UNIVERSITY OF COLORADOUNIVERSITY OF COLORADOSCHOOL OF MEDICINESCHOOL OF MEDICINE

DEPARTMENT OF PATHOLOGYDEPARTMENT OF PATHOLOGYRESIDENCY TRAINING PROGRAMRESIDENCY TRAINING PROGRAM

MICROBIOLOGYMICROBIOLOGY

Alpha-hemolytic StreptococciAlpha-hemolytic Streptococci and and EnterococciEnterococci

Topic 1: VRE ScreeningTopic 1: VRE Screening

As a point of departure from the case study format As a point of departure from the case study format presented before, the focus this week will be more presented before, the focus this week will be more

informational than self-assessment.informational than self-assessment.

The purpose here is to introduce three topics as The purpose here is to introduce three topics as related to the non-beta hemolytic streptococci based related to the non-beta hemolytic streptococci based

on information presented either during past on information presented either during past CACMLE Teleconferences or during the 2006 “Micro CACMLE Teleconferences or during the 2006 “Micro

in the Mountains” conference.in the Mountains” conference.

The topic reviews will include:The topic reviews will include:• Screening for Vancomycin-Resistant EnterococciScreening for Vancomycin-Resistant Enterococci

•Emergence of penicillin-resistant pneumococciEmergence of penicillin-resistant pneumococci•Clinical relevance of the viridans streptococciClinical relevance of the viridans streptococci

CASE STUDIES AND TOPIC REVIEWSCASE STUDIES AND TOPIC REVIEWS

ENTEROCOCCUS:ENTEROCOCCUS: VRE VRE SCREENSCREEN

A 38-year-old female was admitted to the UCLA hospital for a liver A 38-year-old female was admitted to the UCLA hospital for a liver transplant. Following protocol, a rectal swab was collected to rule out transplant. Following protocol, a rectal swab was collected to rule out vancomycin-resistant vancomycin-resistant EnterococcusEnterococcus sp. Colonies isolated on Columbia sp. Colonies isolated on Columbia colistin-naladixic acid modified agar containing 10colistin-naladixic acid modified agar containing 10uug of vancomycin were g of vancomycin were transferred to sheep blood agar. Dull gray, opaque, alpha-hemolytic transferred to sheep blood agar. Dull gray, opaque, alpha-hemolytic colonies were isolated from the subculture after 24 (left) and 48 (right) colonies were isolated from the subculture after 24 (left) and 48 (right) hours incubation. A Vitek Gram positive identification (GPIhours incubation. A Vitek Gram positive identification (GPITMTM) card gave a ) card gave a profile number of 77367270530 = profile number of 77367270530 = EnterococcusEnterococcus gallinarum/cassiloflavusgallinarum/cassiloflavus. . The susceptibility result for vancomycin was 8 mcg/ml.The susceptibility result for vancomycin was 8 mcg/ml.

Presenter:Presenter: Claudia Claudia

Hinnenbusch, Hinnenbusch, MT(ASCP)MT(ASCP)

Clinical Clinical MicrobiologyMicrobiologyUCLA Medical UCLA Medical

Center, Los AngelesCenter, Los AngelesCACMLE CACMLE

TeleconferenceTeleconferenceOct. 24, 2001Oct. 24, 2001

ENTEROCOCCUS:ENTEROCOCCUS: VRE VRE SCREENSCREEN

RecapitulationRecapitulationThe increase in the numbers of vancomycin-resistant enterococci The increase in the numbers of vancomycin-resistant enterococci has prompted the implementation of surveillance programs in has prompted the implementation of surveillance programs in hospitals to monitor its incidence and spread. hospitals to monitor its incidence and spread. Enterococcus Enterococcus faeciumfaecium is most common vancomycin resistant strain, having is most common vancomycin resistant strain, having acquired either the Van- A or the Van-B gene. acquired either the Van- A or the Van-B gene. E. faecalisE. faecalis possessing these vancomycin-resistant genes are less common.possessing these vancomycin-resistant genes are less common.

