2007 Clinical Meeting WTSH - “Commensal or Pathogen?”
Dr. Wong King Ying and Dr. Chan Yuk Choi
Department of Respiratory Medicine, Wong Tai Sin Hospital
Case 1
A 62-year old gentleman with history of diabetes, pneumoconiosis, old TB, COAD on long term oxygen therapy was referred from chest clinic for shortness of breath presumably due to acute exacerbation of COAD. He developed type 2 respiratory failure despite standard therapy and was put on noninvasive ventilation. A chest drain was inserted for right basal pneumothorax. There was persistent airleak but his condition was too frail to have surgical repair. The patient’s condition deteriorated acutely when chest drain was blocked. He was intubated and put on mechanical ventilation. The chest drain was replaced. His condition stablised and ventilatory support was subsequently removed.
In view of the persistent airleak, talc pleurodesis was planned and the patient was transferred to an acute hospital with intensive care unit. However, his respiratory condition worsened acutely whenever the chest drain was disconnected or blocked. The chest drain was replaced again. The patient developed empyema after the insertion of the third chest drain. Heavy growth of diphterhoid bacilli was cultured from the chest drain wound swab. Pleural fluid was pale yellow and turbid in appearance, with white cell count 938/cmm, 95% polymorphs and gram stain showed gram positive bacilli. Pleural fluid cultured pure heavy growth of Corynebacterium striatum (CS), sensitive to vancomycin, resistant to penicillin, erythromycin and cefepime. Intravenous vancomycin was given accordingly. However, pleural fluid persistently harboured the same bacteria. The patient succumbed at the end of the second week of vancomycin therapy.
Case 2
A 70-year-old gentleman had history of bronchiectasis, COAD, and old TB. He was admitted to the intensive care unit of an acute hospital for pneumonia, respiratory failure and acute coronary syndrome. He was put on mechanical ventilation, and tracheostomy was subsequently performed. A chest drain was inserted for left pneumothorax and talc pleurodesis was followed. He suffered from multiple episodes of ventilator associated pneumonia and received multiple courses of antibiotics. He was weaned off ventilator and transferred to WTSH for further management of the tracheostomy. On arrival to WTSH, patient was on tracheostomy oxygen mask 2L/min and on nasogastric tube feeding. His white cell count, liver and renal function were all within normal limits. However, a few days after admission, he reported increase in sputum volume and sputum became viscous. He developed low grade fever 37.60C. His oxygen requirement was increased from 1L/min to 4L/min. CXR was taken and showed no new shadow. Two consecutive tracheal aspirates showed the same findings: on microscopy many pus cells and many Gram positive bacilli were seen and cultures yielded pure heavy growth of CS. The bacterium was sensitive to vancomycin, resistant to penicillin and intermediate resistant to erythromycin. A week of intravenous vancomycin was given. The clinical response was good and the patient was subsequently discharged after completion of rehabilitation program.
Retrospective Analysis
CS was previously regarded as a colonizer on skin and nasal mucosa. The bacterium was increasingly encountered in WTSH since year 2006 raising the possibility of a pathogenic role.
All respiratory specimens with positive CS culture between January 2006 and June 2007 were retrieved with the assistance of the infection control nurse. A retrospective analysis was done to review all the patients’ records. CS was isolated in 17 patients over 17 months. There were two patients referred from the chest clinic and 15 patients transferred from 6 different hospitals. All patients suffered from multiple comorbidities on admission. All patients transferred from other hospitals were bedbound and totally dependent for their activities of daily living.
In 9 patients the bacterium was definitely pathogenic or probably pathogenic including 1 case of community acquired pneumonia (CAP), 1 case of empyema and 7 cases of hospital acquired bronchitis/pneumonia. In 3 patients, CS was a saprophyte without causing any symptom. In 5 patients, the role of CS was indeterminate. Except in the patient with CAP, in 16 cases, CS showed resistant or intermediate resistant to penicillin. All except one isolates were resistant to erythromycin. In 13 isolates tested for levofloxacin, all showed resistance. All isolates were sensitive to vancomycin.
