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Preventing Bacterial Infections and Antimicrobial Resistance in
Dialysis Patients
Jeffrey S. Berns, MD, and Jerome I. Tokars, MD ● Antimicrobial use, in concert with patient-to-patient transmission of resistant strains, has caused a rapid
increase in the prevalence of antimicrobial resistance in recent years. This increase is a particular threat to dialysis
patients, who often have been in the forefront of the epidemic of resistance. In this report, which was written in
collaboration between the American Society of Nephrology and the Centers for Disease Control and Prevention and
has been endorsed by the Executive Council of the Infectious Diseases Society of America, we review and
summarize existing clinical practice guidelines and recommendations concerning the prevention, diagnosis, and
treatment of certain bacterial infections in dialysis patients and present four strategies to limit the spread of
antimicrobial resistance in dialysis patients. First, preventing infection eliminates the need for antimicrobials,
thereby reducing selection pressure for resistant strains. Efforts to prevent infection include avoidance of
hemodialysis catheters, when possible, and meticulous care of hemodialysis and peritoneal catheters and other
hemodialysis vascular access sites. Second, diagnosing and treating infections appropriately can facilitate the use
of narrower spectrum agents, rapidly decrease the number of infecting organisms, and reduce the probability of
resistance emerging. This entails the collection of indicated specimens for culture and avoidance of contamination
of cultures with common skin microorganisms. Third, optimizing antimicrobial use helps protect the efficacy of
such critical agents as vancomycin. Published guidelines for the use of vancomycin should be followed, and
alternate agents should be used when infections with
-lactam–resistant bacteria are unlikely or not documented.
Fourth, preventing transmission in health care settings is important to limit the spread of resistant organisms. In
this regard, such basic measures as glove use and hand hygiene are most important. Am J Kidney Dis
2002 by the National Kidney Foundation, Inc.
INDEX WORDS: Antimicrobial resistance; methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-
resistant enterococci (VRE); catheter-related bacteremia; peritoneal dialysis (PD); peritonitis; infection control.

RESISTANCE OF bacteria to antimicrobial centage of enterococcal isolates resistant to van-
comycin increased from an average of 14% in during the last decade. Infections with methicillin- 1995 to 1998 to 25% in 1999.2 During the same resistant Staphylococcus aureus (MRSA), coagu- period, the percentage of S aureus isolates resis- lase-negative staphylococci (CoNS), and vanco- tant to methicillin increased from 32% to 54%.
Antimicrobial use and transmission of resistant particular concern.1 Among intensive care unit strains from patient to patient are the two pri- patients with hospital-associated infections that mary factors contributing to this increasing preva- have been reported to the Centers for Disease Control and Prevention’s (CDC’s) National Noso- The American Society of Nephrology and the comial Infections Surveillance system, the per- CDC have collaborated to produce this review ofstrategies to limit the spread of antimicrobialresistance in patients with end-stage renal dis- From the University of Pennsylvania School of Medicine, ease (ESRD). This report summarizes existing Presbyterian Medical Center, Philadelphia, PA; and the recommendations and clinical practice guide- Centers for Disease Control and Prevention, Atlanta, GA. Received March 20, 2002; accepted in revised form May lines. It is not intended to propose new clinical practice guidelines or critique existing recommen- The use of trade names is for identification only and does dations and clinical practice guidelines. The Ex- not constitute endorsement by the Public Health Service or ecutive Council of the Infectious Diseases Soci- the US Department of Health and Human Services. Address reprint requests to Jeffrey S. Berns, MD, Presby- ety of America (IDSA) has reviewed and endorsed terian Medical Center, Renal, Electrolyte, and Hypertension the contents of this report. Although many of the Division, 39th and Market Sts; MOB 240, Philadelphia, PA principles discussed here are applicable to chil- 19104. E-mail: dren, there are insufficient clinical studies to 2002 by the National Kidney Foundation, Inc. allow specific recommendations for this patient 0272-6386/02/4005-0014$35.00/0doi:10.1053/ajkd.2002.36332 American Journal of Kidney Diseases, Vol 40, No 5 (November), 2002:pp 886-898 After a brief overview of antimicrobial resis- tested; most are assumed to be resistant, so a tance in staphylococci and enterococci, organ- precise estimate of the prevalence of methicillin- isms of particular importance in patients with resistant CoNS in this setting is not known.
ESRD, we present four strategies for the control Methicillin (and cefazolin) resistance is present of antimicrobial resistance. (1) Prevent infection.
