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Rothia bacteremia – A 10 year experience at Mayo Clinic, Rochester, Minnesota. 1 Poornima Ramanan 1 , MD, Jason N. Barreto 2 , Pharm.D, R.Ph, Douglas R. Osmon 1 , MD, Pritish 2 K. Tosh 1 , MD 3 4 Division of Infectious Diseases 1 and Department of Pharmacy 2 , Mayo Clinic College of 5 Medicine, Rochester MN 6 7 Running title: Rothia bacteremia 8 Corresponding author: 9 Pritish K. Tosh, MD 10 Division of Infectious Diseases 11 Mayo Clinic 12 200 First Street SW 13 Rochester, MN 55905 14 Phone: 507-284-3747 15 Fax: 507-255-7767 16 E-mail: [email protected] 17 18 JCM Accepts, published online ahead of print on 20 June 2014 J. Clin. Microbiol. doi:10.1128/JCM.01270-14 Copyright © 2014, American Society for Microbiology. All Rights Reserved. on July 17, 2018 by guest http://jcm.asm.org/ Downloaded from
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Rothia bacteremia – A 10 year experience at Mayo Clinic, Rochester, Minnesota. 1 

Poornima Ramanan1, MD, Jason N. Barreto2, Pharm.D, R.Ph, Douglas R. Osmon1, MD, Pritish 2 

K. Tosh1, MD 3 

Division of Infectious Diseases1 and Department of Pharmacy2, Mayo Clinic College of 5 

Medicine, Rochester MN 6 

Running title: Rothia bacteremia 8 

Corresponding author: 9 

Pritish K. Tosh, MD 10 

Division of Infectious Diseases 11 

Mayo Clinic 12 

200 First Street SW 13 

Rochester, MN 55905 14 

Phone: 507-284-3747 15 

Fax: 507-255-7767 16 

E-mail: [email protected] 17 

18 

JCM Accepts, published online ahead of print on 20 June 2014J. Clin. Microbiol. doi:10.1128/JCM.01270-14Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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Abstract 19 

Rothia spp. are Gram-positive cocco-bacilli that cause a wide range of serious infections, 20 

especially in immunocompromised hosts. Risk factors for Rothia mucilaginosa (previously 21 

known as Stomatococcus mucilaginosus) bacteremia include prolonged and profound 22 

neutropenia, malignancy, indwelling vascular foreign body, among others. We describe 67 adults 23 

with positive blood cultures for Rothia at Mayo Clinic Rochester, MN, 2002 – 2012. Twenty five 24 

of these patients had multiple positive blood cultures indicating true clinical infection. Among 25 

these, 88% (22/25) were neutropenic and 76% (19/25) had leukemia. Common sources of 26 

bacteremia were presumed gut translocation, mucositis and catheter related infection. One 27 

patient died with Rothia infection. Neutropenic patients were less likely to have single positive 28 

blood culture when compared to non-neutropenic patients. Antimicrobial susceptibility testing 29 

was able to be performed in 21% of isolates; all tested isolates were susceptible to vancomycin 30 

and most beta-lactams, however four of six tested isolates were resistant to oxacillin. There was 31 

no difference between neutropenics and non-neutropenics in need for ICU care, mortality, or 32 

attributable mortality. 33 

34 

Key words: 35 

Rothia; mucilaginosa; bacteremia 36 

Abstract word count: 166 37 

Manuscript word count: 2,769 38 

39 

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Background and aims: 40 

Rothia mucilaginosa, previously known as Stomatococcus mucilaginosus, and other Rothia 41 

species (R.dentocariosa, R.aeria, R.nasimurium and R.amarae) are part of the normal flora of the 42 

human oropharynx and upper respiratory tract (16). They are aerobic or facultatively anaerobic, 43 

non-motile, non-spore forming, Gram positive cocco-bacilli that can form filamentous 44 

branches(16).Rothia are commonly associated with dental caries and periodontal 45 

disease(16).Invasive disease does occur, predominantly in immunocompromised hosts, but has 46 

rarely been reported in normal hosts. The clinical syndromes associated with Rothia infection 47 

have included bacteremia(17), endocarditis(2), meningitis(13), peritonitis(11), bone and joint 48 

infections(16), pneumonia(5), skin and soft tissue infection, endophthalmitis(15) and prosthetic 49 

device infection(2) among others. The main risk factors described for invasive disease have been 50 

hematological malignancy, severe neutropenia(14), although other risk factors include diabetes 51 

mellitus, alcoholism, chronic liver disease, and infection with human immunodeficiency virus(2). 52 