Isolates of Isolates of E. cassiloflavusE. cassiloflavus and and E. gallinarumE. gallinarum, that have MIC levels , that have MIC levels to vancomycin that are elevated (between 4 and 32 mcg/ml) are to vancomycin that are elevated (between 4 and 32 mcg/ml) are also encountered. Since this low level resistance is intrinsic, also encountered. Since this low level resistance is intrinsic, such isolates are not reported as VRE.such isolates are not reported as VRE.

Automated bacterial identification systems are not always reliable Automated bacterial identification systems are not always reliable in identifying the enterococci to the species level. Thus, when in identifying the enterococci to the species level. Thus, when screening for VRE, one should accept results from these systems screening for VRE, one should accept results from these systems only if they correlate with the colony morphology and the known only if they correlate with the colony morphology and the known antimicrobial profile of the organism in question.antimicrobial profile of the organism in question.

ENTEROCOCCUS:ENTEROCOCCUS: VRE VRE SCREENSCREEN

Screening ProtocolScreening Protocol VRE Screening Protocol used at the UCLA Medical CenterVRE Screening Protocol used at the UCLA Medical Center

1.1. Patients being admitted for organ transplant have admission cultures, as Patients being admitted for organ transplant have admission cultures, as well as cultures when they are transferred to another ward, or released. well as cultures when they are transferred to another ward, or released. Cultures include a nasal swab to screen for MRSA, and a rectal swab to Cultures include a nasal swab to screen for MRSA, and a rectal swab to screen for VRE.screen for VRE.

2.2. Stool cultures from inpatients are only processed for VRE surveillance Stool cultures from inpatients are only processed for VRE surveillance when the Infection Control team has given prior approval. They are rarely when the Infection Control team has given prior approval. They are rarely used to demonstrate clearance in patients previously found to have VRE.used to demonstrate clearance in patients previously found to have VRE.

3.3. Since a correlation has been made showing an increased incidence of Since a correlation has been made showing an increased incidence of VRE in patients whose stool samples are positive for VRE in patients whose stool samples are positive for C. difficileC. difficile toxin, toxin, stool samples positive for stool samples positive for C. difficileC. difficile are screened quarterly for the are screened quarterly for the presence of VRE. In our institution, this has proven to be a cost-effective presence of VRE. In our institution, this has proven to be a cost-effective and efficient way to screen for VREand efficient way to screen for VRE..

NOTE: IS THERE ANY SUCH PROTOCOL IN EFFECT AT UCHSC?NOTE: IS THERE ANY SUCH PROTOCOL IN EFFECT AT UCHSC?

UNIVERSITY OF COLORADOUNIVERSITY OF COLORADOSCHOOL OF MEDICINESCHOOL OF MEDICINE

DEPARTMENT OF PATHOLOGYDEPARTMENT OF PATHOLOGY

RESIDENCY TRAINING PROGRAMRESIDENCY TRAINING PROGRAM

MICROBIOLOGYMICROBIOLOGY

Alpha-hemolytic StreptococciAlpha-hemolytic Streptococci and and

EnterococciEnterococci

Topic 2: Penicillin Resistant Topic 2: Penicillin Resistant PneumococciPneumococci

Abbreviated Identification of Abbreviated Identification of Streptococcus pneumoniaeStreptococcus pneumoniae

SUMMARYSUMMARYMucoid alpha-hemolytic colonies Mucoid alpha-hemolytic colonies

on Blood agar on Blood agar

Lancet-shaped, gram-positive cocci Lancet-shaped, gram-positive cocci in pairs, with haloin pairs, with halo

Bile SolubleBile Soluble

Susceptible to Optochin (“P” DiskSusceptible to Optochin (“P” Disk))

Streptococcus pneumoniaeStreptococcus pneumoniae

Perform antimicrobial Perform antimicrobial susceptibility testsusceptibility test WHY IS THIS NECESSARY?WHY IS THIS NECESSARY?

Antibiotic ResistantAntibiotic Resistant PneumococcusPneumococcus

A respiratory isolate was A respiratory isolate was found to have no zone of found to have no zone of inhibition around the 1inhibition around the 1uug g oxacillin disk (6mm) in a oxacillin disk (6mm) in a screening disk diffusion test. screening disk diffusion test. It was reported out as It was reported out as “penicillin resistant”.“penicillin resistant”.