in approximately 50% to 60% of CoNS strains If infections are prevented, the need for antimi- isolated in peritoneal dialysis–related peritonitis; crobial agents and resulting selection pressure the actual prevalence varies widely among cen- for bacterial strains with resistance to these agents ters.10,11 The prevalence of methicillin resistance will decrease. (2) Diagnose and treat infections in peritoneal catheter exit-site and tunnel infec- effectively. Prompt identification and treatment tions has not been clearly established. Most CoNS will reduce or eliminate the bacterial load and are susceptible to vancomycin, although strains tend to minimize the need for antimicrobials. (3) with vancomycin-intermediate resistance have Use antimicrobials wisely. Antimicrobial agents often are used inappropriately. Adherence to rec-ommendations for appropriate antimicrobial use is important in efforts to control the development VRE initially were reported in the late 1980s,13 and spread of antimicrobial-resistant microorgan- with one of the first reports including patients isms. (4) Prevent transmission. This will limit with kidney failure in a London hospital renal the spread of antimicrobial-resistant strains. The unit.14 The gastrointestinal tract is the major CDC recently has updated recommendations for reservoir for enterococci; colonized patients serve preventing the transmission of infection in hemo- as a potential reservoir for the spread of VRE to other patients. There is no known way to eradi- cate colonization with VRE; thus, efforts must A CDC survey found that the percentage of Strains of S aureus that are resistant to methi- dialysis units that had identified at least one cillin (ie, MRSA) also are resistant to other patient with VRE increased from 11.5% in 1995 -lactam antimicrobials, such as cephalosporins.
to 32.7% in 2000.4 The reported prevalence of A recent CDC survey found that one or more VRE in dialysis outpatients has varied from 0% hemodialysis patients with MRSA was being to 12% and was as high as 28% among hospital- treated in 71% of dialysis units, an increase from ized hemodialysis patients.15-19 In stable chronic 40% in 1995 and 56% in 1997.4 MRSA has been ambulatory peritoneal dialysis patients, peritoni- isolated relatively infrequently in community- acquired peritoneal dialysis–related exit-site in-fection and peritonitis.5-7 S aureus isolates with reduced sensitivity to vancomycin (referred to as vancomycin-interme- diate S aureus [VISA]) have been isolated from Influenza is readily transmissible in health eight patients in the United States.8,9 Of concern care settings and can result in secondary bacte- is that five of these patients had been treated with rial pneumonia requiring antimicrobial therapy.
peritoneal dialysis or hemodialysis. All these Streptococcus pneumoniae is the most common patients had been on prolonged therapy with causative organism of community-acquired pneu- vancomycin, and several patients had recurrent monia in dialysis patients.23 Therefore, it is rec- catheter-related bacteremia caused by MRSA.
ommended that all adult dialysis patients be The first documented case of infection with van- offered pneumococcal vaccine every 5 years and comycin-resistant S aureus (VRSA) was recently influenza vaccine yearly.24 Other vaccines, such reported in a hemodialysis patient who had been as those for hepatitis B and tetanus toxoid, should treated with multiple courses of antibiotics, in- also be administered, when appropriate. Dialysis- center staff members should be offered influenza In hemodialysis-related bacteremias caused by vaccine yearly.25 A conjugate vaccine recently CoNS, susceptibility to methicillin often is not was shown to confer partial short-term immunity against S aureus bacteremia in dialysis pa- However, a recent CDC annual survey indicated tients.26 Further testing of this vaccine, which is that the percentage of chronic hemodialysis pa- not commercially available, will be necessary to tients treated through a catheter increased from clarify its long-term efficacy, safety, and clinical 12.7% in 1995 to 24.0% in 2000.4 The most important strategy in preventing infections inhemodialysis patients is to use the lowest risk Elimination of Nasal S aureus Carriage vascular access, ie, arteriovenous (AV) fistulae in The anterior nares are a reservoir for S au- preference to grafts, and minimize the use of reus.27 Hemodialysis and peritoneal dialysis pa- hemodialysis catheters. Timely referral of pa- tients with S aureus nasal colonization, including tients for AV access creation before the need for MRSA, are at increased risk for infections caused dialysis therapy has been recommended to re- by these organisms.28 Several studies have shown duce dependence on hemodialysis catheters.41 that elimination of nasal carriage with oral ri-fampin or intranasal mupirocin reduces the risk Reducing Hemodialysis and Peritoneal for peritoneal dialysis catheter exit-site infection and bacteremia in hemodialysis patients.29-34 However, effects on nasal carriage often are reduce hemodialysis catheter–related infections transient, and strains of S aureus with resistance are listed in Table 1.40,41,47-49 Povidone-iodine to these drugs may develop.35,36 For these rea- and mupirocin ointment applied to the catheter sons and because of the associated inconve- exit site have been shown to reduce the incidence nience, expense, and side effects, the routine use of hemodialysis catheter–related exit-site and of oral rifampin or intranasal mupirocin has not bloodstream infections.50,51 NKF-K/DOQI guide- been generally recommended in peritoneal dialy- lines recommend the use of povidone-iodine or mupirocin ointment at hemodialysis catheter exit In hemodialysis patients, the IDSA has recom- sites after catheter placement and each dialysis mended treatment with nasal mupirocin in docu- treatment.41 CDC/HICPAC guidelines and others mented S aureus carriers who have a catheter- recommend that povidone-iodine be applied rou- related