Streptococci and Enterococci

Classification of Streptococci
• Strep: gram positive, catalase negative
– Nutritionally fastidious
– Facultative anaerobes but don’t use oxygen metabolically (create
lactic acid)
• Initial classification based on hemolysis on sheep blood agar plates
– α (partial, reduction), β (complete), and γ (none)
• 1930’s: Lancefield defines cell wall antigen groups
– Concentrated on virulent, β-hemol species
• Sherman: pyogenic, viridans, enterococci, lactic
• 1980’s: Enterococci get own genus
• Lactic acid Strep (Lancefield N): Lactobacillus
• Nutritionally variant Strep (require pyridoxal): Abiotrophia and
Granulicatella
Hemolysis Patterns of Streptococci
Classification of Strep from Humans
Species Lancefield Hemolytic Comments
S. pyogenes A β
S. agalactiae B β, γ Group B Strep
S. dysgalactiae C, G β Formerly S. equisimilis;
subsp. equisimilis pyogenic; respiratory, SSTI
S. pneumoniae None α
S. bovis species D α, γ Viridans; associated with colon
group cancer; IE
S. mutans group not useful α, γ, rarely β Viridans; dental caries and IE
S. salivarius group not useful α, γ Viridans; opportunistic
S. mitis group not useful α Viridans; IE, opportunistic
S. anginosus group A, C, F, G, α, β, γ Viridans; formerly known as S.
or no milleri; 3 species S. anginosus, S.
detectable constellatus, and S.
intermedius; purulent infxns
 Zoonotic Strep Species
Species Lancefield Hemolysis Comments
S. dysgalactiae C, L α, β, γ Domesticated animals
subsp dysgalactiae
S. equi subsp equi C β Equine strangles; limited
documentation of human infxn
S. equi subsp C β Bovine mastitis; outbreaks of human
zooepidemicus nephritis
S. pornicus E, P, U, V β Swine; human female genital tract;
may cross react w/ GBS antigen
testing
S. canis G β Dogs; infrequent human pathogen
S. suis R, S, T α, β Swine; infrequent human meningitis
S. iniae None β Fish; SSTI, sepsis
detectable
 Case 1
• 12F
– Developed fevers, sore throat, swollen cervical lymph
nodes 3 days ago
– Several kids at school sick recently
– Today, developed an erythematous, blanching rash on
torso, a redness on face sparing area around lips, and a
coating on tongue.
– She’s allergic to PCN.
• Questions
– What clinical condition? What pathogen?
– How to diagnose? How to treat?
– What complications to worry about?
 Streptococcus pyogenes
• Group A Strep, GAS; human-restricted pathogen
• Cell-associated virulence factors
– Hyaluronic acid capsule
• Antiphagocytic
• Not immunogenic
– M protein (over 150 types); other genes with similar proteins
• Antiphagocytic
• Bind IgG, IgA
• Iron transport
• Resistance to antimicrobial peptides
– Lipoteichoic acid (LTA)
• Extracellular products
– Streptolysin S (SLS): oxygen stabile
– Streptolysin O (SLO): oxygen labile
– DNases
– Streptokinase: dissolves clots
– SpeB (streptococcal pyogenic exotoxin): protease
– SpeA and SpeC: scarlatinal toxins associated with scarlet fever
– Superantigens
 S. pyogenes
• Asymptomatic colonization
• Pharyngitis
– Scarlet fever
• Pyoderma, impetigo
• Invasive SSTI: erysipelas, cellulitis, NF, myositis,
peripartum sepsis
• Strep TSS
• Bacteremia
• Sequelae: rheumatic fever, glomerulonephritis
 Antibiotic Options for GAS
• Try to use PCN or β-lactam if at all possible!
• Cephalosporins, carbapenems have great
activity
• Clinda generally active; sporadic resistance
• Increasing resistance to azithro, quinolones
• Common resistance to tetracycline family
• TMP/SMX questionable (assume inactive)
• Vanco, dapto, linezolid
 Streptococcal Pharyngitis
• Ages 5-15 highest incidence; adults also infected (e.g., military
recruits)
– Person-to-person transmission via droplets or secretions; proximity
and crowding worsen!
