2014 Volume 37 Issue 1 Pages 26-30
An outbreak of Multi-Drug Resistance Pseudomonas aeruginosa (MDRP) infections occurred in intensive care unit (ICU) and emergency room (ER) between June and August 2007. Five patients who isolated MDRP in the outbreak of 2007 were all used bronchoscopes, thus, we suspected contamination of the bronchoscopes as the cause of outbreak. Although we did not detect MDRP from any bronchoscopes, the outbreak finally ended after all the bronchoscopes had been disinfected appropriately with the reexamination of washing process in 2008 and 2009. We retrospectively reviewed eleven patients who isolated MDRP in 2006 and 2007, and the fact was revealed that bronchoscopes were used in most patients in ICU and ER. Bronchoscopes were significantly used during 2006–2007 period, compared with 2008–2009 period in ICU and ER, and the case-control analysis among all Pseudomonas aeruginosa isolated patients identified that bronchoscopes [risk ratio (RR) 8.25, 95% confidence interval (CI) 1.328–51.26] was one of the most important risk factors for MDRP isolation. Duration from admission to MDRP isolation was significant longer in MDRP-isolated cases (19.82±12.77 d), compared with in non MDRP-isolated controls (11.76±11.69 d: p=0.0453). Our epidemiological analysis suggested the significant risk factors for an MDRP outbreak, and could contribute the estimation of the focus and prevention of future outbreaks.
The importance of Pseudomonas aeruginosa (P. aeruginosa) as a cause of sporadic cases of nosocomial infection, particularly pneumonia, and outbreaks in intensive care units (ICUs) and emergency rooms (ERs) are well established.1) Among these, special vigilance is required when nosocomial outbreaks arise due to multidrug-resistant P. aeruginosa (MDRP).2)
Several nosocomial cross-infections of P. aeruginosa due to medical devices have been reported,3,4) and bronchoscopes have been thought as one of the most important instruments related to outbreaks in the ICU and ER. Bronchoscopes are semicritical instruments that come into contact with mucous membranes and require high-level disinfection.
Between June and August 2007, MDRP was isolated from several patients in the ICU and ER of our hospital, and all of whom had recently undergone flexible bronchoscope examinations. Active epidemiological surveillance was commenced and additional cases were detected in 2006 and 2007.
The present epidemiological investigation was conducted to verify the primary hypothesis of a relationship between infections and bronchoscopes, to identify other potential risk factors for infection, and to implement infection control measures to terminate the outbreak.
Our hospital is a 1076-bed university hospital located in Osaka. A surveillance of hospital-acquired infections using 1-year data from April 2003 to March 2004 found that the mean number of MDRP strains isolated in this hospital is 1.08±0.67 per month. As soon as the hospital’s infection control team recognized that an outbreak of MDRP had occurred in the 8-bed surgical ICU and 20-bed ER, epidemiological information was collected and analyzed in 2007.
The clinical investigation comprised a medical chart review, patient examination, and discussion with nurses and physicians. Cases were defined as patients admitted to the ICU and ER between April 2006 and August 2009 from whose sputum MDRP was isolated.
Case-Control StudyIsolated cases were defined as patients who had stayed in the ICU or ER more than 2 d and from whom MDRP was isolated. Non-isolated controls were defined as patients from whom non-multidrug-resistant P. aeruginosa was isolated, but showed similar histories and backgrounds, such as age and sex, and stayed in the ICU or ER in same period as isolated cases.
Microbiological StudiesP. aeruginosa identification and susceptibility tests were performed using a MicroScan WalkAway systems (Siemens, Munich, Germany).5) P. aeruginosa was considered multidrug-resistant if the bacteria proved resistant to three or more families of antimicrobial agents.2,6) In this study, MDRP was defined as P. aeruginosa resistant to carbapenems (such as imipenem or meropenem), fluoroquinolones, and amikacin.7)
Statistical AnalysisThe chi-squared test and Fisher’s exact test were used to compare categorical variables, and Student’s t-test was employed to compare continuous variables.
Risk ratios (RRs) were calculated to estimate the magnitude of associations between each exposure and outcome using logistic regression analyses. All tests of significance were two-tailed, and values of p<0.05 were considered statistically significant.
