Originalia A. K a u f h o l d , R. R. R e i n e r t , W. K e r n

Bacteremia Caused by Stomatococcus mucilaginosus: Report of Seven Cases and Review of the Literature Summary: During a three-year period eight patients with blood cultures positive for Stomatococcus mucilaginosus were identified at two university hospitals. One patient without any signs of infection had a central venous catheter that was colonized with this organism, two patients had transient bacteremia without definite relationship to underlying disease, whereas the remaining five patients suffered from clinically significant infections. Of these last five patients, one had undergone prior head and neck surgery and four had hematologic malignancy with mild to severe neutropenia; two of the latter patients developed the infection subsequent to dental surgery. Besides neutropenia and mucosal damage in the oropharynx, quinolone antibacterial prophylaxis may have been an additional risk factor for the development of S. mucilaginosus bacteremia in these patients. A

thorough review of the literature revealed that in addition to our findings, endocarditis and foreign body infections are further typical clinical manifestations. Although the overall antibiotic susceptibility pattern of S. mucilaginosus resembles that of streptococci, it is suggested that penicillin G may not be the drug of choice for initial therapy of particularly severe infections. $. mucilaginosus can be easily differentiated from other gram-positive bacteria when certain key criteria (e.g. adherence to agar surfaces, poor growth on Mueller-Hinton agar, presence of a capsule) as well as an array of biochemical tests, including commercially available identification systems, are applied. Our own and published data emphasize that both microbiologists and clinicians should be increasingly aware of this opportunistic pathogen.

Zusammenfassung: Stomatococcus mucilaginosusBakteriiimie - Bericht ftber sieben Fiille und Literaturiibersicht. In zwei Universit/itskliniken wurde w/ihrend eines Zeitraumes von drei Jahren bei acht Patienten Stomatococcus mucilaginosus aus Blutkulturen isoliert. Der zentral-ven6se Katheter eines Patienten war mit diesem Organismus ohne Zeichen einer Infektion kolonisiert, zwei Patienten hatten eine passagere Bakterifimie ohne eindeutige Beziehung zur Grunderkrankung, w~ihrend die /Jbrigen fiinf Patienten unter klinisch bedeutsamen Infektionen litten. Von diesen letzteren Patienten war bei einem Patienten ein chirurgischer Eingriff im Kopf-Halsbereich durchgeftihrt worden, vier Patienten wiesen maligne hfimatologische Erkrankungen mit milder bis schwerer Neutropenie auf; zwei dieser Patienten entwickelten die Infektion im Anschlut3 an einen zahnfirztlichen Eingriff. Neben oropharyngealen Schleimhautl~isionen und Neutropenie k6nnte eine antibakterielle Prophylaxe mit Chinolonen ein zus~itzlicher Risikofaktor fiir das

Entstehen der S. mucilaginosus- Bakterifimie bei diesen Patienten gewesen sein. Eine grtindliche Literaturtibersicht belegte, dab zus~itzlich zu unseren Beobachtungen, Endokarditiden und Fremdk6rperinfektionen weitere typische Krankheitsmanifestationen sind. Obgleich die Antibiotikaempfindtichkeit insgesamt der yon Streptokokken fihnelt, ist zu unterstellen, dab Penicillin G nicht das Mittel der ersten Wahl bei besonders schwerwiegenden Infektionen ist. S. mucilaginosus kann leicht yon anderen grampositiven Bakterien differenziert werden, wenn bestimmte SchliJsselkriterien (z.B. Adhfirenz zu Agaroberflfichen, schtechtes Wachstum auf MueUer-Hinton Agar, Kapseldarstellung) sowie eine Reihe yon biochemischen Tests, einschliet31ich kommerziell erh~iltlicher Identifizierungssysteme, Anwendung finden. Unsere eigenen und publizierte Daten unterstreichen, dab Mikrobiologen und Kliniker diesem opportunistischen Erreger verst/irkt Beachtung schenken sollten.

Introduction Stomatococcus mucilaginosus [t] is considered part of the normal flora of the mouth and upper respiratory tract of humans [2,3]. Thus far this gram-positive coccus has been rarely encountered in the clinical microbiology laboratory, but in recent years several case reports of human infections have appeared in the literature [4-23]. The spectrum of disease has ranged from peritonitis and catheter-associated bloodstream infections to cases of

fatal endocarditis and septicemia, indicating that this bacterium is able to cause aggressive disease in patients with certain underlying conditions. In the present communication we describe seven patients with S. Received: 14 January1992/Revisionaccepted: 16 March 1992 Dr. med. A. KaufhoM, R. R. Reinert, Institut for MedizinischeMikrobiologie, Rheinisch-Wesff/iliseheTechnische HochschuleAachen, Pauwelsstrage 30, W-5100Aachen;Dr. reed, W..Kern, MedizinischeUniversit~itsklinikundPoliklinik,Robert-Koch-Strage8, W-7900Ulm,Germany.

