Ultrastructure of Proteus mirabilis swarmer cell rafts and role of swarming in catheter-associated urinary tract infection

Proteus mirabilis is a common cause of catheter-associated urinary tract infection (C-UTI). It blocks indwelling urethral catheters through the formation of extensive crystalline biofilms. The obstruction of urine flow can induce episodes of pyelonephritis, septicemia, and shock. P. mirabilis exhibits a type of motility referred to as swarming, in which multicellular rafts of elongated, hyperflagellated swarmer cells form and move rapidly in concert over solid surfaces. It has been suggested that swarming is important in the pathogenesis of C-UTI. In this study we generated a set of stable transposon mutants deficient in swarming and used them to assess the role of swarming in the migration of P. mirabilis over urinary catheters. Swarming was found to be essential for migration over all-silicone catheters. Swarming-deficient mutants were attenuated in migration over hydrogel-coated latex catheters, but those capable of swimming motility were able to move over and infect these surfaces. A novel vapor fixation technique for the preparation of specimens and scanning electron microscopy were used to resolve the ultrastructure of P. mirabilis multicellular rafts. The flagellar filaments of P. mirabilis were found to be highly organized during raft migration and were interwoven in phase to form helical connections between adjacent swarmer cells. Mutants lacking these novel organized structures failed to swarm successfully. We suggest that these structures are important for migration and formation of multicellular rafts. In addition, the highly organized structure of multicellular rafts enables P. mirabilis to initiate C-UTI by migration over catheter surfaces from the urethral meatus into the bladder.     

Evaluation of the discriminatory powers of the Dienes test and ribotyping as typing methods for Proteus mirabilis

A total of 63 clinical isolates of Proteus mirabilis collected over a 19-month period were typed by the Dienes test and ribotyping. Ribotyping was performed using the fully automated RiboPrinter Microbial Characterization System (Qualicon, Wilmington, Del.). Isolates that were indistinguishable by the Dienes test and/or ribotyping were characterized further by pulsed-field gel electrophoresis (PFGE). Most of the isolates represented unique strains as judged by the Dienes test and ribotyping. Forty isolates represented 40 different ribotypes and Dienes types. The remaining 23 isolates were grouped into 13 Dienes types, 12 ribotypes, and 14 PFGE types. The index of discrimination was 0.980 for the Dienes test, 0.979 for ribotyping, and 0.992 for PFGE. Both the Dienes test and ribotyping are useful methods for identifying individual strains of P. mirabilis. The Dienes test is simple, inexpensive, and easy to perform. It can be performed in virtually any laboratory and should be used in the initial epidemiologic characterization of P. mirabilis isolates.     

Bacterial adherence to bladder uroepithelial cells in catheter-associated urinary tract infection

To assess the role of bacterial adherence to uroepithelial cells in the pathogenesis of nosocomial urinary tract infection, we prospectively studied 55 patients with indwelling urinary catheters. We obtained uroepithelial cells from the bladder and urine for culture on the patients' entry into the study and every two to four days during catheterization. In all, 235 collections of uroepithelial cells from these patients were used in an in vitro adherence assay with six gram-negative bacterial strains. With uroepithelial cells from patients who did not have bacterial infections, the adherence of the bacteria used in the assay differed significantly according to species. The least adherence occurred with Escherichia coli GR12; the adherence increased with (in order) Proteus mirabilis, E. coli J96, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa. With cells collected just before the onset of bacteriuria, adherence of these gram-negative strains was higher in patients in whom gram-negative rod infections developed than in those with gram-positive coccal infections (P = 0.005). Analysis with the Cox proportional-hazards model demonstrated that a significant increase in bacterial adherence to uroepithelial cells in the bladder occurred two to four days before the onset of bacteriuria, but that adherence returned to base-line values with the onset of bacteriuria. These results suggest that a transient increase in the adherence of gram-negative bacteria to bladder epithelial cells may be an important early event in the development of catheter-associated bacteriuria.     

Studies on the formation of crystalline bacterial biofilms on urethral catheters

A model of the catheterised bladder was used to test the ability of urease-producing urinary tract pathogens to encrust urethral catheters. Encrustation was assessed by determining the amounts of calcium and magnesium deposited on the catheters and visualised by scanning electron microscopy. Urease-positiveMorganella morganii, Klebsiella pneumoniae, andPseudomonas aeruginosa failed to raise the urinary pH and form crystalline biofilms. In contrast, strains ofProteus mirabilis, Proteus vulgaris, andProvidencia rettgeri generated alkaline urine (pH 8.3–8.6) and extensive catheter encrustation within 24 h.     

