Treatment

Empiric Pharmacological Therapy

Empiric Therapy
  • In uncomplicated cases, antibiotics may be postponed up to 48 hr until results of initial BCs are known
  • Empiric antibiotic treatment should be initiated immediately after 3 BCs have been taken in cases complicated by:
    • Sepsis, severe valvular dysfunction, conduction disturbances or embolic events
  • Empiric therapy should include use of agents that are effective against streptococci, staphylococci & enterococci
  • Subsequent changes in the antibiotic regimen should be based on the results of culture & sensitivity testing

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Pathogen-Specific Pharmacological Therapy

Streptococcal IE

Highly Penicillin-Susceptible Viridans Group Streptococci (MIC ≤0.12 mg/L)
  • Penicillin, Amoxicillin or Ceftriaxone
    • These agents when used alone x 4 wk obtain high bacteriologic cure rates
    • 4 wk of monotherapy has the advantage of avoiding the potential ototoxic or nephrotoxic effects of Gentamicin
    • Ceftriaxone has the advantage of once-daily dosing
  • (Penicillin, Amoxicillin or Ceftriaxone) plus Gentamicin or Netilmicin for the 1st 2 wk
    • When given in selected patients, gives similar cure rates to 4 wk of monotherapy
    • Once-daily dosing of Gentamicin may be used
  • Vancomycin
    • Reserved for patients who are unable to tolerate Penicillin or Ceftriaxone
  • Teicoplanin
    • Alternative drug that may be used once daily to treat streptococcal IE in penicillin-allergic patients
    • Inadequate doses can result in treatment failure
    • Steady-state serum is achieved only after 1 wk

Relatively Resistant Viridans Group Streptococci (MIC >0.12 to ≤0.5 mg/L)
  • (Penicillin or Amoxicillin) x 4 wk plus Gentamicin x 2 wk should be given
    • Once-daily dosing of Gentamicin may be used
  • Vancomycin
    • Reserved for patients who are unable to tolerate Penicillin or Amoxicillin

Highly Resistant Viridans Group Streptococci (MIC >0.5 mg/L)
  • Should be treated w/ regimens recommended for enterococcal endocarditis

Enterococcal IE
  • All enterococci causing IE should be tested for antimicrobial susceptibility to determine optimal therapy
    • In vitro susceptibility to Penicillin & Vancomycin along w/ high-level resistance to Gentamicin & Streptomycin should be tested
  • Successful treatment requires the synergistic action of Penicillin, Ampicillin or Vancomycin w/ either Gentamicin or Streptomycin
  • Multi-daily dosing should be used for the aminoglycosides

Ampicillin or Penicillin + Aminoglycoside
  • Treatment duration for 4-6 wk
  • For enterococcal strains susceptible to Penicillin:
    • Bactericidal activity of Ampicillin is 2x that of Penicillin against E faecalis
    • Penicillin may be preferred because higher serum conc of Penicillin will compensate for the difference & because it is important to avoid Ampicillin rash during long-term treatment

Enterococci w/ High-level Resistance to Gentamicin
  • These enterococci are usually resistant to all other aminoglycosides except Streptomycin
  • Combination therapy w/ Ampicillin & Ceftriaxone should also be considered

Glycopeptides (Vancomycin, Teicoplanin) + Aminoglycoside
  • Should be reserved for patients allergic to Penicillin or in Penicillin-resistant strains
  • Glycopeptides need to be combined w/ aminoglycosides since they are not usually bactericidal against enterococci

Vancomycin-Resistant Strains & Strains Resistant to Both Gentamicin & Streptomycin
  • Consultation w/ microbiologist/infectious disease specialist is recommended

Staphylococcal IE
  • Appropriate antibiotic therapy should be started promptly to improve overall prognosis
  • S aureus in non-IVDA usually involves the left-sided cardiac valves
  • Factor in determining antibiotic treatment is whether the organism is sensitive to Methicillin
  • Gentamicin in the following regimens should be administered in multiple daily dosing at 3 mg/kg/day

NVE - Penicillin Susceptible S aureus
  • <10% of IE strains of S aureus are susceptible to Penicillin
  • Penicillin may be used x 4 wk combined w/ Gentamicin for the 1st 3-5 days of therapy

