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An outbreak of multiresistant Klebsiella in a neonatal intensive care unit
Journal of Hospital Infection (1993) 25, 287-291
SHORT
REPORT
An outbreak of multiresistant neonatal intensive 0. Reish,*§
S. Ashkenazi,t$
Klebsiella care unit
N. Naor,*$
in a
Z. Samrat@ and P. Merlob*§
Department of *Neonatology, TInfectious Disease Unit, and SMicrobiology Laboratory, Children’s Hospital and Beilinson Medical Center, Petah Tiqva, Israel, #Tel Aviv University, Suckler Faculty of Medicine, Israel Accepted for publication
18 August 1993
Summary:
An outbreak of multiresistant Klebsiella pneumoniae occurring in a neonatal intensive care unit is described. All infections developed at least 5 days after admission to the unit (range, S-40 days). Four infants had septicaemia and one had urinary tract infection. Three of the infected infants died. All klebsiella isolates were resistant to ampicillin, cefotaxime, cefuroxime, co-amoxiclav, mezlocillin, chloramphenicol, gentamicin, and ceftazidime (except in two); all were susceptible to imipenem, amikacin and quinolones. An extensive case-control study identified the following significant risk factors for colonization: prematurity; presence of indwelling catheters; previous antibiotic treatment; and parenteral nutrition. The outbreak was controlled with re-emphasis on strict handwashing practices, cohorting, closure of the unit to outborn admissions, and changing the regimen of empirical antibiotic therapy. Physicians should be aware of multiresistant Klebsiella spp. and change treatment whenever clinically indicated, even before culture results are available.
Keywords: catheter;
Multiresistance; total parenteral
Klebsiella
pneumoniae;
antibiotics;
indwelling
nutrition.
Introduction
Infants cared for in a neonatal intensive care unit (NICU) are particularly susceptible to infectious complications. Among the possible reasons are immaturity, prolonged hospitalization, and numerous invasive procedures, such as intubation and insertion of indwelling catheters.’ Most such reported infections have been caused by Escherichia coli, Klebsiella species, Streptococcus group B and, in recent years, also Staphylococcus
epidermidis.2-3 Correspondence 49181, Israel. 0195-6701/93/120287+05
to: Dr
Shai
Ashkenazi,
Pediatric
Infectious
$0X.00/0
Diseases,
PO Box
8145,
0 1993 The Ilospital
287
Petah
Infection
Tiqva,
Society
0. Reish et al.
288 Table
I. Cultwes positive for
Klebsiella
pneumoniae
&ring
an outbreak in
NICV No. of positive cultures
Specimen Blood Suprapubic aspirate Stool Sputum Tip of catheter *Two neonates were colonized cultures were negative.
No. of infants infected
8
4
1; 4 2
:
before being infected.
; Cerebrospinal
fluid
(CSF)
The frequent use of antibiotics in NICUs increases the likelihood of resistant strains. 4-6 This may be due to either selection of drug resistance in the infant microflora or colonization with new resistant strains. The emergence of resistant strains has been associated with epidemic infections and increased mortality. ‘-lo We report an outbreak of klebsiella infection in our NICU, which was resistant to most of the antibiotics that are usually used empirically for suspected septicaemia in neonatal units. Patients
and methods
The NICU of Beilinson Medical Center is a tertiary care centre, serving obstetric departments of several hospitals in the area. It is also a referral center for surgical, cardiological and neurosurgical neonatal patients. The data for this report included all newborns treated in the Department of Neonatology from 7 July to 10 October, 1991. During this period 53 infants were admitted to the NICU, 43 of whom were born in our hospital. Cultures were taken from every infant upon admission, as done routinely in-our NICU. Body sites sampled included the nose, throat and external auditory canal. When infection was suspected clinically, cultures were also taken from blood, cerebrospinal fluid, urine, stools, and sputum. Samples were handled and cultured in the bacteriology laboratory according to routine laboratory methods. Infections were defined according to the criteria published by Centers for Disease Control (CDC), Atlanta.” In-vitro antimicrobial susceptibility was assessed by the Kirby-Bauer disc sensitivity method. Results During the three months of the outbreak, four cases of septicaemia and case of urinary tract infection due to K. pneumoniae were observed. In infant, septicaemia occurred after abdominal operation for ileal atresia. number of positive cultures and the site from which they were obtained shown in Table I. In addition, three uninfected neonates were colonized K. pneumoniae.
one one The are by
Multiresistant Table II. Distribution
outbreak
Klebsiella
289
of risk factors among patients hospitalized in NICU Noninfected (n=48)
Gestational age < 30 weeks Birthweight < 1500 g Total parenteral nutrition > 2 weeks Indwelling catheter > 2 weeks Previous antibiotic treatment > 5 days
No.