Mannose-resistant Proteus-like fimbriae are produced by most Proteus mirabilis strains infecting the urinary tract, dictate the in vivo localization of bacteria, and contribute to biofilm formation

Proteus mirabilis, an etiologic agent of complicated urinary tract infections, expresses mannose-resistant Proteus-like (MR/P) fimbriae whose expression is phase variable. Here we examine the role of these fimbriae in biofilm formation and colonization of the urinary tract. The majority of wild-type P. mirabilis cells in transurethrally infected mice produced MR/P fimbriae. Mutants that were phase-locked for either constitutive expression (MR/P ON) or the inability to express MR/P fimbriae (MR/P OFF) were phenotypically distinct and swarmed at different rates. The number of P. mirabilis cells adhering to bladder tissue did not appear to be affected by MR/P fimbriation. However, the pattern of adherence to the bladder surface was strikingly different. MR/P OFF colonized the lamina propria underlying exfoliated uroepithelium, while MR/P ON colonized the luminal surfaces of bladder umbrella cells and not the exfoliated regions. Wild-type P. mirabilis was usually found colonizing intact uroepithelium, but it occasionally adhered to exfoliated areas. MR/P ON formed significantly more biofilm than either P. mirabilis HI4320 (P = 0.03) or MR/P OFF (P = 0.05). MR/P OFF was able to form a biofilm similar to that of the wild type. MR/P ON formed a three-dimensional biofilm structure as early as 18 h after the initiation of the biofilm, while MR/P OFF and the wild type did not. After 7 days, however, P. mirabilis HI4320 formed a 65-mum-thick biofilm, while the thickest MR/P ON and MR/P OFF biofilms were only 12 mum thick. We concluded that MR/P fimbriae are expressed by most P. mirabilis cells infecting the urinary tract, dictate the localization of bacteria in the bladder, and contribute to biofilm formation.     

Serotyping and the Dienes reaction on Proteus mirabilis from hospital infections

The serotype of 320 strains of Proteus mirabilis from clinical material was determined. Using 20 O antisera and four H antisera 61% of strains could be fully identified and 90% partially identified. A large number of serotypes were recognized but no difference was found between the serotype of organisms infecting the urinary tract and those from other infections. Biochemically identical organisms found in the same ward generally differed in serology. Proteus mirabilis was isolated from the faeces of 84.5% of 84 patients with urinary infection and from none of 20 normal controls. By serology and the Dienes test 61% of the organisms isolated from the urine and faeces of a single patient were identical, indicating that infection arose from the intestine.Most groups of serologically identical strains could, by the Dienes test, be further divided into a number of subtypes indicating that the strains were different and that cross infection had not been responsible for their spread. With three serological groups, however, the majority of strains belonged to a single Dienes type and it was concluded that these organisms had been spread from a common reservoir or carrier.Because of the unreliability of the Dienes test when carried out on random organisms it is suggested that reliable results can only be obtained by combining the Dienes test with serotyping.     

Elucidating the Genetic Basis of Crystalline Biofilm Formation in Proteus mirabilis

Proteus mirabilis forms extensive crystalline biofilms on urethral catheters that occlude urine flow and frequently complicate the management of long-term-catheterized patients. Here, using random transposon mutagenesis in conjunction with in vitro models of the catheterized urinary tract, we elucidate the mechanisms underpinning the formation of crystalline biofilms by P. mirabilis. Mutants identified as defective in blockage of urethral catheters had disruptions in genes involved in nitrogen metabolism and efflux systems but were unaffected in general growth, survival in bladder model systems, or the ability to elevate urinary pH. Imaging of biofilms directly on catheter surfaces, along with quantification of levels of encrustation and biomass, confirmed that the mutants were attenuated specifically in the ability to form crystalline biofilms compared with that of the wild type. However, the biofilm-deficient phenotype of these mutants was not due to deficiencies in attachment to catheter biomaterials, and defects in later stages of biofilm development were indicated. For one blocking-deficient mutant, the disrupted gene (encoding a putative multidrug efflux pump) was also found to be associated with susceptibility to fosfomycin, and loss of this system or general inhibition of efflux pumps increased sensitivity to this antibiotic. Furthermore, homologues of this system were found to be widely distributed among other common pathogens of the catheterized urinary tract. Overall, our findings provide fundamental new insight into crystalline biofilm formation by P. mirabilis, including the link between biofilm formation and antibiotic resistance in this organism, and indicate a potential role for efflux pump inhibitors in the treatment or prevention of P. mirabilis crystalline biofilms.     