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213 / 37

A. K a u ~ o l d et al.: Stomatococcus rnuci~gm'osus Bacteremia

mucilaginosus bacteremia seen at two university hospitals during a three-year period (1989-1991). Another case of asymptomatic colonization of a central venous catheter (patient no. 4 of this communication) is included in the analysis. Besides the very recently published experience from a U.S. hospital [23], our cases represent the second series of a larger number of documented S. mucilaginosus infections. Since these data indicate an increasing incidence of infections due to this opportunistic agent and since S. mucilaginosus is not well known among both microbiologists and clinicians, we wish to thoroughly review some aspects of the microbiology of this bacterium as well as the clinical features of all Stomatococcus infections reported to date.

Case Reports Patient no. 1: A previously healthy 18-year-old woman presented with fever (39°C) of four days' duration accompanied by headache, general fatigue, myalgia and abdominal pain. The physical examination failed to reveal any focus of infection. A chest and abdominal radiograph was unremarkable and there was no evidence of endocarditis. The leucocyte count was 11,000/mm s and the erythrocyte sedimentation rate was 27 in the first hour. The results of other routine laboratory tests were all within normal limits. The aerobic bottle of a blood culture set yielded S. mucilaginosus (strain Aachen 19) after four days of incubation. Soon after admission the patient became afebrile and asymptomatic without special therapy. The clinical course was interpreted as an infection of unknown origin and the positive blood culture probably represented a transient bacteremia. Patient no. 2: A n 83-year-old woman was admitted to receive a second course of chemotherapy for treatment of immunoblastic lymphoma. One week after initiation of chemotherapy she experienced a first episode of fever of unknown origin. Several blood cultures remained sterile. Fever resolved promptly during one week of therapy with cefotiam plus tobramycin. Four days later the patient developed mild enteritis and fever (38.6°C), and after one day of incubation four of four blood cultures (two aerobic and two anaerobic bottles) were positive for Streptococcus sanguis and S. mucilaginosus (strain Aachen 234). The leucocyte count at that time was 1,500/mm s. Antibiotic therapy with ampicillin and tobramycin was started. The temperature decreased slowly while the leucocyte count rose to normal levels. Several control blood cultures were sterile and the clinical recovery was uneventful. Patient no. 3: A 64-year-old man underwent hemimaxillectomy because of carcinoma of the palate. Immediately after surgery he had high fever of up to 39.8°C, but two blood cultures were sterile. A regimen of cefotiam plus gentamicin initiated perioperatively was continued and the patient became afebrile. The following day fever relapsed and the aerobic bottle of a blood culture set yielded S. mucilaginosus (strain Aachen 479)

38 / 214

after five days of incubation. Clinically, there was no documented site of infection, including the surgical wound. Antibiotic therapy was changed to ciprofloxacin plus amoxicillin-clavulanate and fever resolved within a few days. Three days after surgery the patient was extubated and could be discharged from the intensive care unit without further complications. Patient no. 4: A 2-year-old girl with acute lymphoblastic leukemia had completed a course of cytotoxic chemotherapy two weeks before readmission for radiation therapy. As a routine procedure in order to detect colonization of the Hickman catheter, a single blood sample for aerobic culture was drawn from the catheter and S. mucilaginosus (strain Aachen 480) was isolated after one day of incubation. During the subsequent hospital stay the child was afebrile and no signs or symptoms of infection were seen. The complete blood count was normal and there was no need for antibiotic therapy. Follow-up blood cultures were not performed. Patient no. 5: A 13-year-old boy with known paroxysmal tachycardia was admitted with a three-day history of high fever, tachycardia and vertigo. Physical examination was remarkable for a temperature of 39.6°C and mild pharyngitis. A throat culture yielded physiologic flora. Laboratory studies showed leucocytosis of 12,300 cells/ram 3, and C-reactive protein was elevated to 36 mg/dl. An electrocardiogram and chest radiograph were normal, and there was no evidence of endocarditis. On admission one blood sample for aerobic culture was drawn and S. mucilaginosus (strain Aachen 483) grew after one day of incubation. The patient rapidly became afebrile without initiation of antibiotic therapy. Four days after admission the C-reactive protein and leucocyte count were normalized and the child was discharged. The clinical picture was interpreted as a febrile infection of the upper respiratory tract accompanied by transient bacteremia. Patient no. 6: A 27-year-old male was admitted to receive chemotherapy for chronic granulocytic leukemia in accelerated phase. He had excessive periodontitis and several gingival and mucosal ulcers. One week after admission dental surgery was performed with extraction of two teeth. Postoperative complications included fever. A blood culture was positive for Fusobacterium nucleaturn. Fever resolved promptly after appropriate treatment. Three weeks later the wound and ulcers in the oral cavity were almost completely healed, and cytotoxic chemotherapy was initiated. The patient was then given ofloxacin orally for antibacterial prophylaxis. Two weeks after completion of chemotherapy he developed fever (39.3°C). A set of blood specimens was drawn (two from peripheral veins, one from a Hickman catheter), and all three blood cultures (three of three aerobic and one of three anaerobic bottles) grew S. mucilaginosus (strain Ulm 19295) after two days of incubation. Empiric therapy with piperacillin plus netilmicin was initiated. The granulocyte count at that time was < 100 cells/mm 3. Fever persisted for the following eight days, with daily spikes of > 40°C