NVE - MSSA
  • Antistaphylococcal Penicillin w/ or w/o Gentamicin
    • Antistaphylococcal Penicillin is the treatment of choice
    • Adding Gentamicin for the 1st 3-5 days may protect the infected valve from further damage & may decrease the duration of bacteremia which may result in faster defervescence
  • Antistaphylococcal Penicillin + Fusidic acid
    • This combination may be an option for Fusidic acid-sensitive strains
  • Cephalosporin (1st Generation) w/ or w/o Gentamicin
    • May be used for the treatment of MSSA endocarditis when patient has non-anaphylactoid Penicillin allergy
  • 4 wk of therapy w/ antistaphylococcal Penicillin or cephalosporin may be used for uncomplicated infection
    • Complicated IE eg abscess formation or septic metastatic complications should be treated x 6 wk
  • Vancomycin + Gentamicin
    • Reserved for patients allergic to beta-lactams; there are recent reports of suboptimal outcomes w/ Vancomycin therapy for serious S aureus infections
    • Vancomycin + Gentamicin x 3-5 days in MSSA is associated w/ faster clearing of bacteremia

NVE-MRSA
  • Vancomycin
    • Treatment of choice in MRSA
    • Treatment duration for 4-6 wk
    • Addition of Gentamicin or Rifampin to Vancomycin is not recommended for native valve IE
  • Linezolid or (Co-trimoxazole, Doxycycline or Minocycline w/ or w/o Rifampicin)
    • These agents may be an option in patients who are intolerant of Vancomycin or fail therapy
    • Data on clinical efficacy is limited compared to other agents

PVE-MSSA
  • (Antistaphylococcal penicillin + Rifampicin) x 6-8 wk, + Gentamicin for the 1st 2 wk of treatment
    • S aureus IE in PVE patients has a high mortality rate & surgery should be combined w/ antimicrobial therapy
    • Though in vitro & clinical studies are lacking, it is accepted that this 3-drug combination is used to treat MSSA in PVE
    • Cefazolin may be substituted for those w/ non-anaphylactoid-type Penicillin allergy
  • Vancomycin + Rifampicin + Gentamicin
    • Used for MRSA & coagulase-negative staphylococci
  • Quinolone
    • May be used in combination w/ Vancomycin & Rifampicin when the causative microorganism is resistant to all aminoglycosides


IVDA

Right-Sided Uncomplicated MSSA in IVDA
  • 2 wk antistaphylococcal penicillin + Gentamicin
    • Should be reserved for uncomplicated cases
  • 4 wk oral Ciprofloxacin + Rifampicin
    • Can be used in uncomplicated cases when compliance can be monitored
    • Though oral Ciprofloxacin & Rifampicin combination has been shown to be effective in IV drug users, currently, oral treatment for IE cannot be recommended

Left-Sided or Complicated MSSA in IVDA
  • Patient should be treated w/ standard 4-6 wk treatment if:
    • After >96 hr patient fails to show clinical or microbiological response to antibiotic therapy, CHF, vegetations >20 mm, acute resp failure, septic metastatic foci outside the lungs, extra-cardiac complications (eg renal failure) or IVDA w/ severe immunosuppression w/ or w/o AIDS

Organisms Other Than MSSA in IVDA
  • Treat as in non-addict

IE Caused by HACEK
  • HACEK group may not be identified in BCs for a wk or longer & empiric antibiotics may be necessary while awaiting culture results
  • Beta-lactamase-producing strains of HACEK are appearing w/ increased frequency
    • Difficult to perform antimicrobial susceptibility tests on HACEK organisms; therefore, these should now be considered Ampicillin resistant & Ampicillin should not be used for treatment
  • Ceftriaxone
    • Single-agent use is justified by its excellent pharmacokinetic profile
    • Effective against both β-lactamase-producing & non-β-lactamase-producing strains of the HACEK group
    • May be administered alone x 4 wk in NVE & x 6 wk in PVE
    • Alternative: Another 3rd or 4th generation cephalosporin
  • Ampicillin/Sulbactam
    • Limited published clinical data demonstrating efficacy
  • Quinolone
    • In vitro activity against the HACEK group but limited clinical use; therefore, consult w/ infectious disease specialist before using in patients intolerant to β-lactam therapy

