55
Outbreak of a Multiresistant Klebsiella pneumoniae Strain in an Intensive Care
Unit: Antibiotic Use as Risk Factor for Colonization and Infection
Angel Asensio,1 Antonio Oliver,2
Paulino González-Diego,1 Fernando Baquero,2
Jose Claudio Pérez-Dı́az,2 Purificación Ros,4
Javier Cobo,3 Margarita Palacios,1 Dolores Lasheras,1
and Rafael Cantón2
From 1Servicio de Medicina Preventiva, 2Servicio de Microbiologı́a,
3
Unidad de Enfermedades Infecciosas, and 4Unidad Pediátrica
de Cuidados Intensivos, Hospital Ramón y Cajal,
Universidad de Alcalá, Madrid, Spain
An observational study was undertaken to describe a nosocomial outbreak caused by multiresistant Klebsiella pneumoniae (MRKP). Ten patients in the pediatric intensive care unit
(ICU) at a hospital in Madrid were colonized by or infected with MRKP from October 1997
to April 1998. Thirty-two patients with MRKP-negative surveillance cultures who were admitted to the ICU during the outbreak period were selected as control patients. Random
amplified polymorphic DNA analysis of MRKP isolates revealed patterns that were indistinguishable from each other. After identification of colonized patients by surveillance cultures
and implementation of standard and contact precautions, the outbreak was controlled. An
age !12 weeks (odds ratio [OR], 13.1) and previous treatment with third-generation cephalosporins and aminoglycosides (OR, 31.2) were independently associated with MRKP colonization and/or infection. Individual exposure to antibiotics, irrespective of other clinical
determinants, is a risk factor for MRKP acquisition. Screening high-risk patients during
outbreaks and reducing the use of third-generation cephalosporins and aminoglycosides contribute to the control of these epidemics.
Klebsiella pneumoniae has been associated with 2%–5% of
nosocomial infections, particularly those involving the lower
respiratory and urinary tracts [1, 2]. Resistance of this species
to third-generation cephalosporins was first described in the
early 1980s, and a linear increase in resistance has occurred
since 1986 [3, 4]. Resistant isolates most likely gain their resistance by producing extended-spectrum b-lactamases (ESBLs).
These enzymes are derivatives of common b-lactamases that
have undergone one or more amino acid substitutions near the
active site of the enzyme, thus increasing the affinity and the
hydrolytic ability of the enzyme for third-generation cephalosporins and monobactams [5]. Genes encoding these enzymes
are generally located in transferable plasmids, which often code
resistance determinants to other antimicrobial agents such as
aminoglycosides [6].
The epidemiology of ESBL has previously been studied, and
several works have described the potential risk factors associated with multiresistant K. pneumoniae (MRKP) isolates
[7–10]. Nevertheless, studies addressing independent risk factors associated with K. pneumoniae colonization or infection
are scant in the literature. The present study describes a noReceived 10 March 1999; revised 25 August 1999; electronically published
22 December 1999.
Reprints or correspondence: Dr. Angel Asensio, P.O. Box 145, Torrelodones, Madrid, Spain E-28250 ([email protected]).
Clinical Infectious Diseases 2000; 30:55–60
q 2000 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2000/3001-0012$03.00
socomial outbreak caused by a K. pneumoniae strain that was
resistant to third-generation cephalosporins, gentamicin, and
tobramycin, but not to amikacin. Measures implemented for
control of the outbreak and independent potential risk factors
associated with colonization or infection with this MRKP strain
are reported.
Subjects and Methods
Setting. The present study was carried out in the pediatric
intensive care unit (ICU) and the cardiosurgical pediatric ward of
Ramón y Cajal Hospital, in Madrid, Spain. The pediatric ICU
serves an average of 50 patients (either medical or cardiosurgical)
per month. The unit has a 6-bed box (space in the ward set apart
by a transparent partition) and an independent and contiguous 5bed box. The cardiosurgical pediatric ward is endowed with 6 single
boxes and 3 double boxes. Ramón y Cajal Hospital is a university
tertiary level medical referral center with 1120 beds (452 medical,
560 surgical, 56 pediatric, and 70 intensive care beds). The center
has ∼30,000 admissions per year.
Study design. This case-control study compared the frequency
of exposure and the features of case patients with those of control
patients in order to identify and quantify potential independent
risk factors associated with MRKP colonization/infection.
