Antimicrobial Use in Outpatient Hemodialysis Units
(See the commentary by Malani and Heung, on pages 358–360.)
Objective. To quantify and characterize overall antimicrobial use, including appropriateness of indication, among patients receiving chronic hemodialysis.
Design. Retrospective and prospective observational study.
Setting. Two outpatient hemodialysis units.
Patients. All patients receiving chronic hemodialysis.
Methods. The rate of parenteral antimicrobial use (number of doses per 100 patient-months) was calculated retrospectively from September 2008 through July 2011. Indication and appropriateness of antimicrobial doses were characterized prospectively from August 2010 through July 2011. Inappropriate administration was defined as occasions when criteria for infection based on national guidelines were not met, failure to choose a more narrow-spectrum antimicrobial on the basis of culture data, or occasions when indications for surgical prophylaxis were not met.
Results. Over the 35-month retrospective study period, the rate of parenteral antimicrobial use was 32.9 doses per 100 patient-months. Vancomycin was the most commonly prescribed antimicrobial, followed by cefazolin and third- or fourth-generation cephalosporins. Over the 12-month prospective study, 1,003 antimicrobial doses were prescribed. Among the 926 (92.3%) doses for which an indication for administration was available, 276 (29.8%) were classified as inappropriate. Of these, a total of 146 (52.9%) did not meet criteria for infection, 74 (26.8%) represented failure to choose a more narrow-spectrum antimicrobial, and 56 (20.3%) did not meet criteria for surgical prophylaxis. The most common inappropriately prescribed antimicrobials were vancomycin and third- or fourth- generation cephalosporins.
Conclusions. Parenteral antimicrobial use was extensive, and as much as one-third was categorized as inappropriate. The findings of this study provide novel information toward minimizing inappropriate antimicrobial use.
Infections are a leading cause of hospitalization and death in the chronic hemodialysis (CHD) population, and the rates of hospitalization due to infection continue to increase. The United States Renal Data System reported that from 1993 to 2010, the number of hospitalizations due to infection rose by 45.8%.1 These infections are associated with up to 20% mortality, and mortality rates are substantially higher for infections by multidrug-resistant organisms (MDROs).2-5
The increased mortality associated with MDRO infections is of great concern because rates of MDRO colonization and infection are among the highest in the CHD population.6-8 The high prevalence of MDROs harbored by CHD patients compared to that in lower-risk populations, compounded by the rising rate of infections, emphasizes the need to reduce the emergence and spread of MDROs in the CHD population. Since antimicrobial exposure is the main risk factor for the emergence and spread of MDROs, minimizing inappropriate antimicrobial use is imperative.8,9
Antimicrobial stewardship has consistently shown a decrease in inappropriate antimicrobial use.10 The efficacy of these programs, however, requires a priori knowledge of antimicrobial use and characterization of inappropriate prescribing patterns. Despite the high prevalence of MDROs in the CHD population, there are limited data pertaining to antimicrobial use in outpatient hemodialysis units. For example, previous studies have reported only antimicrobial starts in dialysis units, and therefore the overall burden of antimicrobial exposure in the CHD population remains to be defined.11,12 Furthermore, previous studies have generally addressed inappropriate prescribing patterns of vancomycin, and only in the hospital setting.13,14 There are therefore no outpatient dialysis unit data available to understand inappropriate prescribing patterns of vancomycin and other frequently used antimicrobials. To characterize such patterns in the outpatient setting, we measured antimicrobial use and evaluated its appropriateness in two outpatient dialysis units, including overall and individual rates of use and rates of inappropriate prescribing patterns for all antimicrobials administered.
Material and Methods
This study was conducted at two outpatient hemodialysis units in Boston, Massachusetts. Each unit was affiliated with an academic center and had a typical census of 100 patients. The medical and nursing staffs were aware of the general aims of the study but not of the specific methodology, including the criteria for inappropriate administration. Antimicrobials were prescribed by unit nephrologists (6 in unit A and 10 in unit B). All data were collected by a study investigator (G.M.S.). This study was approved by the institutional review boards at the investigators’ institutions and the medical centers.
