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Chapter 2.  Empiric Therapy Based on Clinical Syndrome

151

Pubic Lice (Phthirus pubis) Crabs

Clinical Presentation:  Genital pruritus..

Diagnostic Considerations:  Seen on groin, eyelashes, axilla.. May survive away from body × 1 day.. Pitfalls:  Smaller than head lice, but easily seen..

Therapeutic Considerations:  Treat partners.. Wash, dry, and iron clothes; heat from dryer/iron kills lice.. Non-washables may be placed in a sealed bag × 7 days..

Prognosis:  Good if clothes are also treated..

Ischiorectal/Perirectal Abscess

Subset

Pathogens

Preferred Therapy

 

 

 

Ischiorectal/

Enterobacteriaceae

Treat the same as mild/severe peritonitis (p.. 100) ± surgical

perirectal

B.. fragilis

drainage depending on abscess size/severity

abscess

 

 

 

 

 

Clinical Presentation:  Presents in normal hosts with perirectal pain, pain on defecation, leukocytosis, erythema/tenderness over abscess ± fever/chills.. In febrile neutropenia, there is only tenderness.. Diagnostic Considerations:  Diagnosis by erythema/tenderness over abscess or by CT/MRI.. Pitfalls:  Do not confuse with perirectal regional enteritis (Crohn’s disease) in normal hosts, or with ecthyma gangrenosum in febrile neutropenics..

Therapeutic Considerations:  Antibiotic therapy may be adequate for mild cases. . Large abscesses require drainage plus antibiotics × 1–2 weeks post-drainage.. With febrile neutropenia, use an antibiotic that is active against both P.. aeruginosa and B.. fragilis e..g.., meropenem..

Prognosis:  Good with early drainage/therapy..

Sepsis/Septic Shock

Sepsis/Septic Shock

 

Usual

Preferred IV

Alternate IV

IV-to-PO

Subset

Pathogens

Therapy

Therapy

Switch

 

 

 

 

 

Unknown

Entero-

Meropenem 1 gm (IV)

Quinolone* (IV) ×

Moxifloxacin

source

bacteriaceae

q8h × 2 weeks

2 weeks

400 mg (PO)

 

B.. fragilis

or

plus either

q24h × 2 weeks

 

E.. faecalis

Piperacillin/

Metronidazole 1 gm

 

 

(VSE)

tazobactam 3..375 gm

(IV) q24h × 2 weeks

 

 

 

(IV) q6h × 2 weeks

or

 

 

 

or

Clindamycin 600 mg

 

 

 

Moxifloxacin 400 mg

(IV) q8h × 2 weeks

 

 

 

(IV) q24h × 2 weeks

 

 

 

 

 

 

 

VSE/VRE = vancomycin-sensitive/resistant enterococci. Duration of therapy represents total time IV or IV + PO..

*Ciprofloxacin 400 mg (IV) q12h or Levofloxacin 500 mg (IV or PO) q24h..

Treat initially for E.. faecalis (VSE); if later identified as E.. faecium (VRE), treat accordingly (urosepsis­ see pp.. 154–155)..

152 A n t i b i o t i c E s s e n t i a l s

Sepsis/Septic Shock (cont’d)

 

Usual

Preferred IV

 

Alternate IV

IV-to-PO

Subset

Pathogens

Therapy

 

Therapy

Switch

 

 

 

 

 

 

Lung source

S.. pneumoniae

Respiratory

 

Any 2nd generation

Respiratory

Community-

H.. influenzae

quinolone(IV) q24h

 

cephalosporin (IV)

quinolone(PO)

acquired

K..