As a follow up, a routine disk As a follow up, a routine disk antibiotic susceptibility test antibiotic susceptibility test panel was performed. As panel was performed. As illustrated in the photograph, illustrated in the photograph, the isolate was found to be the isolate was found to be susceptible to other susceptible to other antibiotics (cefuroxime, antibiotics (cefuroxime, tetracycline, erythromycin, tetracycline, erythromycin, chloramphenicol, and chloramphenicol, and ceftriaxone). The 15mm in ceftriaxone). The 15mm in diameter zone around the disk diameter zone around the disk at the 1 o’clock position at the 1 o’clock position indicates intermediate indicates intermediate resistance to SXT.resistance to SXT.

Antibiotic Resistant Antibiotic Resistant PneumococcusPneumococcus

Emergence of world-wide resistance to pneumococci Emergence of world-wide resistance to pneumococci

South Africa, Baraguanath Hospital, Johannesburg (Am J Dis Child South Africa, Baraguanath Hospital, Johannesburg (Am J Dis Child 146:920-923, 1992) revealed resistance in 40% of community acquired 146:920-923, 1992) revealed resistance in 40% of community acquired and 80% of hospital acquired isolates of and 80% of hospital acquired isolates of S. pneumoniaeS. pneumoniae recovered from recovered from 83 children with meningitis and/or bacteremia.83 children with meningitis and/or bacteremia.

South Africa: Witwaters-rand University: Of a study population of 4766 South Africa: Witwaters-rand University: Of a study population of 4766 consecutive isolates of Sconsecutive isolates of S. pneumoniae. pneumoniae recovered from blood and CSF recovered from blood and CSF during the period 1979-1986, the average penicillin resistance climbed during the period 1979-1986, the average penicillin resistance climbed from 3.8% in 1979 to 14.2% in 1986. 92.2% of serogroups were 6 or 19.from 3.8% in 1979 to 14.2% in 1986. 92.2% of serogroups were 6 or 19.

Spain: Bellvitge Principes ‘Espanya Hospital, Barcelona: 23% rate of Spain: Bellvitge Principes ‘Espanya Hospital, Barcelona: 23% rate of resistance among 66 episodes of pneumococcal meningitis (Am J Med resistance among 66 episodes of pneumococcal meningitis (Am J Med 84:839-846,1988).84:839-846,1988).

Spain: Hospital General Gregorio Mara-nor, Madrid: 42.5% of strains Spain: Hospital General Gregorio Mara-nor, Madrid: 42.5% of strains isolated from 139 patients were “non-susceptible” (Clin Infect Dis isolated from 139 patients were “non-susceptible” (Clin Infect Dis 14:427-425, 1992).14:427-425, 1992).

Emergence of world-wide resistance to pneumococciEmergence of world-wide resistance to pneumococci

Africa: Nairobi, Kenya. Study population—of 150 Africa: Nairobi, Kenya. Study population—of 150 S. pneumoniaeS. pneumoniae isolates isolates from HIV-positive patients, 19% were resistant with MIC’s ranging from 0.12 from HIV-positive patients, 19% were resistant with MIC’s ranging from 0.12 – 0.25ug/ml. Rare serotype 14 in 18% of cases.– 0.25ug/ml. Rare serotype 14 in 18% of cases.

Hungary, Heim Pal Children’s Hospital, Budapest. Epidemiologic study Hungary, Heim Pal Children’s Hospital, Budapest. Epidemiologic study revealed 58% of all revealed 58% of all S. pneumoniaeS. pneumoniae isolates to be resistant to penicillin (70%; isolates to be resistant to penicillin (70%; of isolates recovered from children.) (J Infect Dis 163:542-548, 1991).of isolates recovered from children.) (J Infect Dis 163:542-548, 1991).