Virulence genes and antimicrobial resistance pattern in Proteus mirabilis strains isolated from patients attended with urinary infections to Tertiary Hospitals,in Iran

BackgroundProteus mirabilis is a frequent reason for catheter-associated urinary tract infections (UTIs). The aim of this study was to identify virulence genes and antimicrobial resistance patterns in P. mirabilis strains isolated from patients who attended a tertiary hospital in Iran.MethodsIn this study, 100 P. mirabilis strains from urine samples were isolated. These isolated strains were identified by biochemical and PCR-based tests, and their antibiotic resistance was profiled through a standard procedure using 14 antibiotics. PCR assays were used to detect virulence-related genes in P. mirabilis strains. The biofilm formation of each P. mirabilis strain was examined.ResultsOf the 100 P. mirabilis isolates, 16 (16%) were multidrug-resistant. High resistance was observed against cotrimoxazole (97%), nalidixic acid (93%), cefotaxime (77%), and amoxicillin (62%). Sixty of the 100 isolates showed resistance against extended-spectrum cephalosporins. The prevalence rates of the genes related to the virulence factors in this study were mrpH (100%), ucaA (91%), hpmA (94%), zapA (95%), ptaA (100%), ureG (100%), pmfA (100%), fliC (97%), and mrpA (90%) using PCR method. Strong biofilm formation was observed in 20% (5/25) of the strains isolated from non-catheterized samples and 80% (20/25) of strains isolated from catheterized samples.ConclusionsResistance to antibiotics and the prevalence of pathogenicity genes are high in Proteus mirabilis strains iolated from UTIs.     

Visualization of Proteus mirabilis morphotypes in the urinary tract: the elongated swarmer cell is rarely observed in ascending urinary tract infection

Proteus mirabilis, a common cause of nosocomial and catheter-associated urinary tract infection, colonizes the bladder and ascends the ureters to the proximal tubules of the kidneys, leading to the development of acute pyelonephritis. P. mirabilis is capable of swarming, a form of multicellular behavior in which bacteria differentiate from the short rod typical of members of the family Enterobacteriaceae, termed the swimmer cell, into hyperflagellated elongated bacteria capable of rapid and coordinated population migration across surfaces, called the swarmer cell. There has been considerable debate as to which morphotype predominates during urinary tract infection. P. mirabilis(pBAC001), which expresses green fluorescent protein in both swimming and swarming morphotypes, was constructed to quantify the prevalence of each morphotype in ascending urinary tract infection. Transurethral inoculation of P. mirabilis(pBAC001) resulted in ascending urinary tract infection and kidney pathology in mice examined at both 2 and 4 days postinoculation. Using confocal microscopy, we were able to investigate the morphotypes of the bacteria in the urinary tract. Of 5,087 bacteria measured in bladders, ureters, and kidneys, only 7 (0.14%) were identified as swarmers. MR/P fimbria expression, which correlates with the swimmer phenotype, is prevalent on bacteria in the ureters and bladder. We conclude that, by far, the predominant morphotype present in the urinary tract during ascending infection is the short rod-the swimmer cell.     

The production and activity in vivo of Proteus mirabilis IgA protease in infections of the urinary tract

Immunoblotting of urine from 21 patients of both sexes and of wide age range who had a Proteus mirabilis urinary tract infection (UTI) showed that 14 (64%) specimens contained immunoglobulin A (IgA). In nine (64%) of these the IgA heavy chain had been degraded to fragments of a size identical to those formed when purified IgA was degraded by pure P. mirabilis protease. Urine from patients with clinical evidence of upper UTI contained fragmented IgA and in some of these urine samples P. mirabilis protease activity was detectable. Urine infected with a non-proteolytic strain contained only intact IgA. It is concluded that P. mirabilis IgA protease is produced and is active during infections of the urinary tract.     