Patients. In December 1997, the Department of Microbiology
and Infectious Diseases at our facility reported the occurrence of
a cluster of MRKP isolates from the pediatric ICU. The infection
control personnel were immediately engaged in the outbreak investigation. A review of microbiological records disclosed a single
previous case on 7 October 1997. In addition to clinical samples,
56
Asensio et al.
screening samples were obtained prospectively twice a week from
all patients admitted to the pediatric ICU or to the pediatric ward,
where the children were transferred after a stay in the pediatric
ICU. These screening samples were obtained from the rectum,
pharynx, and, if possible, bronchoalveolar aspirates and surgical
wounds.
A case patient was defined as a patient who was admitted to the
pediatric ICU or pediatric ward during the period of 7 October
1997 to 15 April 1998 and then was either clinically infected with
[11] or colonized by K. pneumoniae that was resistant to thirdgeneration cephalosporins and aminoglycosides. A control patient
was defined as a patient admitted to the pediatric ICU from 19
December 1997 to 15 April 1998 whose screening cultures were all
negative for MRKP. A total of 32 patients met these criteria.
Clinical and epidemiological data were prospectively and retrospectively collected from the medical records of all patients admitted to the unit during that period. The sociodemographic variables recorded were age and sex. In addition, the following
potential risk factors were also assessed: birth weight, gestational
age, admission diagnosis, hospital clinical course, surgical procedures, number of days of hospital stay prior to admission in the
pediatric ICU, length of stay in the unit, and invasive procedures
(i.e., mechanical ventilation, central and peripheral venous catheterizations, nasogastric or urinary catheterization, parenteral nutrition, and thoracic drainage), as well as duration in days of such
procedures. In addition, the length and type of antimicrobial treatment were recorded.
For the study of risk factors, the period from admission to the
first positive culture (for case patients) and from admission to
discharge from the pediatric ICU (for control patients) was
considered.
Microbiological Studies
Screening for the MRKP strain. Clinical and screening samples were plated onto MacConkey agar plates with and without
1 mg/mL of ceftazidime. Plates were incubated at 377C for 48
h. K. pneumoniae isolates were identified with the semiautomatic
PASCO system (Difco, Detroit) and conventional biochemical
tests.
Susceptibility testing. MICs were determined by agar dilution according to the guidelines of the National Committee
for Clinical Laboratory Standards (NCCLS; M7-A4, 1997) [12]
and with the semiautomatic PASCO system. In addition, disk
diffusion (NCCLS, M2-A6, 1997) [13] was performed to determine the presence of specific aminoglycoside-modifying enzymes, according to the aminoglycoside-resistance patterns [14].
b-lactamase studies. ESBL production by MRKP isolates
was detected by the double-disk–synergy test [15]. b-lactamase
crude sonic extracts for analytical isoelectric focusing were obtained by ultrasonication, as described elsewhere [16], and the
isoelectric point (pI) was determined by application of crude
sonic extracts to Phast gels (pH gradients of 3–9 and 4.5–6.5)
in a PhastSystem apparatus (Pharmacia AB, Uppsala, Sweden).
b-lactamases with known pIs were focused in parallel with the
CID 2000;30 (January)
MRKP extracts. Gels were stained with nitrocefin (500 mg/mL;
Oxoid, Basingstoke, Hampshire, England).
Random amplified polymorphic DNA analysis. MRKP and
control isolates were grown overnight in brain-heart infusion
agar. Chromosomal DNA extraction was performed with the
Quiagen DNA extraction kit (Quiagen, Bonn, Germany). PCR
conditions were modified from those of Gori et al [17]. In brief,
1 m of DNA extract was introduced in the PCR mixture (10
mM of Tris-HCl, 50 mM of KCl, 4 mM of primer, 400 mM
each of dNTP, and 2.5 U of Ampli-Taq-Gold DNA polymerase
[Perkin Elmer, Branchburg, NJ]) in a final volume of 50 mL.
The following primers were used: 50-TCACGATGCA-30, 50GTATTGCCCT-30, and 50-ACGTATCTGC-3.
Amplification was performed in a thermal cycler with 1 cycle
of 10 min at 947C; 45 cycles of 1 min at 947C, 1 min at 367C,
and 1.5 min at 727C; and a final cycle of 5 min at 727C. PCR
products were run in 0.8% agarose gel and stained with ethidium bromide. Random amplified polymorphic DNA (RAPD)
analysis was performed on 10 K. pneumoniae outbreak isolates
(1 isolate from each patient) and 3 third-generation cephalosporin–susceptible K. pneumoniae clinical isolates.