Houston, Baylor college of Medicine. Of 95 isolates of Houston, Baylor college of Medicine. Of 95 isolates of S. pneumoniaeS. pneumoniae, 34 , 34 were susceptible at <0.1were susceptible at <0.1uug/ml, 42 were intermediate at 0.1 – 1.0 g/ml, 42 were intermediate at 0.1 – 1.0 uug/ml; and, g/ml; and, 19 were resistant at >219 were resistant at >2uug/ml (12.1% of all isolates). (Antimicrob Agents g/ml (12.1% of all isolates). (Antimicrob Agents Chemother 36:1703-1707. 1992).Chemother 36:1703-1707. 1992).

Atlanta, Georgia, CDC. Pneumococcal Surveillance Working Group Atlanta, Georgia, CDC. Pneumococcal Surveillance Working Group (Facklam, et al. J Infect Dis 163:1273-1278, 1991): Study population—5,459 (Facklam, et al. J Infect Dis 163:1273-1278, 1991): Study population—5,459 isolates of isolates of S. pneumoniaeS. pneumoniae submitted from 35 hospitals during the period submitted from 35 hospitals during the period 1979 to 1987. Overall resistance was 5% at MIC’s >0.11979 to 1987. Overall resistance was 5% at MIC’s >0.1uug/ml.g/ml.

Emergence of world-wide resistance to pneumococciEmergence of world-wide resistance to pneumococci

These accounts were considered quite worrisome at the time. The high These accounts were considered quite worrisome at the time. The high prevalence of penicillin-resistant prevalence of penicillin-resistant S. pneumoniaeS. pneumoniae in certain locales in certain locales undoubtedly represents antibiotic pressure, where antibiotic therapy has undoubtedly represents antibiotic pressure, where antibiotic therapy has been administered virtually without restriction.been administered virtually without restriction.

Recent studies reveal that resistance has increased in many parts Recent studies reveal that resistance has increased in many parts of the world to 15% - 35% depending on the geographic region. of the world to 15% - 35% depending on the geographic region.

(Whitney, et al. NEJM 343:1917-1924, 2000)(Whitney, et al. NEJM 343:1917-1924, 2000)

Thus it is currently recommended that Thus it is currently recommended that S. pneumoniaeS. pneumoniae isolates from isolates from blood, CSF, and other closed body sites, and from treatment failures, blood, CSF, and other closed body sites, and from treatment failures, should be tested routinely for susceptibility to penicillin.should be tested routinely for susceptibility to penicillin.

GuidelinesGuidelines::

Susceptible: MIC <0.06 Susceptible: MIC <0.06 uug/ml (oxacillin zones >20mm)g/ml (oxacillin zones >20mm)

Relatively resistant: MIC 0.12 – 1.0 Relatively resistant: MIC 0.12 – 1.0 uug/ml (oxacillin zones <19mm)g/ml (oxacillin zones <19mm)

Resistant: MIC >1.0 Resistant: MIC >1.0 uug/ml (oxacillin testing cannot distinguish between g/ml (oxacillin testing cannot distinguish between relatively resistant and resistant).relatively resistant and resistant).

UNIVERSITY OF COLORADOUNIVERSITY OF COLORADOSCHOOL OF MEDICINESCHOOL OF MEDICINE

DEPARTMENT OF PATHOLOGYDEPARTMENT OF PATHOLOGYRESIDENCY TRAINING PROGRAMRESIDENCY TRAINING PROGRAM

MICROBIOLOGYMICROBIOLOGY

Alpha-hemolytic StreptococciAlpha-hemolytic Streptococci and and EnterococciEnterococci

Topic 3: Viridans StreptococciTopic 3: Viridans Streptococci

Case Study: Human MeningitisCase Study: Human MeningitisThe case is that of a 59 y.o. male The case is that of a 59 y.o. male

farmer with sudden onset of farmer with sudden onset of fever, and confusion fever, and confusion

Peripheral Blood count: Peripheral Blood count: 12,800 wbc’s/mm12,800 wbc’s/mm33 (73% (73% neutrophils; 12% bands)neutrophils; 12% bands)

