0
Articles |

Antibiotic Utilization*: Is There an Effect on Antimicrobial Resistance? FREE TO VIEW

Jan E. Patterson, MD
Author and Funding Information

*From the Department of Medicine, University of Texas Health Science Center, San Antonio, TX.

Correspondence to: Jan E. Patterson, MD, University of Texas Health Science Center, Department of Medicine, 7703 Floyd Curl Dr, Mail Code 7881, San Antonio, TX 78229-3900; e-mail: pattersonj@uthscsa.edu



Chest. 2001;119(2_suppl):426S-430S. doi:10.1378/chest.119.2_suppl.426S
Text Size: A A A
Published online

The antimicrobial resistance problem in hospitals continues to worsen. In particular, extended-spectrum β-lactamase–producing Klebsiella pneumoniae (ESBL-KP) and vancomycin-resistant enterococci (VRE) are significant causes of morbidity and mortality among critically ill patients. Treating infections caused by these pathogens presents therapeutic dilemmas. The association between broad-spectrum β-lactam overutilization and selection for ESBL-KP has been appreciated for some time; several institutions have reported a decrease in the prevalence of ESBL-KP with a shift in antibiotic utilization from third-generation cephalosporins to other broad-spectrum drugs. Currently, optimal treatment of ESBL-KP includes the carbapenems, but widespread use of these drugs is expensive and may be associated with further selection of antibiotic resistance and/or superinfection with other inherently resistant pathogens. VRE are especially difficult organisms to treat because of their inherent and acquired resistance to most currently available antibiotics. The prevalence of VRE has also been documented to decrease upon a shift in antibiotic use from third-generation cephalosporins to broad-spectrum antibiotics of other classes. Thus, antibiotic utilization measures appear to contribute to the control of the emergence of multidrug-resistant pathogens such as ESBL-KP and VRE.

Figures in this Article

In 1992, nosocomial infections were reported to cause > 8 million excess hospital days, approximately 80,000 deaths, and a burden of $4.5 billion on the health-care system.1The factors responsible for increasing antibiotic resistance are listed in Table 1 . Antibiotic-resistant pathogens such as extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) and vancomycin-resistant enterococci (VRE) are important causes of nosocomial infections among critically ill, hospitalized patients. Outbreaks of ESBL-KP often involve the emergence of several different strains that have acquired plasmids encoding multidrug resistance.2 VRE are commonly placed into two types of resistance classes, termed vanA or vanB. Resistance of the vanA phenotype is acquired from a transferable plasmid, whereas vanB resistance may be chromosomally mediated or transferable. Emergence of the vanA phenotype may be clonal but is often polyclonal, whereas emergence of the vanB phenotype may be polyclonal but is often clonal.3 The presence of genes encoding multidrug resistance limits therapeutic options in many cases.

A strong correlation between the use of third-generation cephalosporins, such as ceftazidime, and antibiotic resistance in K pneumoniae has been repeatedly demonstrated.2,47 In addition, a number of studies3,810 have also shown an association between broad-spectrum cephalosporin use and VRE. While antibiotic use in general cannot always be correlated with the emergence of antibiotic resistance, the association of cephalosporin use with these two problem pathogens has been the focus of several studies.211 A decline in the prevalence of ESBL-KP and VRE has been documented upon implementing an institution-wide shift to other classes of broad-spectrum antipseudomonal agents. The purpose of this article is to review existing data implicating antibiotic use in increasing the prevalence of ESBL-KP and VRE. In addition, evidence that decreasing third-generation cephalosporin use has been associated with significant decreases in the rates of ESBL-KP and VRE isolation will be presented.

The presence of antibiotic resistance in a bacterial strain is clearly a factor in increasing mortality rates. At New York Hospital Medical Center (Queens, NY), 23 of 43 evaluable patients with ceftazidime-resistant K pneumoniae (CRKP) died.4 Paterson and colleagues12 demonstrated the association between ESBL-KP and mortality in an ongoing prospective multicenter study taking place in seven hospitals on six continents. Of 216 cases of K pneumoniae bacteremia, 15% were caused by ESBL-KP. Patients with ESBL-KP who received empiric treatment to which their strains were resistant had a significantly higher rate of mortality (75%) compared with patients who received appropriate antibiotics (28%; p = 0.02). These data illustrate the importance of a correct empiric antibiotic choice for critically ill patients.

