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Prevention and treatment of catheter-associated urinary tract infections
Journal of Infection (I985) xo, 96-IO6
REVIEW ARTICLE
Prevention and treatment of catheter-associated tract infections
urinary
D . E. M a c f a r l a n e
Department of Microbiology, University of the West Indies, Kingston, Jamaica Accepted for publication 29 May 1984 Introduction
It has been estimated that urinary tract infections account for approximately 4o % of all hospital-acquired infections, 1 and that 75 % of all patients with nosocomial urinary tract infections have a history of urological instrumentation, usually catheterisation, before infection. 2 In some hospitals, catheter-associated urinary tract infections constitute a m i n i m u m of 1% of all hospital admissions? Moreover patients with urinary catheters are often colonised or infected with highly resistant organisms 4 which are then transmitted to other patients. 5 Indwelling urinary catheters therefore represent a major problem in nosocomial infection. i n c i d e n c e o f catheter-associated urinary tract infections
T h e incidence of bacteriuria after catheterisation depends on various features including method of insertion, duration of catheterisation, and type of drainage. Bacteriuria develops in I-5 % of patients with single short-term catheterisation; 5' ~ 50 % of patients with intermittent catheterisation 7, 8 and 93 % of patients with indwelling catheters and open drainage have bacteriuria after 4 days2 T h e use of a closed-drainage system may maintain urinary tract infection rates below 2o % for up to I4 days, provided that the sterility of the system is preserved? °,11 Since the risk of developing bacteriuria has been estimated to be 5-IO % for each day that a catheter is in situ 12' 1~most patients on long-term catheterisation eventually develop bacteriuria. Sequelae o f catheter-associated urinary tract infections
It is often assumed that urinary tract infections inevitably follow catheterisation, are usually benign, and will resolve on removal of the catheter. Unfortunately, many patients with urinary catheters are prone to complications that include acute pylonephritis, nephrolithiasis, cystolithiasis, epididymitis, abscess formation, vesicoureteral reflux and chronic interstitial renal failure. 14 In patients with spinal injuries, long-term catheterisation is associated with a mortality of 20-40 %.15 In some hospitals, catheter-associated urinary tract infections are the main cause of Gram-negative septicaemia, a potentially serious condition with a mortality of 20-50 % .16,17 Bacteriuria in a patient with an indwelling catheter may therefore have serious implications. oi63-4453/85/o2oo96 + I I $02.00/0
~ I985 The British Society for the Study of Infection
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E p i d e m i o l o g y o f catheter-associated urinary tract infections
Bacteria which colonise or infect the urinary tract of catheterised patients may be endogenous or exogenous. Organisms which constitute the normal colonic flora, or which colonise the gastrointestinal tract during a stay in hospital, may gain access to the urinary tract during insertion of a catheter 18 or by ascending from the catheter-meatal junction, via the fluid-filled space between the catheter and the urethral mucosa. 19 Exogenous organisms may gain access to the bladder via the junction of the catheter with the drainage tube or via the collecting bag. Failure to take precautions against infection when opening the catheter-drainage tube connection in order to irrigate the bladder is a well recognised source of contamination.2°, 21 Bacterial contamination of the collecting bag inevitably follows repeated openings required to drain the system, and usually precedes urinary tract infection, thereby indicating probable retrograde spread of bacteria from the bag to the bladder. TM 22 T h e marked reduction in urinary tract infections achieved with closed sterile drainage systems, 1°, 11 suggests that contamination of the drainage system is an important cause of infection in patients with indwelling urinary catheters. Although endogenous bacteria from the gastrointestinal tract have been implicated in catheter-associated urinary tract infections, 1° surveys indicate that many outbreaks of infection are caused by cross-infection. Endemic strains of Proteus, Providencia, Klebsiella, Pseudomonas and Serratia have been recovered from the hands of nursing staff in several studies, 4 and clustering of patients with catheters was noted to be a major risk factor. Separation of patients with urinary catheters is important in the control of nosocomial outbreaks of catheter-associated urinary tract infection and emphasises the role of cross-infection in the spread of infection. 23 P a t h o g e n e s i s o f catheter-associated urinary tract infections
T h e healthy urinary tract is normally sterile except for a few organisms present in the distal urethra. 24 Organisms that may ascend to the bladder are usually removed by intrinsic clearance mechanisms. 2~ Additional protection is offered by humoral immunity and the intact mucosa of the bladder which is resistant to infection unless damaged. 26 T h e urinary catheter with drainage-tube and collecting bag together represent an extension to the urinary tract and provide direct access to the bladder. Organisms entering this system may multiply rapidly in the stagnant urine of the collecting bag so as to reach a concentration > Io 9 organisms/1. 27 Thus, large numbers of bacteria have ready access to a urinary tract which is often predisposed to infection either because of the effects of the catheter, which may vary from irritation of the mucosa to trauma that results in an abscess, or as a result of surgical procedures or because of abnormalities of the urinary tract. Distension of the bladder often arises before catheterisation or may result from blockage of the catheter. Experimental work in animals has shown that prolonged increases in intravesical pressure may result in decreased blood flow and obstruction of capillaries, venules and arterioles, with extravasion of red blood cells 28 and even bleeding into the bladder. If this also happens in catheterised patients, areas of haemorrhage may
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be liable to infection by organisms which have ascended to the bladder via the urethra or the lumen of the indwelling catheter. According to Lapides, 29 this important predisposing factor in urinary tract infections explains why some patients with indwelling catheters develop infection, and others may have repeated episodes of bacteriuria without infection. B a c t e r i o l o g y o f c a t h e t e r - a s s o c i a t e d u r i n a r y tract i n f e c t i o n
Whereas multiple organisms in a midstream specimen of urine usually indicate contamination of the sample, bacteriuria with more than one species of organism is common in catheterised patients. T h e diagnosis of urinary tract infection is usually based on the number of organisms in a properly collected sample of urine. Counts of < IO8 colonyforming units (cfu)/1 of voided urine are often considered to indicate the presence of contaminating organisms derived from the anterior urethra or peri-meatal skin. 9 Similar criteria are sometimes applied to the diagnosis of urinary tract infections in patients with indwelling catheters. This seems illogical because catheter urine has not come into contact with the urethra. A count of < IO8 organisms/1 of urine may represent contamination from the catheter but any number of bacteria, however small, in the catheter may colonise or infect the bladder, thereby rendering such a finding significant. A recent study has shown that the recovery of IO6 cfu/1 of catheter urine often heralded subsequent microbial densities > IO8 cfu/1 of urine in patients with indwelling urinary catheters. 30 It may therefore be more appropriate to regard counts > IO6 cfu/1 as significant in catheter specimens of urine. Catheter-associated urinary tract infections are usually caused by members of the enterobacteriaceae. Staphylococci, streptococci and coryneforms may cause bacteriuria in catheterised patients, but do not usually persist in the bladder. 31 Conversely, Escherichia coli, Proteus, Klebsiella, Pseudomonas and Serratia species are often repeatedly cultured from the urine of catheterised patients over a period of several weeks, thereby indicating the ability of these organisms to colonise the urinary tract. 