Development of an "early warning" sensor for encrustation of urinary catheters following Proteus infection

Biofilm formation in long-term urinary catheterized patients can lead to encrustation and blockage of urinary catheters with serious clinical complication. Catheter encrustation stems from infection with urease-producing bacteria, particularly Proteus mirabilis. Urease generates ammonia from urea, and the elevated pH of the urine results in crystallization of calcium and magnesium phosphates, which block the flow of urine. The aim of this research is to develop an "early warning" silicone sensor for catheter encrustation following bacterial infection of an in vitro bladder model system. The in vitro bladder model was infected with a range of urease positive and negative bacterial strains. Developed sensors enabled catheter blockage to be predicted ~17-24 h in advance of its occurrence. Signaling only occurred following infection with urease positive bacteria and only when catheter blockage followed. In summary, sensors were developed that could predict urinary catheter blockage in in vitro infection models. Translation of these sensors to a clinical environment will allow the timely and appropriate management of catheter blockage in long-term catheterized patients.     

Role of bacterial growth rates in the epidemiology and pathogenesis of urinary infections in women.

The mean minimum generation time in shake culture in urine of 6 urinary isolates of Escherichia coli (21.7 +/- 0.6 min) was significantly shorter (P = 0.0003) than that of 14 isolates of less common urinary pathogens (46.0 +/- 18.6 min). Mixed populations of approximately equal numbers of E. coli cells paired with other urinary, fecal, and urethral organisms were introduced into a laboratory model of the lower human urinary tract. This model used urine as a medium and reproduced some features of the balance between bacterial growth and the flushing effect of urine. After 24 h E. coli formed greater than or equal to 99% of the bacterial population in the bladder model for 16 our of 18 pairs of isolates examined. Relatively high oxygen tensions in urine sample from 18 healthy women (10.9 +/- 22. kPA) and 18 infected patients (8.0 +/- 4.3 kPa) may explain why anaerobic urinary infections are uncommon. The rapid growth rate of E. coli may be one explanation why it is the commonest cause of urinary infection even though it is relatively uncommon at the urethral meatus.     

Noninvasive biophotonic imaging for monitoring of catheter-associated urinary tract infections and therapy in mice

Urinary tract infections (UTIs) are among the most common bacterial infections acquired by humans, particularly in catheterized patients. A major problem with catheterization is the formation of bacterial biofilms on catheter material and the risk of developing persistent UTIs that are difficult to monitor and eradicate. To better understand the course of UTIs and allow more accurate studies of in vivo antibiotic efficacy, we developed a catheter-based biofilm infection model with mice, using bioluminescently engineered bacteria. Two important urinary tract pathogens, Pseudomonas aeruginosa and Proteus mirabilis, were made bioluminescent by stable insertion of a complete lux operon. Segments of catheter material (precolonized or postimplant infected) with either pathogen were placed transurethrally in the lumen of the bladder by using a metal stylet without surgical manipulation. The bioluminescent strains were sufficiently bright to be readily monitored from the outside of infected animals, using a low-light optical imaging system, including the ability to trace the ascending pattern of light-emitting bacteria through ureters to the kidneys. Placement of the catheter in the bladder not only resulted in the development of strong cystitis that persisted significantly longer than in mice challenged with bacterial suspensions alone but also required prolonged antibiotic treatment to reduce the level of infection. Treatment of infected mice for 4 days with ciprofloxacin at 30 mg/kg of body weight twice a day cured cystitis and renal infection in noncatheterized mice. Similarly, ciprofloxacin reduced the bacterial burden to undetectable levels in catheterized mice but did not inhibit rebound of the infection upon cessation of antibiotic therapy. This methodology easily allows spatial information to be monitored sequentially throughout the entire disease process, including ascending UTI, treatment efficacy, and relapse, all without exogenous sampling, which is not possible with conventional methods.     