– Food- and water-borne outbreaks occur
• Acute onset sore throat, fever, malaise, HA
– Look for GI sx in kids
– Enlarged, hypermic tonsils, exudates
– Tender cervical LAD
– Cough, coryza, conjunctivitis should suggest alternative dx.
• Self-limiting in about one week
– Treat to hasten resolution, stop spread, reduce sequelae
• Dx by cx or rapid antigen testing
• Oral PCN-V, IM PCN-G, oral amox; cephalexin, azithro, clinda
 Strep Pharyngitis (con’t)
• Remember that 10% of kids asymptomatically
colonized (lower in adults)
• Cultures or rapid antigen test may remain positive
after tx; don’t retreat unless sx have recurred.
• Watch for suppurative complications: peritonsillar
abscess, retropharyngeal abscess, lymphadenitis,
mastoiditis, meningitis, brain abscess, thrombosis of
intracranial venous sinuses
 Scarlet Fever
• Classically associated with pharyngitis, but may occur
after infxns at other sites
• Recent outbreak in China and Hong Kong
• Requires GAS strain with erythrogenic toxins
• Rash typically on 2nd day
– Face flushed except for circumoral pallor
– Enanthem: small, hemorrhagic spots on hard and soft
palate
– Exanthem: upper chest to torso, extremities; face, palms,
soles spared; diffuse blush with points of deeper red that
blanch; Pastia’s lines (skin folds deeper red)
– Tongue: coated to red strawberry tongue
Scarlet Fever Pictures
 Acute Rheumatic Fever (ARF)
• Non-suppurative inflammatory lesions of heart, joints,
subcutaneous tissues, CNS
• Follows an upper respiratory GAS infection
• Molecular mimicry?: Ig’s to M protein react with
cardiac myosin, synovium, and articular cartilage
• Occurs in 0.4 to 3% of untreated GAS pharyngitis cases
– More recent ECHO studies suggest rate may be 10x higher
than thought
• Worldwide: 500,000 ARF per year, with 300,000
developing rheumatic heart disease
• Recurrence rate higher with subsequent GAS infection
 ARF
• Major manifestations
– Carditis: murmur, CHF, pericardial friction rubs or effusions; chronic mitral >
aortic valves
– Polyarthritis: knees, ankles, elbows, wrists
– Chorea: Syndenham’s chorea (St Vitus dance); emotional lability, weakness,
involuntary purposeless movements
– Subcutaneous nodules: firm, painless; few mm to 2cm
– Erythema marginatum: non-pruritic, non-painful eruption on trunk;
evanescent, serpiginous.
• Minor: fever, arthralgia, heart block, acute-phase reaction in blood labs
• 1-5 weeks after GAS infxn; avg 19 days. Lasts 3 months.
• Carditis in 40-50% first ARF, only sx posing long-term disability or death
• Dx using criteria above, plus evidence of GAS infection by either culture or
rising GAS antibody titer (ASO or DNaseB).
• Tx: depends on severity, analgesics to aspirin to steroids
ARF Pictures
 Chorea
http://youtu.be/RsIQFeYOkAg
ARF Treatment: Secondary Prevention
• Prevention of recurrence
– IM benzathine PCN-G q3-4 weeks
– Oral PCN-V or sulfasalazine 2nd line
– Erythro for allergic
– Duration depends on severity
Category Duration after last attack
RF w/o carditis 5 years or age 21 (whichever longer)
RF w/ carditis but no residual heart 10 years or age 21 (whichever
(valvular) disease longer)
RF w/ carditis and residual heart 10 years or age 40 (whichever
(valvular) disease longer); maybe lifelong
 Poststreptococcal Acute
Glomerulonephritis
• GAS, but also group C (S. equi subsp
zooepidemicus); certain M-types and groups
associated
• Occurs after either pharyngitis or pyoderma; up to
15% untreated cases
• Recurrences less frequent than with ARF
• Believed to be immunologic etiology: cross-
reaction vs. deposition of Ab-Ag complexes
• Worldwide: 470,000 cases/year, with 5000 deaths
 PS-AGN
• S/Sx (10-21 days latent): HTN, edema, discolored urine;
malaise, HA, anorexia. Fever very uncommon.
