Surgical Foundations: INFECTIONS Lecture # 2
Anti-infective agents including prophylaxis
January 21, 2014 - Dr. J M A Bohnen
NB Lectures 2-4 topic order has changed: Please edit your Lect 1 notes page 1 (Jan 14, 2014) to show:
Lecture 1: Infection determinants: bacteria, local environment, host defenses, duration
Lecture 2: Anti-infective agents including prophylaxis
Lecture 3: Hospital acquired infections
Lecture 4: Abdominal and other serious surgical infections
ANTI-INFECTIVE AGENTS: PRINCIPLES AND CAVEATS
Terminology: Disinfectants eg JAVEX clean floors+walls, not people CID2004; 39:702. Antiseptics are
used externally (surgical prep, hand wash), sometimes in wound, body cavity; not parenterally.
Chlorhexidine, povidone-iodine (an iodophor) and alcohols are used for surg prep, see Lecture 3. Topical
rx of chronic wounds has options, few good trials CID 2009;49:1541. “Antimicrobial agents” are used
systemically or topically “antibiotics” are really a subset of antimicrobial agents that are excreted by
micro-organisms, but in common use include synthetic drugs ie “antibiotics” = “antimicrobial agents.”
Antibiotics kill bacteria, cure infections and save lives. Inappropriate use generates resistance, adverse
clinical effects, costs, and tunnel vision.
Consult CPS, Sanford, pharmacist: resistance patterns, dose adjustments, side effects, drug-drug,
especially when unexpected signs appear
Prophylaxis and therapy
 appropriate prophylaxis just before incision prevents SSIs effectively
 therapeutic antibiotics succeed in perfused tissues (eg pneumonia) against moderately dense
microbial inocula, indicated generally till and not beyond clinical recovery
 therapeutic antibiotics work poorly in lo redox, dead tissue, foreign material and hi bacterial
density (eg abd infections, necrotizing fasciitis), where operation/drainage/debridement have
primacy, use generally till clinical recovery
 FB infections usually need early rx for cure without removal, before bacterial biofilms thicken
 certain conditions need prolonged antibiotics eg enterococcal and staphylococcal bacteremias (at
least 2 wk); endocarditis, deep S. aureus infections; actinomycosis, TB
 seek cause of poor response to antibiotics: undrained material; wrong drug, dose, frequ, route, duration
too short; wrong or missed dx; wrong approach (needs OR or something else)
Resistance:
 Many mechs CMAJ 2009;180:408, NEJM 2010;363:2377; much use in agri-/aquaculture
 prevention: appropriate use; infection control; combos prevent some resistance (eg ticar+AG, anti-TB)
 clinically, MRSA; ESKAPE bugs: E. fecium (VRE); S. aureus; K. pneumoniae (carbapenemases);
Acinetobacter baumanii: P. auruginosa (flouroquin resist); Enterobacter spp. etc etc
 E. coli, other Gm negs produce NDM-1 CMAJ 2011:183:1257; resists betalactams, carbas AGs, quins;
sens aztreonam, colistin tigecycline; India, Pakistan, world, now ON
Pharmacokinetics: where and when drug goes by each route; usually 1st order. Route generally IV, IM
or po, but other routes (enteral, intrathecal, local etc), strategies studied to ↑ tissue conc eg antibiotic
sponge promising for sternal infections, but failed in large RCT JAMA, 2010;304:755.
Minimum inhibitory concentration MIC measures drug potency against an organism: lowest conc that
inhibits bug growth in vitro; may not reflect in vivo action, esp if lo ox, pH, hi bact conc, dead tiss. Cidal
vs static not clinically important CID 2004;38:864 but may appear on exam.
Pharmacodynamics: timing of drug conc effects. Try to sustain B-lactams above MIC; give AGs and
quinolones high peak, captures postantibiotic effect. Antibiotic sens testing reviewed CID 2009;49:1749
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Cost: Hospital pharmacy decides inpatients; consider cost for outpatients
Serum levels: ask pharmacy if renal/hepatic; vanco controvers, do Cr + serum levels 1/wk. AGs do 1/wk.
once/day dose keep trough  2.0
MECHANISM
MECHANISM OF ACTION OF ANTIBIOTICS
EXAMPLES
↓ CELL
WALL SYNTH
PENS, CEPH'S, CARBAPENEMS, VANCO, BACITRACIN
ALL C
↓ PROT
SYNTH
AG, MACROLIDES, CLINDA, TETRA
OXAZOLIDINONES, STREPTOGRAMINS*
AG:C
OTHERS:S
(* S/C)
CIDAL OR STATIC
↓ NUCLEIC
ACID SYNTH
RIFAMP, METRON, QUINOLONES,
TRIMETH, SULFON, TMP/SMZ
FIDAXOMICIN
C
S, C
C
↓ FUNGAL CELL
MEMB SYNTH
ANTIFUNGALS (AMPHO, FLUC, VORI)
AMPHO:C
OTHERS: C/S
↓ FUNGAL CELL
WALL SYNTH
ECHINOCANDINS (CASPOFUNGIN etc)
C
CLINICALLY IMPORTANT PROPERTIES OF ANTIBIOTICS
DRUG
AEROB/FAC
Gm +
Gm -
ANAER
Gm +
Dose  in RF?
TOX
Gm -
PENICILLINS