At Johns Hopkins Hospital, patients with VRE had significantly increased lengths of stay in the hospital and ICU and higher crude mortality rates (45% vs 27%; p = 0.007) compared with patients with vancomycin-susceptible enterococci (VSE).13Similarly, at the University of Pittsburgh Medical Center, Linden et al14 found an association between VRE and mortality among liver transplant patients. In this study, 46% of patients with VRE died from enterococcal bacteremia compared with 25% of patients with VSE (p = 0.04). Confirming observations at Johns Hopkins, Linden et al14 found that patients with VRE had significantly longer hospital stays than patients with VSE (p = 0.03).

In a presentation by Paterson and coworkers,12 31% of patients with ESBL-KP had received a third-generation cephalosporin at least 14 days preceding bacteremia compared with 3% of non-ESBL-KP patients (p < 0.01). Rice and colleagues5 showed that ceftazidime use was a risk factor for increased prevalence of CRKP in the Cleveland Department of Veterans Affairs Medical Center between January and December 1994. Notably, there was a strong association between the amount (in grams) of ceftazidime used in a particular ward and the prevalence of CRKP in that ward (p = 0.002). At New York Hospital Medical Center, CRKP comprised 17.3% of all K pneumoniae isolates recovered between October 1988 and April 1990. Interestingly, 91 of 127 patients (72%) with CRKP had received > 7 days of antibiotic treatment; 41% of CRKP isolates were from patients previously treated with ceftazidime.,4 Furthermore, there was a strong correlation between prior ceftazidime use and serious infections caused by CRKP.4

A study by Tokars and coworkers8 from the Atlanta Veterans Affairs Medical Center showed that exposure to broad-spectrum antimicrobials that lack enterococcal activity, including cephalosporins (ceftriaxone, ceftazidime, vancomycin, clindamycin, cefuroxime, and ticarcillin-clavulanic acid), was strongly associated with VRE colonization. In addition, the number of days in which patients received antimicrobials correlated with VRE prevalence.

In 1997, Gerding15 reviewed the literature regarding the relationship between prior antibiotic use and the emergence of VRE. Of 18 studies, 15 studies implicated vancomycin use in the emergence of VRE, 4 of 6 studies implicated cephalosporins, 4 of 5 studies implicated metronidazole, and 5 of 6 studies implicated use of any type of antimicrobial.15 A case-control study3 of seven hospitals in the San Antonio, TX, area determined that the risk factors for acquiring VRE as compared with VSE were prior use of third-generation cephalosporins (p = 0.03), parenteral vancomycin (p = 0.002), or any antibiotics (p = 0.04).

A case-control study by Pallares and colleagues16 sought to determine whether the use of second-generation and third-generation cephalosporins is a risk factor for nosocomial bacteremia due to Enterococcus faecalis. Included in this study,16 were 207 patients with nosocomial enterococcal bacteremia, of which 156 patients (75.4%) were matched with nonbacteremic control patients based on age, sex, date of admission, hospital service, days of hospitalization, primary diagnoses, and similar operative procedures. Patients who had contracted nosocomial enterococcal bacteremia were more likely to have been treated with second-generation and third-generation cephalosporins (odds ratio, 4.8; 95% confidence interval, 2.3 to 9.8),16 while prior use of other antibiotics did not appear to increase the risk of contracting nosocomial enterococcal bacteremia.16 These data indicate that cephalosporins may allow enterococcal overgrowth.16

Dahms and coworkers9 reported that use of either third-generation cephalosporins or vancomycin is a risk factor for postoperative infections due to VRE. In this study,9 surgical patients with VRE infections were matched with similar patients with VSE infections. Patients with VRE received third-generation cephalosporins, vancomycin, and a combination of both for significantly more days than patients with VSE. The risk for VRE infection was 1.6 for patients with prior use of third-generation cephalosporins, 1.8 for vancomycin, and 2.7 for concurrent use of both. Since existing evidence points to a role of cephalosporin use in the increasing prevalence of ESBL-KP and VRE, mandating the decreased use of cephalosporins may help to control outbreaks of these antibiotic-resistant organisms.