The clinical significance of isolation of Rothia from blood culture is frequently unclear, 53 

especially in the setting of a single blood culture set positivity with polymicrobial infection 54 

suggesting contamination. To our knowledge, a large, systematic evaluation of invasive Rothia 55 

infections that has not been published to date. We sought to describe the epidemiology and 56 

clinical significance of Rothia bacteremia in the past decade at our institution and to evaluate 57 

differences in clinical outcomes between neutropenic and non-neutropenic patients. The other 58 

aim of our study was to describe the antimicrobial susceptibility pattern of Rothia isolates at our 59 

institution. 60 

Methods: 61 

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We conducted a single-center, retrospective cohort study of adult patients with blood cultures 62 

positive for Rothia between January 2002 to December 2012 at Mayo Clinic in Rochester, MN. 63 

The protocol was approved by the Institutional Review Board of Mayo Clinic. Cases were 64 

obtained through query of microbiology records for Rothia spp. or Stomatococcus spp. grown 65 

from blood culture from January 1, 2002 to December 31, 2012 among patients presenting for 66 

medical care at Mayo Clinic Rochester, MN. Patients were excluded from analysis if they were 67 

under age 18 years or did not consent to use of their medical records for research purposes. 68 

Medical records of patients included for analysis were manually reviewed for patient 69 

demographics, medical comorbidities, antimicrobial exposure within the prior month, clinical 70 

outcomes and microbiological data including antimicrobial susceptibilities. The source of 71 

bloodstream infection was determined through review of medical records for suspected source as 72 

documented by the infectious diseases attending physician (preferred) or by the attending 73 

physician of the primary service if infectious diseases consultation was not involved in the 74 

patient’s care. All documented potential sources were abstracted. If a suspected source was not 75 

documented, then the source was categorized as “no source identified”. Attributable mortality 76 

was determined by medical record review of all deaths with Rothia bacteremia by two of the 77 

investigators (PR and PKT). Mortality cases were considered non-attributable if a clear 78 

alternative cause of mortality was identified. 79 

The Charlson comorbidity index score was used to assess the severity of underlying diseases(3). 80 

Analysis of microbiologic characteristics including species identification and antimicrobial 81 

susceptibility testing was performed on all isolates recovered from blood culture. Analysis of 82 

clinical characteristics was performed on those with blood cultures positive for Rothia spp. from 83 

more than one set of blood cultures to minimize the inclusion of potential contaminants. 84 

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Descriptive analysis was performed as well as comparative analysis of patients who were 85 

neutropenic (absolute neutrophil count ≤ 1000 /µL) at the time of bacteremia to those who were 86 

not neutropenic as well as those with monomicrobial infection to those with polymicrobial 87 

infection. Two-tailed Fisher’s exact and Kruskal-Wallis tests were used for comparisons of 88 

proportions and medians, respectively, with p-values <0.05 considered statistically significant. 89 

At our institution, blood samples are cultured using BACTEC instrumented blood culture system 90 

(Becton, Dickinson, and Company, Franklin Lakes, NJ, USA) and antimicrobial susceptibility 91 

was performed using agar dilution using isolates from pure subculture. The clinical microbiology 92 

laboratory at Mayo Clinic uses CLSI breakpoints for Corynebacterium for reporting 93 

susceptibility for Rothia isolates. Most of the Rothia isolates were identified using 94 

morphological and biochemical properties; recent isolates were identified using MALDI-TOF 95 