Clostrid, actino
Not staph
enterococci: add AG
Pen G
above belt

fever, hypersens
neuro in RF
serum sick
For other pens and 1stgen cephs below, effects include those of pen. Severe pen allergy: use macrolides,
clinda, vanco, new quinolones; mild pen allergy, individualize: ceph's (7% cross-reactive); imi 25% cross)
AMP
AMOX
+enterococcus
some
coliforms
PIP,
TICAR
=amp
coliforms
pseudo
monas
CLOX
(METH)
S. aureus

PIP/TAZ, AMP/SULB,
TICAR/CLAV
AMOX/CLAV (po)




-
rash.
PMC

some
B. frag

Platelets

as for Pen




“
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CEPHALOSPORINS (some are cephamycins)
DRUG
AEROBES
ANAEROBES
+
+
-
RF
TOX

as Pen
-
1st GEN:
CEFAZOLIN
3+
2+
2+ (not B. frag)
CEPHALEXIN po (inc S. aureus)
Cefazolin long t½, cheap, tested: good for proph
2ND GEN:
CEFUROXIME
4+
3+
1+ (no B. frag)

CEFOXITIN
CEFOTETAN
2+
2+
2+
3+
2+ (B. frag ↓ing)
 cefotetan:
disulfiram;
Vit k if 1 wk,
avoid on coum
CEFACLOR po
4+ 2+
3RD/4th GEN:
CEFTAZIDIME
1+ 4+ (inc Pseud)
1+ (no B. frag)

as pen
CEFTRIAXONE
CETOTAXIME
CEFTIZOXIME
2+ 3+ (no Pseud)
1+ (no B. frag)
ceftri: bil
sludge
1+ 3+(no Pseud)
2+ (some B.frag)
none


CEFIPIME
CEFTAROLINE
3+ 4+ (inc Pseud)
1+ (no B. frag)
as pen
like cephalexin, better vs H. influenzae, ↑ cost

3rd gen cephs: cover gm pos less (exc cefipime, ceftaroline), gm neg better, cost much more than
1st gen; alternates for AGs, quins, carbapenems. Ceftaz, cefip, ceftar cover P. aeruginosa. Ceftri,
ceftiz: once/d. Cefotet vs cefox: cefotet covers gram neg facultatives better, longer t½, BID;
cefoxitin gets anaerobes better though both losing anaer effects. Many more 3rd/4th gen cephs.
*** Cephalosporins don’t cover Enterococcus.
AMINOGLYCOSIDES
DRUGS
NEO
GENTA
TOBRA
NETIL, AMIK
AEROBES/FACULTATIVES ONLY
Enteric bacteria incl Lactose afermenters
Enterococcus in combo w/ pen amp or pip
S. aureus in comination
RF