× 2 weeks

 

× 2 weeks

q24h ×2 weeks

pneumonia§

pneumoniae**

or

 

 

or

 

 

Ceftriaxone 1 gm

 

 

Doxycycline

 

 

(IV) q24h × 2 weeks

 

 

200mg (PO) q12h

 

 

 

 

 

×3 days, then

 

 

 

 

 

100 mg (PO) q12h

 

 

 

 

 

×11 days

 

Influenza A

MSSA/MRSA

 

(see pp.. 62–63)

(see p.. 52)

 

(ILI with rapidly

 

 

 

 

 

cavitating <72

 

 

 

 

 

hours multiple

 

 

 

 

 

pulmonary

 

 

 

 

 

infiltrates)

 

 

 

 

 

 

 

 

 

Nosocomial

P.. aeruginosa

Same as ventilator-associated pneumonia (see p.. 68)

pneumonia

K.. pneumoniae

 

 

 

 

 

E.. coli

 

 

 

 

 

S.. marcescens

 

 

 

 

 

(not MSSA/

 

 

 

 

 

MRSA)

 

 

 

 

CVC

S.. epidermidis

Meropenem 1 gm

 

Ceftriaxone 1 gm (IV)

Respiratory

source***

(CoNS)

(IV) q8h ×2 weeks

 

q24h × 2 wks

quinolone* (PO)

Bacteremia

S.. aureus (MSSA)

or

 

or

q24h × 2 weeks

(Treat initially

Klebsiella

Cefepime 2 gm (IV)

 

Respiratory

or

Enterobacter

q12h ×2 wks

 

quinolone* (IV) q24h

Cephalexin 500

for MSSA; if later

 

Serratia

 

 

× 2 wks

mg (PO) q6h × 2

identified as

 

 

 

 

 

 

weeks

MRSA, etc.., treat

 

 

 

 

accordingly)

S.. aureus

Daptomycin 6 mg/kg (IV) q24h × 2 weeks

Linezolid 600

 

(MRSA)

 

or

mg (PO) q12h ×

 

 

Linezolid 600 mg (IV) q12h × 2 weeks

2 weeks

 

 

 

 

 

 

ILI = Influenza like illness..

MRSA/MSSA = methicillin resistant/sensitive S. aureus. Duration of therapy represents total time IV or IV + PO..

*Moxifloxacin 400 mg or Levofloxacin 500 mg.. **  In alcoholics only

***If clinically possible, remove CVC as soon as possible..

Patients with ILI/influenza A (human/swine) presenting with simultaneous MSSA/MRSA CAP often present in shock..

Levofloxacin 750 mg (IV) q24h or Moxifloxacin 400 mg (IV) q24h..

§Uncomplicated by cardiopulmonary decompensation/failure, CAP does not present with hypotension/shock in normal hosts. Hyposplenia/asplenia should be ­suspected if CAP presents with hypotension/shock in patients with good cardiopulmonary function.

Chapter 2.  Empiric Therapy Based on Clinical Syndrome

153

Sepsis/Septic Shock (cont’d)

 

Usual

Preferred IV

Alternate IV

IV-to-PO

Subset

Pathogens

Therapy

Therapy

Switch

 

 

 

 

 

 

Quinupristin/dalfopristin 7..5 mg/kg (IV) q8h

Minocycline 100

 

 

× 2 weeks

 

mg (PO) q12h ×

 

 

 

or

2 weeks

 

 

Vancomycin 1 gm (IV) q12h × 2 weeks

 

Candidemia

Candida

If less critically ill, not neutropenic, and no

Fluconazole 400

(disseminated/

albicans

recent azole exposure: fluconazole is usual

mg (PO) q24h

invasive)

(or other

first choice alternates an echinocandin may

× 2 weeksor

Unless species is

fluconazole-

be used..

 

Voriconazole

susceptible

In critically ill, neutropenia or recent azole

(see “usual dose,”

known, empiric

therapy as for

species)

exposure: an echinocandin is preferred..

p.. 714)

non-albicans/

 

or Micafungin 100 mg (IV) q24h ×2 weeksor

 

possibly

 

Caspofungin 70 mg (IV) ×1 dose, then 50 mg

 

fluconazole-

 

(IV) q24h ×2 weeksFluconazole 800 mg (IV)

 

resistant Candida

 

×1, then 400 mg (IV) q24h ×2 weeksor Lipid-

 

is preferred if

 

associated formulation of amphotericin B (p..

