Yang et al. Pneumonia (2018) 10:10 https://doi.org/10.1186/s41479-018-0054-5 Pneumonia CASEREPORT Open Access Corynebacteria as a cause of pulmonary infection: a case series and literature review Katharine Yang1, Robert L. Kruse1, Weijie V. Lin1 and Daniel M. Musher1,2* Abstract Background: In most cases of community-acquired pneumonia (CAP), an etiologic agent is not determined; the most common report from the microbiological evaluation of sputum cites “normal respiratory flora.” Non-diphtheria Corynebacterium spp., a component of this flora, is commonly viewed as a contaminant, but it may be the cause of pneumonia and the frequency with which it causes CAP may be underestimated. Case presentations: This report present 3 cases of CAP in which Corynebacterium spp. was clearly the predominant isolate; identification was confirmed by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Two cases were caused by C. propinquum and one by C. striatum. Two patients had a tracheostomy and one was on hemodialysis. Patients who received an appropriate antibiotic responded well. Conclusion: When identified as the predominant isolate in sputum from a patient with CAP, Corynebacterium spp. should be considered as a potential cause of the infection. In cases with patients who have compromised airway clearance or who are immunocompromised, microaspiration may be responsible. While some Corynebacterium spp. are suspectible to antibiotics usually prescribed for CAP, others are susceptible only to vancomycin or aminoglycosides. Vancomycin is thus the appropriate empiric antibiotic, pending speciation and susceptibility test results. The number of reported cases with result of antibiotic susceptibility testing, however, remains limited, and further investigation is needed. Non-diphtheria Corynebacterium spp. represent a noteworthy clinical cause of pneumonia. Identification by Gram stain and as a predominant organism on culture demands careful consideration for management. Keywords: Pneumonia, Corynebacteria, Diphtheroids, Normal respiratory flora Background The most common laboratory report for sputum Pneumonia is an important cause of medical morbidity samples submitted for microbiological study is “mixed and mortality worldwide; pneumonia and influenza are respiratory flora.” Pneumonia caused by S. pneumoniae listed as the 8th leading cause of death in the United is thought to result from unrecognized microaspiration States, with 57,062 deaths in 2015 [1]. Well-recognized of pneumococci that have colonized the nasopharynx and common causes of community-acquired pneumonia [4]. The authors of the present study have previously (CAP) in adults include bacteria such as Streptococcus hypothesized that unrecognized aspiration of less viru- pneumoniae, Haemophilus influenzae, and Staphylococ- lent bacteria that normally inhabit the nasopharynx cus aureus, and viruses such as influenza virus, respira- might also cause pneumonia, especially in persons whose tory syncytial virus, human metapneumovirus, and upper airways are bypassed or whose ability to clear parainfluenza virus. Intensive recent investigations have aspirated organisms is damaged [5]. The present study failed to identify a causative organism in 50–62% of pa- examined the possibilities that: (i) careful examination of tients hospitalized for CAP [2, 3]. Gram-stained sputum and culture plates may reveal a pre- dominant bacterium such as Corynebacterium spp. that are not generally regarded as a pulmonary pathogen; (ii) * Correspondence: [email protected] quantitative cultures may document a high concentration 1 Baylor College of Medicine, Houston, TX 77030, USA of these bacteria in sputum; and (iii) these organisms are 2Infectious Disease Section, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030, USA in fact the cause of some cases of pneumonia. © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Yang et al. Pneumonia (2018) 10:10 Page 2 of 8 Corynebacterium spp. Gram-positive bacilli that are were decreased bilaterally. WBC count was 7200 cells/ often dismissed as contaminants have been reported to mm3, lactate 1.2 mg/dL. Chest X-ray showed a new cause pneumonia (Table 1). New technologies, such as left-sided infiltrate. Sputum Gram stain revealed many matrix-assisted laser desorption ionization time of flight Gram-positive rods, including those found within PMNs. (MALDI-TOF) mass spectrometry enable rapid and Sputum yielded many Corynebacteria, identified