Finally, Donskey and colleagues10 recently published data from examiners in northeast Ohio who experienced an outbreak of VRE. Five teaching hospitals were surveyed, and it was found that the rates of isolation of VRE correlated with ticarcillin/clavulanate use (p = 0.005). Third-generation cephalosporins and clindamycin had a positive, but not significant, correlation.

A study performed by Rice and colleagues5 demonstrated that a decrease in ceftazidime utilization and concurrent increase in piperacillin/tazobactam use correlated with a decrease in CRKP without a concurrent increase in piperacillin/tazobactam-resistant strains. Furthermore, their data indicated that ceftazidime use increased resistance to other agents, while increased use of piperacillin/tazobactam did not show evidence of selecting for resistance either to other agents or to piperacillin/tazobactam.5A study at New York Hospital also found a decrease in the rate of ESBL-KP upon a shift in antibiotic utilization from cephalosporins to other antibiotics.6 An 80.1% reduction in hospital-wide cephalosporin use correlated with a 44.0% reduction in CRKP infection and colonization throughout the hospital (p < 0.01), a 70.9% reduction in all ICUs (p < 0.001), and an 87.5% reduction in the surgical ICU (p < 0.001).6 However, increased imipenem/cilastatin use in this study was associated with an increased incidence of imipenem-resistant Pseudomonas aeruginosa.,6

A significant decrease in multidrug-resistant K pneumoniae at our two university-affiliated hospitals in Texas was observed after a decrease in ceftazidime use and an increase in piperacillin/tazobactam use.7 Piperacillin/tazobactam resistance decreased despite the increase in piperacillin/tazobactam use. In addition to monitoring the decrease in multidrug-resistant K pneumoniae, we have also monitored the prevalence of infections due to Gram-negative bacilli that are resistant to third-generation cephalosporins. Decreased cephalosporin use and increased piperacillin/tazobactam use has been associated with a decrease in infections caused by cephalosporin-resistant Gram-negative bacilli in our adult ICUs (Fig 1 , top and bottom).

Infection control practices to combat VRE have been implemented with varying success at several institutions. Two studies published by Boyce and colleagues1718 documented that barrier precautions were effective at controlling two consecutive clonal strain outbreaks of vanA and vanB class vancomycin-resistant Enterococcus faecium. However, at the University of Maryland, when barrier precautions and vancomycin restriction were instituted to control a VRE outbreak, the prevalence of polyclonal VRE did not decrease between 1993 (16.9%) and 1994 (18.7%).19 Because of the emergence of polyclonal VRE in many institutions, other measures besides infection control, such as antibiotic utilization, may be needed to control antibiotic selection pressure for VRE.

At the Brooklyn Veterans Affairs Medical Center in New York, limiting hospital-wide use of cefotaxime, ceftazidime, vancomycin, and clindamycin was associated with a significant decrease in the prevalence of fecal colonization with VRE from 47 to 15% (p < 0.001).11 A study by Bradley et al20 demonstrated that restriction of third-generation cephalosporins in febrile, neutropenic patients was associated with a reduction in VRE prevalence. In phase 1 of this study, there was no change in antibiotic administration, with ceftazidime prescribed as empiric therapy for febrile, neutropenic patients. Phases 2a and 2b consisted of two 2- to 4-month intervals in which piperacillin/tazobactam was substituted for ceftazidime. Finally, in phase 3, ceftazidime was substituted for piperacillin/tazobactam for 4 months. The results of this study are summarized in Table 2 . Piperacillin/tazobactam use significantly decreased the prevalence of VRE colonization, and this decrease was promptly reversed upon return to ceftazidime utilization.

In our bone marrow transplant unit at the Department of Veterans Affairs hospital, we have also seen a decrease in VRE colonization and infection after reemphasizing infection control measures and changing our empiric regimen for febrile neutropenic patients from ceftazidime to piperacillin/ tazobactam.21

Antibiotic usage patterns exert a significant influence over the rates of resistance observed in problematic multidrug-resistant nosocomial pathogens. Emergence and spread of ESBL-KP are clearly promoted by widespread use of extended-spectrum cephalosporins, especially ceftazidime. Emergence of VRE within institutions is promoted both by poor infection control techniques and by use of broad-spectrum antimicrobial agents. In particular, increased rates of VRE colonization and infection have been associated with use of vancomycin, extended-spectrum cephalosporins, and antianaerobic drugs. Strict adherence to well-accepted infection control guidelines, along with caution in use of broad-spectrum antimicrobial agents, represents the best strategy for preventing the emergence and spread of nosocomial multidrug-resistant pathogens.