TOX
RENAL
8th nerve
neuromusc
blockade
↑RENAL TOX risk with ↑ total amt, age,  BP; order 5-7.5 mg/kg/d; sick patients with ↑ Vd need full
dose; narrow therapeutic range; short course lo dose genta caused nephrotox CID 2009; 48:713. Check serum
levels pre-dose; NEO toxic IV, poorly absorbed po, used po to prep bowel;
Polymixin E (= COLISTIN); Poly B
POLYMYXINS E, B
multi-resistant Gm neg rods
Renal, NV
Polymyxins: new life for old drug colistin a last resort for multi-resistant Gm negs CID2005;40:1333, CID
2012;54:1720
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"URINARY AGENTS:" these drugs started as UTI rx but have expanded indications
NALIDIXIC
ACID po
SPECTRUM
RF
TOX
Coliforms
Avoid
GI
Hypersens
Avoid
"
Pneumonitis
Hematologic
NITROFURANTOIN Coliforms
po
Staph
TMP/SMZ
IV, po
Coliforms
GM + incl Staph
Nocardia
Pneumocystis
Shigella
Salmonella
Enterococcus (+/-)
Stenotrophomonas maltophilia

(get
levels)
GI
Skin
Megalo Anem
esp in Preg,
Etoh, renal
failure; Rx:
folic acid
Sulfonamide antibiotics don’t cross-react with sulfonamide nonantibiotics (NEJM 2003;349:1628)
FLOUROQUINOLONES
CIPROFLOXACIN
LEVO, MOXI
GATI,OTHERS
IV, po
Gram +
(esp. LEVO)
(some enteroc)
coliforms, P. aeruginosa
CNS, drug
interactions
only gati for anaerobes
CARBAPENEMS
IMIPENEM/
CILASTATIN
MEROPENEM
ERTAPENEM
DORIPENEM
4+
4+
4+
4+
(resistance especially for Pseudomonas)

(erta narrower, no Pseudo, once daily)
(signif carbapenem resistance emerging JAMA 2008;300:2911)
similar to
Pen; 25%
allergy cross
reactivity
MACROLIDES
ERYTHRO, AZITHRO,
CLARITHRO, IV, po
FIDAXOMICIN

-


(erythro base gets
some Bacteroides

(° azith)
GI
avoid
GI
teeth
bones<12
(main use C. diff)
TETRACYCLINES


doxycycline:
B. frag
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GLYCOPEPTIDES
VANCO

iv
Gm + only
po for PM colitis
fever phlebitis, nephro
"red pt”,pmn, plts
NEJM 356:904
VRE= vanco resistant enterococcus; Vanco covers what pen does + staph, is indicated for MRSA, severe
pen allergy, enterococcus. Vanco-resistant MRSA could defeat vanco CID 2008; 47:S55. Vanco causes
nephrotox in 5%, 25% if given with AGs; vanco levels controversial, aim 5-10 mg/ml pre, 20-40 post.
METRONIDAZOLE
ANAEROBES ONLY
po,
IV
RF
All anaerobes exc a few
lesser ones (proprion,
eubacteria, lacto, bifido)
 DOSE IF LIVER FAILURE (get levels)
po formulation cheaper than IV
TOX
Tongue
Disulfiram

CLINDAMYCIN
AEROBES
+
IV, po
ANAEROBES
+
-
-

(incl S. aureus)