Antimicrobial Utilization Rates
The overall rate of parenteral antimicrobial use was calculated retrospectively from September 2008 through July 2011. These data include the monthly patient census and the number of antimicrobial doses administered and were extracted from the hemodialysis unit–specific electronic medical record (EMR). Antimicrobial utilization rates included all doses administered during the study period and were calculated as doses per 100 patient-months (doses/100PM), using the dialysis units’ census and medication administration data.11
Indication and Appropriateness of Antimicrobial Doses
From August 2010 through July 2011, data characterizing the appropriateness of parenteral antimicrobial doses were collected prospectively every 2–4 weeks. Each administered dose was identified by using the hemodialysis unit–specific EMR and confirmed by review of hemodialysis unit documents and discussion with the healthcare workers, if clarification was required.
Data Collection and Definitions
Administered doses were categorized as (1) the first dose, (2) a continuing dose, or (3) surgical prophylaxis. The first-dose category was defined as the first dose of an antimicrobial received in the dialysis unit. First doses were administered empirically or targeted a specific pathogen identified from clinical cultures. The continuing-dose category was defined as any dose administered after the first dose. A surgical prophylaxis dose was defined as any dose administered perioperatively, without documentation of a suspected infection.
Each dose was classified as appropriate or inappropriate. An inappropriate dose was defined as (1) one administered when criteria for infection based on national guidelines published by major infectious-disease and nephrology societies15-28 were not met, (2) failure to use a more narrow-spectrum antimicrobial on the basis of culture results, or (3) one administered when indications for surgical prophylaxis were not met (antimicrobials were not indicated or were continued beyond 24 hours after the procedure, in the absence of infection).29
Presumed sites of infections were categorized as bloodstream infections (BSIs), skin and soft-tissue infections (SSTIs), pneumonia (PNA), or urinary tract infections (UTIs). Centers for Diseases Control and Prevention (CDC) criteria were used to define vascular-access-related BSIs.15 Given the high prevalence of bacteremia caused by coagulase-negative staphylococci in the dialysis population, BSI criteria were modified to include appropriate antimicrobial administration if this pathogen was cultured from at least one blood culture, as opposed to at least 2 blood cultures, in patients with fever, chills, or hypotension.11,13 If the physician suspected a BSI before microbiological data were available, then the criteria for presumed BSI were fever, chills, or hypotension. Fever was defined as a temperature above 100°F, as opposed to the standard 100.4°F.15,28 The threshold was lowered in this dialysis population because of their immunosuppressed state and conforms with published guidelines for fever among other immunosuppressed populations.21 Appropriate antimicrobials for empiric treatment of a presumed BSI included vancomycin with or without an antimicrobial targeting gram-negative bacteria.
Criteria for SSTIs required either purulent drainage or at least 2 of the following: warmth, erythema, swelling, and tenderness.19 Criteria for vascular-access-related SSTIs required pus, redness, or increased swelling at the vascular-access site.25 Criteria for PNA and UTIs were based on national guidelines.17,18 All assessments of appropriateness took into consideration documented patient allergies.
Demographic data and medical history were documented for all patients. The Charlson score was used as a composite score of comorbidities and has been validated in the dialysis population.30,31 A history of colonization or infection with MDROs in the 12 months preceding enrollment was ascertained by reviewing dialysis unit and hospital medical records.
The rates of antimicrobial use in the 2 units were calculated as pooled means and were compared using Poisson regression. Demographic variables were compared using a χ2 test or a Wilcoxon rank-sum test, as appropriate. Statistical analyses were performed in STATA (ver. 10.0; StataCorp).
Rates of Antimicrobial Utilization: Retrospective Analysis from September 2008 through July 2011
Over the 35-month retrospective study period, a total of 2,313 parenteral antimicrobial doses were administered in the 2 outpatient hemodialysis units. Total follow-up time was 7,023 patient-months. The overall rate of parenteral antimicrobial use was 32.9 doses/100PM (range, 5.2–67.2), with higher rates in unit B (37.3 doses/100PM) than in unit A (28.3 doses/100PM; ; Table 1).
