3
False-positive blood cultures, or pseudobacteraemias, are an unnecessary drain on hospital and laboratory resources and can undermine clinical confidence in blood culture results. Con- siderable time may be wasted in repeating blood cultures to determine the significance of the isolated organism. In addition, erroneous results may obscure and delay the correct diagnosis and may lead to serious patient mismanagement. In 1998, the sudden appearance of an unusual organism, Pseudomonas fluorescens, in several paediatric blood cultures collected in Townsville General Hospital, suggested that con- tamination was occurring at some stage of the collection or processing procedure. The aims of this study were to investigate the cause of this outbreak of P. fluorescens pseudobacteraemia, to arrest the problem, to assess its effect on patient management, and to determine how best to prevent a recurrence. METHODS This study involved staff interviews, review of medical records, and microbiological investigations during the outbreak itself, in order to establish the cause. Microbiology Laboratory techniques were reviewed to exclude possible laboratory-based contamination. All blood cultures were collected using PediBact (BacTalert; Organon-Teknika, North Carolina, USA) blood culture bottles. Unused PediBact bottles were cultured to exclude contamination. Positive blood culture bottles were Gram-stained and sub- cultured using standard methods. Isolates were identified using the Crystal system (Becton Dickinson; Cockeysville, USA) and Microscan (Dade Behring; West Sacramento, California, USA). All blood collection tube types and equipment involved in blood collection were examined for microbiological contamin- ation. This included lithium heparin tubes used for electrolyte studies, ethylene diamine tetra-acetic acid (EDTA) tubes used for full blood counts, alcohol skin wipes, local anaesthetic cream, plasters, chlorhexidine and iodine solutions, syringes and needles. Any isolates obtained from these sources were identified using the Crystal System and Microscan. Patient review During the outbreak, medical notes were reviewed to determine the reasons for the blood sampling, where blood was collected and by whom, and what other investigations had been performed. The staff involved with blood collection were inter- viewed to determine their techniques of blood collection and inoculation into the blood culture bottles. The medical records were also reviewed retrospectively, in order to determine the extent to which the pseudobacteraemia had affected patient management. Changes in patient manage- ment, which could be attributed to the false positive blood cultures, were assigned one of the following grades: J. Paediatr. Child Health (2002) 38, 63–65 Pseudomonas fluorescens pseudobacteraemia: A cautionary lesson J SMITH, 1 C ASHHURST-SMITH 2 and R NORTON 2 1 Department of Paediatrics and 2 Department of Clinical Microbiology, Townsville General Hospital, Townsville, Queensland, Australia Objectives: To describe an outbreak of pseudobacteraemia caused by Pseudomonas fluorescens in a paediatric population. To document and highlight the effect this outbreak had on clinical management and the steps taken to determine the source. Methods: A clinical and microbiological investigation was carried out into a cluster of 38 pseudobacteraemias caused by Pseudomonas fluorescens in paediatric patients over a 10 month period. Results: The source of the outbreak of pseudobacteraemia was found to be contaminated lithium heparin tubes, which were being filled prior to the filling of the blood culture bottle. Cultures of the same tubes yielded Pseudomonas fluorescens. As a result of the initial positive blood cultures, clinical management was altered in 18 cases. A staff education programme was instituted and eventually resulted in a cessation of the pseudobacteraemia. Conclusions: Pseudobacteraemias are a major cause of potentially inappropriate therapy in febrile children. Attention to detail in the collection of blood cultures can help reduce this outcome. Staff involved in the collection of blood cultures need to be aware of this potential source of contamination. Key words: pseudobacteraemia; Pseudomonas fluorescens. Correspondence: Dr R Norton, Townsville General Hospital, Townsville, Queensland 4810, Australia. Fax: +61 7 4771 5002; email: [email protected] Accepted for publication 9 May 2001.

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Page 1: Pseudomonas fluorescens pseudobacteraemia: A cautionary lesson

False-positive blood cultures, or pseudobacteraemias, are anunnecessary drain on hospital and laboratory resources and canundermine clinical confidence in blood culture results. Con-siderable time may be wasted in repeating blood cultures to determine the significance of the isolated organism. Inaddition, erroneous results may obscure and delay the correctdiagnosis and may lead to serious patient mismanagement.

In 1998, the sudden appearance of an unusual organism,Pseudomonas fluorescens, in several paediatric blood culturescollected in Townsville General Hospital, suggested that con-tamination was occurring at some stage of the collection orprocessing procedure.

The aims of this study were to investigate the cause of thisoutbreak of P. fluorescens pseudobacteraemia, to arrest theproblem, to assess its effect on patient management, and todetermine how best to prevent a recurrence.