%
1: 5 6 6
14.5 31.0 IO.5 12.5 12.5
during the outbreak
Infected No (n=5) 4 4 5 :
%
P
80 80 100 100 100
0.01 0.18 0.006 0.01 0.01
All the documented infections were diagnosed after the fifth day of life, thus fulfilling the CDC criteria for nosocomial infections. The distribution of infections among affected newborns according to birth weight, gestational age and total parenteral nutrition, as well as other risk factors, such as previous antibiotic treatment and presence of an indwelling catheter, are shown in Table II. The case-control study data gathered showed a significantly higher percentage of certain risk factors among the infected patients in comparison to noninfected patients who were hospitalized in the NICU during the outbreak period. The significant risk factors included: gestational age below 30 weeks, use of total parenteral nutrition, or indwelling catheters, and previous antibiotic treatment. The klebsiella isolates were indole-negative K. pneumoniae. All isolates were resistant to ampicillin, cefotaxime, cefuroxime, co-amoxiclav, mezlocillin, chloramphenicol and gentamicin; all isolates except two were resistant to ceftazidime. All isolates were susceptible to amikacin, imipenem, and quinolones. Multiple-antibiotic resistance of other microorganisisms was not noted in our NICU during that period or thereafter. In addition, background data on infection, which is collected routinely in our NICU, showed no multiresistant klebsiella isolate before the outbreak or after its resolution. After the recovery of one multiresistant isolate, whenever sepsis was suspected, treatment with imipenem and amikacin was initiated. However, mortality was still high: 3 of 5 infected patients (60%). One of these patients, a dysmorphic term infant with multiple anomalies, including ileal atresia and cornea1 dysgenesis, died at the age of 40 days from multisystem failure and septic shock. The other two fatalities were extremely low birth weight preterm infants with hyaline membrane disease and septic shock. Cohorting of infected and colonized neonates, education concerning strict handwashing practices and temporary closure of the unit to outborn admissions resolved the outbreak. Discussion
Suspected treatment,
bacterial usually
infection in the newborn requires prompt antimicrobial before culture results are available.‘s3 The choice of
290
0. Reish et al.
antimicrobial agents in the nursery should be based on the prevalence of pathogens that are acquired during delivery (vertical transmission) and on the specific environment of the nursery (horizontal transmission). Klebsiella species are common nosocomial bacteria in the NICU.‘s6 Hamburg et al. found a colonization rate of KZebsieZZa of about 60% in their infants, in agreement with the findings of other studies.4vs The first site colonized was usually the rectum, indicating a faecal-oral route of transmission. Although the umbilicus has been shown by some authors to be an important source of epidemic spread in the nursery,4 others have found that the umbilicus alone was the first site of colonization in only 5% of infants. During the outbreak in our NICU, stool cultures were positive in all five infected infants, in four of whom blood cultures were also positive. Spread to the CSF was not shown in any of these newborns. This may have been due to immediate administration of appropriate antibiotics in accordance with the first culture of multiresistant KZebsieZZa reported by our laboratory. The important measures which should be undertaken to decrease colonization in a neonatal ward are strict hygienic practices, cohort nursing care, appropriate antibiotic policy,5,‘o and, in addition, temporary closure of the unit to outborn admission. The extensive use of antibiotics, especially ampicillin, has been reported as an important cause of the emergence of multiresistant strains of KZebsieZZa.‘*@’ Indeed, ampicillin and gentamicin were used as the empirical treatment in our NICU before the outbreak. Changing the regimen of antimicrobial treatment to amikacin and imipenem (according to the results of susceptibility testing) terminated the serious outbreak in our NICU. The case-control study, which was performed during the outbreak, identified several risk factors for colonization of this KZebsieZZu sp.: prematurity (< 30 weeks), prolonged antibiotic treatment, insertion of indwelling catheters, and total parenteral nutrition. All these factors are found in particular in severely ill patients and may explain the very high mortality rate (60%). Outbreaks of multiresistant KZebsieZZu have been rarely reported4s6v9 and represent a difficult therapeutic problem. Physicians should be aware of this multiresistant KZebsieZZu in NICUs and change their antibiotic treatment promptly, whenever required. Attention should be given to the stool cultures as an indication of the emergence of a resistant strain, and as a possible source of a significant systemic infection in the severely ill newborns in NICUs. References 1. Grauel EL, Halle E, Bollman R, Buchholz P, Battenberg S. Neonatal septicaemia-incidence, etiology and outcome. A 6 years analysis. Acta Puediutr Band 1989; (suppl) 360: 113-119. 2. Malfin G. Ecological impact of antibiotics in neonatal units. Lancet 1989; 26: 509.