31 Organisms which are endemic in certain institutions often colonise or infect catheterised patients. For example, Providencia stuartii, an unusual urinary tract pathogen was recently listed in a study as the main cause of catheter-associated bacteriuria. 31 Organisms more commonly implicated in outbreaks of nosocomial catheter-associated urinary tract infection include Pseudomonas, Klebsiella, Proteus, Providencia and Serratia species, the latter having a tendency to be associated with outbreaks involving cross-infection. 4, 32. zz Patients with indwelling urinary catheters often have repeated episodes of bacteriuria. This may result in the repeated administration of antimicrobial agents and the emergence of highly resistant bacteria. Indiscriminate use of antimicrobial drugs has encouraged the emergence of multiresistant bacteria in many hospitals, and catheterised patients are at risk from cross-infection with these organisms. Outbreaks of nosocomial catheter-associated urinary tract infections are often caused by multiresistant bacteria. In a recent study of plasmid-mediated antibiotic resistance, multiresistant strains of Serratia marcescens, Klebsiella pneumoniae and Providencia rettgeri were recovered from
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36I patients over a period of 3 years. Almost all of these organisms were cultured from the urine o f patients with indwelling catheters. 3~ T h e same three organisms have been implicated in several other outbreaks of nosocomial catheter-associated urinary tract infections caused b y multiresistant bacteria. 4 Preventive
measures
Indwelling urinary catheters are often associated with illness and deathX4,15. 21, 34 and should n o t be used unless they are absolutely necessary. I n t e r m i t t e n t catheterisation should be considered as an alternative w h e n feasable. T h e clearly established advantages of a closed sterile drainage systemlO. 11.35, 36 make it m a n d a t o r y for patients w h o m u s t have an indwelling catheter. M o s t m o d e r n c o m m e r c i a l l y - p r o d u c e d urinary drainage systems consist of a sterile p r e a s s e m b l e d catheter, drainage tube, and collecting bag. T h e catheter should n o t be disconnected from these systems during insertion, as this is likely to result in contamination at the catheter-drainage t u b e junction. 21 Insertion of a sterile catheter and s u b s e q u e n t attachment o f a separate drainage t u b e and collecting bag is therefore contra-indicated. Before insertion of a catheter the peri-meatal skin should be cleansed with a suitable antiseptic solution, such as aqueous p o v i d o n e iodine. Aseptic catheter insertion is obviously important, TM 37 and is best achieved b y means of sterile packs containing drapes, gloves, lubricant jelly and a p r e a s s e m b l e d urinary drainage system. After insertion, the catheter m u s t be taped to p r e v e n t traction, the drainage-tube positioned in order to allow u n o b s t r u c t e d downhill flow, and the collecting bag secured below the patient so as to p r e v e n t its being inadvertently raised above the level of the bladder with c o n s e q u e n t retrograde flow of contaminated urine. Each time the closed sterile drainage system is breached, the risk of contamination increases. M o s t openings take place at the outlet t u b e where urine is e m p t i e d from the collecting bag. Organisms entering there are likely to come from hands o f nurses. Conversely, bacteria present in the drainage system m a y contaminate the hands of nurses e m p t y i n g the collecting bag. This m a y explain w h y outbreaks of hospital cross-infection are often associated with urinary catheters. 4 A l t h o u g h various ' n o t o u c h ' outlet tubes have been devised b y manufacturers, the most effective solution to this p r o b l e m is to ensure that nurses wear sterile disposable gloves w h e n e m p t y i n g urine bags and take care to avoid spillage. Sterile closed-drainage systems are often o p e n e d at the catheter-drainage-tube junction for bladder irrigation and occasionally for collecting specimens of urine. F o r patients likely to need f r e q u e n t irrigation, a triple-lumen catheter with n e o m y c i n p o l y m y x i n rinses is preferredfl 8 although the inclusion of an irrigation lumen in this system necessitates a narrower drainage-tube which is m o r e easily obstructed. Some urologists therefore prefer to use a closed irrigation system with a Y t u b e attached to a d o u b l e - l u m e n catheter similar to the system described b y D u k e s in I928. 36 T h i s system also benefits patients on long-term catheterisation, because daily irrigation with sterile water or saline, interspersed with p o l y m y x i n - n e o m y c i n rinses as required, m a y p r e v e n t
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accumulation of a pool of stagnant urine in the bladder, and remove contaminating organisms. Alternatively, a semi-automatic, siphon-pressure, closed drainage system is commercially available.* Several commercial urinary collection systems have a sealed catheterdrainage-tube junction which cannot be opened accidentally; a break in the seal indicates any disconnections. Using such a system, Platt and colleagues demonstrated a significant reduction in urinary tract infection and mortality, compared with urinary drainage systems which did not have this facility. 21 T h e i r study once again emphasised the importance of the catheter-drainage-tube junction as a portal of entry for bacteria. Disconnections, however, are sometimes necessary for irrigation when an aseptic technique should be used, and irrigation performed with a sterile syringe and neomycin-polymyxin solution. T h e catheter-drainage-tube junction should never be disconnected for the collection of urine samples. Instead, after clamping the drainage tube, and disinfecting the puncture site with an alcoholic solution of iodine or plain alcohol, urine should be aspirated by means of a sterile needle and syringe either through a sample port or via the distal end of the catheter. Growth of contaminating organisms in the collecting bag' may be inhibited by the presence of a disinfectant. At one time, formalin was added to glass collecting bottles. 3a More recently, Gillespie and colleagues4° have shown that chlorhexidine can maintain sterility in drainage bags. Others have shown that periodic instillation of 3o ml of a 3 % solution of hydrogen peroxide into the drainage reservoir prevented bacteria growth in the collecting bag and significantly delayed the onset of bacteriuria. 41 Disinfectmxts which maintain the sterility of the collecting bag obviously prevent the ascent of bacteria from the drainage bag to the bladder and in addition may considerably reduce cross-infection in catheterised patients. Most modern drainage systems contain an air lock or valve. Although these devices prevent reflux of urine from the collecting bag to the bladder, they do not halt the ascent of bacteria. This probably explains the failure of several authors to demonstrate reduced infection rates when collecting bags with drip chambers, air locks or one-way valves have been used. 13, ~2 Because patients who require long-term catheterisation are at such serious risk of infection, intermittent catheterisation has been proposed. Based on the premise that a healthy intact bladder is capable of eliminating small numbers of bacteria, Lapides devised a system of intermittent clean catheterisation. 8 Patients with obstructive uropathy, decompensated detrussor, or a neuropathic bladder have been taught how to insert a clean urinary catheter while observing normal standards of personal hygiene and with emphasis on regular emptying of the bladder. During long-term surveillance of 218 patients, the incidence of bacteriuria was reduced from 90 % to 48 %, and complications were few. In a spinal injuries unit Guttman and coUeagues7 used repeated intermittent sterile catheterisation as an alternative to indwelling catheters and thereby reduced the incidence of bacteriuria to 50 %. T h e use of prophylactic antibiotics in patients with indwelling urinary catheters is contentious. Some authors have failed to demonstrate any reduction * Cystamat, Leo Pharmaceuticals, Copenhagen, Denmark.
