patients. Arch Intern Med. 2000;160:678.
22. Saint S. Clinical and economic consequences of nosocomial catheter-related bacteriuria. Am J Infect Control. 2000;28:68.
23. Inan D, Saba R, Gunseren F, et al. Daily antibiotic cost of nosocomial infections in a Turkish university hospital. BMC Infect Dis. 2005;5:5.
24. Garibaldi RA, Mooney BR, Epstein BJ, et al. An evaluation of daily bacteriologic monitoring to identify preventable episodes of catheter-associated urinary tract infection. Infect Control. 1982;3:466.
25. Tissot E, Woronoff-Lemsi MC, Cornette C, et al. Cost-effectiveness of urinary dipsticks to screen asymptomatic catheter-associated urinary infections in an intensive care unit. Intensive Care Med. 2001;27:1842.
26. Legras A, Cattier B, Perrotin D. Dépistage des infections urinaires dans un service de réanimation: intéret des bandelettes réactives. Med Mal Infect. 1993;23:34.
27. Mimoz O, Bouchet E, Edouard A, et al. Limited usefulness of urinary dipsticks to screen out catheter-associated bacteriuria in ICU patients. Anaesth Intens Care. 1995;23:706.
28. Nicolle LE, Bradley S, Colgan R, et al. Infectious diseases society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643.
29. Warren JW. Catheter-associated urinary tract infections. Int J Antimicrob Agents. 2001;17:299.
30. Kunin CM, McCormack RC. Prevention of catheter-induced urinary-tract infections by sterile closed drainage. N Engl J Med. 1966;274:1155.
31. Huth TS, Burke JP, Larsen LA, et al. Clinical trial of junction seals for the prevention of urinary catheter-associated bacteriuria. Arch Intern Med. 1992;152:807.
32. Degroot-Kosolcharoen J, Guse J, Jones JM. Evaluation of a urinary catheter with a preconnected closed drainage bag. Infect Control Hosp Epidemiol. 1998;9:72.
33. Wille JC, Blusse Van Oud Alblas A, Thewessen EAPM. Nosocomial catheter-associated bacteriuria: a clinical trial comparing two closed urinary drainage systems. J Hosp Infect. 1993;25:191.
34. Leone M, Garnier F, Dubuc M, et al. Prevention of nosocomial urinary tract infection in ICU patients. Comparison of effectiveness of two urinary drainage systems. Chest. 2001;120:220.
35. Leone M, Garnier F, Antonini F, et al. Comparison of effectiveness of two urinary drainage systems in intensive care unit: a prospective, randomized clinical trial. Intensive Care Med. 2003;29:410.
36. Leone M, Garnier F, Avidan M, et al. Catheter-associated urinary tract infections in intensive care units. Microbes Infect. 2004;6:1026.
37. Davenport K, Keeley FX. Evidence for the use of silver-alloy-coated urethral catheters. J Hosp Infect. 2005;60:298.
38. Brosnahan J, Jull A, Tracy C. Types of urethral catheters for management of short-term voiding problems in hospitalized adults. Cochrane Database Syst Rev. 2004;1:CD004013.
39. Johnson JR, Kuskowski MA, Wilt TJ. Systematic review: antimicrobial urinary catheters to prevent catheter-associated urinary tract infection in hospitalized patients. Ann Intern Med. 2006;144:116.
40. Thibon P, Le Coutour X, Leroyer R, et al. Randomized multi-centre trial of the effects of a catheter coated with hydrogel and silver salts on the incidence of hospital-acquired urinary tract infections. J Hosp Infect. 2000;45:117.
41. Bologna RA, Tu LM, Polansky M, et al. Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates in intensive care unit patients: a multicenter study. Urology. 1999;54:982.
42. Huth TS, Burke JP, Larsen RA, et al. Randomized trial of meatal care with silver sulfadiazine cream for the prevention of catheter-associated bacteriuria. J Infect Dis. 1992;165:14.
43. Carapeti EA, Andrew SM, Bentley PG. Randomised study of sterile versus non-sterile urethral catheterisation. Ann R Surg Engl. 1994;76:59.
44. Warren JW, Platt R, Thomas RJ, et al. Antibiotic irrigation and catheter-associated urinary-tract infections. N Engl J Med. 1978;299:570.