Multiresistant
Klebsiella
outbreak
291
3. Siegel JD, McCracken GH Jr. Sepsis neonatorum. N Engl J Med 1981; 304: 642-647. 4. Hamburg A, Lagergvist-Widh A, Zettersten U, Engberg S, Sedin G, Sjoberg L. Spread of Klebsiella in a neonatal ward. ScandJ Infect Dis 1991; 23: 189-194. 5. John JF Jr, McKee KT Jr, Twitty JA, Schaffner W. Molecular epidemiology of sequential nursery epidemics caused by multiresistant Klebsiella pneumoniae. J Pediatr 1983; 102: 825-830. . 6. Morgan ME, Hart CA, Cooke RW. Klebsiella infection in a neonatal intensive care unit: role of bacteriological surveillance. J Hasp Infect 1984; 5: 377-385. 7. Bennett R, Erikson M, Zetterstrom R. Bacterial etiology of neonatal septicaemia in relation to prior antibiotic treatment. Acta Paediatr Stand 1987; 76: 673-674. 8. Sprizer R, Kamp HJV, Ozaljic G, Sauer PJJ. Five years of cefotaxime use in a neonatal intensive care unit. Pediatr Inf Dis J 1990; 9: 92-96. 9. Tullus K, Berglund B, Burman LG. Emergence of cross-resistance to J3-lactam antibiotics in fecal Escherichia coli and Klebsiella strains from neonates treated with ampicillin or cefuroxime. Antimicrobial Agents Chemother 1990; 34: 361-362. 10. Wielunsky E, Drucker M, Cohen T, Reisner SH. Replacement of gentamicin by amikacin as a means of decreasing gentamicin resistance of Gram-negative rods in a neonatal intensive care unit. Isr J Med Sci 1983; 19: 1006-1008. 11. Centersfor Disease Control. Outline for surveillance and control of nosocomial infections. Atlanta, Georgia, 1983.
SHORT
REPORT
An outbreak of multiresistant neonatal intensive 0. Reish,*§
S. Ashkenazi,t$
Klebsiella care unit
N. Naor,*$
in a
Z. Samrat@ and P. Merlob*§
Department of *Neonatology, TInfectious Disease Unit, and SMicrobiology Laboratory, Children’s Hospital and Beilinson Medical Center, Petah Tiqva, Israel, #Tel Aviv University, Suckler Faculty of Medicine, Israel Accepted for publication
18 August 1993
Summary:
An outbreak of multiresistant Klebsiella pneumoniae occurring in a neonatal intensive care unit is described. All infections developed at least 5 days after admission to the unit (range, S-40 days). Four infants had septicaemia and one had urinary tract infection. Three of the infected infants died. All klebsiella isolates were resistant to ampicillin, cefotaxime, cefuroxime, co-amoxiclav, mezlocillin, chloramphenicol, gentamicin, and ceftazidime (except in two); all were susceptible to imipenem, amikacin and quinolones. An extensive case-control study identified the following significant risk factors for colonization: prematurity; presence of indwelling catheters; previous antibiotic treatment; and parenteral nutrition. The outbreak was controlled with re-emphasis on strict handwashing practices, cohorting, closure of the unit to outborn admissions, and changing the regimen of empirical antibiotic therapy. Physicians should be aware of multiresistant Klebsiella spp. and change treatment whenever clinically indicated, even before culture results are available.
Keywords: catheter;
Multiresistance; total parenteral
Klebsiella
pneumoniae;
antibiotics;
indwelling
nutrition.
Introduction
Infants cared for in a neonatal intensive care unit (NICU) are particularly susceptible to infectious complications. Among the possible reasons are immaturity, prolonged hospitalization, and numerous invasive procedures, such as intubation and insertion of indwelling catheters.’ Most such reported infections have been caused by Escherichia coli, Klebsiella species, Streptococcus group B and, in recent years, also Staphylococcus
epidermidis.2-3 Correspondence 49181, Israel. 0195-6701/93/120287+05
to: Dr
Shai
Ashkenazi,
Pediatric
Infectious
$0X.00/0
Diseases,
PO Box
8145,
0 1993 The Ilospital
287
Petah
Infection
Tiqva,
Society
0. Reish et al.
288 Table
I. Cultwes positive for
Klebsiella
pneumoniae
&ring
an outbreak in
NICV No. of positive cultures
Specimen Blood Suprapubic aspirate Stool Sputum Tip of catheter *Two neonates were colonized cultures were negative.