bloodstream infection caused by S aureus tinely to hemodialysis catheter exit sites, but and continue to need the hemodialysis catheter.39 because of concern about resistance and effects Otherwise, neither CDC/Healthcare Infection on certain types of catheters, routine use of Control Practices Advisory Committee (HICPAC) mupirocin was not recommended.39,40 Resis- guidelines nor the National Kidney Foundation- tance to mupirocin has developed after pro- Kidney Disease Outcomes Quality Initiative longed use at insertion sites of central venous (NKF-K/DOQI) vascular access guidelines rec- catheters.52 Mupirocin should be avoided with ommend the routine use of nasal mupirocin in polyurethane catheters because of the potential patients with hemodialysis catheters.40,41 Instillation of antimicrobial agents into hemo- Reducing Hemodialysis Catheter Use dialysis catheters (antibiotic lock) is not recom- Indwelling hemodialysis catheters are the mended as a routine preventive measure, but has single most important factor contributing to bac- been recommended when there is a history of teremia in hemodialysis patients.42,43 Noncuffed multiple catheter-related bacteremias despite op- temporary hemodialysis catheters are particu- timal aseptic technique40 or when the catheter is larly notorious in this regard.44,45 In a surveil- retained during an episode of catheter-related lance study sponsored by the CDC, rates of access-related bacteremia per 100 patient-months Prevention of hemodialysis AV graft or fistula were 0.25 for native fistulae, 0.53 for synthetic infections involves both good patient hygiene bridge grafts, 4.8 for cuffed catheters, and 8.7 for and meticulous care by well-trained dialysis per- noncuffed catheters.46 NKF-K/DOQI guidelines sonnel (Table 2). Tracking access-related infec- cited a goal of having less than 10% of chronic tions in hemodialysis patients should be part of hemodialysis patients maintained with perma- ongoing quality improvement and quality assur- nent catheter-based hemodialysis treatments.41 Recommendations for the Prevention of
Recommendations for the Prevention of AV
Hemodialysis Catheter Infection
Fistula and Graft Infection
Use sterile technique (cap, mask, sterile gown, large Wash the area to be punctured with antibacterial soap or sterile drapes, and gloves) for catheter insertion.
scrub (eg, 2% chlorhexidine) and treat the area with Limit use of femoral vein catheters to 5 days.
tincture of chlorhexidine, 70% alcohol, or Limit use of noncuffed central venous catheters to 3 to 4 povidone-iodine before cannulation (NOTE:Alcohol should be applied in a rubbing motion for 1 minute Use the catheter solely for hemodialysis unless there is immediately before cannulation. Povidone-iodine should be applied for 2 to 3 minutes and allowed to dry Restrict catheter manipulation and dressing changes to Use clean gloves for access puncture, with new gloves Examine exit site for infection at each hemodialysis used for each patient. Gloves should be changed if Consider soaking caps or blood catheter connectors in Ensure that dialysis personnel receive adequate training povidone-iodine for 3 to 5 minutes and allow to dry and follow recommended access-puncture techniques.
Keep catheter lumens sterile:maintain aseptic technique tice may be necessary. Mupirocin should not be Do not leave the catheter lumen open to air.
applied directly to polyurethane catheters with- Replace catheter-site dressing at each dialysis treatment out first consulting the manufacturer’s recommen- Disinfect skin before catheter insertion and dressing dations because some of these catheters have changes. Use a 2% chlorhexidine-based preparation deteriorated when mupirocin was applied.53,54 (preferred), tincture of iodine, an iodophor, or 70% Other recommendations for the prevention of peritoneal dialysis–associated infection are listed Consider having patients wear surgical masks when the catheter cap is removed and the bloodstream isaccessed and for dressing changes.
Ensure that catheter-site care is compatible with the Have dialysis health care workers wear gloves and Prevention of antimicrobial-resistant bacterial surgical masks or face shields when removing the infections depends in part on the avoidance of catheter cap and accessing the bloodstream and fordressing changes.
unnecessary antimicrobial use and the selection Consider the use of nasal mupirocin for documented of optimal antimicrobial therapy when bacterial carriers of S aureus in patients with previous catheter- infection is suspected or documented.62 When related bacteremia if ongoing catheter-basedhemodialysis is necessary.
Recommendations for the Prevention of
Peritoneal Dialysis Catheter–Associated Infection
Peritonitis and peritoneal dialysis catheter and exit-site infections can be reduced with the use of Insert catheter under operating room–like sterile downward-directed exit sites, subcutaneous cath- Place catheter with downward-directed exit site and eter tunnels, and, possibly, double-cuffed rather than single-cuffed catheters.37,55 Application of mupirocin to the exit site as part of routine Immobilize the catheter in the postoperative period (at exit-site care is effective in reducing staphylococ- least 3 to 4 weeks), cover exit site with several layers ofgauze (avoid occlusive dressings), and keep exit site cal exit-site infections and peritonitis and has been advocated as a practical alternative to the Restrict catheter care to experienced staff and trained use of intranasal mupirocin.37,38,56-59 However, recently, routine use of mupirocin at the exit site Use aseptic technique with sterile gloves and face masks has been found to lead to high-level resistance to when performing exit-site care in the postoperativeperiod.
this agent in S aureus isolates.60,61 Although Use liquid soap or cleansing solutions regularly, but avoid discontinuation of the prophylactic application of mupirocin to peritoneal catheter exit sites is Once the exit site has healed, wash the exit site daily.