|Antimicrobial use, doses/100 patient-months (range)|
|Type of antimicrobial||Unit A||Unit B||Combined|
|All antimicrobials||28.4 (5.2–50.0)||37.3 (10.4–67.2)||32.9 (5.2–67.2)|
|Vancomycin||18.5 (5.2–35.0)||26.1 (7.6–50.0)||22.3 (5.2–50.0)|
|Cefazolin||5.2 (0.0–22.1)||4.9 (0.0–25.9)||5.1 (0.0–25.9)|
|Third- or fourth-generation cephalosporinsa||2.1 (0.0–10.1)||3.9 (0.0–13.0)||3.0 (0.0–13.0)|
|Aminoglycosidesb||1.2 (0.0–12.1)||0.8 (0.0–7.1)||1.0 (0.0–12.1)|
|Daptomcyin||1.1 (0.0–13.0)||1.6 (0.0–12.1)||1.3 (0.0–13.0)|
|Carbapenemsc||0.08 (0.0–2.9)||0.3 (0.0–5.5)||0.2 (0.0–5.5)|
|Piperacillin-tazobactam||0.07 (0.0–2.3)||0.0||0.03 (0.0–2.3)|
|Levofloxacin||0.06 (0.0–1.1)||0.0||0.03 (0.0–1.1)|
Antimicrobial Prescribing Patterns: Prospective Analysis from August 2010 through July 2011
Patient demographics and antimicrobial doses
A total of 278 patients were enrolled in this study (129 in unit A and 149 in unit B). Patient demographics and past medical history are shown in Table 2. During the study period, 90 individuals became new patients of one of the study hemodialysis units after enrollment began, and 62 patients unenrolled from the study during follow-up. The most common cause for unenrollment was death (36 [58.1%] of 62 unenrolled patients). The average daily census in the 2 units was 102.7 patients, 96.5 patients in unit A and 108.9 patients in unit B.
|Variable||Total study sample (N = 278)||Unit A (N = 129)||Unit B (N = 149)||P value|
|Age, mean ± SD, years||66.7 ± 15.5||67.7 ± 15.3||65.8 ± 15.7||.47|
|Male sex||144 (51.8)||71 (55.0)||73 (49.0)||.31|
|White||145 (52.2)||74 (57.4)||71 (47.7)|
|Black||93 (33.5)||26 (20.2)||67 (45.0)|
|Hispanic||29 (10.4)||4 (3.1)||3 (2.0)|
|Asian||7 (2.5)||23 (17.8)||6 (4.0)|
|Other/unknown||4 (1.4)||2 (1.6)||2 (1.3)|
|Primary indication for hemodialysis||.21|
|Diabetes mellitus||124 (44.6)||60 (46.5)||64 (43.0)|
|Hypertension||50 (18.0)||20 (15.5)||30 (20.1)|
|Glomerulonephritis||40 (14.4)||14 (10.9)||26 (17.5)|
|Cystic disease||10 (3.6)||4 (3.1)||6 (4.0)|
|Other||54 (19.4)||31 (24.0)||23 (15.4)|
|Hemodialysis access type at time of enrollment||.34|
|Arteriovenous fistula||149 (53.6)||72 (55.8)||77 (51.7)|
|Arteriovenous graft||37 (13.3)||13 (10.1)||24 (16.1)|
|Tunneled catheter||92 (33.1)||44 (34.1)||48 (32.2)|
|Mean duration of hemodialysis at time of enrollment ± SD, years||2.8 ± 3.19||2.97 ± 3.68||2.59 ± 2.70||.58|
|Median Charlson score (range)||4 (2–10)||5 (2–10)||4 (2–9)||.04|
|Immunosuppressive medication at time of enrollmenta||25 (9.0)||10 (7.8)||15 (10.1)||.50|
|Requires wheelchair or bedbound||37 (13.3)||28 (21.7)||9 (6.0)||<.001|
|Chronic wound present at enrollment||17 (6.1)||14 (10.9)||3 (2.0)||.002|
|Dementia||11 (4.0)||8 (6.2)||3 (2.0)||.07|
|History of prior transplant||21 (7.6)||7 (5.4)||14 (9.4)||.21|
|Malignancy||16 (5.6)||6 (4.7)||10 (6.7)||.46|
|HIV-positive||3 (1.1)||2 (1.6)||1 (0.7)||.48|
|History of colonization with multidrug-resistant organisms in previous 12 months|
|Methicillin-resistant Staphylococcus aureus||11 (4.0)||9 (7.0)||2 (1.3)||.02|
|Vancomycin-resistant enterococci||10 (3.6)||10 (7.8)||0||.001|
|Multidrug-resistant gram-negative bacteria||9 (3.2)||6 (4.7)||3 (2.0)||.22|
|Penicillin allergy||37 (13.3)||17 (13.2)||20 (13.4)||.95|
|Cephalosporin allergy||9 (3.2)||3 (2.3)||6 (4.0)||.42|
A total of 1,003 antimicrobial doses were administered during the 12-month study period. Eighty-nine (32%) patients received at least one antimicrobial dose. The average number of doses received per patient was 11.3 (median, 7; range, 1–78). An average of 1.5 different antimicrobial types were received per patient (range, 1–5). Of the 1,003 doses, 394 were administered in unit A and 609 were administered in unit B. There were 2,549 patient-months of follow-up (1,196 in unit A and 1,353 in unit B), and an antimicrobial use rate of 39.3 doses/100PM (32.9 in unit A and 45.0 in unit B).