Mating and transformation assays. Conjugation was performed with the JMG 21 Escherichia coli strain (MC 4100, with
kanamycin and nalidixic acid as resistance markers). Transconjugants were selected in Mueller-Hinton agar with a 100mg/Ml concentration of ampicillin and a 100-mg/mL concentration of nalidixic acid. The TG-1 E. coli strain was used as
the receptor strain in transformation assays, and the transformants were selected in Mueller-Hinton agar with ampicillin
(100 mg/mL).
Statistical analysis. The cumulative incidence of colonization/infection by MRKP during the outbreak, as well as on
a monthly basis, was calculated. Data were stored and analyzed
by means of the Statistix statistical software package [18] (Analytical Software, St. Paul, MN) and Epi Info [19] (Centers for
Disease Control and Prevention, Atlanta, GA). Univariate
analysis was carried out for determination of variables significantly associated with colonization/infection with MRKP.
Contingency tables were analyzed by two-tailed Mantel-Haenzel x2 test or by Fisher’s exact test. The Mantel-Haenzel test
for trend was used when a dose-response association was suspected. Quantitative variable differences between case and control patients were compared by Student’s t-test or the Wilcoxon
rank-sum test when appropriate.
A multiple-regression logistic model was developed to identify the potential independent factors associated with colonization/infection by MRKP. From a maximum model including
all potential risk factors showing a P value !.25 in the univariate
analysis, a final model was developed by a backward strategy
[20]. Ninety-five percent CIs were calculated for estimators.
Two-sided tests were used for all analyses. P ! .05 was considered to be statistically significant.
CID 2000;30 (January)
Multiresistant K. pneumoniae Outbreak
Results
Outbreak description and control measures. A total of 235
patients were admitted to the pediatric ICU and cardiosurgical
pediatric ward over the study period. Ten of the patients were
colonized/infected with MRKP. Four patients were infected,
and periodic screening of all patients in the pediatric ICU and
the ward allowed us to identify 6 colonized patients. Indeed,
isolation of all these patients may have helped limit the spread
of the MRKP outbreak.
The MRKP outbreak strain was first isolated in cultures of
blood and umbilical cord specimens from a 16-day-old neonate
on 7 October 1997. This newborn was admitted to the hospital
on 24 September 1997. The diagnosis was great-vessels transposition, and he had remained in the cardiosurgical pediatric
ward until admission to the pediatric ICU in October, when
his general health status worsened. He died on 17 February
1998 of cardiogenic shock. This patient was considered the
index case of the outbreak.
The MRKP strain was isolated again, on 13 December 1997,
from a sample of bronchoalveolar aspirate from a 7-day-old
neonate with faulty pulmonary drainage and interatrial communication. From 19 December 1997 to 23 January 1998, cultures of specimens from 6 additional patients revealed the same
MRKP strain. In February 1998, 2 more positive samples were
obtained from the rectums of 2 neonates (aged 3 and 8 months).
Four of the 6 treated patients had persistent MRKP colonization evident in rectal samples. All the above patients underwent surgery during hospitalization because of congenital
heart abnormalities (table 1).
Cultures of 27 environmental samples (from water reservoirs,
medical devices, and surfaces) and of 17 samples from the hands
Table 1.
57
of health care personnel working in the affected areas were
performed, and all of them were negative for MRKP. On 15
April 1998, the outbreak was considered to be extinguished,
when the last affected patient was discharged from the hospital.
On 28 May 1998, screening was carried out in the hospital
areas involved by the outbreak, and 14 patient samples were
all negative for MRKP.
The outbreak was controlled by implementation of certain
measures: case patients were either isolated in single boxes
(whenever possible) or grouped in cohorts, and the standard
and contact isolation precautions were strengthened. Health
care personnel were reminded to wash their hands carefully
before and after contact with patients and to wear disposable
gloves and gowns.