Cerebrospinal Fluid:Cerebrospinal Fluid:– 3520 wbc’s/mm3520 wbc’s/mm33 (100% (100%

neutrophils)neutrophils)– Glucose: <1 mg/deciliterGlucose: <1 mg/deciliter– Protein: 368 mg/deciliterProtein: 368 mg/deciliter

Case presented by:Case presented by:William M. Janda, Ph.D. D(ABMM)William M. Janda, Ph.D. D(ABMM)

Assoc Prof Dept. PathologyAssoc Prof Dept. PathologyDirector Clinical Microbiolog Director Clinical Microbiolog

LaboratoryLaboratoryUniversity of Illinois Medical CenterUniversity of Illinois Medical Center

Chicago, IllinoisChicago, Illinois““Micro in the Mountains” 2006Micro in the Mountains” 2006

Illustration of gray white, alpha-Illustration of gray white, alpha-hemolytic colonies recovered on hemolytic colonies recovered on

sheep blood agar from spinal fluid sheep blood agar from spinal fluid sediment after 48 hours incubation.sediment after 48 hours incubation.

The isolate was identified as:The isolate was identified as:

Streptococcus suisStreptococcus suis

Case Study: Human MeningitisCase Study: Human Meningitis

Based on the clinical history and the laboratory findings, Based on the clinical history and the laboratory findings, the patient was empirically started on ceftriaxone and the patient was empirically started on ceftriaxone and vancomycin.vancomycin.

When the isolate was identified as When the isolate was identified as Streptococcus suisStreptococcus suis, the , the therpapy was switches to IV ampicillin.therpapy was switches to IV ampicillin.

The patient complained of lower back pain. MRI studies The patient complained of lower back pain. MRI studies revealed diskitis and osteomyelitis of L3 and L4.revealed diskitis and osteomyelitis of L3 and L4.

The patient was discharged after 13 days to complete a 6-The patient was discharged after 13 days to complete a 6-week course of IV ampicillin and oral clindamycin.week course of IV ampicillin and oral clindamycin.

This was the first reported case in the United States.This was the first reported case in the United States.

(NEJM 354:13-25, 2006)(NEJM 354:13-25, 2006)

Streptococcus suisStreptococcus suis: Characteristics: Characteristics• αα-hemolytic streptococcus-hemolytic streptococcus• No growth at 10No growth at 10ooC or 45C or 45ooCC• LAP-PositiveLAP-Positive• Esculin hydrolysis – PositiveEsculin hydrolysis – Positive• Growth, 6.5% NaCl-NegativeGrowth, 6.5% NaCl-Negative• Arginine Dihydrolase-PositiveArginine Dihydrolase-Positive• Hippurate hydrolysis, urease, acetoin Hippurate hydrolysis, urease, acetoin

production – Negativeproduction – Negative• Acid from glucose, maltose, sucrose, Acid from glucose, maltose, sucrose,

and lactoseand lactose• No acid from mannitol, sorbitol, or riboseNo acid from mannitol, sorbitol, or ribose• Included in the API Strep data baseIncluded in the API Strep data base

Streptococcus suisStreptococcus suis: Epidemiology: Epidemiology• Although found worldwide, there has never been a case Although found worldwide, there has never been a case

reported in the U.S. (until 2006!!!)reported in the U.S. (until 2006!!!)

– Two cases reported in CanadaTwo cases reported in Canada

• Majority of human disease reported in Asia (Thailand, Majority of human disease reported in Asia (Thailand, China, and Hong Kong)China, and Hong Kong)

– Third most common agent of bacterial meningitis in Third most common agent of bacterial meningitis in Hong KongHong Kong

– Human cases reported from the Netherlnds, Denmark, Human cases reported from the Netherlnds, Denmark, Great Britain, France, Belgium, Germany, and SwedenGreat Britain, France, Belgium, Germany, and Sweden

• Human infections most common in those who work Human infections most common in those who work directly with swine or in the manufacture of pork productsdirectly with swine or in the manufacture of pork products

– Abattoir and slaughterhouse workers, pig farmers,Abattoir and slaughterhouse workers, pig farmers, meat inspectors, veterinariansmeat inspectors, veterinarians