From June to August 2007, five cases with detection of MDRP were identified among patients in the ICU and ER (Table 1). The number of MDRP isolation at that time were much more than that of the previous three months of 2007 (p<0.0001) (Fig. 1). An outbreak investigation was therefore initiated.
While examining potential failures in contact isolation precautions, mechanical ventilators and breathing circuits, we discovered that all five cases had recently undergone flexible bronchoscope (Olympus BF-PE2; Olympus, Tokyo, Japan) examination in the ER or ICU.
Bronchoscope Cleaning Procedures and ImprovementWhen we became aware of the potential association between infection and bronchoscope exposure, we performed tests to detect MDRP from these bronchoscopes. Unfortunately, we could not detect any MDRP from bronchoscopes, but a careful review of disinfection protocols and maintenance of the bronchoscope revealed major deviations from hospital policies.
According to our manual, bronchoscopes were usually cleaned just after use. They were manually cleaned by wiping the outer surface and brushing the inner channel and suction ports. The suction button was removed and cleaned. Bronchoscopes were then disinfected in an automated endoscope reprocessor (AER) (Olympus, Tokyo, Japan). We always ensured that bronchoscopes were immersed in germicide and that all channel connectors were attached to the reprocessor, in accordance with the instructions from the manufacturer. After disinfection, the bronchoscopes were rinsed and the channels flushed with sterile water to remove the disinfectant. Channels were then flushed with 70% alcohol. Finally, bronchoscopes are air-dried and stored in a vertical position.
All the steps for cleaning and disinfection of endoscope equipment were checked. We had an endoscope center and most endoscopes in the hospital were disinfected or sterilized there according to our manual. However, bronchoscopes used in the ICU and ER were disinfected separately from other scopes. Unfortunately, compliance with the guidelines and recommendations for the cleaning of those bronchoscopes appeared poor. This cleaning step was sometimes skipped before the outbreaks in the ICU and ER.
We therefore started washing and disinfection in the material management section to centralize the disinfection of endoscopes. Washing spaces were separated depending on each kind of endoscope, and flow lines of endoscopes delivery were simplified. Staff numbers were increased and detailed records of washing and disinfection processes were also renewed. In addition, high-level disinfection was reexamined, and ortho-phthalaldehyde (Cidex OPA; Johnson & Johnson, Tokyo, Japan) was used as the liquid germicide.
Recommended changes included improvements in cleaning, disinfection and maintenance of the bronchoscope. Since then, the number of patients from whom MDRP was isolated in our hospital were decreased (Fig. 1), and no additional patients undergoing bronchoscope examinations have shown isolation of MDRP in 2008 and 2009, compared with 2006 (3 cases) and 2007 (8 cases) (p=0.0076).
Characteristic Changes of Admitted Patients in the ICU and ER during 2006–2007 and 2008–2009We suspected that potential outbreaks have occurred in the whole period of 2006 to 2007 in the ICU and ER, and therefore, retrospectively reviewed all patients in the ICU and ER from whom MDRP was isolated in 2006 and 2007. Overall, 11 patients were identified with MDRP, including isolation from the respiratory tract (sputum in 5 cases, throat swab in 3 cases) and urinary tract (3 cases).
We then retrospectively compared patients admitted to the ICU or ER from April 2006 to March 2008 (n=2607) and from April 2008 to September 2009 (n=2281) (Table 2), and also found that bronchoscope examinations were performed more frequently during the former period than in the latter period (p=0.0062). Duration of hospitalization (p=0.0216), surgery (p=0.045), use of a urinary catheter (p=0.0001), and use of an upper intestine scope (p=0.0418) also differed significantly between 2006–2007 and 2008–2009.
However, the doses (AUD) of anti-Pseudomonas antibiotics used, including 4th generation cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones, did not differ significantly between the two above-mentioned periods.
Risk Factors for P. aeruginosa InfectionNext, we performed a case-non-case study based on comparative data between 2006–2007 and 2008–2009 to detect risk factors for MDRP isolation in the ICU and ER. Multivariate analysis identified bronchoscopes as the one of the most important risk factors for isolation of MDRP (p=0.0238; RR, 8.25; 95% confidence interval (CI), 1.328–51.26) (Table 3).
In addition, duration from admission to P. aeruginosa isolation was significantly longer in MDRP-isolated cases (19.82±12.77 d) than in non-MDRP-isolated controls (11.76±11.69 d; P=0.0453).