– Facial, periorbital swelling common
– CHF-like respiratory sx
– Labs: anemia; ESR up; low serum protein; BUN, Cr up; total
complement and C3 down
– Urine: mild hematuria, mild proteinuria
• Dx: clinical hx, physical findings, evidence of recent Strep
infection; maybe bx
• Tx: fluid management; treat Strep (PCN); check contacts
• Secondary prophylaxis is unnecessary (b/c recurrences very
rare).
 Case 2
• 39M, no pmhx
• Pulled calf exercising at gym 4 days ago, took ibuprofen
• 2 days later, developed pain, redness near site
• ED: low grade temp; erythema on calf, warm, traced; dx
cellulitis, started IV vanco.
• Overnight, redness expands, becomes more tender, spiking
fevers
• Noon: febrile, tachycardic, soft BP; erythema deeper, no
pain. WBC 15.
• Questions
– FIRST intervention?
– Change in treatments?
 Necrotizing Fasciitis
• Erysipelas or cellulitis progresses from excessive pain to
loss of pain sensation, hemorrhagic bullae, rapidly
advancing border
• Commonly very ill
• Dx: need to think of it; pathologic dx
– Laboratory Risk Indicator for NF (LRINEC): combines WBC, Hgb,
CRP, Na, glucose, Cr
• Tx:
– Debridement (often multiple times)
– Antibiotics: PCN and clindamycin
• Consider toxic shock syndrome
• Remember: not all NF is GAS
 Streptococcal Toxic Shock Syndrome
• Any Strep infxn with sudden onset of shock and organ
failure (most common with skin site)
• At least 11 toxins with superantigen activity, but likely
many factors contribute
– Activates 1 in 5 T cells (compare to 1 in 10,000 to 100,000
in normal infections) (Mueller-Alouf et al., 1994).
– Result is cytokine Armageddon

TNF-α, IL-1β,
IL-6, TNF-β,
IL-2, IFN-γ
 Strep TSS
• Sx:
– Phase 1: fevers, chills, myalgias, GI sx, confusion, combative
– Phase 2: tachycardia, tachypnea, fevers
– Phase 3: shock and organ failure
– If skin focus, sx evolve at site
• Tx:
– Source control!
– ICU (ARDS in 55% cases)
– RRT (renal failure in 50% cases)
– Abx: PCN and clinda (high dose) (A-II rec)
• Vanco, dapto, linezolid, Synercid for PCN-allergic
– Maybe IVIg (B-II rec)
 Why clinda?
• Protein synthesis inhibitor: shuts down toxin production
• PCN has Eagle effect: less active against stationary phase GAS
– May be due to change in PBP expression
– No such issue for clinda
• Clinda 600-900mg IV q8h
• Limited clinical data
– Zimbelman et al., 1999 (looked at NF)
 So what about IVIg?
• IVIg: some Abs to GAS toxins; improve immune milieu
• Clinical data is incomplete
– Darenberg et al., 2003
• PCN (12 g/day), clindamycin (600 IV TID), +/- IVIG (1 g/kg day 1,
0.5 g/kg days 2 and 3)
• 10 IVIg, 11 placebo
• IVIg had trend towards decreased mortality at 28 days (p=0.3),
faster resolution of shock, faster improvement in end-organ
failure; slower resolution of NF
• No adverse events from IVIg.
• Cost: about $75-100/gram…so this study regimen
would add between $10,500 and $14,000 for 70kg
adult.
 Case 3
• 23F IVDU admitted with septic arthritis
• No hx recurrent infxns as child
• Aspirated fluid shows GPC diplococci
• Blood cultures later grow same, α hemolytic
• Questions
– Antibiotic tx?
– Other testing?
 Streptococcus pneumoniae
• Micro lab identifies by α hemolysis, catalase negative,
susceptible to Optochin, and dissolved by bile acids.
• Polysaccharide capsule: 91 serogroups and counting
• Naturally competent (can take up DNA)
• Doesn’t make highly toxic, tissue-damaging products
• Niche is human nasopharynx: 5-10% healthy adults and
20-40% healthy kids colonized
• Very young and very old most susceptible to invasive
disease, but epidemiology changing with vaccination.