45. Schneeberger PM, Vreede RW, Bogdanowicz JFTA, et al. A randomized study on the effect of bladder irrigation with povidone-iodine before removal of an indwelling catheter. J Hosp Infect. 1992;21:223.
46. Thompson RL, Haley CE, Searcy MA, et al. Catheter associated with bacteriuria. Failure to reduce attacks rates using periodic instillations of a disinfectant into urinary drainage system. JAMA. 1984;251:747.
47. Vandoni RE, Lironi A, Tschantz P. Bacteriuria during urinary tract catheterization: suprapubic versus urethral route: a prospective randomized trial. Acta Chir Belg. 1994;94:12.
48. Niel-Weise BS, van den Broek PJ. Urinary catheter policies for short-term bladder drainage in adults. Cochrane Database Syst Rev. 2005;3:CD004203.
49. Harti A, Bouaggad A, Barrou H, et al. Prévention de l'infection urinaire nosocomiale: sondage vésical versus Pénilex. Cah Anesthesiol. 1994;42:31.
50. Tang MW, Kwok TC, Hui E, et al. Intermittent versus indwelling urinary catheterization in older female patients. Maturitas. 2006;53:274.
51. Ghalayini IF, Al-Ghazo MA, Pickard RS. A prospective randomized trial comparing transurethral prostatic resection and clean intermittent self-catheterization in men with chronic urinary retention. BJU Int. 2005;96:93.
52. Bregenzer T, Frei R, Widmer AF, et al. Low risk of bacteremia during catheter replacement in patients with long-term urinary catheters. Arch Intern Med. 1997;157:521.
53. van der Wall E, Verkooyen RP, Mintjes-de Groot J, et al. Prophylactic ciprofloxacin for catheter-associated urinary-tract infection. Lancet. 1992;339:946.
54. Hustinx WNM, Mintjes-de Groot AJ, Verkooyen RP, et al. Impact of concurrent antimicrobial therapy on catheter-associated urinary tract infection. J Hosp Infect. 1991;18:45.
55. Niel-Weise BS, van den Broek PJ. Antibiotic policies for short-term catheter bladder drainage in adults. Cochrane Database Syst Rev. 2005;3:CD005428.
56. Verwaest C, Verhaegen J, Ferdinande P, et al. Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit. Crit Care Med. 1997;25:63.
57. Senkal M, Mumme A, Eickhoff U, et al. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Crit Care Med. 2000;28:1255.
58. Nourdine K, Combes P, Carton MJ, et al. Does noninvasive ventilation reduce the ICU nosocomial risk? A prospective clinical survey. Intensive Care Med. 1999;25:567.
59. Beetz R. Mild dehydration: a risk factor of urinary tract infection? Eur J Clin Nutr. 2003;57(Suppl 2):S52.
60. Harding GKM, Nicolle LE, Ronald AR, et al. How long should catheter-associated urinary tract infection in women be treated. Ann Intern Med. 1991;114:713.
61. Stamey TA, Fair WR, Timothy MM, et al. Serum versus urinary antimicrobial concentrations in case of urinary tract infections. N Engl J Med. 1974;291:1159.
62. Frimodt-Moller N. Correlation between pharmacokinetic/pharmacodynamic parameters and efficacy for antibiotics in the treatment of urinary tract infection. Int J Antimicrob Agents. 2002;19:546.
63. Leone M, Albanese J, Tod M, et al. Ceftriaxone (1 g intravenously) penetration into abdominal tissues when administered as antibiotic prophylaxis during nephrectomy. J Chemother. 2003;15:139.
64. Leroy A, Oser B, Grise P, et al. Cefixime penetration in human renal parenchyma. Antimicrob Agents Chemother. 1995;39:1240.
65. Saito I, Saiko Y, Tahara T, et al. Penetration of cefpirome into renal and prostatic tissue. Int J Clin Pharmacol Res. 1993;13:317.
66. Charalabopoulos K, Karachalios G, Baltogiannis D, et al. Penetration of antimicrobial agents into the prostate. Chemotherapy. 2003;49:269.
67. Neu HC. Optimal characteristics of agents to treat uncomplicated urinary tract infections. Infection. 1992;20(Suppl 4):S266.