Antibiotic resistance ofPseudomonas aeruginosa colonizing a urinary catheter in vitro

A modified Robbins Device was used to establish coherent biofilms ofPseudomonas aeruginosa on the surface of catheter material in an artificial urine milieu and the ability of an antibiotic to penetrate the biofilm and kill the enclosed bacteria was assessed. ThePseudomonas aeruginosa strain used had been isolated from a patient with urinary tract infection. Although planktonic (floating) cells of thePseudomonas aeruginosa strain were inhibited by less than 1 mg/l of tobramycin and killed by 50 mg/l, contact with 1,000 mg/l of tobramycin for 12 h failed to kill all the sessile (adherent) bacteria in the biofilms on the surface of the catheter material. Surviving sessile bacteria recovered directly from the exposure to 1,000 mg/l of tobramycin were inhibited by 0.4 mg/l of this agent when tested as dispersed planktonic cells by standard MIC methods. It is suggested that growth within thick adherent biofilms confers upon cells ofPseudomonas aeruginosa a large measure of resistance to aminoglycosides and other antibiotics that may help to explain the frequent failure of antibiotic chemotherapy in catheter-associated urinary tract infections.     

输尿管支架细菌生物膜观察及病原菌分布和耐药性

文题释义：细菌生物膜：细菌及其细胞外产物在载体表面聚集形成的一种有序群落，其主要成分为多糖蛋白复合物，是多种细菌相互粘连而产生得具有特定结构的细菌复合体。细菌生物膜分3层：连接膜附着于组织或生物材料表面；基底膜包含致密的菌群；表面膜为最外层，浮游菌可从其表面被释放后自由飘浮和播散。微菌落是生物膜的基本结构单位，微菌落相互融合连接形成大片均一的生物膜。  导管相关性尿路感染：导尿管相关尿路感染主要是指患者留置导尿管后或者拔除导尿管48 h内发生的泌尿系统感染。 背景：输尿管支架被广泛用于肾盂输尿管交界处狭窄、原位尿流改道重建、输尿管或肾镜碎石、肾移植和肿瘤等泌尿系疾病，但长期留置输尿管支架可导致导管相关性尿路感染等并发症。 目的：观察输尿管支架表面细菌生物膜的形态学特点，分析细菌生物膜的病原学分布特征及耐药性。 方法：收集2016年1至12月重庆医科大学附属永川医院127例患者的输尿管支架标本，扫描电镜观察支架表面细菌生物膜的形态学特征，刚果红培养基分别筛选肾盂段、输尿管段和膀胱段支架的细菌生物膜菌株，同时进行尿培养，对检出的病原菌进行药敏试验分析。实验获得重庆医科大学附属永川医院伦理委员会批准，批准号：2014年科伦审22号。 结果与结论：①在留置7，15，30 d的输尿管支架表面均能够观察到细菌生物膜及数量不等的炎性附着物或结晶体，细菌生物膜的细菌被大量纤维膜包裹；留置7，15 d的输尿管支架表面可见呈片状散在分布的菌落，以杆菌为主；留置30 d的输尿管支架表面可见呈堆状分布的菌落，以球菌、杆菌为主；②127份输尿管支架标本中检出细菌生物膜106份，阳性率为83.5%，其中膀胱段阳性率最高，其次为肾盂段和输尿管段；尿培养阳性为25份，阳性率为19.7%，尿液培养的细菌生物膜阳性率明显低于输尿管支架培养结果(P < 0.05)；③106份阳性标本中检出细菌227株，其中革兰阴性菌株数显著高于革兰阳性菌株数(P < 0.05)；输尿管支架细菌生物膜和尿培养细菌均主要以大肠杆菌、铜绿假单胞菌、粪肠球菌和屎肠球菌最为常见；④输尿管支架管表面细菌生物膜菌株的耐药率高；⑤结果表明输尿管支架细菌生物膜是诱发导管相关性尿路感染的重要因素。 ORCID: 0000-0001-9204-7321(张家模) 中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程     

Is Escherichia coli urinary tract infection a zoonosis? Proof of direct link with production animals and meat

Recently, it has been suggested that the Escherichia coli causing urinary tract infection (UTI) may come from meat and animals. The purpose was to investigate if a clonal link existed between E. coli from animals, meat and UTI patients. Twenty-two geographically and temporally matched B2 E. coli from UTI patients, community-dwelling humans, broiler chicken meat, pork, and broiler chicken, previously identified to exhibit eight virulence genotypes by microarray-detection of approximately 300 genes, were investigated for clonal relatedness by PFGE. Nine isolates were selected and tested for in vivo virulence in the mouse model of ascending UTI. UTI and community-dwelling human strains were closely clonally related to meat strains. Several human derived strains were also clonally interrelated. All nine isolates regardless of origin were virulent in the UTI model with positive urine, bladder and kidney cultures. Further, isolates with the same gene profile also yielded similar bacterial counts in urine, bladder and kidneys. This study showed a clonal link between E. coli from meat and humans, providing solid evidence that UTI is zoonosis. The close relationship between community-dwelling human and UTI isolates may indicate a point source spread, e.g. through contaminated meat.     