METHODS

This study involved staff interviews, review of medical records,and microbiological investigations during the outbreak itself, inorder to establish the cause.

Microbiology

Laboratory techniques were reviewed to exclude possiblelaboratory-based contamination. All blood cultures werecollected using PediBact (BacTalert; Organon-Teknika, North

Carolina, USA) blood culture bottles. Unused PediBact bottleswere cultured to exclude contamination.

Positive blood culture bottles were Gram-stained and sub-cultured using standard methods. Isolates were identified usingthe Crystal system (Becton Dickinson; Cockeysville, USA)and Microscan (Dade Behring; West Sacramento, California,USA).

All blood collection tube types and equipment involved inblood collection were examined for microbiological contamin-ation. This included lithium heparin tubes used for electrolytestudies, ethylene diamine tetra-acetic acid (EDTA) tubes usedfor full blood counts, alcohol skin wipes, local anaestheticcream, plasters, chlorhexidine and iodine solutions, syringesand needles. Any isolates obtained from these sources wereidentified using the Crystal System and Microscan.

Patient review

During the outbreak, medical notes were reviewed to determinethe reasons for the blood sampling, where blood was collectedand by whom, and what other investigations had beenperformed. The staff involved with blood collection were inter-viewed to determine their techniques of blood collection andinoculation into the blood culture bottles.

The medical records were also reviewed retrospectively, inorder to determine the extent to which the pseudobacteraemiahad affected patient management. Changes in patient manage-ment, which could be attributed to the false positive bloodcultures, were assigned one of the following grades:

J. Paediatr. Child Health (2002) 38, 63–65

Pseudomonas fluorescens pseudobacteraemia:A cautionary lesson

J SMITH,1 C ASHHURST-SMITH2 and R NORTON2

1Department of Paediatrics and 2Department of Clinical Microbiology, Townsville General Hospital,Townsville, Queensland, Australia

Objectives: To describe an outbreak of pseudobacteraemia caused by Pseudomonas fluorescens in a paediatric population.To document and highlight the effect this outbreak had on clinical management and the steps taken to determine the source.Methods: A clinical and microbiological investigation was carried out into a cluster of 38 pseudobacteraemias caused byPseudomonas fluorescens in paediatric patients over a 10 month period.Results: The source of the outbreak of pseudobacteraemia was found to be contaminated lithium heparin tubes, whichwere being filled prior to the filling of the blood culture bottle. Cultures of the same tubes yielded Pseudomonas fluorescens.As a result of the initial positive blood cultures, clinical management was altered in 18 cases. A staff education programmewas instituted and eventually resulted in a cessation of the pseudobacteraemia.Conclusions: Pseudobacteraemias are a major cause of potentially inappropriate therapy in febrile children. Attention todetail in the collection of blood cultures can help reduce this outcome. Staff involved in the collection of blood cultures needto be aware of this potential source of contamination.

Key words: pseudobacteraemia; Pseudomonas fluorescens.

Correspondence: Dr R Norton, Townsville General Hospital, Townsville, Queensland 4810, Australia. Fax: +61 7 4771 5002; email:[email protected]

Accepted for publication 9 May 2001.

Page 2: Pseudomonas fluorescens pseudobacteraemia: A cautionary lesson

• Grade 3. Alteration to management involving any of thefollowing: readmission or extension of hospital admission;further investigation; administration of antibiotics; or adverseside effects of altered management.• Grade 2. Patient recalled for clinical review, but manage-ment otherwise unchanged.• Grade 1. Follow-up telephone call, with no further actionrequired.• Grade 0. No alteration in patient management.

RESULTS

The medical records of 38 patients were reviewed. The chartsof one patient could not be traced. The outbreak of pseudo-bacteraemia occurred over a 10 month period from 26 March1998 until 19 January 1999. The distribution of these pseudo-bacteraemia over time is shown in Table 1. There were 22 maleand 16 female patients, ranging in age from 1 day old to 17 years of age. Each patient had one set of false-positiveblood cultures. Thirty-three of the patients had been admittedto a tertiary referral centre. Blood had been collected from 32of these patients in the Accident and Emergency Department,by either accident and emergency or paediatric medical staff,and in one case the blood had been collected in the paediatricward. In two other cases, blood had been collected by theneonatal registrars at the district obstetric hospital. In afurther three patients, the blood had been collected in ruralgeneral practices and sent to the Townsville General Hospitallaboratory.