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in infection rates42, 43,44 while others have claimed a reduced incidence of bacteriuria.45, 46 T h e results of these studies will have been markedly influenced by choice of antibiotic, sensitivity patterns of urinary isolates, duration of catheterisation and catheter-care techniques. If prophylactic agents are considered necessary they should be limited to locally acting ones such as nalidixic acid, nitrofurantoin or methenamine hexamine. Disadvantages of prophylactic antibiotics include adverse reactions, increased costs and selection of resistant organisms. In addition, prophylactic antibiotics are unlikely to protect patients from multiresistant organisms. Because maintenance of a sterile urinary drainage system depends on strict observation of correct precedures, adequate training and supervision of doctors and nurses responsible for patients with indwelling urinary catheters are essential. In an attempt to achieve a high standard of catheter care, some authors have recommended the formation of catheter care teams which have total responsibility for the insertion of catheters and their maintenance. 47 Although this is an excellent idea, it is unlikely to be practical in small hospitals having only a few patients with urinary catheters. T r e a t m e n t o f u r i n a r y tract i n f e c t i o n s in c a t h e t e r i s e d p a t i e n t s
Bacteriuria in a catheterised patient indicates that the urinary tract has become colonised or infected. Colonisation may be distinguished from infection by the lack of pus cells in the urine and the absence of clinical symptoms. Infection is usually confined to the lower urinary tract except in those patients with vesicoureteric reflux or evidence of pyelographic renal or ureteric abnormalities. 14, 48Because bacteraemia and septicaemia commonly complicate urinary tract infections in patients in hospital, blood should always be cultured from patients with suspected systemic infection. Although bacteriuria alone does not necessarily imply infection, it does indicate that the urinary drainage system has become contaminated, and should be replaced. Colonisation often preceeds infection, and colonised patients represent a serious cross-infection hazard. 42 Organisms may be removed from the bladder by instilling 5o ml of a polymyxin-neomycin solution (4o mg neomycin, 2oo,ooo units polymyxin/1 saline) into the bladder through the existing catheter. 49 Following this procedure, the entire contaminated drainage system should be removed, and a new sterile system aseptically installed. As a further precaution, 30 ml of a solution of hydrogen peroxide may be added to the drainage bag. Nalidixic acid is active against a wide range of Gram-negative bacteria • including most urinary pathogens except Pseudomonas species. It is not active against Gram-positive organisms. It has been claimed that bacteria may often become resistant during a course of treatment and repeated cultures of urine and sensitivity testing have therefore been advocated. 5oRecent studies however do not support this contention. 51 Urine concentrations of active drug between Ioo and 5oo mg/1 are achieved after giving I g nalidixic acid orally every 6 h. Such concentrations are well in excess of the 16 m g / l required to inhibit most bacteria. Increased toxicity has not been observed in patients with advanced renal failure given normal doses ofnalidixic acid, and bactericidal concentrations can be maintained in their urine. 52
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Nitrofurantoin is active against most Gram-negative and Gram-positive organisms except Pseudomonas and Proteus species. After an oral dose of xoo mg every 6 h, urine concentrations range from 5o to 2oo mg/1. T h e activity of nitrofurantoin is decreased in alkaline urine. Recovery of the drug from urine is directly related to creatinine clearance and urine concentrations in uraemic patients may be inadequate to inhibit some bacteria. When the creatinine clearance is < 60 m l / m i n , the drug will accumulate in the serum, thereby increasing the possibility of systemic toxicity, especially peripheral neuropathy. Nitrofurantoin is one of the few antibacterial drugs to achieve higher concentrations in renal lymph than in the blood 5a and is therefore suitable for treating both upper and lower urinary tract infections. Methenamine was first introduced by Nicolaier in 1895 for treating urinary tract infections. 54 It is available either as the pure base or in combination with mandelic acid or hippuric acid. Methenamine itself has no antibacterial activity, but at an acid pH is hydrolysed to ammonia and to a bactericidal concentration of formaldehyde35 Most bacteria are inhibited by 2o mg/1 of formaldehyde.~6 Urea-splitting organisms such as Proteus, however, tend to produce an alkaline urine. Methenamine is often given in combination with mandelic or hippuric acid because these two compounds are bacteriostatic and produce an acid urine. Currently available commercial preparations contain these two acids at such low concentrations that they are unable to affect urinary p H or inhibit bacteria; they do not therefore contribute to the antibacterial action of methenamine. 56 Besides, a i g dose of methenamine mandelate or methenamine hippurate contains only 48o mg of methenamine which is less than half the recommended dose. Methenamine is usually administered orally at a dose of I-2 g every 6 h. Acidifying agents such as ascorbic acid (4-I2 g/d) methionine (9-I2 g/d) or amonium chloride (3-4 g/d) may be required to reduce urine pH to the 5.o-5- 5 range. This is not usually necessary because normal urine in the absence of diuresis is sufficiently acid to liberate formaldehyde from methenamine. 57 Antibacterial activity is not present in urine within the renal pelvis or ureter because the transit time through the tubules and pelvis is too short to allow generation of enough formaldehyde.56 Methenamine therefore is suitable only for treating lower urinary tract infections. It is unlikely to be effective in the treatment of bacteriuria in patients with indwelling urinary catheters because the constant flow of urine from the bladder will prevent the accumulation of enough formaldehyde. Indeed many studies have failed to demonstrate the efficacy of methenamine in permanently catheterised patients, 58, 69 although it may be suitable for prophylaxis or treatment of bacteriuria in patients being intermittently catheterised provided that it is properly administered. In patients with systemic infections or infections involving the renal parenchyma, antimicrobial agents which achieve good concentrations in the blood and tissues are required. Selection should be based on the sensitivity pattern of the infecting organisms. Suitable drugs of first choice include ampicillin, co-trimoxazole, carbenicillin or a first generation cephalosporin. In catheter-associated infections involving Proteus, Providencia, Pseudomonas, Serratia and Klebsiella species, these antimicrobial agents, with the possible exception of carbeniciUin, are unlikely to be effective. It is therefore not surprising that such infections often require treatment with aminoglycosides.