No significant differences were found in use of other devices, including gastrointestinal scopes and urinary catheters, or administration of antibiotics such as carbapenems and fluoroquinolones.
P. aeruginosa has been implicated in three reported hospital outbreaks involving flexible bronchoscopes.3,4,8,9) The present report studied outbreaks of MDRP isolation suggested to be attributable to use of a flexible bronchoscope, revealing how deficits in decontamination can contribute to the transmission of P. aeruginosa. Recent exposure to bronchoscopes among the first identified cases suggested that use of flexible bronchoscopes could have been associated with MDRP transmission. Important failures in processing and storage of flexible bronchoscopes were discovered, and cross-infection might also represent a significant risk factor in the development of infections, probably via the hands of healthcare workers.10,11)
Many reports can be found on nosocomial infections associated with endoscopes, including our previous report about an outbreak associated with transesophageal echocardiography (TOE) in 2004.7) Proper disinfection and sterilization is essential if we are to avoid transmitting infectious pathogens to patients via endoscopes, including bronchoscopes. P. aeruginosa is one of the most important organisms related to bronchoscope-associated nosocomial infections. Failure to comply with hygiene guidelines has led to numerous outbreaks of infection.12) Flaws related to bronchoscopes; such as a loose biopsy port cap, have also caused large nosocomial outbreaks.12,13) In these reports of nosocomial outbreaks, bronchoscopes had been used for bronchoscopic observation, for collecting bronchoalveolar lavage fluid samples, for therapy for medical disorders, and as an aid in medical procedures. In addition, bronchoscopes are also used during anesthesia procedures. The one-lung technique is widely used to facilitate thoracic surgical visualization.4,14)
Bacteriological investigations, including genetic analysis of MDRP by pulse field gel electrophoresis (PFGE), of the bronchoscopes unfortunately could not confirm its transmission, because we did not detect any bacteria from bronchoscopes used in the ICU and ER, or the detergent tank of the AER, although we could detected the MDRP from TOE and performed PFGE in the outbreak of 2004.7) However, the epidemiological study strongly suggested that bronchoscopes were associated with transmission of MDRP in these sections. We therefore changed the recommendations, including improvements in bronchoscope cleaning, disinfection and maintenance. Subsequently, no additional patients undergoing bronchoscope examinations showed isolation MDRP in 2008 and 2009.
Several reports have indicated that cleaning alone reduces microbial contaminants, with a reduction rate of 99.99%.12,15) Without the removal of protein, disinfectant becomes useless for killing bacteria.12,16) Cleaning should be performed promptly after each use of an endoscope, to prevent the drying of secretions. Once secretions have dried, thick biofilms may form, reducing the effectiveness of detergents and disinfectants.
In our case, we could not detect any P. aeruginosa from bronchoscopes, but outbreak of MDRP were suspended by renewal of process of disinfection of bronchoscopes and its related devices. Therefore, we could not neither determine the only bronchoscopes as the focus of the outbreak and nor there was the possibility that the other roots/focus of transmission of MDRP, however, it became clear that the disinfection of devices, reexamination of the process, and education of the medical stuffs were also very critical although the items other than bronchoscopes exist as the focus of the outbreak.
Furthermore, we retrospectively compared patients admitted the ICU or ER from the April 2006–2007 period and from 2008–2009, and also found that more bronchoscope examinations were performed during the former period than in the latter period. Conversely, used doses (AUD) of anti-Pseudomonas antibiotics did not differ between the two periods. These findings suggest that use of antibiotics might be unrelated to this outbreak, and MDRP isolates were not a result of drug pressures in patients, but rather transferred from other patients.
A case-control study was then performed and revealed bronchoscopes and duration from admission to MDRP isolation as significant factors in patients with MDRP. Bou et al. reported an outbreak of P. aeruginosa infection in a 27-bed ICU, and performed epidemiological analysis.3) Their logistic regression analyses demonstrated that cases were more likely than non-controls to have had a longer stay in the ICU, and to have undergone mechanical ventilation and antimicrobial treatment. Multivariate analysis yielded results similar to our own, identifying recent bronchoscope examinations and exposure to an infected patient as independent risk factors. Kanemitsu et al. also reported the usefulness of case-control studies in contributing to the detection and confirmation of TOE as the causative factor in an Enterobacter cloaca outbreak in a cardiovascular ward.17) Epidemiological analysis might strongly contribute to the detection and confirmation of causative factors in outbreaks.