not being recommended on the basis of these Review patients’ exchange techniques and reeducate as new findings, some reexamination of this prac- possible, cultures should be obtained before anti- peripheral vein rather than through a catheter.
microbial therapy is started to identify pathogens However, avoidance of peripheral venipuncture and determine their antimicrobial-susceptibility in hemodialysis patients may be desirable either profile. This allows targeted antimicrobial therapy because of limited venous sites or with the goal as opposed to broad-spectrum or empiric therapy of preserving future AV access sites. If blood that is not based on culture results. Cultures of cultures are obtained through a catheter or blood normally sterile fluids, such as blood, urine, and port, at least one blood culture also should be peritoneal fluid, are most likely to be useful.
obtained by venipuncture, if possible.63 In pa- Cultures of intact skin are not useful, and cul- tients with central venous catheters (not hemodi- tures of wounds and drainage must be interpreted alysis catheters), there appears to be a lower with caution because skin flora that are isolated positive predictive value of blood cultures ob- may be either pathogens or contaminants. Rou- tained from a catheter compared with venipunc- tine culturing of removed hemodialysis catheter tips is not recommended because positive cul- Organisms most likely to represent contamina- tures from catheter tips may be caused by coloni- tion or colonization include such typical skin zation with common skin contaminants, rather flora as CoNS, micrococci, Bacillus species, Pro- pionibacterium species, Corynebacterium spe-cies, and ␣-hemolytic streptococci.65 Isolation of one of these organisms is more likely to be Blood cultures should be obtained before treat- clinically significant when multiple blood cul- ment with antimicrobials in patients with such tures are positive for the same organism, signs signs of sepsis as fever, chills, or hypotension; and symptoms of sepsis are present, and no focus those with suspected infections of unknown of infection other than the vascular access is source; and patients in whom access infection, apparent. When clinical and laboratory data are including catheter-associated bacteremia, is sus- equivocal, especially in patients with single posi- pected.63 One blood culture is defined as a blood tive cultures with possible skin contaminants, sample drawn from a single site or with a single careful observation without antimicrobial therapy venipuncture, regardless of the number of blood and repeated blood cultures may be appropriate culture bottles into which the specimen is placed.
in selected patients (ie, those without persistent Obtaining two blood cultures as opposed to one fever, rigors, hypotension, or leukocytosis).
increases the chance of identifying a pathogenand assists in determining whether such isolates Peritoneal Dialysis Exit-Site, Tunnel, and as CoNS are true pathogens or contaminants. It is preferable to obtain two blood cultures from Peritoneal dialysis catheter exit-site infection separate sites at different times. It usually is not is diagnosed when there is purulent or bloody necessary to draw more than two or three blood drainage from an exit site that also may be cultures during the initial 24 hours.63 To prevent erythematous, edematous, and tender.37,66 Crust- contamination of the specimen, the site should be ing alone is not indicative of infection. Cultures disinfected carefully with 70% isopropyl alcohol of normal skin or a scab at the exit site indicate or povidone-iodine (which should be allowed to only colonization and are not clinically useful.
dry). To assist in the interpretation of positive Almost all exit sites are colonized by bacteria blood cultures, the time, date, and sites of cul- within a few weeks after catheter placement.
tures (ie, peripheral vein versus catheter); num- However, any purulent drainage should be cul- ber of cultures drawn; and number of cultures tured. Tunnel infection usually is accompanied positive for each organism should be recorded.
by erythema, edema, and tenderness along the In the absence of a true bacteremia, blood subcutaneous portion of the catheter, but also cultures may be positive because of contamina- may be clinically silent. Often, there also is tion of the specimen or, if the blood culture evidence of an exit-site infection with drainage sample is drawn through a catheter, colonization from the exit site, which should be cultured.37,66 of the catheter without true bacteremia. It is Cultures of possibly infected peritoneal dialy- preferable to draw all blood cultures from a sate should be obtained as soon as peritonitis is suspected; ideally, from the first cloudy bag of gram-positive organisms commonly isolated in dialysate.38 Large volumes of the dialysate should dialysis patients, and in part, because of the be cultured or concentrated to maximize culture convenience of being able to administer infre- results. Centrifugation of 50 mL of peritoneal quent doses to patients with ESRD.68 However, effluent followed by resuspension in sterile sa- now the threat of antimicrobial resistance neces- line and inoculation of this material into a stan- sitates the use of alternate antimicrobials that are dard blood culture medium is one recommended likely to be of equivalent efficacy and safety.
approach. Use of rapid blood-culture techniques Reduction of vancomycin use is considered to (eg, BACTEC system; Becton Dickinson, Sparks, be one of the most important strategies to limit the spread of vancomycin resistance. In 1995,the CDC/HICPAC published “Recommenda- tions for Preventing the Spread of Vancomycin General Principles of Antimicrobial Use Resistance.”69 These and subsequent recommen- Antimicrobial use can be categorized as pro- dations from the CDC concerning vancomycin phylactic (administered to uninfected patients in use in circumstances likely to be encountered in an effort to prevent infection), empiric (adminis- dialysis patients are listed in Table 4.