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T h e use of aminoglycosides in patients with urinary catheters, however, often poses problems due to frequently co-existing renal failure and the consequent risks of nephrotoxocity and ototoxicity. In patients with renal failure, urinary concentrations of aminoglycosides may be considerably reduced and high concentrations of calcium and magnesium together with low urine p H may inhibit the activity of these drugs. ~° T h e use of aminoglycosides in catheterised patients has encouraged the emergence of gentamicin-resistant organisms which have been implicated in several epidemics of nosocomial infection. 4, 3a Widespread resistance of Gram-negative bacteria to aminoglycosides could have serious implications. Conditions which encourage the emergence of resistant organisms should therefore be avoided. T h e new broad-spectrum penicillins such as mezlocillin and piperacillin or the third generation cephalosporins such as cefotaxime or lactamoxef disodium may overcome some of the problems associated with the aminoglycosides. Most of these penicillins and cephalosporins achieve good urinary concentrations depite severe renal impairment and constant monitoring of the serum is not required. Nevertheless, selection of resistant organisms is likely to remain a major problem. T h e difficulties and frustrations of treating urinary tract infections in patients with urinary catheters emphasise the importance of preventive measures. S u m m a r y o f r e c o m m e n d a t i o n s for preventing infection in patients with indwelling urinary catheters
I. Indwelling urinary catheters should be inserted only when absolutely necessary and removed as soon as possible. Serious consideration should be given to intermittent catheterisation. 2. Use a pre-assembled closed sterile urinary drainage system if possible. Insertion of a catheter should be performed by properly trained staff using an aseptic technique and without disconnecting the drainage tube on the collecting bag from the pre-assembled unit. 3. T h e urinary drainage system should include a 'no touch' outlet tube on the collecting bag, an antireflux valve, a sealed catheter-drainage-tube junction, and an access port for irrigation. 4. Secure the collecting bag well below the level of the bladder, position the drainage tube to avoid kinks and tape the catheter to prevent traction. 5. E m p t y the collecting bag regularly. Wear sterile disposable gloves a n d / o r use a 'no touch' technique in order to avoid contamination of the outlet tube. T h e drainage system may be further protected by instilling 3o ml of a 3 % solution of hydrogen peroxide into the collecting bag through a suitable access port, or (by means of a syringe and needle) through the urine sampling site in the catheter. 6. Urine for culture should be aspirated from the distal end of the catheter or from a designated sample port by means of a sterile needle and syringe. Before aspiration, the puncture site must be disinfected with an alcoholic solution of iodine or plain alcohol. 7. Routine inspection of the drainage system so as to ensure unobstructed
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D.E. MACFARLANE d o w n h i l l flow o f u r i n e is i m p o r t a n t . M a l f u n c t i o n in a n y o n e a r e a r e q u i r e s replacement of the complete system. Disconnection and replacement of p a r t s o f t h e u r i n a r y d r a i n a g e s y s t e m c a r r y a s i g n i f i c a n t risk o f c o n tamination. F o r i r r i g a t i o n , u s e saline or a p o l y m y x i n - n e o m y c i n s o l u t i o n (4o m g n e o m y c i n , 2 o o , o o o u n i t s p o l y m y x i n / 1 saline) in c o n j u n c t i o n w i t h a c l o s e d d r a i n a g e s y s t e m t h a t h a s a sealed access p o r t * or a Y t u b e a t t a c h e d to a d o u b l e - l u m e n c a t h e t e r . 61 I f d i s c o n n e c t i o n o f t h e c a t h e t e r - d r a i n a g e - t u b e j u n c t i o n is u n a v o i d a b l e , u s e a n a s e p t i c t e c h n i q u e a n d a sterile s y r i n g e a n d i r r i g a t i o n fluid. A v o i d all u n n e c e s s a r y d i s c o n n e c t i o n s o f t h e c a t h e t e r drainage-tube junction. D a i l y p e r i n e a l toilet w i t h s o a p a n d w a t e r m a y b e beneficial. If any part ofthe urinary drainage system becomes contaminated the whole s y s t e m s h o u l d b e r e p l a c e d as s o o n as p o s s i b l e . B e f o r e r e m o v i n g t h e e x i s t i n g c a t h e t e r , instil 5o m l o f p o l y m y x i n - n e o m y c i n s o l u t i o n i n t o t h e bladder. P o s i t i o n p a t i e n t s w i t h i n d w e l l i n g u r i n a r y c a t h e t e r s as f a r a p a r t as p o s s i b l e , p a r t i c u l a r l y if t h e y h a v e b a c t e r i u r i a . A p p r o p r i a t e t r a i n i n g o f d o c t o r s a n d n u r s e s in g o o d c a t h e t e r c a r e t e c h n i q u e s is essential.
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I5. Moloney PJ, Doyle AA, Robinson BL, Fenster H, McLaughlin M G . Pathogenesis of infection in patients with acute spinal cord injury on intermittent catheterisation. -7 Urol 1981 ; Lz 5 : 672-673. I6. Mycrovitz RL, Meduros AA, O'Brien T F . Recent experience with bacillemia due to gram negative organisms. _7 Infect Dis I 9 7 I ; I24: 239-243. 17. Dupont H L , Spink W W . Infection due to gram negative organisms. An analysis of 86o patients with bacteremia at the University of Minnesota Medical Center 1958-1966. Medicine I969; 48: 3o7-315. I8. Helmholz H F . Determination of the bacterial content of the urethra. -7 Urol 195o; 64: I58--I62.
19. Kass EH, Schneiderman IJ. Entry of bacteria into the urinary tract of patients with inlying catheters. N Engl-7 Med I957; 256: 556-557. 20. Warren JW, Platt R, Thomas RJ, Rosner B, Kass EH. Antibiotic irrigation and catheter associated urinary tract infections. N Engl-7 Med 1978; 299:570-573 • 2 I. Platt R, Polk BF, Murdock B, Rosner B. Reduction of mortality associated with nosocomial urinary tract infections. Lancet I983 ; I : 893-897. 22. Thornton G F , Andriole VT. Bacteriuria during indwelling catheter drainageJAMA I97O; 2I 4 : 339-342. 23. Maki D G , Hennekens CH, Bennett JV. Prevention of catheter associated urinary tract infection, an additional measure. -TAMA 1972; :zii : i27o--i27 I. 24. Bran JL, Levinson ME, Kaye D. Entrance of bacteria into the female urinary bladder. New Engl-7 AIed 1972; 286: 626-629. 25. Cox CE, Hinman F Jr. Experiments with induced bacteriuria, vesical emptying and bacterial growth on the mechanism of bladder defence to infection. J Urol 1961 ; 86: 739-743. 26. Cobbs CG, Kaye O. Antibacterial mechanisms in the urinary bladder. Yale-7 Biol Med 1967; 4o : 93--97. 27. W e b b JK, Blandy JP. Closed urinary drainage into plastic bags containing antiseptic. Brit J Urol I968; 40: 585-588. 28. Mehrotra R M L . An experimental study of the vesical circulation during distension and in cystitis, ff Pathol Bact 1953; 66: 79-82. 29. Lapides J. Mechanisms of urinary tract infection. Urology I979; 14: 215-217. 30. Platt R, Polk BF, Murdock B, Rosner B. Outcome of low density growth during indwelling bladder catheterisation. Abstracts of I982 Interscience Conference on Antimicrobial Agents and Chemotherapy. Abst I96, Washington, Amer Soc Microbiol I982: xoo. 3 I. Warren JW, Tenney JH, Hoopes JM, Muncie H L , Anthony WC. A prospective study of bacteriuria in patients with chronic indwelling urinary catheters. J Infect Dis 1982; I46: 719-723 • 32. Dutton AAC, Rolston M. Urinary tract infections in a male urological ward. Lancet 1957; I : I I 5 - - I I 9.
33. Bryan CS, Parker E, Schoenlein PV, Northey J, Ely B, Joseph FJ. Plasmid mediated antibiotic resistance in a changing hospital environment; efficacy of control measures. Am -7 Infect Control 198o; 8: 65-71. 34. Martin CM, Vaquer F, Mayers MS. Prevention of gram negative rod bacteremia associated with indwelling urinary tract catheterisation. Antimicrob Agents Chemother 1963 ; 3 : 617-623. 35. Andriole VT. Hospital acquired urinary tract infections and the indwelling catheter. Urol Clin N A m e r 1975; z: 451-457. 36. Dukes CM. Urinary infections after excision of the rectum, their cause and prevention. Proc R Soc Med I928; 2z, I - I I . 37- Levin J. T h e incidence and prevention of infection after urethral catheterisation. Ann Intern Med 1964; 60: 914-922. 38. Thornton G F , Lytton B, Andriole VT. Bacteriuria during indwelling catheter drainage; effect of constant bladder rinse. J A M A 1966; I95: I79-183. 39. Gillespie WA, Lennon G G , Linton KB, Slade N. Prevention of urinary infections in gynaecology. Br Med J 1964; z: 423-425. 4 o. Gillespie WA, Simpson R, Jones J, Nashef L, Teasdale C, Speller DCE. Does the addition of disinfectant to urine drainage bags prevent infection in catheterised patients ? Lancet 1983 ; I : Io37-IO39.