(Matrix assisted laser desorption/ ionization- time of flight). 96 

97 

Results: 98 

After excluding 5 patients under age 18 years, we identified 67 adults with blood cultures 99 

positive for Rothia from 2002 to 2012; 42 patients had Rothia grown from a single blood culture 100 

set and were considered potential contaminant, the remaining 25 patients were considered to 101 

have true bloodstream infection (Figure 1). All 67 patients identified with blood cultures positive 102 

for Rothia had at least two sets of blood cultures drawn at the same time, with at least one being 103 

from the periphery; for all of the cases in which only one set was positive for Rothia, there was a 104 

second blood culture set drawn at the same time from which Rothia did not grow. Neutropenic 105 

patients were significantly less likely to have a single positive blood culture set than non-106 

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neutropenic patients (41% vs. 90%, p<0.001). The demographic, clinical, and microbiological 107 

characteristics and clinical outcomes of patients considered to have had true bloodstream 108 

infection are summarized in Table 1. Twenty-two (88%) patients were neutropenic with a 109 

median of 9.5 days of neutropenia (interquartile range 7 – 20 days) at the time of Rothia 110 

bloodstream infection and 19 (76%) had an underlying diagnosis of leukemia. 111 

The most common sources of Rothia bloodstream infection were presumed gut translocation 112 

(n=13, 52%), catheter related infection (n=8, 25%) and mucositis (n=9, 36%). No source of 113 

bacteremia was identified in 5 (20%) patients. 114 

Comparison of the clinical characteristics and outcomes of patients with monomicrobial 115 

infection (N=16) and those with polymicrobial infection (N=9) identified no qualitative or 116 

statistically significant differences between the two groups for any of the variables collected 117 

including, respectively, median age (56 years vs. 53 years, p=0.93), recent corticosteroid use (6% 118 

vs. 11%, p=1.0), presence of neutropenia (88% vs. 89%, p=1.0), ability to perform susceptibility 119 

testing (20% vs. 33%, p=0.63), median duration of hospital stay (20 days vs. 21 days, p=0.32), 120 

median duration of antimicrobial treatment (14 days vs. 14 days, p=0.57), need for ICU care 121 

(44% vs. 44%, p=1.0), or attributable mortality (0% vs. 11%, p=0.36). Of the nine polymicrobial 122 

Rothia bloodstream infections, five cases had additional growth of coagulase-negative 123 

staphylococci (three attributed to central line-related bloodstream infection, one attributed to 124 

presumed gut translocation, and one for which a source was not identified), one case had 125 

additional growth of viridans group streptococci attributed to presumed gut translocation, one 126 

case had additional growth of Enterococcus faecium for which a source was not identified, one 127 

case had additional growth of Candida dubliniensis attributed to central line-related bloodstream 128 

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infection, and one case had additional growth of Clostridium inoculum attributed to presumed 129 

gut translocation. 130 

We identified one patient with Rothia bloodstream infection who died, potentially as a result of 131 

the infection. The patient was a 51 year old man who developed acute abdominal pain, fever, 132 

and hypotension in the setting of profound neutropenia four days after allogeneic peripheral 133 

blood stem cell transplantation for multiple myeloma. Intravenous vancomycin, cefepime, 134 

metronidazole, fluconazole, and acyclovir were started empirically and he was transferred to the 135 

ICU where he required ventilatory support, vasopressor support, and dialysis. All blood culture 136 

bottles from all sets were positive for vancomycin-susceptible Enterococcus faecium and Rothia 137 

mucilaginosa resistant to oxacillin (no other antimicrobial susceptibility tests were resulted) 138 

without any significant differential time to positivity between peripherally drawn cultures and 139 

those drawn from the central venous catheter. He was felt to be too unstable for transportation 140 

for CT imaging of this abdomen. Despite maximal support, the patient developed cardiac arrest 141 

and died with 48 hours of his initial presentation. An autopsy was not performed. 142 

We also identified a 28 year old woman with Rothia prosthetic aortic valve endocarditis 143 