 

recent prior

 

 

 

525) (IV) q24h ×2 weeksor Amphotericin B

 

azole therapy,

 

 

 

deoxycholate 0..7 mg/kg (IV) q24h ×2 weeks

 

severe illness,

 

 

neutropenia

 

orVoriconazole (see“usual dose,” p.. 714) or

 

or high risk for

 

Anidulafungin 200 mg (IV) ×1 dose, then 100 mg

 

infection with

 

(IV) q24h ×2 weeks

 

 

C.. glabrata or C..

 

 

 

 

Non-albicans

Choices are as for C.. albicans (see above),

Voriconazole

krusei

Candida

but Fluconazole should not be used and an

(see “usual dose,”

 

 

(possibly

echinocandin is preferred.. Micafungin 100

p.. 714) × 2

 

fluconazole-

mg (IV) q24h × 2 weeksor Caspofungin (see

weeks¶†

 

resistant)

C.. albicans, above) Use an Amphotericin or

 

 

 

Voriconazole if additional mould coverage

 

 

 

is desired or Lipid amphotericin B (p.. 525)

 

 

 

(IV) q24hor Amphotericin B deoxycholate

 

 

 

(see C.. albicans, above) × 2 weeksor

 

 

 

Voriconazole (see “usual dose,” p.. 714) × 2

 

 

 

weeks¶† or Itraconazole (see C.. albicans,

 

 

 

above) or Anidulafungin 200 mg (IV) ×

 

 

 

1 dose, then 100 mg (IV) q24h × 2 weeks

 

Best agent depends on infecting species. . Fluconazole-susceptibility varies predictably by species. . (See Fluconazole Drug Summary) also, see Amphotericin B (deoxycholate and lipid-associated formulations) Drug Summaries..

Treat candidemia for 2 weeks after negative blood cultures..

154 A n t i b i o t i c E s s e n t i a l s

Sepsis/Septic Shock (cont’d)

 

Usual

Preferred IV

Alternate IV

IV-to-PO

Subset

Pathogens

Therapy

Therapy

Switch

 

 

 

 

 

Intra-

Entero-

Ertapenem 1 gm

Combination

Moxifloxacin

abdominal/

bacteriaceae

(IV) q24h × 2 weeks

therapy with

400 mg (PO)

pelvic source

B.. fragilis

or

either

q24h ×

 

 

Tigecycline 200 mg

Ceftriaxone 1 gm (IV)

2 weeks

 

 

(IV) × 1 dose, then

q24h × 2 weeks

or

 

 

100 mg (IV) q24h ×

combination

 

 

2 weeks

or

therapy with

 

 

Levofloxacin 500 mg

 

 

or

Levofloxacin

 

 

(IV) q24h × 2 weeks

 

 

Meropenem 1 gm

500 mg (PO)

 

 

plus

 

 

(IV) q8h × 2 weeks

q24h × 2 weeks

 

 

Metronidazole 1 gm

 

 

or

plus

 

 

(IV) q24h × 2 weeks

 

 

Piperacillin/

Clindamycin

 

 

 

 

 

tazobactam 3..375

 

300 mg (PO)

 

 

gm (IV) q6h ×

 

q8h × 2 weeks

 

 

2 weeks

 

 

Urosepsis

Entero-

Levofloxacin

Meropenem 1 gm

Levofloxacin

(community-

bacteriaceae

500 mg (IV) q24h

(IV) q8h × 1–2 weeks

500 mg (PO)

acquired)

E.. faecalis (VSE)

× 1–2 weeks

or

q24h × 1–2

 

 

or

Levofloxacin

weeks

 

 

Piperacillin/

 

 

500 mg (IV) q24h

 

 

 

tazobactam 3..375

 

 

 

 

 

 

 

gm (IV) q6h

 

 

 

 

× 1–2 weeks

 

 

 

 

 

 

 

 

E.. faecium

Daptomycin 6 mg/

Quinupristin/

Linezolid 600

 

(VRE)

kg (IV) q24h × 1–2

dalfopristin

mg (PO) q12h

 

 

weeks

7..5 mg/kg (IV) q8h

×1–2 weeks

 

 

or

× 1–2 weeks

or

 

 

Minocycline 100

 

 

Linezolid 600 mg

 

 

 

 

mg (PO) q12h ×

 

 

(IV) q12h × 1–2

 

 

 