Other Causes of IE
  • Treatment of these less common causes of IE is still not adequately defined
  • In patients w/ difficult-to-treat organisms (as below) & those w/ intracardiac device or foreign bodies, surgery combined w/ antibiotic therapy may be considered
Bartonella sp
  • Most cases of Bartonella sp IE have required antibiotic therapy & valve-replacement surgery for cure
Brucella sp
  • Few patients have been cured w/ antimicrobial agents alone; most require valve replacement in combination w/ antibiotics
Coxiella burnetii
  • Clinical response only persists as long as antimicrobial therapy continues; eradication is unlikely & reinfection of prosthetic material occurs after surgical replacement of infected valves
Pseudomonas aeruginosa
  • Most cases occur in IVDA & right-sided pseudomonal IE can usually be treated w/ antibiotic therapy w/ or w/o surgery
  • Valve replacement is usually considered mandatory in left-sided pseudomonal IE since medical therapy is rarely effective alone
Enterobacteriaceae sp
  • Susceptibility of these organisms can be unpredictable; therefore, treatment should be based on susceptibility testing

RECOMMENDED ANTIMICROBIAL THERAPY
Choice of therapy will depend on results of culture & sensitivity, patient’s allergy profile, patient status & CV risk factors. If possible, reserve Teicoplanin & Vancomycin for patients w/ severe Penicillin allergy.
Pathogen NVE PVE

Viridans group streptococci, Streptococcus bovis Penicillin-susceptible

Ceftriaxone IV x 4 wk

Ceftriaxone IV x 6 wk w/ or w/o Gentamicin x 2 wk

Penicillin or Amoxicillin IV x 4 wk
Penicillin IV or Ceftriaxone IV x 2 wk plus Gentamicin IV x 2 wk

Penicillin IV x 6 wk w/ or w/o Gentamicin x 2 wk

Vancomycin IV x 4 wk Vancomycin IV x 4 wk

Viridans group streptococci, Streptococcus bovis Penicillin-relatively resistant (Pen MIC >0.12 but ≤0.5 mg/L)

Ceftriaxone IV x 4 wk plus
Gentamicin x 2 wk

Ceftriaxone IV x 6 wk plus 
Gentamicin x 6 wk

Penicillin or Amoxicillin IV x 4 wk plus 
Gentamicin IV x 2 wk

Penicillin IV x 6 wk plus 
Gentamicin IV x 6 wk

Vancomycin x 4 wk Vancomycin x 6 wk

Viridans group streptococci, Streptococcus bovis Penicillin resistant
(Pen MIC >0.5 mg/L)
or Enterococci strains susceptible to Penicillin, Gentamicin

Ampicillin IV x 4-6 wk
Penicillin IV x 4-6 wk plus Gentamicin IV x 4 wk (6 wk in complicated cases)
Vancomycin IV x 6 wk plus Gentamicin IV x 6 wk
Enterococci strains susceptible to Penicillin, Streptomycin & Vancomycin but resistant to Gentamicin Ampicillin IV x 4-6 wk plus Streptomycin IV x 4-6 wk
Penicillin IV x 4-6 wk plus Streptomycin IV x 4-6 wk
Vancomycin IV x 6 wk plus Streptomycin IV x 6 wk
Enterococci strains resistant to Penicillin & susceptible to aminoglycoside & Vancomycin

Beta-lactamase - producing strain:
Ampicillin-sulbactam x 6 wk plus Gentamicin x 6 wk
Vancomycin x 6 wk plus Gentamicin x 6 wk

Intrinsic Penicillin resistance:
Vancomycin x 6 wk plus Gentamicin x 6 wk

Enterococci strains resistant to Penicillin, aminoglycoside & Vancomycin

E faecium:
Linezolid IV/PO x ≥8 wk
Quinupristin-dalfopristin x ≥8 wk

E faecalis:
Imipenem x ≥8 wk plus Ampicillin IV x ≥8 wk
Ceftriaxone x ≥8 wk plus Ampicillin IV x ≥8 wk

Choice of therapy will depend on results of culture & sensitivity, patient’s allergy profile, patient status & CV risk factors.
Methicillin-susceptible 
S aureus (MSSA)
Antistaphylococcal Penicillin IV x 4-6 wk w/ optional addition of Gentamicin IV x 3-5 days

Antistaphylococcal penicillin IV x
≥6 wk plus
Rifampicin IV x ≥6 wk
plus
Gentamicin IV x 2 wk

Antistaphylococcal Penicillin IV x 4-6 wk plus Fusidic acid PO x 4-6 wk

For Penicillin-allergic patients:
Cephalosporin (1st gen) IV x 6 wk w/ optional addition of Gentamicin IV x 3-5 days