(monomicrobial) who had a history of intravenous drug use and prior native tricuspid and aortic 144 

valve endocarditis with methicillin-susceptible Staphylococcus aureus. The diagnosis was 145 

confirmed with transesophageal echocardiogram. There was not adequate growth to perform 146 

susceptibility testing and the patient was treated with a 6-week course of intravenous ceftriaxone 147 

and vancomycin as well as oral rifampin with clinical resolution of the infection and no evidence 148 

of relapsed disease a year after completion of therapy. 149 

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All of the 25 clinical bloodstream infections were with Rothia mucilaginosa, although one of the 150 

isolates from a patient with a single positive blood culture set (possible contaminant) was with 151 

Rothia dentocariosa. Susceptibility testing was able to be performed in only 14 (21%) of the 152 

total 67 isolates and in 6 (24%) of the 25 isolates from true bloodstream infection due to the poor 153 

growth of the organism on Mueller-Hinton agar (supplemented with 5% lysed horse blood). 154 

There was no significant association between the ability to grow the organism for susceptibilities 155 

and whether or not the patient received penicillin (40% vs. 20%, p=0.29), levofloxacin (25% vs. 156 

18%, p=0.55), cefepime (9% vs. 24%, p=0.43), or vancomycin (14% vs. 23%, p=0.72) within 30 157 

days prior to bacteremia. All tested isolates were susceptible to penicillin (9/9), ceftriaxone (8/8), 158 

ertapenem (2/2), meropenem (8/8), and vancomycin (13/13). Four isolates were resistant to 159 

oxacillin (4/6), although none of these four resistant isolates had concomitant penicillin 160 

susceptibility testing performed. 161 

162 

Discussion: 163 

We conducted a retrospective review of all adult patients with blood cultures positive for Rothia 164 

in a single academic institution during the past decade and have described the epidemiology and 165 

clinical characteristics of Rothia bacteremia. In addition, we performed comparative analysis of 166 

clinical outcomes between neutropenic and non-neutropenic patients was well as between 167 

monomicrobial and polymicrobial infections Rothia bloodstream infections often occurred in 168 

patients with significant medical comorbidities, most commonly hematologic malignancy. A 169 

majority of the patients were exposed to at least one antimicrobial agent (predominantly a 170 

fluoroquinolone) within the month preceding the infection. Most patients had an indwelling 171 

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central venous catheter at the time of bacteremia, most likely related to the need for central 172 

venous access for administration of chemotherapeutic agents in patients with hematologic 173 

malignancy. There was no apparent temporal change in the incidence of bacteremia in the past 174 

decade, although a transient increase was noted in 2011; the reason for this transient increase is 175 

not clear as there were no notable changes in patient management or concomitant increases in 176 

central line related infections elsewhere in our institution. In this study, Rothia mucilaginosa 177 

caused all of the clinical bloodstream infections. Gut translocation was the most commonly 178 

identified source of Rothia bloodstream infection, although central line related infections and 179 

mucositis were also common. There were no differences detected in clinical characteristics or 180 

clinical outcomes between those with monomicrobial and polymicrobial Rothia bloodstream 181 

infection. 182 

When encountering Rothia bacteremia in clinical practice, many clinicians are faced with the 183 

challenge of deciding whether this represents a true bloodstream infection or contamination; 63% 184 

of Rothia isolates in our study were potential contaminants since they only grew from a single 185 

positive blood culture. Transient Rothia bacteremia has been previously reported in the literature 186 

and its clinical significance remains unknown (10). In our study, neutropenic patients were less 187 

likely to have single blood culture set positivity than non-neutropenic patients. This implies that 188 

when Rothia bacteremia is identified in neutropenic patients, it is likely to represent true 189 

infection. We did find that the vast majority of neutropenic patients had an underlying diagnosis 190 

of leukemia and had prolonged and profound neutropenia at the time they were diagnosed with 191 

Rothia bacteremia. Potential reasons for this predilection towards patients with leukemia include 192 

a higher preponderance of mucositis due to the chemotherapeutic agents used to treat the 193 

underlying disease and prolonged duration of chemotherapy-induced neutropenia. Furthermore, 194 