 

1–2 weeks

 

 

weeks

 

 

 

 

 

(nosocomial)

P.. aeruginosa

Meropenem 1 gm

Aztreonam 2 gm (IV)

Levofloxacin

 

Entero-

(IV) q8h × 1–2 weeks

q8h × 1–2 weeks

750 mg (PO)

 

bacteriaceae

or

or

q24h × 1–2

 

Doripenem 1 gm (IV)

 

 

Cefepime 2 gm (IV)

weeks

 

 

q8h ×1–2 weeks

 

 

q12h × 1–2 weeks

 

 

 

or

 

 

 

 

 

 

 

Levofloxacin 750

 

 

 

 

mg (IV) q24h × 1–2

 

 

 

 

weeks

 

 

 

CRE

Ceftazidime/

Colistin 5 mg/kg (IV)

 

 

 

avibactam 2..5 gm

q8h × 1–2 weeks

 

 

 

(IV) q 8 h × 1–2

 

 

 

 

weeks

 

 

 

 

 

 

 

Chapter 2.  Empiric Therapy Based on Clinical Syndrome

155

Sepsis/Septic Shock (cont’d)

 

Usual

Preferred IV

 

Alternate IV

IV-to-PO

Subset

Pathogens

Therapy

 

Therapy

Switch

 

 

 

 

 

Urosepsis

E.. faecalis (VSE)

Ampicillin 2 gm (IV) q4h × 1–2 weeks

Amoxicillin 1 gm

(group D

 

 

or

(PO) q8h × 1–2

enterococci)

 

Piperacillin/tazobactam 3..375 gm (IV) q6h ×

weeks

 

 

1–2 weeks

 

 

or

 

 

or combination therapy with

Levofloxacin 500

 

 

Vancomycin 1 gm (IV) q12h × 1–2 weeks

mg (PO) q24h ×

 

 

 

plus

1–2 weeks

 

 

Gentamicin 240 mg (IV) q24h ×1 week

 

 

 

 

 

 

 

E.. faecium

Linezolid 600 mg (IV) q12h × 1–2 weeks

Linezolid 600

 

(VRE)

 

or

mg (PO) q12h ×

 

 

Quinupristin/dalfopristin 7..5 mg/kg (IV) q8h

1–2 weeks

 

 

× 1–2 weeks

 

 

or

 

 

 

 

 

Minocycline 100

 

 

 

 

 

mg (PO) q12h ×

 

 

 

 

 

3 days, then 100

 

 

 

 

 

mg (PO) q12h ×

 

 

 

 

 

4–11 days

 

 

 

 

 

 

Overwhelming

S.. pneumoniae

Ceftriaxone 2 gm

 

Cefepime 2 gm (IV)

Levofloxacin 500

sepsis with

H.. influenzae

(IV) q24h × 2 weeks

 

q12h × 2 weeks

mg (PO) q24h ×

purpura

N.. meningitidis

or

 

or

2 weeks

(asplenia or

 

Levofloxacin 500 mg

 

Cefotaxime 2 gm (IV)

or

hyposplenia)

 

(IV) q24h ×2 weeks

 

q6h × 2 weeks

Amoxicillin

 

 

 

 

 

1 gm (PO) q8h ×

 

 

 

 

 

2 weeks

 

 

 

 

 

Steroids (high

Aspergillus

Treat as Aspergillus pneumonia (see p.. 55)

 

chronic dose)

 

 

 

 

 

 

 

 

Miliary TB

M.. tuberculosis

Treat as pulmonary TB (see p.. 53) plus steroids ×1–2 wks

 

 

 

Miliary BCG

Bacille

Treat with INH plus RIF × 9 months; EMB, until susceptibilities

(disseminated

Calmette-

known; may add steroids e..g.., prednisolone 40 mg q24h × 1–2

BCG)

Guérin (BCG)

weeks

 

 

 

 

 

 

 

Septic shock

Gram-

Meropenem 1 gm (IV) q8h × 1-2 weeks*

 

 

negative or

 

 

 

 

 

gram-positive

 

 

 

 

 

bacteria

 

 

 

 

 

 

 

 

 

 

Duration of therapy represents total time IV or IV + PO.. * Plus surgical decompression/drainage if needed..