 Factors that Predispose to
Pneumococcal Disease
• Extremes of age • Excess exposure
• Defective Ab formation (daycare, prison,
• HIV shelter)
• • Prior respiratory infxn,
Complement defects
esp flu
• Few or ineffective
• Pulmonary
PMNs (steroids, EtOH,
DM) inflammatory (smoking,
COPD)
• Asplenia (incl sickle cell)
 Pneumococcal Pneumonia
• Often multiple risk factors
• Cough, fatigue, fever, chills, SOB
• Lung exam abnormal
• CXR: usually infiltrate; air bronchograms correlate with
bacteremia; frequent effusion, and rare empyema.
• Labs: leukocytosis, but rare leukopenia
• Dx: sputum cx +/- blood cx (can have neg sputum but
pos blood cx). Ag test positive in 80% of cases, 10%
w/o pneumococcus; can pick up colonization in kids so
don’t use in pediatrics.
• Complications: empyema; cardiac events
 Other Clinical Syndromes of
Pneumococcus
• Otitis media
– Usually #1 or #2 to H. flu.
• Sinusitis
– Usually #1 or #2 to H. flu.
• Meningitis
– Most common bacterial meningitis in adults; also in kids >6 mos in countries w/ Hib vaccine
– Direct extension or bacteremia
• Exacerbation of chronic bronchitis
– 2nd to H. flu.
• Conjunctivitis
• Endocarditis (uncommon)
• Purulent pericarditis (rare)
• Septic arthritis
• Osteomyelitis (esp of vertebrae)
• SSTI
• If an uncommon pneumo infection in young person…check HIV.
 Treating Pneumococcus
• In 2008, MIC breakpoints for pneumococcus differentiated CNS
from all other sites
• Came from observation that you can’t get PCN into CSF at high
concentrations, but good levels in lung and other sites.
• Also picking up genes for altered PBPs.

Antibiotic Susceptible Intermediate Resistant

PCN (oral) ≤0.06 0.12-1 ≥2
PCN (IV), non-CNS ≤2 4 ≥8
PCN (IV), CNS ≤0.06 n/a ≥0.12
Amox (oral), non-CNS ≤2 4 ≥8
CTX, non-CNS ≤1 2 ≥4
CTX, CNS ≤0.5 1 ≥2
Resistance to Other Antibiotics
Antibiotic % Suscept.
PCN (IV), non-CNS 95%
PCN (IV), CNS 49%
CTX, non-CNS 95%
CTX, CNS 90%
Ery 56%
Levo 97%
Bactrim 66%
Vanco 100%
Linezolid 98%
Tetracycline 61%

BMC Antibiogram, all adult inpatient

pneumococcus, 2011 (N=67)
 Treatment Recommendations
• Otits media: amox; amox/clav, quinolone, or
CTX if fails
• Sinusitis: amox, amox/clav, quinolone…if truly
bacterial (see recent guidelines)
• PNA: quinolone, macrolide, doxy, amox +/-
clav for outpatient; PCN, amp, CTX, vanco,
quinolone; typically 7-8 days total.
• Meningitis: vanco plus CTX, plus steroids;
narrow abx when MICs known
 Pneumococcal Vaccinations
• Two flavors of vaccine:
– Pneumovax: capsular polysaccharide of 23 serotypes; PPS23
– Prevnar: capsular polysaccharide conjugated to protein
(improves humoral response), 7 serotypes originally, now up to
13; PCV13
• Recommendations
– Use PCV13 for kids; multiple shot protocol
– Adults with immunocompromise, asplenia, etc…get one dose of
PCV13, then one PPS23 at least 8 weeks later, and 5 years
thereafter.
– Adults over 65: PPS23 once
• These guidelines change frequently!
 Changes in Capsule Type after
Vaccination Introduced
• May have replacement in colonization types.
• Other countries found invasive diseases increasing
from non-vaccine strains.
• Herd protection.

Invasive pnuemo
infections in kids
<5. From CDC.