Infection 20 (1992) No. 4 © MMV Medizin Verlag GmbH Miinchen, Miinchen 1992

A. Kaufhold et al.: Stornatococcus mucilaginosus Bacteremia despite a change of treatment to ceftazidime/teicoplanin on day 4. Repeated blood cultures on days 2, 3, 4 and 8 after the onset of fever were negative, as were cultures of the catheter tip and flush cultures of the Hickman catheter, which was removed on day 8. Defervescence ensued in the following days, during which time the granulocyte count rose rapidly to normal levels. Clinically, there was no clearly documented site of infection, although at the site of the previous teeth extractions there was a radiographically suspected small bone sequestrum. Patient no. 7: A 69-year-old woman was admitted to receive a second course of chemotherapy for treatment of relapsed acute nonlymphocytic leukemia. Pretreatment investigation revealed apical periodontitis of a tooth, and a few days later this tooth was extracted. Chemotherapy was initiated one week later. Small ulcerations of the lips and perianally were noted subsequently, and oral ofloxacin was prescribed. The patient remained afebrile until her granulocyte count fell below 100 ceils/ram 3 another week later. Two aerobic blood cultures obtained on the same day grew S. mucilaginosus (strain L~m 19500) after two days of incubation. The patient continued to have daily spikes of fever (> 39°C) despite therapy with piperacillin plus netilmicin and subsequently with ceftazidime/ teicoplanin. Fever resolved after six days, when the granulocyte count rose to > 500/mm 3. Control blood cultures on day 4 of fever were sterile. Clinical recovery was uneventful and there were no sequelae. Patient no. 8: A 20-year-old female was admitted with a second relapse of acute nonlymphocytic leukemia. Chemotherapy was initiated and the patient was discharged on oral ofloxacin for antibacterial prophylaxis. She was seen at the outpatient clinic several days later, but was considered free of infection and clinically doing well. She was readmitted ten days later because of fever (> 39°C). There was no sign of localized infection. The oral cavity was normal, the lungs were clear and she had no subjective complaints. Her granulocyte count was < 100/mm 3. Two blood cultures were obtained and both aerobic bottles were positive for S. mucilaginosus (strain Ulm 30680) after two days of incubation. The patient was given imipenem/cilastatin. She continued to have low-grade fever during this therapy for five days, but repeat blood cultures failed to grow an organism. Thereafter, her granulocyte count gradually increased very slowly, but fever subsequently resolved. Therapy was discontinued and the patient remained afebrile until discharge.

Microbiological Findings The S. mucilaginosus isolates formed nonpigmented to whitish, nonhemolytic colonies on sheep blood agar after 24 h of incubation. All isolates grew finder aerobic and anaerobic (GasPak R jar) conditions. The colonies were strongly adherent to the agar surface, and this property increased after prolonged incubation. The lack of or very

Figure 1: India ink preparation of methylene blue stained Stomatococcus cells. The cocci are heavily encapsulated and arranged in pairs, tetrads and small clusters.

poor growth on unsupplemented Mueller-Hinton agar, commonly used for antimicrobial susceptibility testing, was a characteristic feature of all our isolates. The gram-positive organisms were nonmotile and the cocci were arranged in pairs, tetrads or small clusters. In India ink preparations, the cells were surrounded by capsules (Figure 1). Applying conventional procedures, all strains were oxidase and catalase negative and failed to grow in the presence of 5% NaC1. They did hydrolyze esculin but gave negative bile-esculin reactions. Resistance to lysostaphin (Lysostaphin Roche, Hoffmann-La Roche) was found in all cases. Further biochemical testing was done using three commercial identification systems (API 20 Strep, API Staph, and ATB 32 Staph, all obtained from API Systems, La Balme-les Grottes, France). As shown in Table 1, the reaction profiles obtained for the isolates were very similar within each identification system, and except for minor discrepancies the different systems revealed identical results for comparable physiological reactions. In Table 2, selected biochemical test results of our study are summarized and compared with data reported for S. mucilaginosus by other authors. In a disk diffusion test employing sheep blood agar (the commonly recommended Mueller-Hinton agar was not appropriate because of poor bacterial growth), all isolates appeared susceptible to several penicillins, cephalosporins, doxycycline, erythromycin, clindamycin and vancomycin, whereas all strains were only moderately susceptible or resistant to quinolones and gentamicin. For selected antimicrobial agents the minimal inhibitory concentration (MIC) was determined by an agar dilution method according to the guidelines of the National Committee for Clinical Laboratory Standards [24], except that Mueller-Hinton agar was replaced by sheep blood agar (Columbia agar base, Oxoid, Basingstoke, UK). These results are shown in Table 1.

Infection 20 (1992) No. 4 © MMV Medizin Verlag GmbH MiJnchen, Miinchen 1992

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A. Kaufhold et al.:

Stomatococcus mucilaginosus Bacteremia

Discussion T h e t a x o n o m y o f g r a m - p o s i t i v e c o c c i - first d e s c r i b e d in 1900 as Micrococcus mucilaginosus [26] - r e m a i n e d u n c l e a r u n t i l 1982, w h e n Bergan a n d Kocur [1] p r o p o s e d t h e n e w g e n u s Stomatococcus ( c o n s i s t i n g o f o n e s p e c i e s ) w i t h i n t h e f a m i l y o f Micrococcaceae.