Only 1 patient with underlying bronchiectasis had CS CAP. In the other 16 patients, CS was probably acquired during the hospital stay. By the time CS was isolated, all these 16 patients were characterized by chronic debilitation, prolonged hospital stay ( median 53 d, range 8d to more than 2yr); multiple prior broad spectrum antibiotics (mean 3) and had some form of instrumentation with disturbance to the upper airway. Tracheotomy, nasogastric tube and noninvasive ventilation might have particular importance.
During the study period, 0-3 CS cases were reported in each month. As there was no active surveillance for CS, no information was collected immediately on isolation of CS to find out the source. CS could be innocent commensals in the upper airway of some patients. Multiple drug resistant CS strain was selected and overgrew as a result of multiple broad spectrum antibiotics previously given to the patients. Nosocomial spread could not be excluded as it could be spread by health care workers from the colonized patients to other patients. There was no evidence of spread from the index cases to adjacent patients.
Literature Review
CS was first described in 1889 by von Besser as normal skin flora1. It is a thick diphtherioid with clear- cut bars (hence striatum) and large irregular granules. It forms flat, whitish-grey colonies with creamy consistency after incubation in blood agar for 48hr, brown colonies being also described. The biochemical profiles of corynebacteria are used to identify different species. CS is characterized by reduction of nitrates; utilization of glucose and sucrose but not maltose; failure to produce propionic acid and decomposition of tyrosine. There are two commercial kits which assist to identify corynebacteria. API CORYNE system includes 20 biochemical tests, and identifies many Corynebacteria to species level. It also identifies Arcanobacterium species, Brevibacterium sp, Rhodococcus equi, Listeria monocytogenes, Erysipelothrix rhusiopathiae, Gardnerella vaginalis. RapID CB Plus system correctly identifies 80.9% strains to the species level and an additional 12.2% to the genus level2.
There was a history of misidentification of coryneform bacteria and thus made interpretation of the medical literature difficult. C. amycolatum strains had been misidentified as C striatum in 1980 and 1990’ s. Re-identification is possible only if details of biochemical profiles are included2.
In the past 2 decades, CS was increasingly recognized as a potential pathogen in both immunocompromised and normal hosts in different settings3.
Exit site infection/thromboplebilitis/septicaemia associated with central venous catheters
Peritonitis associated with gastrostomy feeding tube with gastric perforation and in renal failure patient, exit site infection associated with peritoneal dialysis catheter
Meningitis associated with ventriculo-peritoneal shunt, extra-ventricular drain,
Endocarditis associated with pacemaker, ventriculo-atrial shunt, prosthetic heart valve, valvular heart diseases, presence of prosthetic devices other than a valve, or just native valve
Skin, ulcer, soft tissue infection and osteomyelitis
Purulent conjunctivitis in DM patients
Pancreatic abscess associated with gallstones and drain
Intrauterine infection and UTI in 31/F with premature rupture of amniotic membranes
The pathogenic potential of CS to cause respiratory illness was first reported in 1980 in a 79-year old man with chronic lymphocytic leukaemia. CS was isolated in the tracheal secretion, blood and pleural fluid4.
In 1992, CS was reported to have clinical significance in a COAD patient who improved with ampicillin. The diphtheroids found in sputum culture were initially regarded as insignificant, until there were multiple specimens harboring the same organism in heavy growth5.
Outbreak of CS was reported by Leonard et al6. A single strain of CS was isolated and confirmed by DNA finger printing in 11 ICU patients. The strain showed multiple drug resistant: resistant to oxacillin, allβ-lactamase-resistant penicillin, clindamycin, β-lactam antibiotics and erythromycin. Selection pressure of β-lactam antibiotics possibly allowed overgrowth of Corynebacteria. The source of CS was unknown
Nosocomial spread of CS by the hands of health care workers (HCW) was reported in a surgical ICU7. CS was found in 25 routine cultures in 14 patients over 12 months. The same CS strain as confirmed by DNA typing was isolated from surfaces and air sampled in the direct vicinity of the CS infected patients but never from surfaces or air in other places of the ward. The same CS also cultured from the hands of the HCW, all of them attended to the CS patients on the day prior to having the sample.