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the vast majority of patients undergoing chemotherapy for leukemia at our institution receive 195 

levofloxacin prophylaxis during neutropenia, as such there may be a shift in oral and 196 

gastrointestinal flora away from aerobic Gram-negative bacilli and towards other pathogens such 197 

as Rothia. The presence of polymicrobial Rothia bloodstream infection did not appear to be 198 

associated with higher risk clinical characteristics or portend less favorable clinical outcomes 199 

compared to those with monomicrobial infection. We did not record whether the other organisms 200 

were identified in more than one blood culture set raising the possibility that they were 201 

contaminants, but the Rothia species were identified in more than one blood culture set, 202 

suggesting against its presence being from contamination. 203 

Reports of Rothia (Stomatococcus mucilaginosa) bacteremia in neutropenic patients were first 204 

described in the 1990s (1, 9, 14). Ascher et al described 10 patients with Rothia mucilaginosa 205 

bacteremia of which 5 had more than one positive blood culture. Among these 5 patients, 3 were 206 

neutropenic and had malignancies; all had indwelling vascular foreign body. Most patients 207 

recovered with vancomycin (1). Henwick et al characterized 8 cases of Rothia mucilaginosa 208 

bacteremia in children with cancer of which 6 had leukemia, 7 had profound neutropenia, 4 had 209 

mucositis and 5 had central venous catheters. Despite prompt initiation of antibiotics, the 210 

complications in this cohort were high — septic shock (50%), pneumonia, altered mental status, 211 

meningitis and acute respiratory distress syndrome. All the isolates were susceptible to 212 

vancomycin but 50% were penicillin resistant and 29% were methicillin resistant (9). 213 

Fanourgiakis et al described 8 patients with Rothia mucilaginosa bacteremia among which the 214 

majority of them (7/8) had hematological malignancies (6 leukemia); 1 had breast cancer. All 215 

patients had profound neutropenia and chemotherapy-induced disruption in oral or gut mucosal 216 

barrier. All of the patients were on quinolone prophylaxis at the time of bacteremia; 5 of 6 tested 217 

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isolates were quinolone-resistant (6). One patient in our study expired potentially as a result of 218 

Rothia infection despite organism identification, prompt appropriate antimicrobial initiation and 219 

intense supportive management. He possessed many of the previously described risk factors for 220 

Rothia infection demonstrating the pathogenicity of Rothia despite normally being considered a 221 

benign and colonizing organism. However, the case description suggests that the patient may 222 

have died due to catastrophic gut wall breach with resultant polymicrobial bloodstream infection 223 

rather than from the pathogenicity of Rothia bloodstream infection itself. Mortality attributable 224 

to Rothia infections varies in the literature according to age, immune status and site of infection 225 

(4, 8, 12). Immunocompromised patients are more likely to develop severe complications from 226 

Rothia infections including death. To our knowledge, ours is the largest published cohort of 227 

patients with Rothia bacteremia .In prior publications, Rothia mucilaginosa isolates were 228 

generally susceptible to most beta-lactam antimicrobials (penicillin, ampicillin, imipenem, 229 

cefotaxime), rifampin and vancomycin(18). However, isolates with partial resistance to penicillin 230 

have been described in the past (18). In one study, the incidences of penicillin and methicillin 231 

resistance among isolates were 50% and 29% respectively (9). Antimicrobial susceptibility 232 

testing was not able to be performed on most of the Rothia isolates in our study owing to their 233 

poor growth in vitro, even when growth media was supplemented with 5% lysed horse blood. 234 

When able to be performed, all of the isolates from our study were susceptible to penicillin, 235 

ceftriaxone, meropenem, and vancomycin; however, four of six isolates were resistant to 236 

oxacillin. The reasons for this pattern of susceptibility are not clear. 237 

The reason for the preponderance of cases in our study receiving vancomycin as part of dual 238 

therapy is likely because most of the patients had Rothia bloodstream infection in the setting of 239 

febrile neutropenia. Vancomycin is a recommended empiric antimicrobial agent (in combination 240 

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with an anti-pseudomonal beta-lactam antimicrobial) for the treatment of neutropenic fever with 241 