156 A n t i b i o t i c E s s e n t i a l s

Sepsis (Unknown Source)

Clinical Presentation:  Abrupt onset of high spiking fevers, rigors ± hypotension..

Diagnostic Considerations:  Diagnosis suggested by high-grade bacteremia (2/4–4/4 positive blood cultures) with unexplained hypotension.. Rule out pseudosepsis (GI bleed, myocardial infarction, pulmonary embolism, acute pancreatitis, adrenal insufficiency, etc..).. Sepsis usually occurs from a GI, GU, or IV source, so coverage is directed against GI and GU pathogens if IV line infection is unlikely..

Pitfalls:  Most cases of fever/hypotension are not due to sepsis.. Before the label of “sepsis” is applied to febrile/hypotensive patients, first consider treatable/reversible mimics (see p.. 151)..

Therapeutic Considerations:  Resuscitate shock patients initially with rapid adequate volume replacement, followed by pressors, if needed.. Do not give pressors before volume replacement or hypotension may continue/worsen.. Use normal saline, plasma expanders, or blood for volume replacement, not D5W.. If patient is persistently hypotensive despite volume replacement, consider relative adrenal insufficiency: Obtain a serum cortisol level, then give cortisone 100 mg (IV) q6h × 24–72h; blood pressure will rise promptly if relative adrenal insufficiency is the cause of volume-­unresponsive hypotension.. Do not add/ change antibiotics if patient is persistently hypotensive/febrile; look for GI bleed, myocardial infarction, pulmonary embolism, pancreatitis, undrained abscess, adrenal­ insufficiency, or IV line infection.. Drain abscesses as soon as possible.. Remove IV lines if the entry site is red or a central line has been in place for ≥ 7 days and there is no other explanation for fever/hypotension.. Early antibiotic therapy/surgical drainage of abscesses, debridement of necrotic tissue eg.. necrotizing fasciitis or relief of obstruction is critical.. Prognosis:  Related to severity of septic process and underlying cardiopulmonary/immune status..

Sepsis (Lung Source)

Clinical Presentation:  Normal hosts with community-acquired pneumonia (CAP) do not present with sepsis. . CAP with sepsis suggests the presence of impaired immunity/hyposplenic function (see “sepsis in hyposplenia/asplenia,” p. . 157). . Nosocomial pneumonia uncommonly presents as (or is complicated by) sepsis with otherwise unexplained hypotension..

Diagnostic Considerations:  Impaired splenic function may be inferred by finding Howell-Jolly bodies (small, round, pinkish or bluish inclusion bodies in red blood cells) in the peripheral blood smear.. The number of Howell-Jolly bodies is proportional to the degree of splenic dysfunction..

Pitfalls:  CAP with hypotension/sepsis should suggest hyposplenic function, impaired immunity, or an alternate diagnosis that can mimic CAP/shock.. Be sure to exclude acute MI, acute heart failure/COPD, PE/ infarction, overzealous diuretic therapy, concomitant GI bleed, and acute pancreatitis..

Therapeutic Considerations:  Patients with malignancies, myeloma, or SLE are predisposed to CAP, which is not usually severe or associated with shock.. Be sure patients with CAP receiving steroids at less than “stress doses” do not have hypotension/shock from relative adrenal insufficiency.. In patients with SLE, try to distinguish between lupus pneumonitis and CAP; SLE pneumonitis usually occurs as part of a SLE flare, CAP usually does not..

Prognosis:  Related to underlying cardiopulmonary/immune status.. Early treatment is important..

Sepsis (Central Venous Catheter [CVC] Source)

Clinical Presentation:  Temperature ≥ 102°F ± IV site erythema..

Diagnostic Considerations:  Diagnosis by semi-quantitative catheter tip culture with ≥ 15 colonies plus blood cultures with same pathogen.. If no other explanation for fever and line has been in place ≥ 7 days, remove CVC and obtain semi-quantitative catheter tip culture.. Suppurative­ thrombophlebitis presents with hectic/septic fevers and pus at IV site ± palpable venous cord..