Examination of blood collection techniques

Examination of the hospital charts in May 1998 showed that inall cases the blood cultures had been performed as part of aninfection screen, with blood being collected simultaneously forother investigations. Full blood count and electrolyte studieshad been performed in every case. The paediatric and accidentand emergency staff were questioned in May 1998 regardingtheir blood collecting techniques. It became apparent that anumber of staff inoculated the blood culture bottles last whencollecting blood for a number of investigations. In these cases,the blood collecting needle was usually removed from thesyringe nozzle to inject the other tubes before a sterile needlewas attached to inoculate the blood culture bottles. Theirreason for this procedure was that as the blood culture bottlecontains a vacuum, there was a danger that the entire syringecontents could be drawn into the bottle. In addition, somepersonnel filled the coagulation tubes first to avoid the possi-bility of clot formation.

Microbiology

Culture results indicated that the lithium heparin tubes for elec-trolyte studies were contaminated. Nineteen out of the 20 tubestested yielded an organism that biochemically and pheno-typically resembled the organism recovered from the false-positive blood cultures. The organism was later identified as P. fluorescens. Isolates from both blood cultures and the bloodcollection tubes were identified using the Crystal system andMicroscan. All other potential sources of contamination did notyield any growth. The tube isolates had the same susceptibilitypattern as the isolates from the blood cultures. The bloodcollection tubes were supplied by a single company and wereused throughout the district. The tubes tested were selected atrandom from areas in the hospital where the paediatric tubeswere used. No attempt was made to quantify or to performmolecular typing of the organisms.

Effects on patient management

Of the 38 patients, a total of 18 patients (47%) had theirclinical management altered to some extent as a result of thefalse positive blood cultures. In 20 patients (53%), there was nochange to patient management. In these patients, the clinicalpicture did not fit with a bacteraemia, and either they improvedor they had other diagnoses to explain their symptoms. Asummary of this and the grades of alteration to patient manage-ment are shown in Table 2.

64 J Smith et al.

Table 1 Proportion of paediatric blood cultures with pseudo-bacteraemia detected over the outbreak period

Total number of Blood cultures withMonth blood cultures pseudobacteraemia (%)

1998April 65 5 (7.6%)May 67 9 (13.4%)June (Intervention instituted) 82 5 (6.1%)July 63 5 (7.9%)August 82 5 (6.1%)September 59 3 (5.1%)October 72 1 (1.4%)November 91 2 (2.2%)December 96 0 (0.0%)

1999January 38 3 (7.9%)February 44 0 (0.0%)

Table 2 Summary of interventions resulting from the detection of Pseudomonas fluorescens bacteraemia in 38 patients

Intervention grade Interventions (%) Oral Parenteral Investigations Investigations Investigations Readmissionantibiotics antibiotics (blood cultures) (lumbar puncture) (other)

Grade 0 (Management not altered) 20 (52.5%) 0 0 0 0 0 0Grade 1 (Follow up telephone call only) 4 (10.5%) 0 0 0 0 0 0Grade 2 (Clinic review only) 3 (8.0%) 0 0 0 0 0 0Grade 3 (Significant change in management) 11 (29.0%) 4 7 2 1 3 1

Page 3: Pseudomonas fluorescens pseudobacteraemia: A cautionary lesson

Interventions to reduce episodes of pseudobacteraemia

As a result of the outbreak being linked to contaminated lithiumheparin tubes, an extensive education campaign was instituted inJune 1998. This included educational sessions on blood culturecollection techniques for all staff involved in the collection of paediatric blood cultures, and formal notification to heads ofclinical departments. In addition, negotiations with the suppliersof the lithium heparin tubes were carried out that explored alter-natives to the contaminated tubes. Complete replacement of alltubes was prolonged for a further six months due to issues withsupply. Despite these measures, sporadic episodes of pseudo-bacteraemia continued till January 1999. There have been nonesince then, despite the continuing collection of similar numbersof paediatric blood cultures and an awareness among laboratorystaff of this potential contaminant in blood cultures.

DISCUSSION

Indicators of pseudobacteraemia are the sudden appearance ofpositive blood cultures due to an organism infrequently associ-ated with clinical disease, and a poor correlation betweenclinical and laboratory findings. This is suggested by persis-tence of positive cultures in patients whose symptoms haveresolved, absence of any underlying sites of infection or pre-disposing factors, symptoms that are inconsistent with septi-caemia, or an uneventful recovery before blood culture resultsare known or before antibiotic therapy can be started.