tered for initial therapy, with choice of agent Practical issues related to the inconvenience based on clinical features and local antimicrobial- and expense of using alternatives to intravenous resistance data, designed to be active against the vancomycin in patients with ESRD have gener- most likely infecting microorganisms), and di- ated concern about these recommendations.70 In rected (administered after culture and susceptibil- hospitalized dialysis patients with infections ity results are known). As stated in the Society caused by ␤-lactam–susceptible organisms and for Healthcare Epidemiology of America and intravenous access other than that used for hemo- IDSA guidelines for prevention of antimicrobial dialysis, nafcillin or another ␤-lactam can be resistance in hospitals, “The ideal is to have all used readily for susceptible organisms. In outpa- patients treated with the most effective, least tients, the use of ␤-lactams that require frequent toxic, and least costly antibiotic for the precise intravenous dosing would be expensive and in- duration of time needed to cure or prevent an convenient, requiring venous access and the ad- infection.”62 This means use of antimicrobials ministration of antimicrobials in the home set- with a narrow antimicrobial spectrum as much as ting. Recently, cefazolin has been evaluated as possible. Empiric therapy should be avoided in an alternative to vancomycin in hemodialysis circumstances in which bacterial infection is patients as empiric therapy in settings in which unlikely and discontinued once culture results MRSA prevalence is low or for the treatment of are negative or if the organism isolated is most organisms known to be susceptible to ␤-lactams.
likely a contaminant. Once culture and suscepti- In hemodialysis patients, cefazolin, a first- bility results are available, narrower spectrum generation cephalosporin, may be administered agents should promptly replace broader spec- in doses of 1 to 2 g (ϳ15 to 20 mg/kg) three trum agents initiated for empiric therapy.62 times per week postdialysis; this regimen pro- A number of strategies for promoting judicious duces therapeutic blood levels lasting until the antimicrobial use have been recommended, includ- next scheduled dialysis session during both a ing the adoption of written guidelines, educational 2-day and 3-day interdialytic interval and with efforts aimed at changing prescribing practices of either high-efficiency or high-flux hemodialyz- physicians, restriction of formulary, utilization re- ers in most patients.71-74 However, it is not clear view to ensure appropriate use, and requiring con- whether postdialysis cefazolin dosing provides sultation with an infectious diseases specialist for adequate blood levels in the doses described for patients with significant residual renal func-tion.72,74 Use of Vancomycin and Alternatives to Two antimicrobial agents, quinupristin/dalfo- pristin (Synercid; Aventis, Bridgewater, NJ) and Vancomycin frequently has been used by neph- linezolid (Zyvox; Pharmacia & Upjohn, Pea- rologists, in part, because of its efficacy against pack, NJ), with activity against vancomycin- Recommendations Concerning Vancomycin Use in Dialysis Patients
Situations in which vancomycin use is appropriate or acceptable
Treatment of serious infections caused by ␤-lactam–resistant gram-positive microorganisms (eg, MRSA)Treatment of infections caused by gram-positive microorganisms in patients who have serious allergies to ␤-lactam Treatment of antibiotic-associated colitis unresponsive to metronidazole or that is severe and potentially life threateningProphylaxis for endocarditis in patients at high risk for endocarditisProphylaxis for major surgical procedures involving implantation of prosthetic materials or devices (this does not include placement or revision of hemodialysis catheters, fistulae, or grafts) at institutions that have a high rate of MRSA ormethicillin-resistant S epidermidis Empiric therapy of patients who may have serious infections (eg, bacteremia) caused by ␤-lactam–resistant organisms; if cultures are negative for ␤-lactam–resistant organisms, vancomycin should be discontinued Situations in which vancomycin use is discouraged
Routine surgical prophylaxis other than in a patient who has a life-threatening allergy to ␤-lactam antibioticsTreatment in response to a single blood culture positive for CoNS if other blood cultures drawn in the same time frame are negative (ie, if contamination of the blood culture is likely) Continued empiric use for presumed infections in patients in whom cultures are negative for ␤-lactam–resistant gram- Systemic or local (eg, antibiotic lock) prophylaxis for infection or colonization of indwelling central or peripheral Attempted elimination of MRSA colonizationRoutine prophylaxis for patients on continuous ambulatory peritoneal dialysis or hemodialysisTreatment (chosen for dosing convenience) of infections caused by ␤-lactam–susceptible gram-positive microorganisms resistant organisms were approved recently in current guidelines recommend the administra- the United States. Linezolid is active in vitro tion of a first-generation cephalosporin 1 hour against Enterococcus faecium and Enterococcus preoperatively and perhaps again 6 to 12 hours faecalis.75 Quinupristin/dalfopristin is active in postoperatively.37 Vancomycin should not be rou- vitro against E faecium, but not E faecalis.76 tinely administered for prophylaxis for perito- Both agents are active against methicillin-suscep- neal dialysis catheter placement, although a re- tible and methicillin-resistant S aureus and cent prospective randomized study comparing Staphylococcus epidermidis, VISA, and other single doses of vancomycin, cefazolin, and no gram-positive bacteria, but are not active against antibiotics before peritoneal dialysis catheter gram-negative bacteria. These antimicrobials placement suggested a benefit of vancomycin should be used only for treatment of infections over cefazolin.84 Unfortunately, antimicrobial sen- caused by organisms resistant to other available sitivities of isolated