 (inc. B. frag)
RF
TOX
-
PM colitis, diarrh
RIFAMPIN
Gm + cocci
GI
S. aureus
(  in
 LFT
C. diff
liver
"flu"
TB
failure)
inact BCP
Rifampin: for serious staph infection in combination, nasal carriage; don’t give alone because of resistance
po
IV avail
STREPTOGRAMINS
quinupristin
-dalfopristin po, IV
Gm + incl some VRE, MRSA
?
myalgias,
arthralgias
OXAZOLIDINONES
linezolid po, IV
Gm+ incl VRE, MRSA
-
 bone marrow
LIPOPEPTIDE
daptomycin IV
Gm+ incl VRE, MRSA, VISA
↓ if severe
C. diff
ANTIFUNGALS
AMPHO B
ADMIN
Mouth gargle
SPECTRUM
IV :D5W
over
4 hr
Broadest
RF
-
TOX
Fever, chills
BP arrhyth
Rigors demerol
↑Cr, Anemia
RTA,  K
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LIPOSOMAL AMPHO B: ↓ infusion related reactions; very expensive (40 x ampho)
NYSTATIN
Vag supp, gargle,
Gargle, cream
FLUCONAZOLE
po, IV
Candida
Phlebitis
GI, joint/
musc pain
-
?
C. albicans, less nonalbicans, AIDS, crypto 
non-albicans
AIDS Crypto
UGI,  LFT
VORICONAZOLE po, IV
Candida, Aspergillus, others
give po
↓ for liver
transient visual,
skin,
drug
interactions,
others
CASPOFUNGIN, MICAFUNGIN
ANIDULAFUNGIN
IV
Candida, Aspergillus
-
fever, rash, GI
Drug interactns
↓ for liver
Expensive
Anidulafungin sim to fluconazole for invasive candidiasis. NEJM 2007;356:2472. Fluconazole cheaper
NEJM 2007;356;24; An echinocandin (caspo-, anidula-, micafungin now 1st line agent for candidemia,
other invasive fungal infns exc C. parapsilosis CID 2012;54:1110, 1123
Antibiotics kill: C. difficile associated diarrhea
Cause: All antibiotics except vanco. Rare: AGs, sulfa. Clinda, cephs previously worst. Since 2002
hypervirulent strains spread rapidly, kill 7-15%. Worst now quinolones, esp ciproflox CID 2005;
41:1254. Toxin mediated NEJM 2011; 364:5; pseudomemb colitis if colonic mucosa has membrane.
Spread: ↑ prevalence in hospitals, nursing homes, clinics CID 2012;54:i
Microbial Etiology: C.difficile or its toxin in 90%. Neg toxin does not rule out. Klebsiella oxytoca can
cause hemorrhagic colitis, consider if C. diff neg NEJM 2006;355:2418
At risk: antibiotic use, OR, age, proton pump NEJM 2010;365:1693. Now hypervirulent NAP1/BI/027
strains hit healthy people CID 2012;55 (S2):S65.
Prevent: ↓antibiotics esp cipro, clinda, isolate enterically. Soap + water best in outbreak ICHE 2009;30:611
Clinical: Onset 1 (usually) to 4 weeks after start antibiotic. Diarrhea to 20/day may watery, bloody,
mucus. Fever,  WBC, ‘lyte problems, abd pain. Toxic megacolon, septic shock.
Dx: consider if diarrhea esp fever. XR thumbprinting nonspec. Scope if uncertain, not if severe, may →
toxic megacolon. C. diff stool toxin makes dx, takes 48h. May start metro, D/C if toxin neg.
Treat: fluids; d/c antibiotic; no antimotility drug; colectomy if shock,  Cr, ↑lactate, ↓immun;
ileost/lavage/vanco enema Ann Surg 2011;254:423, 427
Antibiotics: metro po 250 mg q6h to 500 q8h x 10-14d, cheaper than vanco; vanco po 125 mg q6h = 250
q4h; IV metro or tube vanco if ileus; mult recurrences: rifamixin, nitazoxanide, cholestyramine,
Saccharomyces boulardii, Lactobacillus GG, donor stool NEJM 2008;359:1932; CID 2011;53:994.