 Streptococcus agalactiae (Group B
Streptococcus)
• Capsule is most significant virulence factor
• Colonizes genital and lower GI tracts of 10-
40% of women; also found in oropharynx,
upper GI
• Pass to baby peripartum by ascension or
during birth
 Neonatal Infections
• Early-Onset
– 12 hours of age average
– Bacteremia (85%), pneumonia (10%), meningitis (5-10%)
– Heavy maternal carriage (untreated), delivery at less than
37 weeks, intra-partum fever, intra-amniotic infection,
ROM >18 hours
• Late-Onset
– Median 36 days (7-89)
– Bacteremia (65%) and meningitis (25-30%)
• Treatment involves ampicillin plus aminoglycoside
initially, before move to PCN-G
 Infections in Adults
• Found with predisposing factors, incl DM, liver disease, malignancy, renal
failure
• Puerperal infection of mother
– Upper genital tract; amniotic fluid, bacteremia, endometritis
• Primary bacteremia
• Pneumonia
• Endocarditis
– Large, friable vegetations; rapid valve destructions
• Arthritis
• Osteomyelitis
• SSTI
• Recurrent GBS infection
– 4% of cases will have another invasive GBS infection
• Treat: PCN-G (or vanco); add gent for endocarditis
 Prevention
• Screening pregnant women led to 65% drop in early-onset
GBS illness in newborns.
– Lower vaginal and rectal swab at 35-37 weeks (unless going to
treat already b/c of hx)
• Intrapartum abx for:
– Positive screening
– Previous infant w/ invasive GBS
– GBS bacteriuria during current pregnancy
– GBS status unknown, plus delivery <37 weeks or ROM >18 hours
or fever
• No intrapartum abx for planned C-section in absence of
labor or membrane rupture.
• PCN; cefazolin or vanco for allergies
 Case 4
• 67M with HTN, DM, COPD, CAD admitted w
cough, SOB, LE edema; afebrile; CXR fluid vs
multifocal PNA
• Given dose of levoflox in ED
• One blood cx drawn at admit: GPC pairs and
chains  Strep viridans
• Questions:
– How do we interpret the blood cx?
 Strep viridans
• Made up of 5 groups
– anginosus group
– mitis group
– mutans group
– salivarius group
– sanguinis group
• Normal flora of animals and humans
• Low virulence; no toxins
 Strep viridans: Endocarditis
• Often with previous valvular pathology
• Proportion increases with time after valve
replacement
• Subacute: often weeks
• Fever, malaise, anorexia
• Low-grade bacteremia (1-30 CFU per mL blood)
 Treatment of Native Valve
Endocarditis from Strep viridans and
Organism
Others
Antibiotic Regimen
PCN-sens Strep viridans (MIC ≤0.12)
PCN-intermed Strep viridans (>0.12
but ≤0.5)
PCN-resistant Strep viridans (>0.5),
Abiotrophia, Granulicatella, Gemella
At BMC in 2011, 20% of Strep viridans were intermediate MIC vs.
80% sensitive.
PCN-G (12-18 million U daily, divided) or CTX
(2g q24h) x 4 weeks
PCN-G or CTX plus gentamicin (3 mg/kg
qday) x 2 weeks
Vancomycin x 4 weeks
PCN-G (24 million U) or CTX (4 weeks) plus
gentamicin (2 weeks)
Vancomycin x 4 weeks
PCN (18-30 million U) or amp (12g/day,
divided) plus gentamicin x 4-6 weeks
Vancomycin x 6 weeks
Treatment of Prosthetic Valve IE with
Strep viridans
Organism
PCN-susceptible (MIC ≤0.12)
PCN-resistant (MIC>0.12)
Regimen
PCN-G (24 million U) or CTX (2g q24h)
x 6 weeks +/- gentamicin (3 mg/kg
q24) x 2 weeks
Vancomycin x 6 weeks
PCN-G (24 million U) or CTX (2g q24h)
plus gentamicin x 6 weeks
Vancomycin x 6 weeks
Other Manifestations of Strep viridans
• Bacteremia
– Account for 2.6% of all positive blood cultures
– After toothbrushing, 25-50% of people have bacteremia
– If transient, may consider limited clinical significance.
– More common and profound in ONC patients, esp BMT.
Bad outcomes (maybe just marker of bad mucosal
barriers?)