Chapter 2.  Empiric Therapy Based on Clinical Syndrome

157

Pitfalls:  Temperature ≥ 102°F with CVC infection, in contrast to phlebitis (temperature ≤ 102°F).. Acute bacterial endocarditis (ABE) may complicate intracardiac or CVC (not peripheral) infection.. Therapeutic Considerations:  Line removal is usually curative, but antibiotic therapy is usually given for 1 week after CVC removal for gram-negative bacilli or 2 weeks after CVC removal for S.. aureus (MSSA/ MRSA).. Antifungal therapy is also usually given for 2 weeks after CVC removal for candidemia.. Dilated ophthalmoscopy by an ophthalmologist is important to exclude candidal endophthalmitis following candidemia..

Prognosis:  Good if CVC is removed before endocarditis/metastatic spread..

Sepsis (Intra-abdominal/Pelvic Source)

Clinical Presentation:  Fever, peritonitis ±hypotension.. Usually a history of an intra-abdominal ­disorder that predisposes to sepsis (e..g.., diverticulosis, gallbladder disease, recent intra-abdominal/pelvic surgery).. Signs and symptoms are referable to the abdomen/pelvis..

Diagnostic Considerations:  Clinical presentation plus imaging studies (e..g.., abdominal/pelvic CT or MRI to demonstrate pathology) are diagnostic..

Pitfalls:  Elderly patients may have little/no fever and may not have rebound tenderness.. Be sure to exclude intra-abdominal mimics of sepsis (e..g.., GI bleed, pancreatitis)..

Therapeutic Considerations:  Empiric coverage should be directed against aerobic gram-negative bacilli plus B.. fragilis.. Anti-enterococcal coverage is not essential.. Antibiotic therapy is ineffective unless ruptured viscus is repaired, obstruction is relieved, abscesses are drained..

Prognosis:  Related to rapidity/adequacy of abscess drainage and repair/lavage of ruptured organs.. The preoperative health of the host is also important..

Sepsis (Urinary Source)

Clinical Presentation:  Fever/hypotension in a patient with diabetes mellitus, SLE, myeloma, pre-exist- ing renal disease, stone disease, or partial/total urinary tract obstruction..

Diagnostic Considerations:  Urine gram stain determines initial empiric coverage.. Pyuria is also present.. Diagnosis confirmed by culturing the same isolate from urine and blood..

Pitfalls:  Pyuria without bacteriuria and bacteremia due to same pathogens is not diagnostic of urosepsis.. Urosepsis does not occur in normal hosts; look for host defect (e..g.., diabetes, renal disease).. Therapeutic Considerations:  If stones/obstruction are not present, urosepsis resolves rapidly with appropriate therapy.. Delayed/no response suggests infected/obstructed stent, stone, partial/total urinary tract obstruction, or renal abscess..

Prognosis:  Good if stone/stent removed, obstruction relieved, abscess drained.. Fatalities rare with urosepsis..

Sepsis (Hyposplenia/Asplenia)

Clinical Presentation:  Presents as overwhelming septicemia/shock with petechiae..

Diagnostic Considerations:  Diagnosis by gram stain of buffy coat of blood or by blood cultures.. Organism may be stained/cultured from aspirated petechiae.. Howell-Jolly bodies in the peripheral smear are a clue to decreased splenic function.. Conditions associated with hyposplenism include sickle cell trait/disease, cirrhosis, rheumatoid arthritis, SLE, systemic necrotizing vasculitis, amyloidosis, celiac disease, chronic active hepatitis, Fanconi’s syndrome, IgA deficiency, intestinal lymphangiectasia, intravenous gammaglobulin therapy, myeloproliferative disorders, non-Hodgkin’s lymphoma, regional enteritis, ulcerative colitis, Sezary syndrome, splenic infarcts/malignancies, steroid therapy, systemic mastocytosis, thyroiditis, infiltrative diseases of spleen, mechanical ­compression of splenic artery/spleen, Waldenstrom’s macroglobulinemia, hyposplenism of old age, congenital absence of spleen..

Pitfalls:  Suspect hyposplenia/asplenia in unexplained overwhelming infection..

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