Streptococcus suisStreptococcus suis: The Pigs’ : The Pigs’ “Group B “Group B StreptococcusStreptococcus””

• Pathogen of swinePathogen of swine– Transmitted from aymptomatic sows to their Transmitted from aymptomatic sows to their

newbornnewborn– Rapidly fatal disease in piglets (sepsis, meningitis, Rapidly fatal disease in piglets (sepsis, meningitis,

pneumonia)pneumonia)

• Sporadic disease in humansSporadic disease in humans– Meningitis is the most seriousMeningitis is the most serious manifestationmanifestation– Human fatality rate of 5-10%Human fatality rate of 5-10%– Serotype 2 (of 35 serotypes) responsible for vast Serotype 2 (of 35 serotypes) responsible for vast

majority of human diseasemajority of human disease

Streptococcus suisStreptococcus suis: Clinical Disease: Clinical Disease

• Human infections enter through breaks in skin, the Human infections enter through breaks in skin, the nasopharynx, or the gastrointestinal tractnasopharynx, or the gastrointestinal tract

• ““Influenza-like” prodrome with rapid development of Influenza-like” prodrome with rapid development of bacteremia and meningitisbacteremia and meningitis

• High rate of cochlear-vestibular involvement High rate of cochlear-vestibular involvement resulting in ataxia, dizzinessresulting in ataxia, dizziness– Cranial nerve involvement leads to hearing lossCranial nerve involvement leads to hearing loss

• Complications associated with bacteremic Complications associated with bacteremic disseminationdissemination– Arthritis, spondylodiscitis, endophthalmitis, Arthritis, spondylodiscitis, endophthalmitis,

peritonitis, pneumonia, and endocarditisperitonitis, pneumonia, and endocarditis

Sichuan, China Outbreak: Sichuan, China Outbreak: July-August, 2005July-August, 2005

• 215 human cases reported among farmers 215 human cases reported among farmers exposed during the slaughter of pigsexposed during the slaughter of pigs– 28% developed toxic shock syndrome28% developed toxic shock syndrome– Sepsis (24%), meningitis (48%) or bothSepsis (24%), meningitis (48%) or both– 62% mortality62% mortality

• Ribotyping revealed that the same strain was Ribotyping revealed that the same strain was reponsible for all casesreponsible for all cases

Streptococcus suisStreptococcus suis

Viridans Streptococcal GroupsViridans Streptococcal Groups• Group II: Sanguis GroupGroup II: Sanguis Group

– S. sanguinisS. sanguinis (3 biotypes), (3 biotypes), S. parasanguinisS. parasanguinis, , S. gordoniiS. gordonii, , S. sinensisS. sinensis

• Group III: Mitis GroupGroup III: Mitis Group

– S. mitisS. mitis, , S. oralisS. oralis, , S. cristatusS. cristatus, , S. perorisS. peroris, , S. infantisS. infantis, , S. australisS. australis, , S. S. oligofermentansoligofermentans

• Group IV: Mutans GroupGroup IV: Mutans Group

– S. mutansS. mutans, , S. sobrinusS. sobrinus, , S. cricetusS. cricetus, , S. downeiS. downei, , S. rattiS. ratti, , S. macacaeS. macacae, , S. ferusS. ferus

• Group V: Salivarius GroupGroup V: Salivarius Group

– S. salivariusS. salivarius, , S. vestibularisS. vestibularis, , S. infantariusS. infantarius, , S. thermophilusS. thermophilus, , S. S. hyointestinalishyointestinalis

• Group VI: Anginosus Group Group VI: Anginosus Group (also included in beta-hemolyic group)(also included in beta-hemolyic group)– S. constellatusS. constellatus subspecies, subspecies, S. anginosus, S. intermediusS. anginosus, S. intermedius

• Group VII: Bovis GroupGroup VII: Bovis Group

– S. bovisS. bovis sensu strictosensu stricto, , S. gallolyticus, S. infantarius, S. gallolyticus, S. infantarius, S. suisS. suis. .