No. of infants infected
8
4
1; 4 2
:
before being infected.
; Cerebrospinal
fluid
(CSF)
The frequent use of antibiotics in NICUs increases the likelihood of resistant strains. 4-6 This may be due to either selection of drug resistance in the infant microflora or colonization with new resistant strains. The emergence of resistant strains has been associated with epidemic infections and increased mortality. ‘-lo We report an outbreak of klebsiella infection in our NICU, which was resistant to most of the antibiotics that are usually used empirically for suspected septicaemia in neonatal units. Patients
and methods
The NICU of Beilinson Medical Center is a tertiary care centre, serving obstetric departments of several hospitals in the area. It is also a referral center for surgical, cardiological and neurosurgical neonatal patients. The data for this report included all newborns treated in the Department of Neonatology from 7 July to 10 October, 1991. During this period 53 infants were admitted to the NICU, 43 of whom were born in our hospital. Cultures were taken from every infant upon admission, as done routinely in-our NICU. Body sites sampled included the nose, throat and external auditory canal. When infection was suspected clinically, cultures were also taken from blood, cerebrospinal fluid, urine, stools, and sputum. Samples were handled and cultured in the bacteriology laboratory according to routine laboratory methods. Infections were defined according to the criteria published by Centers for Disease Control (CDC), Atlanta.” In-vitro antimicrobial susceptibility was assessed by the Kirby-Bauer disc sensitivity method. Results During the three months of the outbreak, four cases of septicaemia and case of urinary tract infection due to K. pneumoniae were observed. In infant, septicaemia occurred after abdominal operation for ileal atresia. number of positive cultures and the site from which they were obtained shown in Table I. In addition, three uninfected neonates were colonized K. pneumoniae.
one one The are by
Multiresistant Table II. Distribution
outbreak
Klebsiella
289
of risk factors among patients hospitalized in NICU Noninfected (n=48)
Gestational age < 30 weeks Birthweight < 1500 g Total parenteral nutrition > 2 weeks Indwelling catheter > 2 weeks Previous antibiotic treatment > 5 days
No.
%
1: 5 6 6
14.5 31.0 IO.5 12.5 12.5
during the outbreak
Infected No (n=5) 4 4 5 :
%
P
80 80 100 100 100
0.01 0.18 0.006 0.01 0.01
All the documented infections were diagnosed after the fifth day of life, thus fulfilling the CDC criteria for nosocomial infections. The distribution of infections among affected newborns according to birth weight, gestational age and total parenteral nutrition, as well as other risk factors, such as previous antibiotic treatment and presence of an indwelling catheter, are shown in Table II. The case-control study data gathered showed a significantly higher percentage of certain risk factors among the infected patients in comparison to noninfected patients who were hospitalized in the NICU during the outbreak period. The significant risk factors included: gestational age below 30 weeks, use of total parenteral nutrition, or indwelling catheters, and previous antibiotic treatment. The klebsiella isolates were indole-negative K. pneumoniae. All isolates were resistant to ampicillin, cefotaxime, cefuroxime, co-amoxiclav, mezlocillin, chloramphenicol and gentamicin; all isolates except two were resistant to ceftazidime. All isolates were susceptible to amikacin, imipenem, and quinolones. Multiple-antibiotic resistance of other microorganisisms was not noted in our NICU during that period or thereafter. In addition, background data on infection, which is collected routinely in our NICU, showed no multiresistant klebsiella isolate before the outbreak or after its resolution. After the recovery of one multiresistant isolate, whenever sepsis was suspected, treatment with imipenem and amikacin was initiated. However, mortality was still high: 3 of 5 infected patients (60%). One of these patients, a dysmorphic term infant with multiple anomalies, including ileal atresia and cornea1 dysgenesis, died at the age of 40 days from multisystem failure and septic shock. The other two fatalities were extremely low birth weight preterm infants with hyaline membrane disease and septic shock. Cohorting of infected and colonized neonates, education concerning strict handwashing practices and temporary closure of the unit to outborn admissions resolved the outbreak. Discussion
Suspected treatment,
bacterial usually
infection in the newborn requires prompt antimicrobial before culture results are available.‘s3 The choice of