S i n c e S. rnucilaginosus r e v e a l s a v a r i a b l e c a t a l a s e r e a c t i o n , it m a y b e c o n f u s e d in t h e clinical m i c r o b i o l o g y l a b o r a t o r y w i t h s e v e r a l g e n e r a o f g r a m - p o s i t i v e cocci. I n c o n t r a s t t o t h e c a t a l a s e - p o s i t i v e m i c r o c o c c i a n d s t a p h y l o c o c c i , S. mucilaginosus c h a r a c t e r i s t i c a l l y fails t o g r o w in t h e p r e s e n c e o f 5 % NaC1 a n d , o f n o t e , strains a r e e n c a p s u l a t e d , a l t h o u g h i s o l a t e s l a c k i n g this p o t e n t i a l

Table 1: Results obtained with commercial identification systems and antibiotic susceptibility tests for eight blood culture isolates of Stomatococcus mucilaginosus. : ...........

isolate of :Strain : : Profile numberobtainedby i ;.::::: p a t i e n t ' designation:: ..... .......... ............../ . . . . . ...... no; ..... : : ...... AP120Strep A P I S ~ a P h ATB32 St~ph: PeNcillinG 1 2 3 4 5 6 7 8

Aachen 19 Aachen234 Aachen479 Aachen 480 Aachen483 Ulm 19295 Ulm 19500 Ulm 30680

5000010 5000010 5140010 5150010 5140010 5000010 5000010 5140010

6310134 6310134 6310114 6312134 6312134 6310134 6310134 6310114

07711571 07717771 07313521 07717531 07713531 07317531 07717771 07313531

: 7 '. . . . .'," ' . . . . . . . . :: 'i :: : Eryt.hromycin :Tetracycline Ciprofloxaein Gentanaiein

0.03 ~0.016 0,03 g0.016 0.03 0.03 g 0.016 0.03

~ 0.125 ~0.125 ~ 0.125 g 0.125 ~0.125 ~ 0.125 g0.125 g0.125

0.5 0.25 0.5 0.5 1.0 0.5 0.5 0.5

4 1 1 16 1 64 64 32

8 8 16 16 8 16 16 16

Table 2: Biochemical characteristics of Stomatococcus mucilaginosus (compilation of data from the present report and from published references; only reports since accepted species designation are included). [ Reference n (_ no~ofstra s tested) Test

:....... " '

.... 'i

.....

'

Voges-Proskauer reaction

Present ..... [1] [51; report (type strain): ( n = l ) : ( n - - - 8 ) ..... ::

:[S] ..... [91'~ (n=i) (n=l) ;0

+

+

+

--

+

+

+

+

+

+

=

........

...... ' .........

......

.... [12] ~ .... [23:] [25] ( n = l ) .... ( n 5 t ) ( , ~ = I ) ..... ( n = ; ! o ) : ( n = l O 0 ) ...... :: : ii: +

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

Urease Hydrolysis of Esculin Sodium hippurate Arginine Acid production from Glucose Fructose Mannose Maltose Sucrose Trehalose Turanose Xylose Arabinose Glycogen Mannitol Melibiose Inulin Raffinose Ribose Sorbitol Starch Xylitol

40 / 216

+

+

--

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

Infection 20 (1992) No. 4 © MMV Medizin Verlag Gmblt Mfinchen, Mfinchen 1992

A. Kaugnold et at.: Stomatococcus mucilaginosus Bacteremia virulence factor have been rarely described [14]. Resistance to lysostaphin distinguishes S. mucilaginosus from staphylococci. In addition to these criteria, a recent report by Mitchell et al. [19] suggested that the application of four diagnostic antimicrobial disks (bacitracin, furazolidone, novobiocin and polymyxin B) may be of some help for discriminating S. mucilaginosus from other catalase-positive organisms. If the isolate fails to produce catalase, S. mucilaginosus may also be misidentified as Streptococcus sp. or Enterococcus sp. It should be pointed out that S. mucilaginosus is often positive for leucine aminopeptidase and pyrrolidonylarylamidase activities, enzymatic tests that are commonly performed as a helpful adjunct for identifying streptococci and enterococci. However, two features that were seen in all of our isolates, namely the characteristic gummy consistency and strong adherence of the colonies to the agar surface and the lack of growth on unsupplemented Mueller-Hinton-agar, should remind the microbiologist of S. mucilaginosus. Definite species identification can easily be accomplished by further biochemical testing. In accordance with other authors, we found a typical and very consistent physiological reaction pattern for epidemiologically unrelated clinical isolates of S. rnucilaginosus (Table 2). Although S. mucilaginosus is only included in the ATB 32 Staph data base, profile numbers obtained with the API 20 Strep and API Staph galleries appear to be very characteristic in order to allow reliable strain identification as well (Table 1). For a comprehensive overview of biochemical characteristics of S. mucilaginosus, the reader is referred to a detailed study conducted by Baldellon and MOgraud [25]. S. mucilaginosus belongs to the indigenous flora of the upper respiratory tract. It constitutes less than 5% of the predominant cultivable microorganisms on the human tongue [2]. In 1978 the first description of a documented human infection due to S. mucilaginosus appeared in the literature [4]. In this case the patient developed endocarditis subsequent to cardiac catheterization. The potential pathogenicity of S. mucilaginosus was later confirmed by the description of several cases of endocarditis, primarily in intravenous drug abusers [8,9,14]. Upon review of the literature, 26 cases of bacteremic infections with the organism have been described since 1978 [4-23], most of them in the last two years. A further seven cases of nonbacteremic infections have been reported in the literature. Table 3 briefly lists patient characteristics, underlying diseases and outcome in reported cases of S. mucilaginosus infection. Two important clinical features of S. mucilaginosus infection evolve from these and our case reports: the associations with foreign bodies and the compromise of host defense mechanisms that appear to play a major role in the epidemiology and clinical significance of this organism. Although no published data are available on the propensity and mechanisms of the organism to adhere to