Appropriateness of prescribing patterns
Data pertaining to the indication for antimicrobial administration was available for 926 (92.3%) of the 1,003 doses. The most common category for antimicrobial administration was continuing treatment, accounting for 798 (86.2%) doses, followed by first dose (70 [7.6%] doses) and surgical prophylaxis (58 [6.3%] doses).
Overall, 276 (29.8%) doses were inappropriate (Figures 1, 2). The most common reason for inappropriate administration was that the criteria for infection were not met, accounting for 52.9% (146/276) of all inappropriate doses. A presumed BSI that did not meet criteria was the most common inappropriate indication and accounted for 48.6% (71/146) doses. Of these, treatment of a single positive blood culture for coagulase-negative staphylococci with absence of any clinical signs or symptoms accounted for 38 (53.5%) doses, and empiric administration of a first dose without appropriate clinical signs or symptoms accounted for 33 (46.5%) doses. In the majority of these cases, documentation referred to the patient as “not feeling well.” The second most common presumed infection for which criteria were not met was SSTI, accounting for 64 (43.8%) doses. The most frequently targeted site of the presumed SSTIs that did not meet criteria was cellulitis of the extremities, accounting for 33 (51.6%) of these doses. Criteria were not met in nearly all of these doses because only redness or swelling was present. The remaining 31 (48.4%) doses were vascular-access related and did not meet criteria because only tenderness was present. Among the 7 (4.8%) inappropriate doses administered for presumed UTIs, patients had either a positive urinalysis or a positive urine culture but did not have any genitourinary symptoms. For the 4 (2.7%) inappropriate doses administered for presumed PNA, only shortness of breath was present, without other signs and symptoms, including fever, cough, or negative radiological findings, when available.
The second most common indication for inappropriate antimicrobial administration was that a more narrow-spectrum antimicrobial was not chosen (74 [26.8%] of 276 inappropriate doses), despite available antimicrobial susceptibility data and absence of contraindicating antimicrobial allergies. Among these doses, vancomycin was administered instead of a β-lactam antimicrobial for 48 (64.9%) doses, and third- or fourth-generation cephalosporins were administered instead of cefazolin for 26 (35.1%) doses.
Criteria for surgical prophylaxis were not met for the remaining 56 (20.3%) inappropriate doses, which were administered for 17 procedures, including 5 (8.9%) doses for one procedure at unit A and 51 (91.1%) doses for 16 procedures at unit B. Twenty-eight postoperative doses were administered for 5 arteriovenous graft revisions. Although indicated before the procedure, these doses were administered 24 hours or more after the procedure (average, 6 doses; range, 3–8 doses). The remaining 28 doses, administered for 12 procedures, were not indicated before the procedure and were administered for at least 24 hours after the procedure. These procedures were as follows (number of procedures): catheter exchange (7), arteriovenous fistula revision, thrombectomy/angioplasty (4), and excision of a skin lesion (1). The average number of doses received 24 hours or more after the procedure was 2 (range, 1–5).