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4 I. Maizels M, Schaefer AJ. Decreased incidence of bacteriuria associated with periodic instillation of hydrogen peroxide into the urethral catheter drainage bag. J Urol 1980; 123: 841-845 . 42. Maki D G , Hennekens CH, Phillips CW, Shaw WV, Bennett YV. l'4osocomial urinary tract infections with Serratia marcescens, an epidemiologic study.ff Infect Dis 1973; i28: 579-587. 43. T u r k M, Petersdorf RG. The role of antibiotics in the prevention of urinary tract infections. J Chronic Dis 1962; I5: 683-689. 44. Appleton D M , Waisbern BA. T h e prophylactic use of chloramphenicol in transurethral resections of the prostate, ff Urol I956; 75: 3o4-313. 45. Britt MR, Gariboldi RA, Miller WA, Herbertson R M , Burke JP. Antimicrobial prophylaxis of catheter associated bacteriuria. Antimicrob Agents Chemother 1977; I I : 240-243. 46. Allen JL, Rampone JF, Wheeless CR. Use of prophylactic antibodies in elective major gynaecologic operations. Obstet Gynecol I972; 39: 218-223. 47. Lindon R. T h e prevention of ascending catheter induced infection of the urinary tract. J Chronic Dis 1969; 22: 321-332. 48. Stoval CW, Miholdzie N, Lloyd FA. Incidence of renal bacteriurua in the presence of long standing bladder infections. Proceedings of Sixteenth Veterans Administration Spinal Cord Injury Conference. 1976: I72-I76. 49- Martin CM, Bookrajian EN. Bacteriuria prevention after indwelling urinary catheterisation, a controlled study_. Arch Intern Med I962; XlO: 707-71 I. 50. Ronald AR, Turck M, Petersdorf RG. A critical evaluation of naladixic acid in urinary tract infections. New EnglJ Med 1966; 275: IO8I-IO82. 51. Iravani A, Richard GA, Baer H, Fennell R. Comparative efficacy and safety of nalidixic acid versus trimethorpim/sulphamethoxazole in treatment of acute urinary tract infections in college age women. Antimicrob Agents Chemother 1981 ; x9: 548-604. 52. Stamey TA, Nemog NJ, Higgins M. T h e clinical use of Nalidixic acid. A review of observations. Invest Urol 1969; 6: 528-587. 53. Chisholm G D , Colman JS, Waterworth P. Antibacterial agents in renal lymph. Urinary Tract Infection, London Oxford Univ. Press, I968: I94-2I I. 54. Nicolaier A. Ueber die Therapeutische verwendung des urotropin (Hexamethylente tramin) Deut Med Wochenschr 1885; 2x: 54I. 55. Jackson J, Stamey TA. T h e Riker method for determining formaldehyde in the presence of methenamine. Invest Urol 1971 ; 9: I24-I27. 56. Stamey TA. General and specific principles of therapy. Urinary Infections, Baltimore, Williams and Wilkins, I972 : 253. 57. Elliott JS, Sharpe R F , Lewis L. Urinary P h . J Urol 1959; 8I : 339-342. 58. Gerstein AR, Otiun R, Gonick HC, Wilner H I , Kleenan CR, Maxwell M H . T h e prolonged use of Methenamine hippurate in the treatment of chronic urinary tract infection. J Urol I968; IOO: 767-772. 59- Vainrub B, Musher D M . Lack of effect of methenamine in suppression'of, or prophylaxis against chronic urinary infections. Antimicrob Agents Chemother 1977; I2: 625-627. 6o. Minuth JN, Masher D M , Thorstainsonn SB. Inhibition of the antibacterial activity of gentamicin by urine. J Infect Dis 1976; x33: I 4 - I 9 . 6I. Kunin CM. Detection, prevention and management of urinary tract infections, Philadelphia: Lea & Febiger, 1979: 182.
REVIEW ARTICLE
Prevention and treatment of catheter-associated tract infections
urinary
D . E. M a c f a r l a n e
Department of Microbiology, University of the West Indies, Kingston, Jamaica Accepted for publication 29 May 1984 Introduction
It has been estimated that urinary tract infections account for approximately 4o % of all hospital-acquired infections, 1 and that 75 % of all patients with nosocomial urinary tract infections have a history of urological instrumentation, usually catheterisation, before infection. 2 In some hospitals, catheter-associated urinary tract infections constitute a m i n i m u m of 1% of all hospital admissions? Moreover patients with urinary catheters are often colonised or infected with highly resistant organisms 4 which are then transmitted to other patients. 5 Indwelling urinary catheters therefore represent a major problem in nosocomial infection. i n c i d e n c e o f catheter-associated urinary tract infections
T h e incidence of bacteriuria after catheterisation depends on various features including method of insertion, duration of catheterisation, and type of drainage. Bacteriuria develops in I-5 % of patients with single short-term catheterisation; 5' ~ 50 % of patients with intermittent catheterisation 7, 8 and 93 % of patients with indwelling catheters and open drainage have bacteriuria after 4 days2 T h e use of a closed-drainage system may maintain urinary tract infection rates below 2o % for up to I4 days, provided that the sterility of the system is preserved? °,11 Since the risk of developing bacteriuria has been estimated to be 5-IO % for each day that a catheter is in situ 12' 1~most patients on long-term catheterisation eventually develop bacteriuria. Sequelae o f catheter-associated urinary tract infections
It is often assumed that urinary tract infections inevitably follow catheterisation, are usually benign, and will resolve on removal of the catheter. Unfortunately, many patients with urinary catheters are prone to complications that include acute pylonephritis, nephrolithiasis, cystolithiasis, epididymitis, abscess formation, vesicoureteral reflux and chronic interstitial renal failure. 14 In patients with spinal injuries, long-term catheterisation is associated with a mortality of 20-40 %.15 In some hospitals, catheter-associated urinary tract infections are the main cause of Gram-negative septicaemia, a potentially serious condition with a mortality of 20-50 % .16,17 Bacteriuria in a patient with an indwelling catheter may therefore have serious implications. oi63-4453/85/o2oo96 + I I $02.00/0
~ I985 The British Society for the Study of Infection
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E p i d e m i o l o g y o f catheter-associated urinary tract infections
Bacteria which colonise or infect the urinary tract of catheterised patients may be endogenous or exogenous. Organisms which constitute the normal colonic flora, or which colonise the gastrointestinal tract during a stay in hospital, may gain access to the urinary tract during insertion of a catheter 18 or by ascending from the catheter-meatal junction, via the fluid-filled space between the catheter and the urethral mucosa. 19 Exogenous organisms may gain access to the bladder via the junction of the catheter with the drainage tube or via the collecting bag. Failure to take precautions against infection when opening the catheter-drainage tube connection in order to irrigate the bladder is a well recognised source of contamination.2°, 21 Bacterial contamination of the collecting bag inevitably follows repeated openings required to drain the system, and usually precedes urinary tract infection, thereby indicating probable retrograde spread of bacteria from the bag to the bladder. TM 22 T h e marked reduction in urinary tract infections achieved with closed sterile drainage systems, 1°, 11 suggests that contamination of the drainage system is an important cause of infection in patients with indwelling urinary catheters. Although endogenous bacteria from the gastrointestinal tract have been implicated in catheter-associated urinary tract infections, 1° surveys indicate that many outbreaks of infection are caused by cross-infection. Endemic strains of Proteus, Providencia, Klebsiella, Pseudomonas and Serratia have been recovered from the hands of nursing staff in several studies, 4 and clustering of patients with catheters was noted to be a major risk factor. Separation of patients with urinary catheters is important in the control of nosocomial outbreaks of catheter-associated urinary tract infection and emphasises the role of cross-infection in the spread of infection. 23 P a t h o g e n e s i s o f catheter-associated urinary tract infections