Gram positive bloodstream infection(7). Upon clearance of the bloodstream infection and 242 

identification of the causative organism, clinicians may have been inclined to continue with 243 

vancomycin, especially if susceptibility data was not available. The results of our study suggest 244 

that the addition of vancomycin to neutropenic fever therapy at the time when Gram-positive 245 

bloodstream infection is identified would be appropriate coverage for Rothia infections and that 246 

ceftriaxone is likely to be an effective definitive antimicrobial agent in the clinical setting where 247 

patients have clinically improved but antimicrobial susceptibility results are not available. 248 

Further research is needed to develop microbiologic techniques to improve the ability to provide 249 

antimicrobial susceptibility results in cases of Rothia infection. Additionally, the potential role 250 

of fluoroquinolone prophylaxis in shifting oral and gastrointestinal flora in patients undergoing 251 

chemotherapy for hematologic malignancy needs further exploration. 252 

In conclusion, members of the genus Rothia, despite their low virulence, have established 253 

themselves as significant pathogens, especially in patients with hematological malignancies and 254 

neutropenia. Mucositis and central venous catheters are common predisposing factors, both 255 

related to treatment for hematologic malignancy. Neutropenic patients are more likely to have 256 

true bloodstream infection as evidenced by multiple positive blood culture sets and 257 

monomicrobial infection. There was no significant difference in clinical outcomes between 258 

neutropenic and non-neutropenic patients. At present, there is limited data available on the 259 

antimicrobial susceptibility patterns of Rothia, however isolates are generally susceptible to 260 

vancomycin and beta-lactam antimicrobials with the exception of oxacillin. 261 

262 

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263 

264 

Funding: none 265 

Conflicts of Interest: None of the authors have any relevant financial disclosures. 266 

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References: 267 

1. Ascher, D. P., C. Zbick, C. White, and G. W. Fischer. 1991. Infections due to 268 

Stomatococcus mucilaginosus: 10 cases and review. Rev Infect Dis 13:1048-1052. 269 

2. Bruminhent, J., M. J. Tokarczyk, D. Jungkind, and J. A. Desimone, Jr. 2013. Rothia 270 

mucilaginosa Prosthetic Device Infections: A Case of Prosthetic Valve Endocarditis. 271 

Journal of clinical microbiology. 272 

3. Charlson, M. E., P. Pompei, K. L. Ales, and C. R. MacKenzie. 1987. A new method 273 

of classifying prognostic comorbidity in longitudinal studies: development and 274 

validation. J Chronic Dis 40:373-383. 275 

4. Chavan, R. S., P. S. Pannaraj, R. A. Luna, S. Szabo, A. Adesina, J. Versalovic, R. A. 276 

Krance, and A. A. Kennedy-Nasser. 2013. Significant morbidity and mortality 277 

attributable to rothia mucilaginosa infections in children with hematological malignancies 278 

or following hematopoietic stem cell transplantation. Pediatr Hematol Oncol 30:445-454. 279 

5. Cho, E. J., H. Sung, S. J. Park, M. N. Kim, and S. O. Lee. 2013. Rothia mucilaginosa 280 

Pneumonia Diagnosed by Quantitative Cultures and Intracellular Organisms of 281 

Bronchoalveolar Lavage in a Lymphoma Patient. Annals of laboratory medicine 33:145-282 

149. 283 

6. Fanourgiakis, P., A. Georgala, M. Vekemans, D. Daneau, C. Heymans, and M. 284 

Aoun. 2003. Bacteremia due to Stomatococcus mucilaginosus in neutropenic patients in 285 

the setting of a cancer institute. Clin Microbiol Infect 9:1068-1072. 286 

7. Freifeld, A. G., E. J. Bow, K. A. Sepkowitz, M. J. Boeckh, J. I. Ito, C. A. Mullen, 287 

Raad, II, K. V. Rolston, J. A. Young, J. R. Wingard, and A. Infectious Diseases 288 

Society of. 2011. Clinical practice guideline for the use of antimicrobial agents in 289 

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neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of 290 