Dr. Joseph Lynch:

Your data, like those of other investigators, show that shifting away from ceftazidime to piperacillin/tazobactam really makes a difference and that reduction in antibiotic resistance is sustained. Have others seen a sustained reduction?

Dr. Jan Patterson:

Dr. Louis Rice continued to see the decline, and our resistance rates have continued to drop. Klebsiella seems to be most amenable to the switch, but we are seeing declines in some other organism resistance rates as well. We are also seeing less VRE since the change.

Dr. George Eliopoulos:

Why do you think that your rates of multidrug-resistant K pneumoniae declined even though you had an organism that was not susceptible to piperacillin/tazobactam?

Dr. Patterson:

One of our hospitals had primarily ESBL-KP, and the other hospital had primarily K pneumoniae with a type-1 β-lactamase enzyme. Decreasing ceftazidime use, along with the infection control measures, was associated with a decline in ceftazidime and piperacillin/tazobactam resistance.

Dr. Rekha Murthy:

What are you giving neutropenic, nontransplant patients?

Dr. Patterson:

Piperacillin/tazobactam plus or minus gentamicin or cefipime. In our Veterans Affairs hospital, piperacillin/tazobactam has slightly better activity against Pseudomonas than ceftazidime and is better than imipenem. We have recently started cycling cefipime and piperacillin/tazobactam in this population.

Abbreviations: CRKP = ceftazidime-resistant Klebsiella pneumoniae; ESBL-KP = extended-spectrum β-lactamase-producing Klebsiella pneumoniae; VRE = vancomycin-resistant enterococci; VSE = vancomycin-susceptible enterococci

Table Graphic Jump Location
Table 1. Factors Increasing Antibiotic Resistance
Figure Jump LinkFigure 1. Increased piperacillin/tazobactam use with a concurrent decrease in cephalosporin use is associated with a decrease in infections due to cephalosporin-resistant Gram-negative bacilli in adult ICUs. Top: Third-quarter 1999 antibiotic usage rates (antibiotic days per 1,000 patient-days) in adult ICUs. The decrease in cephalosporin use and increase in piperacillin/tazobactam use over an extended time is also documented.7Bottom: Prevalence of infections with cephalosporin-resistant Gram-negative bacilli (infection rate per 1,000 patient-days) in the medical/coronary ICU (MI/CICU), surgical ICU (SICU), and transplant ICU (TICU).Grahic Jump Location
Table Graphic Jump Location
Table 2. Restriction of Third-Generation Cephalosporins*
* 

From Bradley et al.20

Martone WJ, Jarvis WR, Culver DH, et al. Incidence and nature of endemic and epidemic nosocomial infections. In: Bennett JV, Brachman PS, eds. Hospital infections. 3rd ed. Boston, MA: Little, Brown and Company, 1992; 577–596.
 
Rice, LB, Willey, SH, Papanicolaou, GA, et al Outbreak of ceftazidime resistance caused by extended-spectrum β-lactamases at a Massachusetts chronic-care facility.Antimicrob Agents Chemother1990;34,2193-2199
 
Moreno, F, Grota, P, Crisp, C, et al Clinical and molecular epidemiology of vancomycin-resistantEnterococcus faeciumduring its emergence in a city in southern Texas.Clin Infect Dis1995;21,1234-1237
 
Meyer, KS, Urban, C, Eagan, JA, et al Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins.Ann Intern Med1993;119,353-358
 
Rice, LB, Eckstein, EC, DeVente, J, et al Ceftazidime-resistantKlebsiella pneumoniaeisolates recovered at the Cleveland Department of Veterans Affairs Medical Center.Clin Infect Dis1996;23,118-124
 
Rahal, JJ, Urban, C, Horn, D, et al Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella.JAMA1998;280,1233-1237
 