In addition, doctors were encouraged to use antibiotics with
caution, particularly third-generation cephalosporins and aminoglycosides. Analysis of the rates of use of third-generation
cephalosporins and aminoglycosides (gentamicin or tobramycin), measured as the number of patient-days of antibiotic therapy per 100 patient-days, showed a linear decreasing trend during the epidemic period (x2 test values for trend, 56.8 and 15.3,
respectively; P ! .001; figure 1). This decreasing use of these
antibiotics parallels the decrease in incidence of colonization/
infection by MRKP.
Microbiological findings. All selected MRKP isolates, 1
from each patient, had RAPD patterns that were indistinguishable from each other. This pattern was clearly different from
that of nonoutbreak control isolates. MRKP isolates were positive in double-disk diffusion tests.
Table 2 shows the MICs of anitmicrobials used against the
MRKP isolates and the corresponding transconjugants and
Main characteristics of patients colonized or infected with Klebsiella pneumoniae.
Diagnosis
Case
no.
Patient’s age,
weight (kg)
at admission
Colonization
a
Day
Type of sample
1
2 d, 4.5
14
Rectal
2
3
48 d, 3
2 d, 2.8
7
57
4
5
6
1 d, 3.2
34 d, 2.9
5 y, 15
6
21
21
Rectal
Rectal, bronchial
aspirate, wound
Bronchial aspirate
Rectal, oropharyngeal
Recal
7
8
1 d, 4
15 d, 3.3
69
12
9
8 mo, 7.8
10
10
3 mo, 3.7
22
Rectal
Rectal, bronchial
aspirate
Rectal
Rectal, bronchial
aspirate
Infection
a
Day
14
46
140
63
7
25
12
14
Type or site
Therapy (d)
Outcome (comment)
Bacteremia, catheter
Bacteremia
Bacteremia
(septic shock)
None
Pneumonia
Imi 1 Amik (21)
Mero 1 Amik
Mero 1 Amik 1 Vm
Bacteremia
None
Pneumonia (no pathogen
recovered)
None
Peritonitis
Mero 1 Amik (14)
None
Mero 1 Amik (18)
Fever (no pathogen
recovered)
None
Mero 1 Amik (21)
Cure
Cure
Death, related to infection (colonization
persisted after therapy)
Death, not related to infection
Cure (alive; colonization persisted after
therapy)
Cure (alive)
Death, not related to infection
Cure (alive; colonization persisted after
therapy)
(Alive)
Cure (alive; colonization persisted after
therapy)
Cure (alive)
NOTE. Amik, Amikacin; Imi, imipenem; Mero, meropenem; Vm, vancomycin.
a
Hospital day of diagnosis.
None
Mero 1 Amik (14)
None
Mero 1 Amik (12)
None
(Alive)
58
Asensio et al.
transformants. All MRKP isolates showed resistance to thirdgeneration cephalosporins and aztreonam and decreased susceptibility to gentamicin (18 mg/mL) and tobramycin (8 mg/mL),
but not to amikacin (<4 mg/mL). b-lactam, gentamicin, and
tobramycin resistance were cotransferred by both conjugation
and transformation.
Analytical isoelectric focusing of MRKP isolates revealed 2
b-lactamase bands of 7.6 and 5.9. The latter b-lactamase band
was also observed in both the transconjugants and the transformants. A similar aminoglycoside-resistance profile, suggesting the production of AAC(30)I enzyme, was detected in all
the isolates and the corresponding transconjugants and
transformants.
Risk-factor assessment. The cumulative rate of MRKP infection/colonization over the outbreak was 4.3% (95% CI,
2.1–7.7), and the highest incidence was observed in December
1997 (cumulative incidence, 15.2%).
The age of colonized/infected patients ranged from 1 day to
5 years (table 1). Six patients were males and 4 were females.
Only 1 patient’s birth weight was low, and another was born
prematurely. All 10 patients with MRKP infection/colonization
underwent surgery because of various congenital abnormalities
at some time during hospitalization. The mean hospital stay
was 10 weeks (range, 3–21 weeks). The average length of stay
in the pediatric ICU was 16.9 days (range, 1–49 days).
The mean age of control patients was 40 weeks (range,
1–124). Five patients (15.6%) had low birth weights and 5
(15.6%) were premature. Twenty-five patients (78%) had undergone surgery at some time during hospitalization because
of congenital heart anomalies. The mean hospital stay was 25.4
days (range, 3 days to 10 weeks). The average stay in the pediatric ICU was 11.3 days (range, 2–54 days).