plastic surfaces, the ability of S. mucilaginosus to cause device-associated infection has clearly been demonstrated in cases of prosthetic valve endocarditis [9,10]. Several other reported cases have been suggested to be catheter-related, for example in cancer patients [17,20,22,23] or in patients on continuous ambulatory peritoneal dialysis [6,11], but few have been proven. It is important to recognize that catheters may, in some cases, represent a portal of entry without causing persistent infection or difficult-to-eradicate colonization. Colonization of an intravenous catheter, as in one of our cases (case no. 4), need not be followed by infection, even in an immunocompromised host. Excessive periodontal disease with prior dental surgery, as in two of our cases (nos. 6 and 7), or head and neck trauma [19] or cancer (case no. 3, and [7]) may be considered a typical though relatively rare history in patients with S. mucilaginosus infection. Mucosal damage, whether clinically recognized or not, in patients with a sufficiently high number of organisms in the oral cavity may enable the bacteria to translocate to the bloodstream. The resulting bacteremia appears to be benign and transient in patients with adequate therapy (case nos. 1 and 5). In patients with neutropenia and S. mucilaginosus bacteremia, the natural history of the infection is unknown but almost definitely can be expected to be closely related to the degree of neutropenia and time to neutrophil recovery (as in cases 4, 6, 7 and 8 in this series, and [12,15,16]). As shown in Table 3, at least one such patient had a fatal outcome [12], and the only other reported patient with a fatal outcome due to a nonbacteremic S. mucilaginosus infection also had neutropenia [17]. Because of the poor growth on the commonly recommended Mueller-Hinton agar, the growth media and techniques employed for antibiotic sensitivity testing varied considerably among different authors, and therefore, published data of test results should be compared with caution. In the two studies conducted by French investigators [27,28] who examined a larger number of S. mucilaginosus strains (32 and 64 strains, respectively), it became clearly evident that major discrepancies may occur between the disk diffusion method and a dilution technique for determining MICs. Thus, a consensus in terms of accepted methods and breakpoints is highly desirable. Nevertheless, the results for the antimicrobial susceptibility of our strains are in general agreement with those reported by other investigators. They suggest that susceptibility of S. mucilaginosus to commonly used antimicrobial agents largely resembles that of streptococci. All of our isolates were sensitive to penicillin G, but several strains showing diminished susceptibility or resistance to penicillin G have recently been described [13,14,17,19,23,27]. Some of these isolates were involved in serious infections such as endocarditis [14] and septicemia [19]. Although treatment failures or poor clinical outcomes have not yet been attributed to penicillin

Infection 20 (1992) No. 4 © MMV Medizin Verlag GmbH M~inchen, Mtinchen 1992

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A, K a u f h o l d et at.: Stomatococcus mucilaginosus B a c t e r e m i a

Table 3: Summary of reported cases of Stomatococcus mucilaginosus infections. Reference v e a r o f ~ Sexlage :Site-of : . Typeof i ' i ~ .... :no. : publication ~ years isolation . :idf~vztion : orStrain: ...... .... . ........ : ' : .... : isolation: :.-: ,.::.:...::.:...::. ,.. ....::.:....! .........:.: ,.::.:..... ........ .....

~ Catheter, i Underlyingcondition :' : or device- ...... ...... . . . . . .... , :associated : ~ :: :: ]rffection~: :, :::: ::: ::::........

.... outcome = .

[ 4] [ 5]

1978 1985

M / 63 M / 64

Blood Blood

Endocarditis Endocarditis (MV)

(+) --

Rheumatic heart disease M V prolapse

No No

[ [ [ [

6] 7] 8] 9]

1985 1986 1987 1987

F / 50 M / 84 F / 34 M / 29

Peritoneal fluid Blood Blood Blood

C A P D peritonitis Bacteremia Endocarditis ( A V ) Prosthetic valve endocarditis (AV)

(+) (+) -+

Renal insufficiency Esophageal carcinoma, radiation M V prolapse, i.v. drug abuse A V replacement, i.v. drug abuse

No No No Yes

[ 10 ]

1988

M / 33

Blood

+

M V replacement

No

[ 11 ]

1988

F / 57

Peritoneal fluid

Prosthetic valve endocarditis (MV) C A P D peritonitis

(+)

No

[ 12 ]

1989

F / 31

Blood

Septic shock

(+)

Renal insufficiency, immunosuppression Hodgkin's disease, neutropenia

[ 13 ]

t 989

M/79

Bacteremia

+

Liver cirrhosis

No

[ 14 ]

t989

M / 35

Blood, i.v. catheter tip Blood

Endocarditis ( A V )

--

No

[ 15 ]

1989

M/24

Bacteremia

(+)

[ 16 ]