Patterson, JE, Hardin, TC, Kelly, CA, et al Association of antibiotic utilization measures and control of multiple-drug resistance inKlebsiella pneumoniae.Infect Control Hosp Epidemiol2000;21,455-458
 
Tokars, JI, Satake, S, Rimland, D, et al The prevalence of colonization with vancomycin-resistant Enterococcus at a Veterans’ Affairs institution.Infect Control Hosp Epidemiol1999;20,171-175
 
Dahms, RA, Johnson, EM, Statz, CL, et al Third-generation cephalosporins and vancomycin as risk factors for postoperative vancomycin-resistant Enteroccocus infection.Arch Surg1998;133,1343-1346
 
Donskey, CJ, Schreiber, JR, Jacobs, MR, et al A polyclonal outbreak of predominantly VanB vancomycin-resistant enterococci in northeast Ohio.Clin Infect Dis1999;29,573-579
 
Quale, J, Landman, D, Saurina, G, et al Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci.Clin Infect Dis1996;23,1020-1025
 
Paterson DL, Ko WC, Mohapatra S, et al.Klebsiella pneumoniae bacteremia: impact of extended spectrum beta-lactamase (ESBL) production in a global study of 216 patients [abstract]. Presented at 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 28 to October 1, 1997; Toronto, Ontario, Canada.
 
Lucas, GM, Lechtzin, N, Puryear, DW, et al Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes.Clin Infect Dis1998;26,1127-1133
 
Linden, PK, Pasculle, AW, Manez, R, et al Differences in outcomes for patients with bacteremia due to vancomycin-resistantEnterococcus faeciumor vancomycin-susceptibleE faecium.Clin Infect Dis1996;22,663-670
 
Gerding, DN Is there a relationship between vancomycin-resistant enterococcal infection andClostridium difficileinfection?Clin Infect Dis1997;25,S206-S210
 
Pallares, R, Pujol, M, Pena, C, et al Cephalosporins as a risk factor for nosocomialEnterococcus faecalisbacteremia: a matched case-control study.Arch Intern Med1993;153,1581-1586
 
Boyce, JM, Mermel, LA, Zervos, MJ, et al Controlling vancomycin-resistant enterococci.Infect Control Hosp Epidemiol1995;16,634-637
 
Boyce, JM, Opal, SM, Chow, JW, et al Outbreak of multidrug-resistantEnterococcus faeciumwith transferablevanBclass vancomycin resistance.J Clin Microbiol1994;32,1148-1153
 
Morris, JG, Jr, Shay, DK, Hebden, JN, et al Enterococci resistant to multiple antimicrobial agents, including vancomycin.Ann Intern Med1995;123,250-259
 
Bradley, SJ, Wilson, ALT, Allen, MC, et al The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage.J Antimicrob Chemother1999;43,261-266
 
Patterson JE, Przykucki J, Callander N, et al. Control of vancomycin-resistant.Enterococcus faecium colonization and infection in a bone marrow transplant unit [abstract]. Presented at 37th annual meeting of the Infectious Disease Society of America; November 18–21, 1999; Philadelphia, PA.
 

Figures

Figure Jump LinkFigure 1. Increased piperacillin/tazobactam use with a concurrent decrease in cephalosporin use is associated with a decrease in infections due to cephalosporin-resistant Gram-negative bacilli in adult ICUs. Top: Third-quarter 1999 antibiotic usage rates (antibiotic days per 1,000 patient-days) in adult ICUs. The decrease in cephalosporin use and increase in piperacillin/tazobactam use over an extended time is also documented.7Bottom: Prevalence of infections with cephalosporin-resistant Gram-negative bacilli (infection rate per 1,000 patient-days) in the medical/coronary ICU (MI/CICU), surgical ICU (SICU), and transplant ICU (TICU).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Factors Increasing Antibiotic Resistance
Table Graphic Jump Location
Table 2. Restriction of Third-Generation Cephalosporins*
* 

From Bradley et al.20

References

Martone WJ, Jarvis WR, Culver DH, et al. Incidence and nature of endemic and epidemic nosocomial infections. In: Bennett JV, Brachman PS, eds. Hospital infections. 3rd ed. Boston, MA: Little, Brown and Company, 1992; 577–596.
 