microorganisms were not drugs. Very limited experience with these drugs in dialysis patients has been reported.77-79 In vitroresistance of VRE and staphylococci to these Therapy for Hemodialysis Access Infection Hemodialysis catheter–related exit-site infec- tions typically are associated with erythema, crusting, and exudate without systemic symp- A single 1-g dose of cefazolin administered toms or positive blood cultures. When there is no within 60 minutes before the skin incision is evidence of a tunnel infection, exit-site infec- recommended for most AV access procedures.83 tions in patients with cuffed tunneled catheters Vancomycin should not be used for routine surgi- generally can be treated with the application of cal prophylaxis in patients who are undergoing topical antibiotic ointments without catheter re- placement of AV grafts or fistulae in the absence moval or systemic antibiotics.41 Because a recent of serious ␤-lactam allergy.69 Antimicrobial pro- study showed that the risk for developing bacte- phylaxis should not be used for placement of remia associated with temporary noncuffed cath- eters increased dramatically if the catheter is left For placement of peritoneal dialysis catheters, in place more than 1 day after an exit-site infec- tion occurs, these catheters should be removed and not exchanged over a guidewire if there is promptly if an exit-site infection develops.44 If suspicion that a bacteremia is catheter related tunnel drainage is present, parenteral antibiotics except as salvage therapy in selected hemodialy- active against staphylococci and streptococci are sis patients with limited venous access.40 Guide- recommended, with accompanying treatment of lines from the IDSA indicate that in the presence of bacteremia caused by S aureus, tunneled hemo- Tunnel infections are manifested by tender- dialysis catheters should be removed, with the ness, erythema, and/or induration. The IDSA duration of antimicrobial therapy guided by find- recommends that tunnel infections be treated ings on transesophageal echocardiography (14 with catheter removal, as well as appropriate days if no evidence of vegetation; 4 to 6 weeks if antibiotics.39 Tunnel infections often are accom- vegetation is present).39 These same guidelines panied by bacteremia, which should be treated as suggest that catheter-related bacteremia caused by CoNS can be treated without catheter re- S aureus (methicillin-susceptible and MRSA) moval, but may require more prolonged antimi- and CoNS are the most common organisms caus- ing hemodialysis catheter–associated bactere- A few reports indicate that catheter replace- mia, although gram-negative organisms are iso- ment over a guidewire within 48 hours of initiat- lated in approximately one third of cases.44,85-88 ing antimicrobial therapy, followed by a period Initial empiric antimicrobial therapy therefore of appropriate antimicrobial therapy, can be suc- should be directed against both gram-positive cessful in carefully selected patients who are not and gram-negative organisms, with subsequent critically ill.87-91 Catheters should be removed therapy based on blood culture results. Vancomy- promptly, rather than exchanged over a guide- cin and an aminoglycoside (ie, gentamicin) or wire, if there is evidence of catheter tunnel or antipseudomonal cephalosporin commonly are exit-site infection, in clinically unstable patients used initially. A ␤-lactam, such as cefazolin, with with features of sepsis, and in patients who or without an aminoglycoside may be reasonable remain febrile or symptomatic for more than 36 initial therapy instead of vancomycin if MRSA hours after the initiation of antimicrobial therapy has not been a frequent pathogen in a particular or have persistently positive blood cultures de- dialysis setting and the patient has not been spite antimicrobial therapy.41 Periodic blood cul- recently hospitalized or administered antibiotic tures should be obtained after completion of therapy. However, reported experiences of long-term results with cefazolin for catheter-related therapy to confirm eradication of the infection.
bacteremia are somewhat limited.71,72 Local anti- Antimicrobial treatment for hemodialysis cath- microbial sensitivity patterns also should influ- eter–related bacteremias for at least 3 weeks is ence decisions regarding empiric vancomycin recommended,41 although the optimal duration therapy. If blood cultures identify a ␤-lactam– of therapy has not been systematically explored.
susceptible organism, vancomycin, if adminis- Circumstances in which a longer or shorter dura- tered initially for empiric therapy, should be tion of therapy might be appropriate or necessary discontinued, and cefazolin or another alternate For empiric therapy for infected AV fistulae or Management of bacteremia related to indwell- grafts, agents providing coverage against both ing double-cuffed hemodialysis catheters is ad- gram-negative and gram-positive organisms, in- dressed in several recent reports and the NKF-K/ cluding Enterococcus species, are recom- DOQI clinical practice guidelines,41 but remains mended.41 Vancomycin or, depending on local controversial. Attempts at salvaging tunneled susceptibility profiles, a ␤-lactam and an amino- cuffed hemodialysis catheters in patients with glycoside would be reasonable, with subsequent catheter-related bacteremia using antimicrobial therapy dictated by culture results. AV grafts that therapy alone without catheter removal are usu- are more than superficially infected should be ally unsuccessful.85,87 The CDC/HICPAC guide- surgically removed, and any newly placed graft lines recommend that central venous catheters (ie, Ͻ1 month old) should be removed regardless (including hemodialysis catheters) be replaced Therapy for Peritoneal Dialysis–Related ity results become available. If the isolate is susceptible to rifampin, this agent can be added In 1996, reflecting concern about the emer- if S aureus is isolated and the infection does not gence of vancomycin resistance, guidelines from resolve promptly in response to initial treatment.