A Japanese group reported CS as nosocomial pathogen in 48 patients8. Their patients characteristics included debilitated patients suffering from brain tumour/infarct, acute myocardial infarction, subarachnoid haemorrhage, cancers….; prolonged hospital stay and multiple prior antibiotics. Multiple drug resistant strains were isolated. Using RFLP typing, they confirmed nosocomial infections in 31 cases and sporadic occurrence in 17 cases.
Outbreak of CS in COPD patients was recently reported9. CS was isolated in 43 samples obtained in 21 patients on admission for COPD exacerbation over 18 month. Outbreak stopped with death of the index patient. The CS strains isolated showed 100% resistance to at least 3 drugs tested: 65% resistant to 4 or 5 drugs; 6.9% sensitive only to imipenem and vancomycin and 11% sensitive to vancomycin only
Universal hygiene measures were advised to avoid spread and outbreaks.
Most of our isolates were sensitive to vancomycin only (68.75%). In the 1980’s CS was usually susceptible to βlactam. Multiple antibiotic resistant isolates were then increasingly reported. In the 2000’s, reports advocated the use of vancomycin as first line treatment against CS. There are concern for increasing reliance on vancomycin and subsequent vancomycin-resistant strain. Both daptomycin and linezolid showed good activity against CS in vitro. 4-week linezolid was used to treat CS pancreatic abscess in a recent report with good outcome3.
In summary, CS, once regarded as a harmless skin commensal, is capable of causing serious infections in human. When the CS was recovered as pure growth in the presence of large number of pus cells in the specimen, its pathogenicity should be suspected. Patients at risk of CS infection are those who are debilitated, with prolonged hospital stay and have received many broad spectrum antibiotics. Those patients who received some form of instrumentation with disturbance to the upper airway integrity or patients carrying indwelling medical devices are also at risk. Nosocomial spread of CS was previously well documented. Vancomycin is the only drug which all CS isolates remains universally susceptible.
Reference:
- von Besser, L. 1889. Uber di Bacterim der nomale Luftwege. Beitr. Patho.Anal. Sllg. Pathol. 6:331-337
- Coryneform Bacteria other than C. diphtheriae. In Mendell’s Principles and Practice of Infectious Diseases, 6th ed. Edited by Mandell GL, Bennett JE, Dolin R, 2005, published by Elsevier; p.2466-2468.
- Lee PP ; Ferguson DA ; Sarubbi FA. Corynebacterium striatum: an underappreciated community and nosocomial pathogen. J Infect. 2005; 50(4):338-43.
- Thomas T. Bowstead and Silverio M. Santiago, Jun. Pleuropulmonary Infection due to Corynebacterium striatum, Br. J. Dis. Chest, 1980; 74:198-200.
- Cowlin. P and Hall L. Corynebacterium striatum: a clinically significant isolate from sputum in chronic obstructive airways disease. J Infect. 1993 May;26(3):335-6.
- Leonard RB, Nowowiejski DJ, Warren JJ, Finn DJ, Coyle MB. Molecular evidence of person-to-person transmission of a pigmented strain of Corynebacterium striatum in intensive care units. J Clin Microbiol. 1994 Jan;32(1):164-9.
- Brandenburg AH, van Belkum A, van Pelt C, Bruining HA, Mouton JW, Verbrugh HA. Patient-to-patient spread of a single strain of Corynebacterium striatum causing infections in a surgical intensive care unit. J Clin Microbiol. 1996 Sep;34(9):2089-94.
- Otsuka Y, Ohkusu K, Kawamura Y, Baba S, Ezaki T, Kimura S. Emergence of multidrug-resistant Corynebacterium striatum as a nosocomial pathogen in long-term hospitalized patients with underlying diseases. Diagn Microbiol Infect Dis. 2006 Feb;54(2):109-14.
- Renom F, Garau M, Rubi M, Ramis F, Galmes A, Soriano JB. Nosocomial outbreak of Corynebacterium striatum infection in patients with chronic obstructive pulmonary disease. J Clin Microbiol. 2007 Jun;45(6):2064-7