Rice, LB, Willey, SH, Papanicolaou, GA, et al Outbreak of ceftazidime resistance caused by extended-spectrum β-lactamases at a Massachusetts chronic-care facility.Antimicrob Agents Chemother1990;34,2193-2199
 
Moreno, F, Grota, P, Crisp, C, et al Clinical and molecular epidemiology of vancomycin-resistantEnterococcus faeciumduring its emergence in a city in southern Texas.Clin Infect Dis1995;21,1234-1237
 
Meyer, KS, Urban, C, Eagan, JA, et al Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins.Ann Intern Med1993;119,353-358
 
Rice, LB, Eckstein, EC, DeVente, J, et al Ceftazidime-resistantKlebsiella pneumoniaeisolates recovered at the Cleveland Department of Veterans Affairs Medical Center.Clin Infect Dis1996;23,118-124
 
Rahal, JJ, Urban, C, Horn, D, et al Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella.JAMA1998;280,1233-1237
 
Patterson, JE, Hardin, TC, Kelly, CA, et al Association of antibiotic utilization measures and control of multiple-drug resistance inKlebsiella pneumoniae.Infect Control Hosp Epidemiol2000;21,455-458
 
Tokars, JI, Satake, S, Rimland, D, et al The prevalence of colonization with vancomycin-resistant Enterococcus at a Veterans’ Affairs institution.Infect Control Hosp Epidemiol1999;20,171-175
 
Dahms, RA, Johnson, EM, Statz, CL, et al Third-generation cephalosporins and vancomycin as risk factors for postoperative vancomycin-resistant Enteroccocus infection.Arch Surg1998;133,1343-1346
 
Donskey, CJ, Schreiber, JR, Jacobs, MR, et al A polyclonal outbreak of predominantly VanB vancomycin-resistant enterococci in northeast Ohio.Clin Infect Dis1999;29,573-579
 
Quale, J, Landman, D, Saurina, G, et al Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci.Clin Infect Dis1996;23,1020-1025
 
Paterson DL, Ko WC, Mohapatra S, et al.Klebsiella pneumoniae bacteremia: impact of extended spectrum beta-lactamase (ESBL) production in a global study of 216 patients [abstract]. Presented at 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 28 to October 1, 1997; Toronto, Ontario, Canada.
 
Lucas, GM, Lechtzin, N, Puryear, DW, et al Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes.Clin Infect Dis1998;26,1127-1133
 
Linden, PK, Pasculle, AW, Manez, R, et al Differences in outcomes for patients with bacteremia due to vancomycin-resistantEnterococcus faeciumor vancomycin-susceptibleE faecium.Clin Infect Dis1996;22,663-670
 
Gerding, DN Is there a relationship between vancomycin-resistant enterococcal infection andClostridium difficileinfection?Clin Infect Dis1997;25,S206-S210
 
Pallares, R, Pujol, M, Pena, C, et al Cephalosporins as a risk factor for nosocomialEnterococcus faecalisbacteremia: a matched case-control study.Arch Intern Med1993;153,1581-1586
 
Boyce, JM, Mermel, LA, Zervos, MJ, et al Controlling vancomycin-resistant enterococci.Infect Control Hosp Epidemiol1995;16,634-637
 
Boyce, JM, Opal, SM, Chow, JW, et al Outbreak of multidrug-resistantEnterococcus faeciumwith transferablevanBclass vancomycin resistance.J Clin Microbiol1994;32,1148-1153
 
Morris, JG, Jr, Shay, DK, Hebden, JN, et al Enterococci resistant to multiple antimicrobial agents, including vancomycin.Ann Intern Med1995;123,250-259
 
Bradley, SJ, Wilson, ALT, Allen, MC, et al The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage.J Antimicrob Chemother1999;43,261-266
 
Patterson JE, Przykucki J, Callander N, et al. Control of vancomycin-resistant.Enterococcus faecium colonization and infection in a bone marrow transplant unit [abstract]. Presented at 37th annual meeting of the Infectious Disease Society of America; November 18–21, 1999; Philadelphia, PA.
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
Feverish illness in children: assessment and initial management in children younger than 5 years.
National Collaborating Centre for Women's and Children's Health | 8/28/2009
Blepharitis.
American Academy of Ophthalmology | 6/5/2009
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543