The univariate analysis yielded the following factors associated with MRKP: age !12 weeks, number of days with a
central or peripheral venous catheter, number of days with a
nasogastric tube, and previous treatment with third-generation
CID 2000;30 (January)
Figure 1. Incidence rates of colonization/infection by multiresistant
Klebsiella pneumoniae and rates of use of antibiotics (no. of patientdays of antibiotic therapy per 100 patient-days) over the epidemic
period, at 5-week intervals. Bars depict no. of new cases per 1000
patient-days; triangles and solid line, rate of third-generation cephalosporin use; and circles and dotted line, rate of aminoglycoside use
(x2 test values for trend and rate of third-generation cephalosporin and
aminoglycoside use: 56.8 and 15.3, respectively; P values, !.001).
cephalosporins and aminoglycosides. The number of antimicrobial agents received was linearly associated with an increased
risk of MRKP acquisition (P ! .01 ; figure 2). In addition, the
univariate analysis showed differences in the numbers of days
of mechanical ventilation, but this difference did not reach statistical significance (P 1 .2; table 3).
The multiple-logistic-regression model showed that an age
!12 weeks (OR, 13.1; 95% CI, 1.3–130) and previous treatment
with third-generation cephalosporins and aminoglycosides
(gentamicin or tobramycin; OR, 31.2; 95% CI, 3.3–298) were
factors independently associated with MRKP infection/
colonization.
Discussion
The most remarkable characteristics of the outbreak we report here of K. pneumoniae that was resistant to third-gener-
Table 2. MICs of antimicrobial agents against multiresistant Klebsiella pneumoniae isolates and corresponding Escherichia coli transconjugants and transformants.
Antimicrobial tested
Amoxicillin
Amoxicillin/clavulanate
Piperacillin
Piperacillin/tazobactam
Cefazolin
Cefotaxime
Ceftazidime
b
Ceftazidime 1 clavulanate
Cefepime
Aztreonam
Cefoxitin
Imipenem
K. pneumoniae
E. coli JMG21
E. coli JMG21
transconjugant
E. coli TG-1
E. coli TG-1
transformant
1024 (>1024)
4/2 (4/2–8/4)
1024 (512–1024)
4/2 (2/2–8/2)
64 (64–128)
64 (32–128)
32 (16–64)
0.5 (0.5)
2 (2–4)
16 (16–32)
4 (4–8)
.12 (<.12–.2)
4
2/1
<16
<2/2
<4
<.12
<.12
<.12
<.12
<.12
<1
<.12
256
4/2
512
<2/2
32
32
4
<.12
.5
2
1
.12
4
4/2
<16
<2/2
<4
<.12
<.12
<.12
<.12
<.12
2
<.12
256
4/2
1024
<2/2
32
64
16
.25
1
8
4
.12
a
NOTE. Data are mg/mL (range for 10 different isolates, 1 from each patient).
a
MICs for K. pneumoniae are modal MICs. MIC range is expressed in parenthesis.
b
4 mg/mL fixed concentration.
CID 2000;30 (January)
Multiresistant K. pneumoniae Outbreak
ation cephalosporins and aminoglycosides were the small number of patients involved and the fact that it subsided in a short
period of time. These characteristics are in contrast with those
of other such nosocomial MRKP outbreaks reported in the
literature, which involved a large number of patients and were
of longer duration [7, 21, 22].
MRKP outbreaks most often start in ICUs [7, 23–26], presumably because in these areas patients are exposed to a considerable number of potential risk factors for colonization/infection. Factors such as severe clinical status, extreme age,
misuse or abuse of antimicrobial agents, performance of many
procedures, and high prevalence of invasive procedures may all
contribute to a decrease in patients’ resistance to exogenous
bacteria and to an increase in cross-infection risk. Therefore
ICU patients are ideal reservoirs for MRKP. The digestive tract
is the most usual colonized site [27, 28]; indeed, in all cases in
our study, cultures of rectal specimens were MRKP-positive.
According to our data, therapy with third-generation cephalosporins and aminoglycosides (gentamicin or tobramycin) is
the most important predictor of acquisition of the epidemic
strain, after an age of !12 weeks is accounted for. Although
previous studies have suggested this association, to our knowledge none of them have demonstrated that individual exposure
to third-generation cephalosporins and aminoglycosides is an
independent risk factor for MRKP acquisition [4, 7, 8, 29, 30].