In conclusion, analytical epidemiological methods contributed to the identification of significant risk factors for an MDRP outbreak in our hospital. We could not detect the pathogen from any bronchoscopes, but the outbreak ended after the washing process was properly established. A case/non-control study might be one of the strong tools to detect and confirm causative factors in the outbreak.
| Male/Female | Underlying disease | Sample | Age | Ward |
|---|---|---|---|---|
| Male | Post-heart transplantation | Throat swab | 45 | ICU |
| Male | Trauma | Sputum | 45 | ER |
| Female | Post livertransplantation | Urine | 35 | ICU |
| Male | Esophageal cancer | Sputum | 55 | ICU |
| Female | Esophageal cancer | Sputum | 62 | ICU |
| 2006–2007 (N=2607) | 2008–2009 (N=2281) | p-Value | |
|---|---|---|---|
| Male (%) | 1641 (63.0) | 1451 (63.6) | 0.6344 |
| Age (years), mean∓S.D. | 54.9±23.6 | 53.6± 24.9 | 0.3865 |
| Duration of hospitalization (d), mean±S.D. | 47.6±104.3 | 40.7±74.8 | 0.0216 |
| Surgery (%) | 1285 (49.3) | 1058 (46.4) | 0.045 |
| Anti-cancer chemotherapy (%) | 4 (0.2) | 8 (0.4) | 0.2462 |
| Immuno-suppresiive drugs (%) | 323 (12.4) | 311 (13.6) | 0.2007 |
| Intravenous hyperalimentation (%) | 1328 (50.9) | 1169 (51.2) | 0.8634 |
| Urinary catheter (%) | 2041 (78.3) | 1678 (73.6) | 0.0001 |
| Mechanical ventilation (%) | 1291 (49.2) | 1115 (48.9) | 0.6672 |
| Bronchoscope (%) | 369 (14.2) | 262 (11.5) | 0.0062 |
| Upper intestine scope (%) | 89 (3.4) | 55 (2.4) | 0.0418 |
| Lower intestine scope (%) | 16 (0.6) | 20 (0.9) | 0.3165 |
| Case (n=11) | Non cases (n=17) | p-Value | Risk ratio (95%CI) | |
|---|---|---|---|---|
| Age (years, mean±S.D.) | 51.2±12.1 | 55.9±12.4 | 0.3001 | |
| Duration from admission to P. aeruginosa isolation (d, mean±S.D.) | 19.8±12.8 | 11.8±11.7 | 0.0453 | |
| Surgery (%) | 8 (72.7) | 15 (88.2) | 0.3531 | 0.3556 (0.04888–2.586) |
| Anti-cancer chemotherapy (%) | 0 (0) | 0 (0) | NA | NA |
| Immuno-suppresiive drugs (%) | 5 (45.5) | 5 (29.4) | 0.4443 | 2 (0.4119–9.712) |
| Urinary catheter (%) | 11 (100) | 13 (81.3) | 0.2579 | NA |
| Mechanical ventilation (%) | 11 (100) | 15 (88.2) | 0.5053 | NA |
| Bronchoscope (%) | 9 (81.8) | 6 (35.3) | 0.0238 | 8.25 (1.328–51.26) |
| Upper intestine scope (%) | 3 (27.3) | 1 (5.9) | 0.2694 | 6 (0.5351–67.28) |
| Lower intestine scope (%) | 0 (0) | 1 (5.9) | 1 | 0 |
| Central venous catheter (%) | 11 (100) | 15 (88.2) | 0.5053 | NA |
| Administration of carbapenem (%) | 4 (36.4) | 3 (17.7) | 0.3809 | 2.667 (0.4632–15.35) |
| Administration of 4th generation cephalosporin (%) | 1 (9.1) | 1 (5.9) | 1 | 1.6 (0.08962–28.57) |
| Administration of aminoglycoside (%) | 2 (18.2) | 1 (5.9) | 0.5433 | 3.556 (0.2817–44.88) |
| Administration of fluoroquinolone (%) | 3 (27.3) | 0 (0) | 0.0504 | NA |