290
0. Reish et al.
antimicrobial agents in the nursery should be based on the prevalence of pathogens that are acquired during delivery (vertical transmission) and on the specific environment of the nursery (horizontal transmission). Klebsiella species are common nosocomial bacteria in the NICU.‘s6 Hamburg et al. found a colonization rate of KZebsieZZa of about 60% in their infants, in agreement with the findings of other studies.4vs The first site colonized was usually the rectum, indicating a faecal-oral route of transmission. Although the umbilicus has been shown by some authors to be an important source of epidemic spread in the nursery,4 others have found that the umbilicus alone was the first site of colonization in only 5% of infants. During the outbreak in our NICU, stool cultures were positive in all five infected infants, in four of whom blood cultures were also positive. Spread to the CSF was not shown in any of these newborns. This may have been due to immediate administration of appropriate antibiotics in accordance with the first culture of multiresistant KZebsieZZa reported by our laboratory. The important measures which should be undertaken to decrease colonization in a neonatal ward are strict hygienic practices, cohort nursing care, appropriate antibiotic policy,5,‘o and, in addition, temporary closure of the unit to outborn admission. The extensive use of antibiotics, especially ampicillin, has been reported as an important cause of the emergence of multiresistant strains of KZebsieZZa.‘*@’ Indeed, ampicillin and gentamicin were used as the empirical treatment in our NICU before the outbreak. Changing the regimen of antimicrobial treatment to amikacin and imipenem (according to the results of susceptibility testing) terminated the serious outbreak in our NICU. The case-control study, which was performed during the outbreak, identified several risk factors for colonization of this KZebsieZZu sp.: prematurity (< 30 weeks), prolonged antibiotic treatment, insertion of indwelling catheters, and total parenteral nutrition. All these factors are found in particular in severely ill patients and may explain the very high mortality rate (60%). Outbreaks of multiresistant KZebsieZZu have been rarely reported4s6v9 and represent a difficult therapeutic problem. Physicians should be aware of this multiresistant KZebsieZZu in NICUs and change their antibiotic treatment promptly, whenever required. Attention should be given to the stool cultures as an indication of the emergence of a resistant strain, and as a possible source of a significant systemic infection in the severely ill newborns in NICUs. References 1. Grauel EL, Halle E, Bollman R, Buchholz P, Battenberg S. Neonatal septicaemia-incidence, etiology and outcome. A 6 years analysis. Acta Puediutr Band 1989; (suppl) 360: 113-119. 2. Malfin G. Ecological impact of antibiotics in neonatal units. Lancet 1989; 26: 509.
Multiresistant
Klebsiella
outbreak
291
3. Siegel JD, McCracken GH Jr. Sepsis neonatorum. N Engl J Med 1981; 304: 642-647. 4. Hamburg A, Lagergvist-Widh A, Zettersten U, Engberg S, Sedin G, Sjoberg L. Spread of Klebsiella in a neonatal ward. ScandJ Infect Dis 1991; 23: 189-194. 5. John JF Jr, McKee KT Jr, Twitty JA, Schaffner W. Molecular epidemiology of sequential nursery epidemics caused by multiresistant Klebsiella pneumoniae. J Pediatr 1983; 102: 825-830. . 6. Morgan ME, Hart CA, Cooke RW. Klebsiella infection in a neonatal intensive care unit: role of bacteriological surveillance. J Hasp Infect 1984; 5: 377-385. 7. Bennett R, Erikson M, Zetterstrom R. Bacterial etiology of neonatal septicaemia in relation to prior antibiotic treatment. Acta Paediatr Stand 1987; 76: 673-674. 8. Sprizer R, Kamp HJV, Ozaljic G, Sauer PJJ. Five years of cefotaxime use in a neonatal intensive care unit. Pediatr Inf Dis J 1990; 9: 92-96. 9. Tullus K, Berglund B, Burman LG. Emergence of cross-resistance to J3-lactam antibiotics in fecal Escherichia coli and Klebsiella strains from neonates treated with ampicillin or cefuroxime. Antimicrobial Agents Chemother 1990; 34: 361-362. 10. Wielunsky E, Drucker M, Cohen T, Reisner SH. Replacement of gentamicin by amikacin as a means of decreasing gentamicin resistance of Gram-negative rods in a neonatal intensive care unit. Isr J Med Sci 1983; 19: 1006-1008. 11. Centersfor Disease Control. Outline for surveillance and control of nosocomial infections. Atlanta, Georgia, 1983.