68. Ray GT, Baxter R, DeLorenze GN. Hospital-level rates of fluoroquinolone use and the risk of hospital-acquired infection with ciprofloxacin-nonsusceptible Pseudomonas aeruginosa. Clin Infect Dis. 2005;41:441.
69. Lautenbach E, Strom BL, Nachamkin I, et al. Longitudinal trends in fluoroquinolone resistance among Enterobacteriaceae isolates from inpatients and outpatients, 1989–2000: differences in the emergence and epidemiology of resistance across organisms. Clin Infect Dis. 2004;38:655.
70. Naber KG, Witte W, Bauernfeind A, et al. Clinical significance and spread of fluoroquinolone resistant uropathogens in hospitalised urological patients. Infection. 1994;22(Suppl 2):S122.
71. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis. 1999;29:745.
72. Milo G, Katchman EA, Paul M, et al. Duration of antibacterial treatment for uncomplicated urinary tract infection in women. Cochrane Database Syst Rev. 2005;2:CD004682.
73. Rafalsky V, Andreeva I, Rjabkova E. Quinolones for uncomplicated acute cystitis in women. Cochrane Database Syst Rev. 2006;3:CD003597.
74. Krieger JN, Riley DE. Prostatitis: what is the role of infection. Int J Antimicrob Agents. 2002;19:475.
75. Wagenlehner FME, Naber KG. Current challenges in the treatment of complicated urinary tract infections and prostatitis. Clin Microbiol Infect. 2006;12(Suppl 3):67.
76. Sampol-Manos E, Leone M, Karouia D, et al. Prophylaxis with ciprofloxacin for open prostatectomy: comparison of tissue penetration with two oral doses. J Chemother. 2006;18:225.
77. Martin C, Viviand X, Cottin A, et al. Concentrations of ceftriaxone (1,000 milligrams intravenously) in abdominal tissues during open prostatectomy. Antimicrob Agents Chemother. 1996;40:1311.
78. Smith WR, McClish DK, Poses RM, et al. Bacteremia in young urban women admitted with pyelonephritis. Am J Med Sci. 1997;313:50.
79. Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women: a randomized trial. JAMA. 2000;283:1583.
80. Naber KG, Bartnicki A, Bischoff W, et al. Gatifloxacin 200 mg or 400 mg once daily is as effective as ciprofloxacin 500 mg twice daily for the treatment of patients with acute pyelonephritis or complicated urinary tract infections. Int J Antimicrob Agents. 2004;23(Suppl 1):S41.
81. Mombelli G, Pezzoli R, Pinoja-Lutz G, et al. Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial. Arch Intern Med. 1999;159:53.
82. Wells WG, Woods GL, Jiang Q, et al. Treatment of complicated urinary tract infection in adults: combined analysis of two randomized, double-blind, multicentre trials comparing ertapenem and ceftriaxone followed by appropriate oral therapy. J Antimicrob Chemother. 2004;53(Suppl 2):ii67.
83. Bochud PY, Bonten M, Marchetti O, et al. Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review. Crit Care Med. 2004;32(11 Suppl):S495.
84. Leone M, Albanese J, Antonini F, et al. Long-term epidemiological survey of Candida species: comparison of isolates found in an intensive care unit and in conventional wards. J Hosp Infect. 2003;55:169.
85. Edwards JE, Bodey GP, Bowden RA, et al. International conference for the development of a consensus on the management and prevention of severe candidal infections. Clin Infect Dis. 1997;25:43–59.
86. Ayeni O, Riederer KM, Wilson FM, et al. Clinician's reaction to positive urine culture for candida organisms. Mycoses. 1999;42:285.
87. Sobel JD, Kauffman CA, McKinsey D, et al. Candiduria: a randomized, doubleblind study of treatment with fluconazole and placebo. Clin Infect Dis. 2000;30:19.
88. Jacobs LG, Skidmore EA, Freeman K, et al. Oral fluconazole compared with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Clin Infect Dis. 1996;22:30.
89. Nassoura Z, Ivatury RR, Simon RJ, et al. Candiduria as an early marker of disseminated infection in critically ill surgical patients: the role of fluconazole therapy. J Trauma. 1993;35:290.