1990

F / 57

Bacteremia

(+)

Pancytopenia

No

[ 17 ]

1990

F / child

Blood, mouth wash Blood, mucosal ulcer CSF

Previous endocarditis, i.v. drug abuse Leukemia, neutropenia

Meningitis

(+)

Leukemia, neutropenia

Yes

1990

M / child

Leukemia, neutropenia

No

1990

F/87

Broviac site cellulitis Subdural empyema

+

[ 18 ]

1990

F/23

1990

F / 39

Blood

1990

F / 74

Blood

[ 20 ] b

1991

F / 13

[ 21 ]

1991 1991

M / 30 M / 26

Central venous catheter blood Blood Bronchial lavage fluid

Subdural hematoma with neurosurgery Diabetes, head and neck trauma, emergency splenectomy Breast carcinoma, possible i.v. drug abuse Myocardial infarction, Swan-Ganz catheter Osteogenic sarcoma, neutropenia AIDS AIDS

No

[ 19 ]

Local inflammation Subdural drainage fluid Blood

[ 22 ]

1991 1991

ND ND

Blood Blood

Bacteremia Bacteremia

+ +

Leukemia Leukemia

ND ND

[ 23 ]

1991

M / 2.5

Blood

(+)

Yolk sac tumor

No

Bacteremia (polymicrobial) Bacteremia (polymicrobial) Bacteremia, pneumonia Fever, catheterrelated infection Bacteremia Bronchopulmonary infection, P. cariniipneumonia

(+) (+) (+) (+) + (+) (+)

Yes

No

No No No No No No

t99t

M / 55

Blood

Bacteremia, pneumonia Bacteremia

(+)

Leukemia, neutropenia

No

1991 1991

F / 80 M / 1~5

Blood Blood

Bacteremia Bacteremia

(+) (+)

Pulmonary embolism Short-bowel syndrome

Yes No

1991

M / 54

Blood

Bacteremia

(+)

Vascular disease, Gortex graft, diabetes

No

1991

M /4

Blood

Bacteremia (polymicrobial)

(+ )

Leukemia

No

1991

M / 28

Blood

--

AIDS

No

1991

M t9

Blood c

Bacteremia (polymicrobial) Catheter-related infection

+

Neuroblastoma, neutropenia

No

a+= probably associated; ( + ) = association uncertain; - = probably not associated. b Also included in reference [ 23 ]. c No details as to whether central venous catheter blood cultures and / or peripheral venous blood cultures were positive. ND = Not documented; C A P D = continuous ambulatory peritoneal dialysis; M V = mitral valve; A V = aortic valve.

Continued on page 43/219

42 / 2 1 8

Infection 20 (1992) No. 4

© M M V Medizin Verlag G m b H Mtinchen, Mtinchen 1992

A. Kaufhold et al.:

Stomatococcus

mucilaginosus

Bacteremia

Table 3 continued

Refere~eno. pubticationYear°f ~ :Sex/agein years Site'0fisotation ,,i " /{ orstraiti ~ ", " " ~ , isolation " "' '

Present report

1991

F! 36

Bloode

1989

F / 18

Blood

1990

F / 83

Blood

1991 1991

M / 64 F/2

1991

M / 13

Blood Central venous catheter blood Blood

1991

M / 27

1991 1991

i=¢ecfioTmype°fn' ,. . . . . '

:

,

'

Catheter-related infection Bacteremia (transient) Bacteremia (polymicrobial) Bacteremia Colonization

:,

0tCatheter'device.- Underlyingcondition associated .... , . . . . . . . . infection~

.....

outc~meFatal "

,

,,, .... "

,

'

+

Ovarian cancer

No

--

Febrile illnessof unknown origin

No

(+)

Immunobtastic lymphoma, mild neutropenia Head and neck cancer, surgery Leukemia, radiation

No

( +) +

Blood

Bacteremia (transient) Bacteremia

-( +)

F / 69

Blood

Bacteremia

(+)

F / 20

Blood

Bacteremia

(+)

Febrile illnessof the upper respiratory tract Leukemia, neutropenia, dental surgery Leukemia, neutropenia. dental surgery Leukemia, neutropenia

No No No No No No

a+=probably associated; ( + ) = associationuncertain;- = probably not associated. b Also includedin reference [ 23 ]. c No details as to whether central venous catheter blood cultures and / or peripheral venous blood cultures were positive. ND = Not documented; CAPD = continuous ambulatoryperitoneal dialysis; MV = mitral valve; AV = aortic valve. resistance, this possibility has to be considered. Patterns of resistance to [3-1actams appear to be rather similar to those currently described for S t r e p t o c o c c u s pneumoniae. Thercfore, ~ in contrast to a previous suggestion [8], penicillin G may no longer be the drug of choice for initial therapy of severe S . m u c i l a g i n o s u s infections. Pending conclusive i n v i t r o susceptibility data, it might be reasonable to include a third-generation cephalosporin or a glycopeptide antibiotic in the empiric treatment of a particularly severe and life-threatening S . m u c i l a g i n o s u s infection such as endocarditis (especially prosthetic valve endocarditis) or septicemia in a profoundly neutropenic patient. Our data, as well as the results of a recently published study [29], show that low-level aminoglycoside resistance is a common feature of S . m u c i l a g i n o s u s . Nevertheless, the possible benefit of combining aminoglycosides with cell-wall active antibiotics in order to achieve bactericidal synergism for the treatment of serious infections has never been investigated; in general, comprehensive data concerning the clinical efficacy are lacking for all antibiotic regimens used thus far. For tess severe infections and for prophylactic purposes (endocarditis prophylaxis, antimicrobial prophylaxis in the neutropenic patient), regimens including a macrolide antibiotic appear appropriate. All isolates described in the present communication as well as the majority of strains reported in the literature were susceptible to erythromycin, whereas the studies conducted by R o c h e t t e et al. [27] and C h o m a r a t et al. [28] revealed an exceptionally high percentage (up to 23% based on MIC values) of strains exhibiting erythromycin resistance.