An age of !12 weeks probably is a surrogate marker for
severity of disease. Younger children in this hospital unit tend
to have serious underlying illnesses demanding cardiosurgical
repair. Another potential explanation could be that they have
different ecosystem flora in their digestive tracts, which, in addition to antibiotic exposure, could make them more vulnerable
to multiresistant bacteria.
Table 3. Potential risk factors associated with colonization or infection with Klebsiella pneumoniae resistant to third-generation cephalosporins (Csp) and aminoglycosides.
Factor
Age !12 w
Days
Of hospitalization
With nasogastric tube
With iv catheter
Prematurity
Low brith weight
Surgery
Inmunosuppression
Exposure to
Aminoglycoside
Gm
Tm
Any
3d gen Csp
3d gen Csp and Gm or Tm
Infected/
colonized
patients
(n = 10)
Control
patients
(n = 32)
7 (70)
5 (15)
67.2 (43.5)
19.8 (19.6)
26 (20.2)
1 (10)
1 (10)
10 (100)
3 (30)
8
5
3
8
9
8
(80)
(50)
(30)
(80)
(90)
(80)
25.4 (17.1)
8 (11.2)
12.4 (13.6)
5 (15.6)
5 (15.6)
25 (78)
10 (31.3)
9
6
2
8
11
5
(28)
(19)
(6.2)
(25)
(34)
(16)
OR (95% CI)
or P
12.6 (1.9–94.9)
.014
.008
.020
0.6 (0.02–6.8)
0.6 (0.02–6.8)
2.8 (0.03–68.5)
1.1 (0.2–6.6)
10.2 (1.5–109)
4.3 (0.7–25.5)
6.4 (0.6–85.7)
12 (1.8–129)
17.8 (1.8–411)
21.6 (2.8–240)
NOTE. Data are no. (%) of patients with factor or mean (SE). Gen, generation; Gm, gentamicin; Tm, tobramycin.
59
Figure 2. Association between an increase in risk of acquiring a
multiresistant Klebsiella pneumoniae strain and no. of antibiotics received (x2 test value for trend, 9.701; P = .0018).
Furthermore, we found an association in the univariate analysis between higher risk of MRKP colonization or infection
and the use of both a nasogastric tube and a central or peripheral venous catheter, but these exposures were not independent predictors in the multivariate analysis. On the contrary,
risk factors observed by other authors [7, 8], such as urinary
catheterization, intubation, or invasive medical or surgical procedures, were not encountered as relevant risk factors in our
study, presumably because of the small size of our outbreak.
The measures we enforced for outbreak control were in keeping with current recommendations reported in the literature [21,
25, 31, 32]. First, we reinforced standard precautions and implemented contact precautions: we isolated case patients in single rooms when possible or in groups, and we strictly adhered
to measures to avoid contact with and transmission of infective
agents (i.e., wearing gloves when entering the room, changing
gloves after contact with infective material, wearing gowns during procedures likely to generate splashes, adequately cleaning
and disinfecting environmental surfaces, and not using reusable
equipment for the care of another patient until it was cleaned
and reprocessed appropriately).
In addition, the restricted use of third-generation cephalosporins and aminoglycosides played an important role in controlling the outbreak in a short time. Furthermore, the periodic
screening of all patients in the pediatric ICU and in the ward
allowed us to identify 6 colonized patients. Indeed, isolation of
these patients may have helped limit spread of the MRKP outbreak. Most case patients were successfully treated with meropenem and amikacin. The pharmacokinetic properties of the
drugs precludes significant action on the intestinal carrier state,
and 4 of the 6 treated patients had persistent MRKP colonization evident in rectal samples.
A crucial point for the early control of this outbreak was the
immediate reporting of cases from the department of microbiology to the infection control team. Thus, fluid communication between the staffs of both departments, as well as col-
60
Asensio et al.
laboration with the personnel of the pediatric ICU, was
essential. It is our belief that such a collaboration is of paramount importance for immediate success in controlling
outbreaks.
In summary, on the basis of our findings, we conclude that
individual exposure to third-generation cephalosporins and
aminoglycosides, irrespective of other clinical determinants,
plays a significant role as risk factor for MRKP outbreaks. In
addition to standard and contact precautions, periodic screening of high-risk patients during outbreaks and reducing the use
of third-generation cephalosporins and aminoglycosides contribute to the prevention and control of these epidemics.
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