Inappropriate prescribing patterns by type of antimicrobial
Total doses of antimicrobials by type and the percentage of doses administered inappropriately are shown in Figure 3. The most common inappropriately prescribed antimicrobial was vancomycin, of which 207 (37%) of 556 doses were classified as inappropriate, followed by third- or fourth-generation cephalosporins, of which 45 (36%) of 125 doses were inappropriate, and cefazolin, of which 23 (13%) of 181 doses were inappropriate. Indications for inappropriate administration, as defined in this study, for these three antimicrobials are shown in Table 3.
cephalosporins (N = 45)
(N = 23)
|Criteria for infection not met: presumed site|
|BSI||63 (30.4)a||10 (22.2)||0 (0)|
|SSTI||44 (21.3)||5 (11.1)||12 (52.2)|
|UTI||0 (0)||4 (8.9)||3 (13.0)|
|PNA||1 (0.5)||0 (0)||3 (13.0)|
|Total||108 (52.2)||19 (42.2)||18 (72.0)|
|Narrower-spectrum antimicrobial not chosen||48 (23.2)||26 (57.8)||0 (0)|
|Surgical prophylaxis||51 (24.6)||0 (0)||5 (11.1)|
This study quantified antimicrobial use in outpatient hemodialysis units and characterized areas in which antimicrobial prescribing patterns could be improved. The main findings were (1) antimicrobial use was extensive, with 1 in 3 CHD patients receiving antimicrobials during the 12-month study period, (2) up to one-third of these antimicrobial doses were classified as inappropriate on the basis of national guidelines, and (3) inappropriate antimicrobial use of vancomycin and third- or fourth-generation cephalosporins was the most common: 37% and 36%, respectively, of all doses of these antimicrobials were prescribed inappropriately.
Similar to the findings of other studies, the most common inappropriate indications for vancomycin use were treatment of blood cultures contaminated with coagulase-negative staphylococci and failure to deescalate to a β-lactam antimicrobial once microbiological results indicated growth of a β-lactam-susceptible pathogen.13,14 The importance of deescalation in improving patient outcomes was recently emphasized in a study that showed that patients receiving nafcillin or cefazolin for the treatment of methicillin-susceptible Staphylococcus aureus had a 79% lower mortality hazards than those receiving vancomycin, a finding that has also been demonstrated in the hemodialysis population.32,33 Novel findings in this study were that a substantial proportion of inappropriate vancomycin use was for the treatment of presumed SSTIs that did not meet criteria for true infection. Future hemodialysis unit–based antimicrobial stewardship programs should also focus on this newly identified area. Surgical prophylaxis is another area that hemodialysis unit–based stewardship programs might target, because this category represented 25% of inappropriate vancomycin doses. The great majority of surgeries were for minor vascular-access-related procedures. Although there is a paucity of data pertaining to surgical prophylaxis in this setting, the National Kidney Foundation guidelines do not state that prophylaxis is required for treatment of stenosis or thrombosis of either arteriovenous fistulas or grafts.16 A study by Salman et al34 showed that the rate of infectious complications after minimally invasive interventions for all types of dialysis access-related procedures was only 0.06% among 3,162 procedures under study. In our study, a more liberal approach was used, and prophylaxis was allowed if the procedure involved arteriovenous grafts. If this criterion were not considered, then the percentage of inappropriate doses would be even greater.
Another novel finding of this study is the substantial inappropriate use of third- or fourth-generation cephalosporins. For this class of antimicrobials, failure to deescalate to a first-generation cephalosporin was the main reason for inappropriate use. In addition to preventing the emergence of MDRO colonization, maximizing deescalation to the least costly first-generation cephalosporins would result in substantial cost savings.
Previous studies addressing antimicrobial use in outpatient dialysis units have focused on antimicrobial starts.11,12 In our study, all antimicrobial doses administered to CHD patients were quantified. This approach provides a more complete assessment of the risk associated with antimicrobial exposure and the emergence and spread of MDROs. In this study, if antimicrobial starts alone were addressed, only 7.6% of all doses administered in the dialysis unit would be captured. Furthermore, doses administered after the first dose represented the largest category of inappropriate antimicrobials use and accounted for 69% of doses that were not indicated. An effective antimicrobial stewardship program would therefore need to focus on all antimicrobial doses, since focusing solely on starts would miss the great majority of inappropriate doses.