America. Clin Infect Dis 52:427-431. 291 

8. Goldman, M., U. B. Chaudhary, A. Greist, and C. A. Fausel. 1998. Central nervous 292 

system infections due to Stomatococcus mucilaginosus in immunocompromised hosts. 293 

Clin Infect Dis 27:1241-1246. 294 

9. Henwick, S., M. Koehler, and C. C. Patrick. 1993. Complications of bacteremia due to 295 

Stomatococcus mucilaginosus in neutropenic children. Clin Infect Dis 17:667-671. 296 

10. Kaufhold, A., R. R. Reinert, and W. Kern. 1992. Bacteremia caused by Stomatococcus 297 

mucilaginosus: report of seven cases and review of the literature. Infection 20:213-220. 298 

11. Keng, T. C., K. P. Ng, L. P. Tan, Y. B. Chong, C. M. Wong, and S. K. Lim. 2012. 299 

Rothia dentocariosa repeat and relapsing peritoneal dialysis-related peritonitis: a case 300 

report and literature review. Renal failure 34:804-806. 301 

12. Korsholm, T. L., V. Haahr, and J. Prag. 2007. Eight cases of lower respiratory tract 302 

infection caused by Stomatococcus mucilaginosus. Scand J Infect Dis 39:913-917. 303 

13. Lee, A. B., P. Harker-Murray, P. Ferrieri, M. R. Schleiss, and J. Tolar. 2008. 304 

Bacterial meningitis from Rothia mucilaginosa in patients with malignancy or undergoing 305 

hematopoietic stem cell transplantation. Pediatric blood & cancer 50:673-676. 306 

14. McWhinney, P. H., C. C. Kibbler, S. H. Gillespie, S. Patel, D. Morrison, A. V. 307 

Hoffbrand, and H. G. Prentice. 1992. Stomatococcus mucilaginosus: an emerging 308 

pathogen in neutropenic patients. Clin Infect Dis 14:641-646. 309 

15. Partner, A. M., S. Bhattacharya, R. A. Scott, and P. Stavrou. 2006. Rothia genus 310 

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16. Trivedi, M. N., and P. Malhotra. 2013. Rothia prosthetic knee joint infection. J 312 

Microbiol Immunol Infect. 313 

17. Vaccher, S., R. Cordiali, P. Osimani, E. Manso, and F. M. de Benedictis. 2007. 314 

Bacteremia caused by Rothia mucilaginosa in a patient with Shwachman-Diamond 315 

syndrome. Infection 35:209-210. 316 

18. von Eiff, C., M. Herrmann, and G. Peters. 1995. Antimicrobial susceptibilities of 317 

Stomatococcus mucilaginosus and of Micrococcus spp. Antimicrob Agents Chemother 318 

39:268-270. 319 

320 

Figure 1. Distribution of patients with Rothia bacteremia per year at Mayo Clinic, 321 

Rochester, MN (2002 – 2012) 322 

Table 1. Demographic and clinical characteristics and clinical outcomes of patients with 323 

Rothia bloodstream infections at Mayo Clinic, Rochester, MN, 2002 – 2012 324 

325 

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Table 1. Demographic and clinical characteristics and clinical outcomes of patients with Rothia bloodstream infections at

Mayo Clinic, Rochester, MN, 2002 – 2012

Variables All patients (n = 25)

Neutropenic (n = 22)

Non-neutropenic (n = 3)

P value

Median Age in years (range) 55 (22 – 78) 60 (22 – 78) 30 (28 – 48) 0.03 Male sex 19 (76%) 18 (82%) 1 (33%) 0.2 Comorbidities Myocardial Infarction Congestive heart failure Peripheral vascular disease Chronic lung disease Connective tissue disease Diabetes mellitus Solid-tumor Leukemia Lymphoma/Multiple myeloma Moderate to severe liver disease Moderate to severe kidney disease Hemodialysis

2 (8%) 1 (4%) 1 (4%) 1 (4%) 1 (4%) 2 (8%)

3 (12%) 19 (76%) 4 (16%) 1 (4%) 2 (8%) 1 (4%)