T h e healthy urinary tract is normally sterile except for a few organisms present in the distal urethra. 24 Organisms that may ascend to the bladder are usually removed by intrinsic clearance mechanisms. 2~ Additional protection is offered by humoral immunity and the intact mucosa of the bladder which is resistant to infection unless damaged. 26 T h e urinary catheter with drainage-tube and collecting bag together represent an extension to the urinary tract and provide direct access to the bladder. Organisms entering this system may multiply rapidly in the stagnant urine of the collecting bag so as to reach a concentration > Io 9 organisms/1. 27 Thus, large numbers of bacteria have ready access to a urinary tract which is often predisposed to infection either because of the effects of the catheter, which may vary from irritation of the mucosa to trauma that results in an abscess, or as a result of surgical procedures or because of abnormalities of the urinary tract. Distension of the bladder often arises before catheterisation or may result from blockage of the catheter. Experimental work in animals has shown that prolonged increases in intravesical pressure may result in decreased blood flow and obstruction of capillaries, venules and arterioles, with extravasion of red blood cells 28 and even bleeding into the bladder. If this also happens in catheterised patients, areas of haemorrhage may
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be liable to infection by organisms which have ascended to the bladder via the urethra or the lumen of the indwelling catheter. According to Lapides, 29 this important predisposing factor in urinary tract infections explains why some patients with indwelling catheters develop infection, and others may have repeated episodes of bacteriuria without infection. B a c t e r i o l o g y o f c a t h e t e r - a s s o c i a t e d u r i n a r y tract i n f e c t i o n
Whereas multiple organisms in a midstream specimen of urine usually indicate contamination of the sample, bacteriuria with more than one species of organism is common in catheterised patients. T h e diagnosis of urinary tract infection is usually based on the number of organisms in a properly collected sample of urine. Counts of < IO8 colonyforming units (cfu)/1 of voided urine are often considered to indicate the presence of contaminating organisms derived from the anterior urethra or peri-meatal skin. 9 Similar criteria are sometimes applied to the diagnosis of urinary tract infections in patients with indwelling catheters. This seems illogical because catheter urine has not come into contact with the urethra. A count of < IO8 organisms/1 of urine may represent contamination from the catheter but any number of bacteria, however small, in the catheter may colonise or infect the bladder, thereby rendering such a finding significant. A recent study has shown that the recovery of IO6 cfu/1 of catheter urine often heralded subsequent microbial densities > IO8 cfu/1 of urine in patients with indwelling urinary catheters. 30 It may therefore be more appropriate to regard counts > IO6 cfu/1 as significant in catheter specimens of urine. Catheter-associated urinary tract infections are usually caused by members of the enterobacteriaceae. Staphylococci, streptococci and coryneforms may cause bacteriuria in catheterised patients, but do not usually persist in the bladder. 31 Conversely, Escherichia coli, Proteus, Klebsiella, Pseudomonas and Serratia species are often repeatedly cultured from the urine of catheterised patients over a period of several weeks, thereby indicating the ability of these organisms to colonise the urinary tract. 31 Organisms which are endemic in certain institutions often colonise or infect catheterised patients. For example, Providencia stuartii, an unusual urinary tract pathogen was recently listed in a study as the main cause of catheter-associated bacteriuria. 31 Organisms more commonly implicated in outbreaks of nosocomial catheter-associated urinary tract infection include Pseudomonas, Klebsiella, Proteus, Providencia and Serratia species, the latter having a tendency to be associated with outbreaks involving cross-infection. 4, 32. zz Patients with indwelling urinary catheters often have repeated episodes of bacteriuria. This may result in the repeated administration of antimicrobial agents and the emergence of highly resistant bacteria. Indiscriminate use of antimicrobial drugs has encouraged the emergence of multiresistant bacteria in many hospitals, and catheterised patients are at risk from cross-infection with these organisms. Outbreaks of nosocomial catheter-associated urinary tract infections are often caused by multiresistant bacteria. In a recent study of plasmid-mediated antibiotic resistance, multiresistant strains of Serratia marcescens, Klebsiella pneumoniae and Providencia rettgeri were recovered from
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36I patients over a period of 3 years. Almost all of these organisms were cultured from the urine o f patients with indwelling catheters. 3~ T h e same three organisms have been implicated in several other outbreaks of nosocomial catheter-associated urinary tract infections caused b y multiresistant bacteria. 4 Preventive
measures
Indwelling urinary catheters are often associated with illness and deathX4,15. 21, 34 and should n o t be used unless they are absolutely necessary. I n t e r m i t t e n t catheterisation should be considered as an alternative w h e n feasable. T h e clearly established advantages of a closed sterile drainage systemlO. 11.35, 36 make it m a n d a t o r y for patients w h o m u s t have an indwelling catheter. M o s t m o d e r n c o m m e r c i a l l y - p r o d u c e d urinary drainage systems consist of a sterile p r e a s s e m b l e d catheter, drainage tube, and collecting bag. T h e catheter should n o t be disconnected from these systems during insertion, as this is likely to result in contamination at the catheter-drainage t u b e junction. 21 Insertion of a sterile catheter and s u b s e q u e n t attachment o f a separate drainage t u b e and collecting bag is therefore contra-indicated. Before insertion of a catheter the peri-meatal skin should be cleansed with a suitable antiseptic solution, such as aqueous p o v i d o n e iodine. Aseptic catheter insertion is obviously important, TM 37 and is best achieved b y means of sterile packs containing drapes, gloves, lubricant jelly and a p r e a s s e m b l e d urinary drainage system. After insertion, the catheter m u s t be taped to p r e v e n t traction, the drainage-tube positioned in order to allow u n o b s t r u c t e d downhill flow, and the collecting bag secured below the patient so as to p r e v e n t its being inadvertently raised above the level of the bladder with c o n s e q u e n t retrograde flow of contaminated urine. Each time the closed sterile drainage system is breached, the risk of contamination increases. M o s t openings take place at the outlet t u b e where urine is e m p t i e d from the collecting bag. Organisms entering there are likely to come from hands o f nurses. Conversely, bacteria present in the drainage system m a y contaminate the hands of nurses e m p t y i n g the collecting bag. This m a y explain w h y outbreaks of hospital cross-infection are often associated with urinary catheters. 4 A l t h o u g h various ' n o t o u c h ' outlet tubes have been devised b y manufacturers, the most effective solution to this p r o b l e m is to ensure that nurses wear sterile disposable gloves w h e n e m p t y i n g urine bags and take care to avoid spillage. Sterile closed-drainage systems are often o p e n e d at the catheter-drainage-tube junction for bladder irrigation and occasionally for collecting specimens of urine. F o r patients likely to need f r e q u e n t irrigation, a triple-lumen catheter with n e o m y c i n p o l y m y x i n rinses is preferredfl 8 although the inclusion of an irrigation lumen in this system necessitates a narrower drainage-tube which is m o r e easily obstructed. Some urologists therefore prefer to use a closed irrigation system with a Y t u b e attached to a d o u b l e - l u m e n catheter similar to the system described b y D u k e s in I928. 36 T h i s system also benefits patients on long-term catheterisation, because daily irrigation with sterile water or saline, interspersed with p o l y m y x i n - n e o m y c i n rinses as required, m a y p r e v e n t