The Infectious Diseases Society of America and Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship provide important strategies toward an effective program.10 Although the guidelines are hospital based, many strategies could be implemented in the outpatient dialysis setting, and the findings of this study provide insight into which strategies may have the most beneficial effect. Among the key recommendations are educational efforts and providing guidelines and clinical pathways for appropriate antimicrobial use. The findings of this study suggest that although ongoing efforts to minimize antimicrobial use for suspected BSIs that do not meet criteria are still needed, educational initiatives should also focus on other sites of infection, including SSTIs, as well as surgical prophylaxis. Deescalation of therapy is another strong recommendation, and in this study failure to deescalate accounted for 27% of inappropriate doses. Finally, measurement of antimicrobial use rates with feedback is another recommended strategy. In this study, overall antimicrobial use was 32.0 doses/100PM. This rate will provide an initial value with which to measure the efficacy of antimicrobial stewardship strategies implemented in the study units, and similar values should be obtained in other dialysis units. Of note, this metric was used to facilitate measurement of antimicrobial use because outpatient dialysis units are currently already reporting rates of BSI per 100 patient-months.11
Several limitations of this study warrant discussion. First, only 2 dialysis units were enrolled, and therefore the findings may not be generalizable to other units. This issue may be especially relevant for surgical prophylaxis because the majority of inappropriate doses for this indication occurred at only one of the 2 units. Second, antimicrobial courses were not addressed. However, this study focused on individual doses because the dialysis unit provides a unique setting whereby the appropriateness of administering each antimicrobial dose can be addressed and readdressed at each dialysis session. Finally, lack of documentation, as opposed to absence of clinical signs and symptoms of infections, may have led to misclassification of those doses that did not meet criteria for infection. To minimize misclassification, study personnel reviewed records at bimonthly to monthly intervals and clarified issues with the healthcare workers. Eliminating misclassification completely would have required study personnel to be present during all shifts over the 12-month study period, which was not logistically feasible. In addition, for the great majority of other inappropriate indications, including surgical prophylaxis, missed opportunity for deescalation to a more narrow-spectrum antimicrobial, and treatment of contaminated blood cultures with coagulase-negative staphylococci, misclassification would be highly unlikely even if additional documentation were available. If only doses characterized as inappropriate for these reasons were included as inappropriate, a substantial 18% of doses would still be inappropriate.
Limiting inappropriate use of antimicrobials has the potential to lead to a decrease in the emergence and spread of MDROs in the CHD population. The beneficial effect of preventing MDRO acquisition among CHD patients would also extend to other patient populations. CHD patients are admitted to the hospital 2 times per year for an average of 12 days, and 36% are readmitted within 30 days.1 During these hospitalizations, CHD patients contribute to the spread and acquisition of MDROs among other hospitalized patients. Dissemination of MDROs from CHD patients into the community has also been described.35 The findings of this study provide important information toward minimizing inappropriate antimicrobial use and the design of future antimicrobial stewardship interventions tailored to outpatient dialysis units by identifying novel areas, including SSTI and surgical prophylaxis, and types of antimicrobials, including third- or fourth-generation cephalosporins, that programs should focus on.
Financial support. This work was funded by the CDC Division of Healthcare Quality Promotion (Intergovernmental Personnel Agreement 10IPA1004108).
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here.
- 1. U.S. Renal Data System. USRDS 2009 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2009.
- 2. Li Y, Friedman JY, O’Neal BF, et al. Outcomes of Staphylococcus aureus infection in hemodialysis-dependent patients. Clin J Am Soc Nephrol 2009;4(2):428–434.
- 3. Engemann JJ, Friedman JY, Reed SD, et al. Clinical outcomes and costs due to Staphylococcus aureus bacteremia among patients receiving long-term hemodialysis. Infect Control Hosp Epidemiol 2005;26(6):534–539.
- 4. Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y. Clinical and economic impact of bacteremia with extended-spectrum-β-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2006;50(4):1257–1262.