by precise identification of bacterial species [6], and highly MALDI-TOF as C. propinquum, and few S. aureus. sensitive techniques such as polymerase chain reaction Sputum was liquefied with 2% N-acetyl cysteine and (PCR) can help exclude a role for viruses, mycoplasma, diluted serially; aliquots were cultured on blood agar and chlamydia. With the advent of these new technolo- and the number of colony forming units (CFU) was cal- gies, there has been greater interest in Corynebacteria, culated [8]. The specimen contained 2 × 109 CFU of and these organisms have been cited as emerging patho- Corynebacteria and < 105 CFU of S. aureus per mL. gens [7]. Blood cultures and viral PCR were negative. The pa- The present study reports on 3 well-documented cases tient was initially given vancomycin, cefepime, and of CAP due to Corynebacteria (2 cases of C. propinquum, ampicillin; treatment was switched to ampicillin/sul- 1 case of C. striatum)thatwerediagnosedina6-month bactam after the Corynebacterium was reported sus- period at a large tertiary care hospital. The study reviews ceptible. His mental status rapidly improved, and he the medical literature on Corynebacterium spp. as etio- was subsequently discharged to complete a 10-day logic agents of pneumonia, with the goal of increasing course of amoxicillin/clavulanate. awareness of the possibility that so-called “normal respira- tory flora” may actually be responsible for an as-yet un- Case 3 determined proportion of cases of CAP. A 59-year-old male with widely metastatic squamous cell carcinoma of the tongue was admitted for bleed- Case presentations ing from his tracheostomy site. His temperature was Case 1 99 °F, blood pressure 108/84, pulse 119, respiratory A 75-year-old man on hemodialysis for end-stage renal rate 24, and oxygen saturation 82% on room air. He disease was hospitalized for cough, fever, and altered had blood at the tracheostomy site and bibasilar mental status. His temperature was 103 °F, pulse 68, rhonchi. WBC count was 22,000 cells/mm3, blood pressure 124/69, respiratory rate 22, and O2 satur- hemoglobin 11.1 g/dL, and lactate 1.8 mg/dL. Chest ation 96% on 2 L of O2 by nasal cannula. He was lethargic, X-ray revealed a left upper-lobe infiltrate. Sputum with bibasilar crackles and a normal cardiac examination. sample showed profuse PMNs and Gram-positive His white blood cell (WBC) count was 20,100 cells/mm3 rods. Culture yielded C. striatum (confirmed by and his plasma procalcitonin was 1.1 ng/mL. Chest X-ray MALDI-TOF) and few Escherichia coli.Thepatient showed bibasilar infiltrates. Microscopic examination of was placed on comfort care and died 8 days later. Gram-stained sputum showed profuse polymorpho- nuclear leukocytes (PMNs) and Gram-positive rods, many Discussion of which appeared to be intracellular (Fig. 1). Sputum cul- Epidemiology ture yielded overwhelmingly predominant Corynebacteria, Non-diphtheria Corynebacterium spp.--commensal flora with rare P. aeruginosa. The Corynebacteria was identified of the skin, respiratory tract, and mucous membranes as C. propinquum by MALDI-TOF. Blood cultures and [9, 10]-- have been characterized as emerging patho- viral PCR were negative. The patient was initially treated gens [7]. Among reported cases, infections of the re- with vancomycin, cefepime, and metronidazole. Based on spiratory tract are second in frequency only to those the predominance of Corynebacteria with the absence of of the urinary tract [11]. The literature search re- other bacteria on Gram stain and a negative PCR for vealed 67 reported cases of pulmonary infection due respiratory viruses, his pneumonia was attributed to to non-diphtheria Corynebacterium spp., summarized C. propinquum, and only vancomycin was continued. in Table 1. Cases include pneumonia (community-ac- He responded and was discharged to complete a quired, hospital-acquired, or ventilator-associated), 10-day course of linezolid. necrotizing pneumonia, and empyema, although pneumonia predominated. Implicated Corynebacter- Case 2 ium spp. include C. pseudodiphtheriticum [12, 13], C. A 61-year-old man was found unresponsive post laryn- propinquum [14], C. striatum [14–18], C. afermen- gectomy and tracheostomy for laryngeal squamous cell tans [19], C. xerosis [20], C. jeikeium [10, 21–23], C. carcinoma. His temperature was 97.8 °F, pulse 99, blood pseudotuberculosis [24, 25], C. mucifaciens [26], C. pressure 114/86, and respiratory rate 22. Breath sounds ulcerans