Construction of a urease-negative mutant of Proteus mirabilis: analysis of virulence in a mouse model of ascending urinary tract infection.

Proteus mirabilis, a urease-producing uropathogen, causes serious urinary tract infections in humans. To specifically evaluate the contribution of urease to virulence, a mutation was introduced into P. mirabilis HI4320 by homologous recombination. Virulence was assessed in the CBA mouse model of ascending urinary tract infection. Twenty mice each were challenged transurethrally with P. mirabilis HI4320 and its urease-negative derivative (1 x 10(9) to 2 x 10(9) CFU). At 48 h animals were sacrificed and the mean log10 CFU per milliliter of urine (parent, 6.23; mutant, 4.19; P = 0.0014) or per gram of bladder (parent, 6.29; mutant, 4.28; P = 0.0002), left kidney (parent, 4.11; mutant, 1.02; P = 0.00009), and right kidney (parent, 4.11; mutant, 2.43; P = 0.036) were all shown to be significantly different. These data demonstrate a role for urease as a critical virulence determinant for uropathogenic P. mirabilis.     

Escherichia coli clonal group A causing bacteraemia of urinary tract origin

Escherichia coli clonal group A (CgA) causes disease in humans. This is the first study investigating the prevalence of CgA among E. coli from non-urine, extraintestinal infections in a northern European country. E. coli blood (n = 196) and paired urine (n = 195) isolates from the same patients with bacteraemia of urinary tract origin were analysed. The isolates were collected from January 2003 through May 2005 at four hospitals in Copenhagen, Denmark. Pulsed-field gel electrophoresis (PFGE) patterns, antimicrobial resistance and patient characteristics were determined for all CgA isolates; presence of virulence-associated genes (VAGs) and serotypes were determined for the blood CgA isolates. Thirty blood isolates (15%) belonged to CgA. CgA blood isolates were associated with female patients and sulfamethoxazole-trimethoprim resistance and they harboured a distinctive VAG profile. The blood and urine isolates from each pair were found to be related in 26 of 27 CgA blood/urine pairs, confirming a urinary tract origin of infection. Furthermore, a relationship between the PFGE patterns of CgA blood/urine isolates and CgA isolates from UTI patients in general practice and a CgA isolate from a community-dwelling human reported previously, was found, suggesting a community origin of CgA. The finding of CgA strains in 15% of the E. coli bloodstream infections with a urinary tract origin in Denmark suggests that CgA constitutes an important clonal lineage among extraintestinal pathogenic E. coli. A reservoir of this pathogenic E. coli group in the community causing not only UTI but also more severe infections such as bacteraemia has implications for public health.     

Role of the Staphylococcus epidermidis slime layer in experimental tunnel tract infections.

An experimental animal model was used to assess the slime layer of Staphylococcus epidermidis as a pathogenic factor in tunnel tract infections. Mice were inoculated with high-slime-producing or non-slime-producing strains of S. epidermidis, either along the length of a subcutaneous catheter or in the area where a catheter had been placed and immediately removed (controls). Among the catheter-bearing mice, the phenotypically distinct staphylococci produced similar, high frequencies of abscess formation (72% [44 of 61] versus 81% [31 of 38]; P = 0.29). In controls, the non-slime-producing organisms were significantly more pathogenic (87% [40 of 46] versus 57% [25 of 44] abscess formation; P = 0.001). No consistent difference was detected between blood isolates obtained from patients with central venous catheter bacteremia and those from neonates with bacteremia in the absence of a prosthetic medical device. Quantitative culture of removed catheters showed greater adherence by the slime-producing isolates (P = 0.014). In this mouse model, slime production by S. epidermidis did not increase the risk of catheter tunnel tract infection, despite the greater catheter adherence of the slime-producing organisms. These findings suggest that traumatized tissue may be a sufficient condition for the development of S. epidermidis catheter-associated infections.