However, as mentioned above, these somewhat conflicting results may be due to technical reasons as well. Three of our neutropenic patients (nos. 6, 7 and 8) developed bacteremia during prophylactic treatment with ofloxacin. In addition, at least one other case report described bacteremia in a neutropenic patient receiving oral ciprofloxacin prophylaxis [15]. The MICs for quinolones reported in this paper and by others [19] indicate that resistance to this group of antibacterial agents is a common feature among S . m u c i l a g i n o s u s strains, suggesting that selection from the upper respiratory tract flora and subsequent translocation to the bloodstream may represent a typical pathogenesis in patients at high risk for mucosal damage. In this respect the clinical course of infection in patients with neutropenia may resemble that of bacteremia due to other microorganisms commonly found in the oropharynx, such as, for example, viridans streptococci [30,31] or, much more rarely, A e r o c o c c u s viridans [32] and others. In summary, the increasing knowledge about the i n v i t r o and i n v i v o properties of S . m u c i l a g i n o s u s appears to indicate that this organism shares many features, both microbiologically and clinically, with those organisms with which it may have been frequently confused, i.e. coagulase-negative staphylococci and micrococci on one side, and streptococci on the other side. It is now evident that the organism behaves as a true opportunistic pathogen more commonly than previously recognized. Cases of bacteremia may be transient and pathogeneticatly unrelated to primary disease, requiring no therapy. At the other end of the spectrum are the immunosuppressed

Infection 20 (1992) No. 4 © MMV Medizin Verlag GmbH Mtinchen. Mfinchen 1992

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43

A. K a u f h o l d et al.: Stomatococcus mucilaginosus B a c t e r e m i a

patients with a possibly severe infection, a difficult-todefine portal of entry of either damaged mucosal surfaces or intravenous catheters or both, and the need for adequate, prompt treatment. Finally, there are infrequent cases of endocarditis in which antimicrobial therapy is mandatory but, in the case of prosthetic valves, appears to be of little value for definite cure. Microbiologists and

infectious disease physicians will certainly have to learn more about this organism. Note added in proof: Since submission of this manuscript, another series of systemic S. mucilaginosus infections appeared in the literature: McWhinney, P. H. M., et al.: Stomatococcus mucilaginosus: An emerging pathogen in neutropenic patients. Clin. Infect. Dis. 14 (1992) 641-646.

References 1. Bergan, T., Kocur, M.: Stomatococcus mucilaginosus gen. nov., sp. nov, ep. rev., a member of the family Micrococcaceae. Int. J. Syst. Bacteriol. 32 (1982) 374-377. 2. Gordon Jr., D. F.: Reisolation of Staphylococcus salivarius from the human oral cavity. J. Bacteriol. 94 (1967) 1281-1286. 3. Bergan, T , Bovre, K., Hovig, B.: Reisolation of Micrococcus muctTaginosus Migula 1900. Acta Pathol. Microbiol. Scand.(B) 78 (1970) 85-97. 4. Rubin, S. J., Lyons, R. W., Murcia, A. J.: Endocarditis associated with cardiac catheterization due to a gram-positive coccus designated Micrococcus mucilaginosus incertae sedis. J. Clin. Microbiol. 7 (1978) 546-549. 5. Prag, J., Kjolicr, E., Espersen, F.: Stomatococcus mucilaginosus endocarditis. Eur. J. Clin. Microbiol. 4 (1985) 422-424.

6. Ragnaud, J. M., Marceau, C., Roche-Bezian, M. C., Wone, C.: P6ritonite ~ rechute ~tStornatococcus mucilaginosus chez une malade 7. 8.

9.

10.

ll.

12.

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14.

15.

16.

17.