IOO
D . E . MACFARLANE
accumulation of a pool of stagnant urine in the bladder, and remove contaminating organisms. Alternatively, a semi-automatic, siphon-pressure, closed drainage system is commercially available.* Several commercial urinary collection systems have a sealed catheterdrainage-tube junction which cannot be opened accidentally; a break in the seal indicates any disconnections. Using such a system, Platt and colleagues demonstrated a significant reduction in urinary tract infection and mortality, compared with urinary drainage systems which did not have this facility. 21 T h e i r study once again emphasised the importance of the catheter-drainage-tube junction as a portal of entry for bacteria. Disconnections, however, are sometimes necessary for irrigation when an aseptic technique should be used, and irrigation performed with a sterile syringe and neomycin-polymyxin solution. T h e catheter-drainage-tube junction should never be disconnected for the collection of urine samples. Instead, after clamping the drainage tube, and disinfecting the puncture site with an alcoholic solution of iodine or plain alcohol, urine should be aspirated by means of a sterile needle and syringe either through a sample port or via the distal end of the catheter. Growth of contaminating organisms in the collecting bag' may be inhibited by the presence of a disinfectant. At one time, formalin was added to glass collecting bottles. 3a More recently, Gillespie and colleagues4° have shown that chlorhexidine can maintain sterility in drainage bags. Others have shown that periodic instillation of 3o ml of a 3 % solution of hydrogen peroxide into the drainage reservoir prevented bacteria growth in the collecting bag and significantly delayed the onset of bacteriuria. 41 Disinfectmxts which maintain the sterility of the collecting bag obviously prevent the ascent of bacteria from the drainage bag to the bladder and in addition may considerably reduce cross-infection in catheterised patients. Most modern drainage systems contain an air lock or valve. Although these devices prevent reflux of urine from the collecting bag to the bladder, they do not halt the ascent of bacteria. This probably explains the failure of several authors to demonstrate reduced infection rates when collecting bags with drip chambers, air locks or one-way valves have been used. 13, ~2 Because patients who require long-term catheterisation are at such serious risk of infection, intermittent catheterisation has been proposed. Based on the premise that a healthy intact bladder is capable of eliminating small numbers of bacteria, Lapides devised a system of intermittent clean catheterisation. 8 Patients with obstructive uropathy, decompensated detrussor, or a neuropathic bladder have been taught how to insert a clean urinary catheter while observing normal standards of personal hygiene and with emphasis on regular emptying of the bladder. During long-term surveillance of 218 patients, the incidence of bacteriuria was reduced from 90 % to 48 %, and complications were few. In a spinal injuries unit Guttman and coUeagues7 used repeated intermittent sterile catheterisation as an alternative to indwelling catheters and thereby reduced the incidence of bacteriuria to 50 %. T h e use of prophylactic antibiotics in patients with indwelling urinary catheters is contentious. Some authors have failed to demonstrate any reduction * Cystamat, Leo Pharmaceuticals, Copenhagen, Denmark.
Urinary Tract Infections
Ioi
in infection rates42, 43,44 while others have claimed a reduced incidence of bacteriuria.45, 46 T h e results of these studies will have been markedly influenced by choice of antibiotic, sensitivity patterns of urinary isolates, duration of catheterisation and catheter-care techniques. If prophylactic agents are considered necessary they should be limited to locally acting ones such as nalidixic acid, nitrofurantoin or methenamine hexamine. Disadvantages of prophylactic antibiotics include adverse reactions, increased costs and selection of resistant organisms. In addition, prophylactic antibiotics are unlikely to protect patients from multiresistant organisms. Because maintenance of a sterile urinary drainage system depends on strict observation of correct precedures, adequate training and supervision of doctors and nurses responsible for patients with indwelling urinary catheters are essential. In an attempt to achieve a high standard of catheter care, some authors have recommended the formation of catheter care teams which have total responsibility for the insertion of catheters and their maintenance. 47 Although this is an excellent idea, it is unlikely to be practical in small hospitals having only a few patients with urinary catheters. T r e a t m e n t o f u r i n a r y tract i n f e c t i o n s in c a t h e t e r i s e d p a t i e n t s
Bacteriuria in a catheterised patient indicates that the urinary tract has become colonised or infected. Colonisation may be distinguished from infection by the lack of pus cells in the urine and the absence of clinical symptoms. Infection is usually confined to the lower urinary tract except in those patients with vesicoureteric reflux or evidence of pyelographic renal or ureteric abnormalities. 14, 48Because bacteraemia and septicaemia commonly complicate urinary tract infections in patients in hospital, blood should always be cultured from patients with suspected systemic infection. Although bacteriuria alone does not necessarily imply infection, it does indicate that the urinary drainage system has become contaminated, and should be replaced. Colonisation often preceeds infection, and colonised patients represent a serious cross-infection hazard. 42 Organisms may be removed from the bladder by instilling 5o ml of a polymyxin-neomycin solution (4o mg neomycin, 2oo,ooo units polymyxin/1 saline) into the bladder through the existing catheter. 49 Following this procedure, the entire contaminated drainage system should be removed, and a new sterile system aseptically installed. As a further precaution, 30 ml of a solution of hydrogen peroxide may be added to the drainage bag. Nalidixic acid is active against a wide range of Gram-negative bacteria • including most urinary pathogens except Pseudomonas species. It is not active against Gram-positive organisms. It has been claimed that bacteria may often become resistant during a course of treatment and repeated cultures of urine and sensitivity testing have therefore been advocated. 5oRecent studies however do not support this contention. 51 Urine concentrations of active drug between Ioo and 5oo mg/1 are achieved after giving I g nalidixic acid orally every 6 h. Such concentrations are well in excess of the 16 m g / l required to inhibit most bacteria. Increased toxicity has not been observed in patients with advanced renal failure given normal doses ofnalidixic acid, and bactericidal concentrations can be maintained in their urine. 52