2 (9%) 0 (0%) 1 (5%) 1 (5%) 1 (5%) 2 (9%) 3 (14%)

19 (86%) 4 (18%) 1 (5%) 2 (9%) 1 (5%)

0 (0%)

1 (33%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

1.0

0.12 1.0 1.0 1.0 1.0 1.0

0.009 1.0 1.0 1.0 1.0

Hematopoietic stem cell transplant Allogeneic Autologous

6 (24%) 4 (16%) 2 (8%)

6 (27%) 4 (18%) 2 (9%)

0 (0%) 0 (0%) 0 (0%)

1.0 1.0 1.0

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Charlson Comorbidity Index 0 1 2 3 4 5 6 7

1 (4%) 1 (4%)

3 (12%) 3 (12%) 3 (12%) 8 (32%) 1 (4%)

5 (20%)

0 (0%) 0 (0%) 3 (14%) 3 (14%) 3 (14%) 8 (36%) 0 (0%) 5 (23%)

1 (33%) 1 (33%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

1 (33%) 0 (0%)

0.002

Corticosteroid use within 30 days prior to bacteremia 2 (8%) 2 (9%) 0 (0%) 1.0 Antimicrobial use within 30 days prior to bacteremia 25 (100%) 22 (100%) 3 (100%) 1.0 Levofloxacin use within 30 days prior to bacteremia 21 (84%) 20 (91%) 1 (33%) 0.06 Penicillin use within 30 days prior to bacteremia 3 (12%) 3 (14%) 0 (0%) 1.0 Presence of central venous catheter at the time of bacteremia 24 (96%) 22 (100%) 2 (67%) 0.12 Source(s) of bloodstream infection Presumed gut translocation with negative CT abdomen Presumed gut translocation without a CT abdomen Neutropenic colitis with consistent CT abdomen Catheter-related bloodstream infection Endocarditis Dental abscess Mucositis No source identified

12 (48%) 1 (4%) 1 (4%)

8 (32%) 1 (4%) 2 (8%)

9 (36%) 5 (20%)

9 (41%) 1 (5%) 1 (5%) 6 (27%) 0 (0%) 2 (9%) 9 (41%) 5 (23%)

3 (100%) 0 (0%) 0 (0%)

2 (66%) 1 (33%) 0 (0%) 0 (0%) 0 (0%)

0.28 1.0 1.0

0.23 0.12 1.0

0.28 1.0

Presence of polymicrobial infection 9 (36%) 8 (36%) 1 (33%) 1.0 Antimicrobial susceptibility test performed 6 (24%) 6 (27%) 0 (0%) 1.0 Median duration of hospitalization in days (range) 21 (1 – 53) 24 (1 – 53) 12 (6 – 21) 0.32 Need for ICU care 11 (44%) 10 (45%) 1 (33%) 1.0 Complications Septic shock Respiratory failure Liver failure Renal failure

3 (12%) 3 (12%) 1 (4%)

3 (12%)

3 (14%) 3 (14%) 1 (3%) 2 (9%)

0 (0%) 0 (0%) 0 (0%)

1 (33%)

1.0 1.0 1.0

0.33

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Altered mental status 2 (8%) 2 (9%) 0 (0%) 1.0 Attributable mortality 1 (4%) 1 (3%) 0 (0%) 1.0 Antimicrobial treatment

Cefepime Ceftriaxone Piperacillin-tazobactam Ertapenem Meropenem Daptomycin Linezolid Vancomycin

9 (36%) 1 (4%)

5 (20%) 3 (12%) 4 (16%) 3 (12%) 2 (8%)

20 (80%)

9 (41%) 1 (4%) 5 (23%) 3 (14%) 4 (18%) 2 (9%) 2 (9%)

18 (82%)

0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

1 (33%) 0 (0%)

2 (67%)

0.28 1.0 1.0 1.0 1.0

0.33 1.0

0.50 Median duration of antimicrobial treatment in days (range) 14 (2 – 42) 14 (2 – 28) 30 (10 – 42) 0.17

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