Viridans Group StreptococciViridans Group Streptococci

• Found in the upper respiratory tract and the Found in the upper respiratory tract and the urogenital tracturogenital tract

• EndocarditisEndocarditis– 30-40% of cases due to viridans streptococci30-40% of cases due to viridans streptococci– Usually isolated from multiple blood culturesUsually isolated from multiple blood cultures– Occur in patients with pre-existing valvular diseaseOccur in patients with pre-existing valvular disease– Also associated with infection of prosthetic valvesAlso associated with infection of prosthetic valves– Complications may include multi-valve infection, Complications may include multi-valve infection,

mitral valve aneurysms, paravalvular mitral valve aneurysms, paravalvular abscesses, abscesses, and glomerulonephritisand glomerulonephritis

– S. mitisS. mitis, , S. sanguisS. sanguis, , S. oralisS. oralis, , S. gordoniiS. gordonii, , S. S. mutansmutans, , S. salivariusS. salivarius, , S. vestibularisS. vestibularis, and , and S. sinensisS. sinensis

Viridans Streptococcal BacteremiaViridans Streptococcal Bacteremia• Prolonged bacteremia with viridans streptococci in neutropenic Prolonged bacteremia with viridans streptococci in neutropenic

pediatric and adult patients now recognized as a distinct clinical entitypediatric and adult patients now recognized as a distinct clinical entity

• Associated with aggressive cytotoxic chemotherapy given for Associated with aggressive cytotoxic chemotherapy given for treatment of leukemias, lymphomas, solid tumors, and bone marrow treatment of leukemias, lymphomas, solid tumors, and bone marrow transplantationtransplantation

• Risk factors: Risk factors: – Administration of high doses of cytotoxic agents (esp. cytarabine)Administration of high doses of cytotoxic agents (esp. cytarabine)– Presence of mucosal ulcerations secondary to Presence of mucosal ulcerations secondary to

chemotherapy/radiation (oral mucositis)chemotherapy/radiation (oral mucositis)– Absence of previous antimicrobial therapyAbsence of previous antimicrobial therapy– Severe neutropeniaSevere neutropenia

• May also be complicated by development of ARDS, hypotension, May also be complicated by development of ARDS, hypotension, shock, and endocarditis shock, and endocarditis

In past years, the viridans streptococci were generally susceptible to penicillin, ampicillin, and most other antimicrobial agents. More recently, resistance has developed against penicillins, cephalosporins, aminoglycosides, and other classes of antibiotics.

In a study of 211 viridans streptococci recovered from blood cultures, 38% were resistant to penicillin (MIC’s >0.25ug/ml) and 41% were resistant to erythromycin (Potgeiter, et al. 1992. Eur J Clin Microbiol Infect Dis 11:543-546). These strains remained susceptible to cephalosporins, imipenem, and vancomycin.

In a second follow-up study (Antimicrob Agents Chemother 37:2740-2742, 1993) 4 strains of S. mitis were resistant to penicillin (MIC’s16-32ug/ml), and two demonstrated high-level gentamicin resistance (MIC >2000 ug/ml). These gentamicin resistant strains contained the same structural gene that codes for gentamicin resistance in E. faecalis and E. faecium, integrated into the chromosome and not the plasmid.

Viridans Streptococcal Susceptibility Testing

Abbreviated Identification of Abbreviated Identification of Viridans StreptococciViridans Streptococci

Gram positive cocci in long chainsGram positive cocci in long chains

PYR NegativePYR Negative

S. mutansS. mutans

Small, dry, gray, alpha-hemolytic colonies on Small, dry, gray, alpha-hemolytic colonies on sheep blood agarsheep blood agar

Optochin resistant; Bile insolubleOptochin resistant; Bile insoluble

S. sanguiusS. sanguius S. mitis S. mitis S. salivariusS. salivarius

VP Positive;VP Positive;Acid from Acid from

mannitol/sorbitolmannitol/sorbitol

Arginine Arginine dihydrolase dihydrolase

PositivePositive

VP Pos;VP Pos;mannitol/sorbitol mannitol/sorbitol

NegativeNegative

Chemically Chemically inertinert