trait6e par dialyse p6riton6ale continu6 ambulatoire. Presse M6d. 14 (1985) 2063. Bariow, J. F., Vogele, K. A., Dzintars, P. F.: Septicemia with Stomatococcus mucilaginosus. Clin. Microbiol. Newsl. 8 (1986) t70. Relman, D. A., Ruoff, K., Ferraro, M. J.: Stomatococcus mucilaginosus endocarditis in an intravenous drug abuser. J. Infect. Dis. 155 (1987) 1080-1082. Coudron, P. E., Markowitz, S. M., Mohanty, L. B., Schatzki, P. F , Payne, J. M.: Isolation of Stomatococcus mucilaginosus from drug user with endocarditis. J. Clin. Microbiol. 25 (1987) 1359-1363. Lazar, H. L., Sulis, C., Hauser, W.: Stomatococcus mucilaginosus prosthetic valve endocarditis. J. Thorac. Cardiovasc. Surg. 95 (1988) 940. Lanzendiirfer, H., Zaruba, K., yon Graevenitz, A.: Stomatococcus mucilaginosus as an agent of CAPD peritonitis. Zentralbl. Bakteriol. Hyg. (A) 270 (1988) 326-328. Oppenheim, B. A., Weightman, N. C., Prendevillc, J.: Fatal Stomatococcus mucilaginosus septicaemia in a neutropenic patient. Eur. J. Clin. Microbiol. Infect. Dis. 8 (1989) 1004-1005. Poirier, L. P., Gaudreau, C. L.: Stomatococcus mucilaginosus catheter-associated infection with septicemia. J. Clin. Microbiol. 27 (1989) 1125-1126. Pinsky, R. L., Piscitelli, V., Patterson, J. E.: Endocarditis caused by relatively penicillin-resistant Stomatococcus mucilaginosus. J. Clin. Microbiol. 27 (1989) 215-216. Weers-Pothoff, G., Novakova, I. R. O., DonneUy, J. P., Muytjens, H. L.: Baeteraemia caused by Stomatococcus mucilaginosus in a granulocytopenic patient with acute lymphocytic leukaemia. Neth. J. Med. 35 (1989) 143-146. Lemozy, J., Maestre, P., Huguet, F., Chomarat, M., Dabernat, H., Lareng, M. B.: Source of infection in Stomatococcus mucilaginosus septicaemia. Lancet 335 (1990) 416. Weinblatt, M. E., Sahdev, I., Berman, M.: Stomatococcus mucilaginosus infections in children with leukemia. Pediatr. Infect. Dis. J. 9 (1990) 678-679.

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18. Magee, J. T., Burnett, I. A., Hindmarch, J. M., Spencer, R. C.: Micrococcus and Stomatococcus spp. from human infections. J. Hosp. Infect. 16 (1990) 67-73. 19. Mitchell, P. S., Huston, B. J., Jones, IL N., Hoicomb, L., Koontz, F. P.: Stomatococcus mucilaginosus baeteremias. Typical case presentations, simplified diagnostic criteria, and a literature review. Diagn. Microbiol. Infect. Dis. 13 (1990) 521-525. 20. Ascher, D. P , Bash, M. C., Zbick, C , White, C.: Stomatococcus mucilaginosus catheter-related infection in an adolescent with osteosarcoma. South. Med. J. 84 (1991) 409-410.

21. Patey, O., Malkin, J. E., Coutaux, A., Leflour, N., Lafaix, C., Emond, J. P., Bublanchet, A.: AIDS-related Stomatococcus mucilaginosus infection. Lancet 338 (1991) 631-632. 22. Wilcox, M. H., Spencer, R. C.: Stomatococcus mucilaginosus infection. Lancet 338 (1991) 884. 23. Ascher, D. P., Zbick, C., White, C., Fischer, G. W.: Infections due to Stomatococcus mucilaginosus: 10 cases and review. Rev. Infect. Dis. 13 (1991) 1048-1052. 24. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2nd edition. Approved standard M7-A2. NCCLS, Villanova, PA, 1990. 25. Baldellon, C., M~graud, F.: Stomatococcus mucilaginosus: charact6res culturaux et biochimiques de 100 souches isol6es de la sph6re ORL. Ann. Inst. Pasteur Microbiol. 136A (1985) 213-226. 26. Migula, W.: System der Bakterien. Handbuch der Morphologie. Entwicklungsgeschichte und Systematik der Bakterien. Gustav Fischer Verlag, Jena 1900. 27. Rochette, A., Chomarat, M., de Montcios, M.: Sensibilit6 aux antibiotiques de soixante-quatre souches de Stomatococcus mucilaginosus isoldes en clinique humaine. Mise en 6vidence d'une r6sistance ~t l'6rythromycine. Pathol. Biol. (Paris) 36 (1988) 394-397. 28. Chomarat, M., Martin, C., Breysse, F.: Sensibilit6 aux antibiotiques de trente-deux souches de Stomatococcus mucilaginosus chez des patients de stomatologie en pratique de ville. Pathol. Biol. (Paris) 37 (1989) 378-381. 29. Chomarat, M., Vital, M. G., Flandrois, J. P.: Susceptibility to aminoglycosides of 63 strains of S. mucilaginosus isolated from sputum. Zentralbl. Bakteriol. 276 (1991) 63-67. 30. Villahlanca, J. G., Steiner, M., Kersey, J., Ramsay, N. K. C., Ferrieri, P., Haake, R., Weisdorf, D.: The clinical spectrum of infections with viridans streptococci in bone marrow transplant patients. Bone Marrow Transplant 6 (1990) 387-393. 31. Kern, W., Kurrle, E., Schmeiser, T.: Streptococcal bacteremia in adult patients with leukemia undergoing aggressive chemotherapy. A review of 55 cases. Infection 18 (1990) 138-145. 32. Kern, W., Vanek, E.: Aerococcus bacteremia associated with granulocytopenia. Eur. J. Clin. Microbiol. 6 (1987) 670-673.

Infection 20 (1992) No. 4

© MMV Medizin Verlag GmbH Mtinchen, Mfinchen 1992