- 5. Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis 2006;42(suppl 2):S82–S89.
- 6. Centers for Disease Control and Prevention. Invasive methicillin-resistant Staphylococcus aureus infections among dialysis patients—United States, 2005. MMWR Morb Mortal Wkly Rep 2007;56(9):197–199.
- 7. Snyder GM, D’Agata EM. Novel antimicrobial-resistant bacteria among patients requiring chronic hemodialysis. Curr Opin Nephrol Hypertens 2012;21(2):211–215.
- 8. Pop-Vicas A, Strom J, Stanley K, D’Agata EM. Multidrug-resistant gram-negative bacteria among patients who require chronic hemodialysis. Clin J Am Soc Nephrol 2008;3(3):752–758.
- 9. Lautenbach E, Patel JB, Bilker WB, Edelstein PH, Fishman NO. Extended-spectrum β-lactamase–producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 2001;32(8):1162–1171.
- 10. Dellit TH, Owens RC, McGowan JE, Jr, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44(2):159–177.
- 11. Klevens RM, Edwards JR, Andrus ML, Peterson KD, Dudeck MA, Horan TC. Dialysis Surveillance Report: National Healthcare Safety Network (NHSN)—data summary for 2006. Semin Dial 2008;21(1):24–28.
- 12. George A, Tokars JI, Clutterbuck EJ, Bamford KB, Pusey C, Holmes AH. Reducing dialysis associated bacteraemia, and recommendations for surveillance in the United Kingdom: prospective study. BMJ 2006;332:1435.
- 13. Green K, Schulman G, Haas DW, Schaffner W, D’Agata EM. Vancomycin prescribing practices in hospitalized chronic hemodialysis patients. Am J Kidney Dis 2000;35(1):64–68.
- 14. Zvonar R, Natarajan S, Edwards C, Roth V. Assessment of vancomycin use in chronic haemodialysis patients: room for improvement. Nephrol Dial Transplant 2008;23(11):3690–3695.
- 16. Vascular Access 2006 Working Group. Clinical practice guidelines for vascular access. Am J Kidney Dis 2006;48(suppl 1):S176–S273.
- 17. Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40(5):643–654.
- 18. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(suppl 2):S27–S72.
- 19. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005;41(10):1373–1406.
- 20. Centers for Disease Control and Prevention. Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep 1995;44(RR-12):1–13.
- 21. High KP, Bradley SF, Gravenstein S, et al. Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48(2):149–171.
- 22. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt) 2010;11(1):79–109.
- 23. Anderson DJ, Sexton DJ. Overview of control measures to prevent surgical site infection. In: Harris A, ed. UpToDate, http://www.uptodate.com/contents/overview-of-control-measures-to-prevent-surgical-site-infection#H1. Published December 2012.
- 24. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005;111(23):e394–e434.
- 26. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52(5):e103–e120.
- 27. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50(5):625–663.
- 28. Mackowiak PA, Wasserman SS, Levine MM. A critical appraisal of 98.6°F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA 1992;268(12):1578–1580.
- 29. Dellinger EP, Gross PA, Barrett TL, et al. Quality standard for antimicrobial prophylaxis in surgical procedures. Infectious Diseases Society of America. Clin Infect Dis 1994;18(3):422–427.
- 30. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40(5):373–383.
- 31. Beddhu S, Zeidel ML, Saul M, et al. The effects of comorbid conditions on the outcomes of patients undergoing peritoneal dialysis. Am J Med 2002;112(9):696–701.
- 32. Schweizer ML, Furuno JP, Harris AD, et al. Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia. BMC Infect Dis 2011;11:279.
- 33. Stryjewski ME, Szczech LA, Benjamin DK, Jr, et al. Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis 2007;44(2):190–196.
- 34. Salman L, Asif A. Antibiotic prophylaxis: is it needed for dialysis access procedures? Semin Dial 2009;22(3):297–299.
- 35. Lu PL, Tsai JC, Chiu YW, et al. Methicillin-resistant Staphylococcus aureus carriage, infection and transmission in dialysis patients, healthcare workers and their family members. Nephrol Dial Transplant 2008;23(5):1659–1665.