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Nitrofurantoin is active against most Gram-negative and Gram-positive organisms except Pseudomonas and Proteus species. After an oral dose of xoo mg every 6 h, urine concentrations range from 5o to 2oo mg/1. T h e activity of nitrofurantoin is decreased in alkaline urine. Recovery of the drug from urine is directly related to creatinine clearance and urine concentrations in uraemic patients may be inadequate to inhibit some bacteria. When the creatinine clearance is < 60 m l / m i n , the drug will accumulate in the serum, thereby increasing the possibility of systemic toxicity, especially peripheral neuropathy. Nitrofurantoin is one of the few antibacterial drugs to achieve higher concentrations in renal lymph than in the blood 5a and is therefore suitable for treating both upper and lower urinary tract infections. Methenamine was first introduced by Nicolaier in 1895 for treating urinary tract infections. 54 It is available either as the pure base or in combination with mandelic acid or hippuric acid. Methenamine itself has no antibacterial activity, but at an acid pH is hydrolysed to ammonia and to a bactericidal concentration of formaldehyde35 Most bacteria are inhibited by 2o mg/1 of formaldehyde.~6 Urea-splitting organisms such as Proteus, however, tend to produce an alkaline urine. Methenamine is often given in combination with mandelic or hippuric acid because these two compounds are bacteriostatic and produce an acid urine. Currently available commercial preparations contain these two acids at such low concentrations that they are unable to affect urinary p H or inhibit bacteria; they do not therefore contribute to the antibacterial action of methenamine. 56 Besides, a i g dose of methenamine mandelate or methenamine hippurate contains only 48o mg of methenamine which is less than half the recommended dose. Methenamine is usually administered orally at a dose of I-2 g every 6 h. Acidifying agents such as ascorbic acid (4-I2 g/d) methionine (9-I2 g/d) or amonium chloride (3-4 g/d) may be required to reduce urine pH to the 5.o-5- 5 range. This is not usually necessary because normal urine in the absence of diuresis is sufficiently acid to liberate formaldehyde from methenamine. 57 Antibacterial activity is not present in urine within the renal pelvis or ureter because the transit time through the tubules and pelvis is too short to allow generation of enough formaldehyde.56 Methenamine therefore is suitable only for treating lower urinary tract infections. It is unlikely to be effective in the treatment of bacteriuria in patients with indwelling urinary catheters because the constant flow of urine from the bladder will prevent the accumulation of enough formaldehyde. Indeed many studies have failed to demonstrate the efficacy of methenamine in permanently catheterised patients, 58, 69 although it may be suitable for prophylaxis or treatment of bacteriuria in patients being intermittently catheterised provided that it is properly administered. In patients with systemic infections or infections involving the renal parenchyma, antimicrobial agents which achieve good concentrations in the blood and tissues are required. Selection should be based on the sensitivity pattern of the infecting organisms. Suitable drugs of first choice include ampicillin, co-trimoxazole, carbenicillin or a first generation cephalosporin. In catheter-associated infections involving Proteus, Providencia, Pseudomonas, Serratia and Klebsiella species, these antimicrobial agents, with the possible exception of carbeniciUin, are unlikely to be effective. It is therefore not surprising that such infections often require treatment with aminoglycosides.
Urinary Tract Infections
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T h e use of aminoglycosides in patients with urinary catheters, however, often poses problems due to frequently co-existing renal failure and the consequent risks of nephrotoxocity and ototoxicity. In patients with renal failure, urinary concentrations of aminoglycosides may be considerably reduced and high concentrations of calcium and magnesium together with low urine p H may inhibit the activity of these drugs. ~° T h e use of aminoglycosides in catheterised patients has encouraged the emergence of gentamicin-resistant organisms which have been implicated in several epidemics of nosocomial infection. 4, 3a Widespread resistance of Gram-negative bacteria to aminoglycosides could have serious implications. Conditions which encourage the emergence of resistant organisms should therefore be avoided. T h e new broad-spectrum penicillins such as mezlocillin and piperacillin or the third generation cephalosporins such as cefotaxime or lactamoxef disodium may overcome some of the problems associated with the aminoglycosides. Most of these penicillins and cephalosporins achieve good urinary concentrations depite severe renal impairment and constant monitoring of the serum is not required. Nevertheless, selection of resistant organisms is likely to remain a major problem. T h e difficulties and frustrations of treating urinary tract infections in patients with urinary catheters emphasise the importance of preventive measures. S u m m a r y o f r e c o m m e n d a t i o n s for preventing infection in patients with indwelling urinary catheters
I. Indwelling urinary catheters should be inserted only when absolutely necessary and removed as soon as possible. Serious consideration should be given to intermittent catheterisation. 2. Use a pre-assembled closed sterile urinary drainage system if possible. Insertion of a catheter should be performed by properly trained staff using an aseptic technique and without disconnecting the drainage tube on the collecting bag from the pre-assembled unit. 3. T h e urinary drainage system should include a 'no touch' outlet tube on the collecting bag, an antireflux valve, a sealed catheter-drainage-tube junction, and an access port for irrigation. 4. Secure the collecting bag well below the level of the bladder, position the drainage tube to avoid kinks and tape the catheter to prevent traction. 5. E m p t y the collecting bag regularly. Wear sterile disposable gloves a n d / o r use a 'no touch' technique in order to avoid contamination of the outlet tube. T h e drainage system may be further protected by instilling 3o ml of a 3 % solution of hydrogen peroxide into the collecting bag through a suitable access port, or (by means of a syringe and needle) through the urine sampling site in the catheter. 6. Urine for culture should be aspirated from the distal end of the catheter or from a designated sample port by means of a sterile needle and syringe. Before aspiration, the puncture site must be disinfected with an alcoholic solution of iodine or plain alcohol. 7. Routine inspection of the drainage system so as to ensure unobstructed
IO4
8.
9. IO.
i i. I2.
D.E. MACFARLANE d o w n h i l l flow o f u r i n e is i m p o r t a n t . M a l f u n c t i o n in a n y o n e a r e a r e q u i r e s replacement of the complete system. Disconnection and replacement of p a r t s o f t h e u r i n a r y d r a i n a g e s y s t e m c a r r y a s i g n i f i c a n t risk o f c o n tamination. F o r i r r i g a t i o n , u s e saline or a p o l y m y x i n - n e o m y c i n s o l u t i o n (4o m g n e o m y c i n , 2 o o , o o o u n i t s p o l y m y x i n / 1 saline) in c o n j u n c t i o n w i t h a c l o s e d d r a i n a g e s y s t e m t h a t h a s a sealed access p o r t * or a Y t u b e a t t a c h e d to a d o u b l e - l u m e n c a t h e t e r . 61 I f d i s c o n n e c t i o n o f t h e c a t h e t e r - d r a i n a g e - t u b e j u n c t i o n is u n a v o i d a b l e , u s e a n a s e p t i c t e c h n i q u e a n d a sterile s y r i n g e a n d i r r i g a t i o n fluid. A v o i d all u n n e c e s s a r y d i s c o n n e c t i o n s o f t h e c a t h e t e r drainage-tube junction. D a i l y p e r i n e a l toilet w i t h s o a p a n d w a t e r m a y b e beneficial. If any part ofthe urinary drainage system becomes contaminated the whole s y s t e m s h o u l d b e r e p l a c e d as s o o n as p o s s i b l e . B e f o r e r e m o v i n g t h e e x i s t i n g c a t h e t e r , instil 5o m l o f p o l y m y x i n - n e o m y c i n s o l u t i o n i n t o t h e bladder. P o s i t i o n p a t i e n t s w i t h i n d w e l l i n g u r i n a r y c a t h e t e r s as f a r a p a r t as p o s s i b l e , p a r t i c u l a r l y if t h e y h a v e b a c t e r i u r i a . A p p r o p r i a t e t r a i n i n g o f d o c t o r s a n d n u r s e s in g o o d c a t h e t e r c a r e t e c h n i q u e s is essential.
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