the International Society for Peritoneal Dialysis were revised to recommend that peritoneal dialy- therapy unless MRSA or methicillin-resistant sis–related peritonitis be treated empirically with CoNS are isolated.37,38 Antimicrobial therapy a first-generation cephalosporin (eg, cefazolin or should be continued until the exit site appears cephalothin) and an aminoglycoside,92 rather than normal, and for tunnel infections, for at least 7 vancomycin, as previously recommended.93-95 days after clinical resolution of infection.
Newer guidelines recommend that ceftazidime Long-term antimicrobial treatment of chroni- be used along with cefazolin or cephalothin cally infected catheter exit sites may lead to the instead of an aminoglycoside for patients with emergence of antimicrobial-resistant microorgan- residual renal function to avoid impairing the isms. In this setting, ongoing surveillance for remaining residual renal function.38 Subsequent changes in antimicrobial sensitivities and the use antimicrobial therapy should be tailored to spe- of combinations of synergistic antimicrobial cific susceptibility characteristics of cultured or- agents may be necessary, and in selected circum- stances, catheter removal may be appropriate.66 Increasing resistance of S epidermidis peritoni- Peritonitis associated with exit-site or tunnel tis to methicillin and other ␤-lactams in patients infections often requires catheter removal, ex- with peritoneal dialysis–related peritonitis has cept perhaps when S epidermidis is isolated.59 been reported.5 Limited studies with historical controls suggest that cefazolin-based therapy forperitoneal dialysis peritonitis does not appear to Dialysis patients may be infected or colonized be less effective as empiric therapy than initial with a variety of pathogens, including antimicro- therapy with vancomycin,10,96,97 although con- bial-resistant bacteria, often unbeknown to staff cern has been expressed about the high rate of members. The numerous contacts between staff cefazolin resistance in staphylococcal isolates in members and patients in the dialysis unit provide peritoneal dialysis–related peritonitis.11 Vancomy- the opportunity for transmission of these patho- cin or clindamycin (if the isolate is susceptible to gens from patient to patient.3,98 Therefore, care- this agent) are recommended for culture-docu- ful infection-control precautions should be used mented MRSA (along with rifampin) and most during the care of all patients to prevent such episodes of peritonitis caused by methicillin- Hand hygiene is the single most important infection-control measure. Hand hygiene can be Therapy for Peritoneal Dialysis Catheter accomplished either by washing hands with soap (plain soap is acceptable for routine use) and S aureus is the most common cause of exit-site water or by using waterless alcohol-based gels or and tunnel infections.37,59 CoNS also frequently foams. Hand washing with soap, rather than the cause exit-site infections, but relatively infre- use of waterless hand rubs, is preferred if hands quently are the cause of tunnel infections. Sug- are visibly contaminated with body fluids or gested initial empiric antimicrobial therapy for secretions. Hand hygiene should be performed possible exit-site or tunnel infections includes after touching blood, body fluids, secretions, oral penicillinase-resistant penicillins, tri- excretions, and contaminated items regardless of methoprim/sulfamethoxazole, or cephalexin if whether gloves are worn. Hand hygiene should Gram stain shows gram-positive organisms and be performed immediately after gloves are re- an oral quinolone if gram-negative organisms are moved, between patient contacts, and when oth- seen.37,38 Vancomycin should not be used for erwise indicated to avoid the transfer of microor- empiric therapy unless the patient is known to be infected or colonized with MRSA. Therapy then Gloves should be worn when it is anticipated should be tailored when culture and susceptibil- that hands may contact blood, body fluids, or General Infection-Control Measures for
any specific pathogen), or (2) fecal incontinence Patient Contacts in the Dialysis Unit
or diarrhea uncontrolled with personal hygienemeasures. For these patients, consider using the Wash hands or use an alcohol-based hand rub after touching one patient and before going to the next following additional precautions: (1) staff mem- bers treating the patient should wear gloves and Wear disposable nonsterile gloves when it is anticipated a separate gown over their usual clothing and that hands may contact blood, body fluids, or remove the gloves and gown when finished car- contaminated items. The CDC recommends use of ing for the patient, and (2) the patient should gloves for all contact with hemodialysis patients andequipment.
undergo dialysis at a station with as few adjacent Remove gloves and perform hand hygiene after patient stations as possible (eg, at the end or corner of Consider any medication or equipment taken to the dialysis station to be potentially contaminated.
Discard or disinfect such items before they are usedon another patient.
Antimicrobial-resistant bacteria are an increas- Wipe all surfaces at the dialysis station, including control ing threat. We review four general strategies to panel and knobs on dialysis machines, with a limit the spread of antimicrobial resistance: pre- venting infection, diagnosing and treating infec- For patients at increased risk for transmitting VRE or tions promptly, optimizing antimicrobial use, and MRSA, with infected skin wounds, or with fecalincontinence or diarrhea, consider: preventing transmission in health care settings.