• Meningitis
– Rare: 0.3 to 5% of culture-positive meningitis
– However, concern about contamination
• Pneumonia
– Very rarely the sole, instigating pathogen
 IE Prophylaxis: IDSA Guidelines
• “bacteremia resulting from daily activities is much more likely to cause IE than
bacteremia associated with dental procedures”
• Only people with certain conditions get ppx:
– Prosthetic valves or perivalvular material
– Previous IE
– Congenital heard disease, only cyanotic CHD, repaired CHD with prosthetic materials within
last 6 mos, repaired CHD with defect
– Cardiac transplant w/ cardiac valvulopathy
• Procedures warranting ppx:
– Dental procedures manipulating gingiva or cutting mucosa
– Respiratory tract
– Infected skin, skin structures, or musculoskeletal tissue
– NOT needed for GI or GU procedures, vaginal delivery, hysterectomy, tattooing.
• Regimens
– Amoxicillin 2g PO x 1, 30-60 min before procedure
– Keflex (2g), clinda (600mg) or azithro (500mg) PO x 1
 Streptococcus anginosus group
• Formerly called Strep milleri group
• S. intermedius, S. constellatus, S. anginosus
• Viridans strep, but cause pyogenic infections
• Caramel-like odor of colonies
• Commensals of oropharyngeal, urogenital, and GI
• Synergize with other bacteria, esp anaerobes
• More toxins than other viridans
• Clinical conditions
– Dental abscess, CNS abscess, liver abscess, empyema
– IE: high myocardial abscess, metastatic abscesses
• Sensitive to PCN, CTX generally; vanco, clinda for allergy;
resistant to AG’s although still synergy; macrolides poor
 Streptococcus dysgalactiae subsp
equisimilis
• Group C or G by Lancefield; had several older species rolled into it.
• Common flora of oropharynx, skin
• Infxns often mimic GAS or GBS infections
– Pharyngitis
• Get ASO bump
• PS-AGN has been documented, but not ARF
– SSTI
• Pyoderma, erysipelas, impetigo
• May be more common cause of cellulitis than GAS
– Arthritis, often polyarticular
– Osteomyelitis
– Endocarditis: acute to subacute; poor response to β-lactam monotherapy;
frequent emboli
• Tx
– PCN; amox, vanco, linezolid, cefazolin
– Naf, ox not effective; high rates of tetra, clinda, ery resistance
– Very good synergy b/w PCN and gent
 Streptococcus bovis group
• Complex phylogeny, but S. gallolyticus subsp
gallolyticus is one associated w/ IE and bacteremia
• Causes 11-27% of all IE, and 24% Streptococcal IE
• High association with colonic malignancy and
hepatobilliary disease (77% of bacteremias found to
have CA in one series)
• Aortic valve most common
• Follows Strep viridans treatment guidelines
• Rare vancomycin resistance (probably acquired from
VRE)
Nutritionally Variant (Deficient) Strep:
Abiotrophia and Granulicatella
• Originally called Streptococcus mitior
• Require pyridoxal or cysteine for growth
• Small colonies; often satellites around other species; somewhat
difficult to culture
• Normal flora of upper respiratory, GI, UG tracts
• In vitro MICs don’t correlate well with clinical responses
– Less susceptible to PCN (33-67% relatively resistant)
– Vancomycin active
– PCN or vanco have synergy with gentamicin
– Decr susceptibility to 3rd gen cephs, azithro, clinda
• Cause IE (esp Abiotrophia): 5% of bacterial IE, majority of culture-
negative IE (although cultures more sens now)
– Compared to other bacterial IE: more complications, more
embolization, more CHF, more surgery needed, more relapses despite
appropriate tx
 Streptococcus iniae
• β hemolytic; no Lancefield antigen
• May be misidentified as a viridans by
automated systems
• Cellulitis of hand(s) with accompanying
bacteremia
• Handling live or dead fish (especially tilapia)
• Good response to β-lactam abx
 Case 5
• 49M admitted 2 week ago with ICH,
complicated ICU post-op course incl MRSA
VAP, today day 5 of 7 vancomycin
• Fever today, tachycardic; WBC up
• Blood cx drawn from CVC growing GPC pairs
and short chains
• Questions:
– What organism(s) do you worry about?
– What is your next step?