Vanco beats metro if severe  Cr, WBC JAC 2005;56:988 CID 2007:45:302, 2008;46:1489. Fidaxomicin
better, ↓recurrence NEJM 2011; 364:5; CID 2012;54:568, 2012;55(S2):S93.
Prognosis: 15-30% relapse; monoclon Abs ↓ recur NEJM 2010;362:197, 264. Hypervirulent strain kills.
Page 6 of 8
ANTIBIOTIC PROPHYLAXIS FOR SURGICAL SITE INFECTIONS
Prophylactic systemic antibiotics prevent incisional ssi and some vascular + ortho implant infections;
not shown clearly to prevent abd infection post colectomy. Dental work with hip implant: lo infection
risk, hygiene more important CID 2010;50:8,17. Except for intraluminal GI antibiotics pre-colectomy,
prophylactic decontamination with topical antiseptics and nonabsorbed antibiotics not accepted despite
good evidence eg CHG showers, selective digestive and nasal decontamination
Antimicrobial prophylaxis principles: 1. Follow the evidence 2. Cost-effective if used right 3. Antibiotic
must be in wound when contaminated, 1st dose <1h before incision (incl C–section NEJM 2010 362:273);
order “to OR with pt” not “on call” Intra-op dose if forget pre-op, OR > 2x T½ 4. Use preop (+/- intraop)
only, not postop 5. Use in selected clean cases: cardiac, implant, groin incision, craniotomy, hernia.
Risks: 1) allergy (esp β-lactams); vanco "red person" 2) drug resistance esp if use postop CID
2003;36:863; prolonged abiotic proph post appendectomy → more C. diff infection, diarrhea, length
of stay JACS 2011;213:778 3) antibiotic-associated diarrhea, colitis
Cardiovascular
Valve or vasc
implant; open heart,
pacemaker, defib;
aorta; groin
S. epi, S. aureus,
Corynebact,
enteric gram-neg
bacilli
Gastrointestinal
Esoph, gastroduod:
bleed, perf, obstr,
achlorhdria
Enteric gram neg
bacilli, gram pos
cocci
Bilary tract (>60,
acute chole, CBD
stone, obstr jaundice,
re-op)
Colorectal
Appendectomy
Urinary if contam
abdominal
hysterectomy, Csection
H&N through oral,
pharyng mucosa
Enteric gram-neg
bacilli,
entreococci,
clostridia
Enteric gram-neg
bacilli, anaerobes,
enterococci
Enteric gram-neg
rods, anaerobes,
enterococci
Enteric gm-neg
bacilli, enterococci
Enteric gram neg,
anaerobes, Grp B
strep, enterococci
Anaerob, enteric
gram-neg rods, S.au
cefazolin or
cefuroxime
(cardiac) or
vancomycin
2 grams IV
2 grams IV
1 gram IV
cefazolin
2 grams IV
cefazolin
2 grams IV
neomycin + erythro
base + IV
cefazolin/metro or
genta/ metro
1g po ea at 1, 2, 11
pm day before +/2g/500mg IV or
2 mg/kg/500mg IV
cefazolin/metro
ciprofloxacin
cefazolin/cefotetan/
cefoxitin
Clinda+genta
2 g/500 mg IV
500 mg
PO or
400 mg IV
2 grams IV
600-900 mg +
1.5mg/kg IV
Page 7 of 8
Neuro:
Clean crani, CSF
shunt
S. aureus, S. epi
Orthopedic
Total jt repl’mt, int
fix fractures
S. aureus, S.
epidermidis
Low limb amp for
ischemia
S. aureus, S. epi
eteric gram-neg
bacilli, clostridia
Thoracic noncardiac
S. aureus, S. epi,
strep, enteric gram
neg bacilli
Cefazolin or
Vanco
2 gm IV
1 gm IV
cefazolin or
vancomycin
2 grams IV
1 gram IV
cefazolin or
cefuroxime
or vancomycin
2 grams IV
2 grams IV
1 gram IV
Colorectal “IV vs po vs both” endless controversy: JACS 2013;217:763 supports combined regimen
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