Use of nonsterile gloves and a separate gown for staff Because patients with ESRD often have been in members treating the patient, to be removed when the forefront of the epidemic of antimicrobial resistance, these strategies should be imple- Dialyzing patient at a station with as few adjacent mented by all health care personnel caring for contaminated items. Because surfaces in the he- modialysis unit often are contaminated with 1. Gold HS, Moellering RC Jr: Antimicrobial-drug resis- minute quantities of blood that are not visible to 2. Fridkin SK: Increasing prevalence of antimicrobial staff members, but which can transmit disease, resistance in intensive care units. Crit Care Med 29:N64- the CDC recommends wearing gloves for all touching of patients or equipment in hemodialy- 3. Centers for Disease Control and Prevention: Recom- mendations for preventing transmission of infections among Infection-control precautions recommended for hemodialysis patients. MMWR Morbid Mortal Wkly Rep50:2-32, 2001 all hemodialysis patients are adequate to prevent 4. Tokars JI, Frank M, Alter MJ, Arduino MJ: National transmission for the majority of patients infected Surveillance of Dialysis-Associated Diseases in the United or colonized with pathogenic bacteria, including States, 2000. Semin Dial 15:162-171, 2002 antimicrobial-resistant strains,3 and contact pre- 5. Zelenitsky S, Barns L, Findlay I, et al: Analysis of cautions such as those recommended for hospital- microbiological trends in peritoneal dialysis–related perito-nitis from 1991 to 1998. Am J Kidney Dis 36:1009-1013, ized patients are not recommended for outpatient dialysis units. There is only very limited reported 6. Lye WC, Leong SO, Lee EJ: Methicillin-resistant experience with specific efforts to control the Staphylococcus aureus nasal carriage and infections in spread of antimicrobial-resistant microorgan- isms in dialysis units.99,100 Nonetheless, addi- 7. Holley JL, Bernardini J, Johnston JR, Piraino B: Meth- icillin-resistant staphylococcal infections in an outpatient tional infection-control precautions should be peritoneal dialysis program. Am J Kidney Dis 16:142-146, considered for the treatment of patients who might be at increased risk for transmitting patho- 8. Smith TL, Pearson ML, Wilcox KR, et al: Emergence genic bacteria. Such patients include those with of vancomycin resistance in Staphylococcus aureus. Glyco- either of the two following syndromes: (1) an peptide-Intermediate Staphylococcus aureus Working Group.
N Engl J Med 340:493-501, 1999 infected skin wound with drainage that is not 9. Fridkin SK: Vancomycin-intermediate and -resistant contained by dressings (the drainage does not Staphylococcus aureus: What the infectious disease special- have to be culture positive for VRE, MRSA, or ist needs to know. Clin Infect Dis 32:108-115, 2001 9a. Centers for Disease Control and Prevention: Staphy- 26. Shinefield H, Black S, Fattom A, et al: Use of a lococcus aureus resistant to vancomycin—United States, Staphylococcus aureus conjugate vaccine in patients receiv- 2002. MMWR Morbid Mortal Wkly Rep 51:565-567, 2002 ing hemodialysis. N Engl J Med 346:491-496, 2002 10. Vas S, Bargman J, Oreopoulos D: Treatment in PD 27. von Eiff C, Becker K, Machka K, Stammer H, Peters patients of peritonitis caused by gram-positive organisms G: Nasal carriage as a source of Staphylococcus aureus with single daily dose of antibiotics. Perit Dial Int 17:91-94, 28. Bargman JM: Nasal carriage of Staphyloccus aureus 11. Troidle LK, Kliger AS, Finkelstein FO: Challenges of in dialysis patients. Semin Dial 8:220-225, 1995 managing chronic peritoneal dialysis-associated peritonitis.
29. Boelaert JR, Van Landuyt HW, Godard CA, et al: Nasal mupirocin ointment decreases the incidence of Staphy- 12. Schwalbe RS, Stapleton JT, Gilligan PH: Emergence lococcus aureus bacteraemias in haemodialysis patients.
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Vaginal progesterone for asymptomatic cervical shortening and the case for universal screening of cervical length Vaginal progesterone for asymptomatic cervical shortening and the case for universal screening of cervical length C. Andrew Combs, MD, PhD A short cervix detected in midpregnancy by transvaginal short cervix, whether or not there is a history of PTB. Using a sonography carries a high risk of early preterm birth (PTB). sophisticated individual patient data metaanalysis based o

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Eur Arch Psychiatry Clin Neurosci (2006) xx:1–4Gabriele Ende Æ Traute Demirakca Æ Sigrid Walter Æ Tim Wokrina Æ Alexander SartoriusDirk Wildgruber Æ Fritz A. HennSubcortical and medial temporal MR-detectable metaboliteabnormalities in unipolar major depressionReceived: 3 January 2006 / Accepted: 27 June 2006 / Published online: 16 August 2006determine whether MR-detectable alterations o

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