 Enterococcus
• Part of Streptococcus until 1984.
• Can grow in 6.5% NaCl and from 10°-45°C;
hydrolyze esculin in presence of 40% bile salts
• Most infections from E. faecalis or E. faecium;
leading cause of nosocomial infxns
• Colonize GI tract; selected for by abx
 Enterococcus: Clinical Manifestations
• Bacteremia +/- IE (1-32%)
– Frequent comorbidities
– IE subacute; fever, constitutional sx; 50% CHF; emboli 27-43%;
death 11-35%
• UTI
• Meningitis
– 0.3 to 4% of cases; usu severe comorbidities
• Abd Infxn
– Unclear contribution to pathology in polymicrobial collections
– Nosocomial peritonitis, PD-related infxn
• Neonatal
• SSTI
 Enterococci: Challenges of Treatment
• Intrinsically resistant to many abx, with
acquisition of additional resistance
• Looking for bactericidal tx for IE
• β-lactams not regularly bactericidal as
monotherapy, requiring AG as synergy
 β-lactams and Enterococci
• MICs 10-100x higher than Streptococci; ampicillin retains
highest potency, followed by PCN-G and carbapenems.
• E. faecium is usually resistant
– Overexpress pbp5, decreasing affinity
• E. faecalis rarely resistant, but may express a β-lactamase
(not readily detected without specific testing)
– For faecaLis, β-Lactams still work.
• Ceftaroline has good in vitro activity against E. faecalis (but
not amp-resistant E. faecium).
• Ceftriaxone or cefotaxime in combination with high-dose
ampicillin for E. faecalis IE with resistance to AGs
 Vancomycin
• Resistance develops through acquisition of
genes that alter cell wall biochemistry
– VanA most common; VanB, VanC also clinically
found
– Changes D-ala-D-ala to D-ala-D-lactate, leading to
1000-fold decrease in affinity
• Televancin not very active against VRE
 Other Drugs
• Daptomycin
– May want to use higher dose, 8-10 mg/kg
– Resistance rare
• Linezolid
– Resistance may be increasing
• Tigecycline
– Appears active against both VSE and VRE
• Synercid (quinupristin/dalfopristin)
– Not active against E. faecalis
• Quinolones
– Sometimes used in combination regimen for salvage
• Chloramphenicol
BMC Enterococcus Sensitivity Patterns
Drug All Enterococcus E. faecalis* E. faecium*
Ampicillin 68% 96% 7%
Gent (synergy) 78% 71% 100%
Levoflox 52% 60% 0%
Linezolid 100% 100% 100%
Nitrofurantoin 67% 100% 0%
PCN 63% 83% 0%
Synercid 34% 0% 100%
Streptomycin 73% 53% 83%
(synergy)
Tetracycline 19% 30% 14%
Vancomycin 71% 77% 0%

* Only speciated for certain cultures, like blood.

Treatment Guidelines for Enterococcal
IE
Resistance Pattern
PCN AG Vanco Regimen
S S S Amp or PCN plus AG x 4-6 weeks
(? Amp plus CTX if lose AG)
Vanco plus AG x 6 weeks
R S S Amp/sulbact + AG x 6 weeks (only if β-
lactamase producer)
Vanco plus AG x 6 weeks

AG: use gent if sensitive; consider streptomycin if sensitive.

Worst-case Scenario: Pan-Resistant
Enterococcus
 Leuconostoc species
• Catalase-negative, GPCs pairs or chains; plants and
dairy products; rare opportunistic pathogens
• Intrinsically resistant to vancomycin
• Bacteremia, IE, pulmonary infections, meningitis, brain
and liver abscesses
• Must get MICs
• Usually sensitive to PCN and Amp, although MIC’s
usually higher than for Strep
• Dapto, carbapenems have good activity
• Poor activity of trimethoprim, sulfonamide, fosfomycin
 Ongoing Areas of Research
• GAS
– Vaccine?
– Linezolid instead of clinda?
– Mechanisms of persistence and recurrence
– Genetic plasticity and evolution of new strains
• Pneumococcus
– Serotype replacement?
– Non-capsule vaccine?
• GBS
– Vaccine?
• Enterococcus
– Management of MDR