The problem of pseudobacteraemia is not new.1–6 Between1956 and 1975, pseudobacteraemia accounted for 11% of 181nosocomial outbreaks investigated by the Centers for DiseaseControl in Atlanta.1 Several different sources of contaminationhave been traced to various aspects of the blood culture processand identified as the cause of pseudobacteraemia, includingthe media itself, skin preparation, collection equipment andhandling of specimens in the laboratory.1–5

A range of environmental organisms has been implicated inthese outbreaks. The duration has varied from a few days to2 years and the number of patients involved has ranged from 6 to 79.1–10

Pseudobacteraemia creates diagnostic confusion and maycause a number of clinical problems. Patients may receiveunnecessary antibiotic treatment, with the potential for adverseeffects, unnecessary investigations, or prolonged hospital admis-sions. False-positive blood cultures may delay investigation forthe true cause of a patient’s symptoms. In addition, the growthof the contaminating organism in the culture may mask theidentification of another organism causing true bacteraemia.

Evacuated blood collection tubes are a potential source ofiatrogenic infection. Pseudomonas fluorescens has been impli-cated in a number of such outbreaks.7,8,11,12 The use of non-sterile collection tubes for biochemistry and haematology hasalso been implicated in these outbreaks.

A study of the microbiology of evacuated blood collectiontubes showed that 14% of the tubes examined containedmicroorganisms: Gram-positive bacteria, Gram-negative bac-teria and fungi.6

A clue to possible sources of contamination in the outbreakdescribed in our report, was the fact that only paediatric bloodcultures were involved. Once the blood culture bottles wereexcluded as a source, attention turned towards the collectionprocess. It was only through a process of elimination that thelithium heparin tubes were subsequently identified as thesource. Once the source of this outbreak was defined, anintensive education campaign was instituted among residentmedical and nursing staff on the importance of inoculatingblood culture bottles first. It is probably a reflection on how theopposite practice is ingrained that pseudobacteraemia con-tinued nearly seven months after the problem source was firstbrought to the attention of staff. The manufacturers of thecollection tubes were also informed and have subsequentlyreplaced the tubes. There have been no further episodes since.Molecular typing of the isolates would have been a usefuladjunct to this investigation, but this was not carried out due tologistic issues.

An awareness that collection tubes may not be sterile needsto be highlighted among staff involved in blood culture collec-tion. This, coupled with a strict adherence to blood culturecollection procedures, will reduce the likelihood of furtheroutbreaks like these from occurring.

REFERENCES

1 Maki D. Through a Glass Darkly. Nosocomial pseudoepidemicsand pseudobacteremias (Editorial). Arch. Intern. Med. 1980; 140:26–8.

2 Kaslow R, Mackel D, Mallison G. Nosocomial pseudobacter-aemia. Positive blood cultures due to contaminated benzalkoniumantiseptic. JAMA 1976; 236: 2407–9.

3 Berkelman R, Lewin S, Allen J et al. Pseudobacteremia attributedto contamination of povidone-iodine with Pseudomonas cepacia.Ann. Int. Med. 1981; 95: 32–6.

4 Keys T, Melton L, Maker M et al. A suspected hospital outbreakof pseudobacteraemia due to Pseudomonas stutzeri. J. Infect. Dis.1983; 147: 489–93.

5 McNeil M, Davis B, Solomon S et al. Ewingella Americana:recurrent pseudobacteremia from a persistent environmentalreservoir. J. Clin. Microbiol. 1987; 25: 498–500.

6 Hoffman P, Arnow P, Goldman D, Parrott P, Stamm W, McgowanJ. False positive blood cultures. Association with nonsterile collec-tion tubes. JAMA 1976; 236: 2073–5.

7 Simor A, Ricci J. Lau et al. Pseudobacteremia due toPseudomonas fluorescens. Pediatr. Inf. Dis. 1985; 85: 508–12.

8 Anderson M, Davey R. Pseudobacteraemia with Pseudomonasfluorescens. Med. J. Aust. 1994; 160: 233–4.

9 Wilson P, Petts D, Baker S. An outbreak of pseudobacteraemia.BMJ. 1981; 283: 866.

10 Cookson B, Mehtar S, Sadler G. Serratia pseudobacteraemia.Lancet 1982; ii: 1276–7.

11 Namnyak S, Hussain S, Davalle J, Roker K, Strickland M. Contaminated lithium heparin bottles as a source of pseudo-bacteraemia due to Pseudomonas fluorescens. J. Hosp. Infect.1999; 41: 23–8.

12 Collignon P, Dreimanis D, Beckingham W. Pseudobacteraemiadue to Pseudomonas fluorescens. J. Hosp. Infect. 1999; 43:321–2.

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