Vancomycin x 6 wk
Methicillin-resistant
S aureus (MRSA)

1st-line agent:
Vancomycin x 4 wk

Vancomycin IV x ≥6 wk plus 
Rifampicin IV x ≥6 wk plus 
Gentamicin IV x 2 wk

Vancomycin treatment failure/ intolerance may try the following:
Linezolid or Co-trimoxazole, Doxycycline or Minocycline w/ or w/o Rifampicin

Right-sided MSSA in uncomplicated IE in IVDA Antistaphylococcal penicillin IV x 
2 wk plus Gentamicin IV x 2 wk
-
Ciprofloxacin PO x 4 wk plus
Rifampicin PO x 4 wk
HACEK organisms Ceftriaxone x 4 wk

Ceftriaxone x 6 wk
Ampicillin/sulbactam IV x 6 wk
Ciprofloxacin IV/PO x 6 wk

Ampicillin/sulbactam IV x 4 wk
Ciprofloxacin IV/PO x 4 wk
Culture-negative endocarditis caused by uncommon organisms including Bartonella sp Ampicillin/sulbactam IV x 4-6 wk plus Gentamicin IV x 4-6 wk

Early, PVE (≤1 yr)
Vancomycin IV x 6 wk plus 
Gentamicin IV x 2 wk plus 
Cefepime x 6 wk plus
Rifampicin PO/IV x 6 wk plus
Late, PVE (>1 yr), Culture negative
Ceftriaxone IV x 6 wk plus 
Gentamicin IV x 2 wk w/ or w/o 
Doxycycline IV/PO x 6 wk
Late, PVE (>1 yr), 
Bartonella confirmed
Doxycycline IV/PO x 6 wk plus 
Gentamicin IV x 2 wk

Vancomycin IV x 4-6 wk plus
Gentamicin IV x 4-6 wk plus
Ciprofloxacin IV/PO x 4-6 wk
Culture-negative endocarditis in patients who received antibiotics prior to blood culture

Acute symptoms of NVE:
Treat as in NVE for MSSA
Subacute symptoms of NVE:
Treatment should cover MSSA, viridans streptococci, enterococci; HACEK may be considered
Ampicillin/sulbactam plus Gentamicin x 4-6 wk

Early, PVE (≤1 yr)
Treat as in MRSA,
Add Cefepime to cover aerobic Gram-negative bacilli
Late, PVE (>1 yr), Culture negative
Treatment should cover MSSA, viridans streptococci & enterococci x
6 wk

Pseudomonas aeruginosa

Treatment should be based on in vitro sensitivity studies
Antipseudomonal beta-lactam x 6 wk plus high-dose Tobramycin x 6 wk

Treatment should be based on in vitro sensitivity studies
Antipseudomonal beta-lactam plus 
Tobramycin
Enterobacteriaceae sp (E coli, Klebsiella sp, Enterobacter sp & Serratia sp)

Treatment should be based on in vitro sensitivity studies
Beta-lactam at high doses x 4-6 wk plus Gentamicin x 4-6 wk

Treatment should be based on in vitro sensitivity studies
Beta-lactam at high doses plus Gentamicin


1. Aminoglycosides

  • Adverse Reactions:
    • Ototoxic effects (can cause irreversible ototoxicity resulting in hearing loss, dizziness, vertigo); Renal effects (reversible nephrotoxicity, acute renal failure has been reported usually when other nephrotoxic drugs have also been administered); Neuromuscular effects (neuromuscular blockade resulting in resp depression & muscular paralysis); Hypersensitivity reactions
  • Special Instructions:
    • Ototoxicity & nephrotoxicity are most likely in geriatric, dehydrated patients, those w/ renal impairment, in patients who are receiving high doses or for long periods or who are also receiving or have received other ototoxic/nephrotoxic drugs
      • Consider monitoring of serum conc &/or peak serum conc/MIC ratio in these patients
    • Use w/ caution in patients w/ conditions associated w/ muscle weakness (eg myasthenia gravis, Parkinson’s disease), patients w/ preexisting renal dysfunction, vestibular or cochlear impairment
  • Dosage Guidelines:
a. Gentamicin
  • 3 mg/kg/day IM/IV 8 hrly
  • Max dose: 5 mg/kg/day divided 6-8 hrly
b. Netilmicin
  • 7.5 mg/kg/day IV divided 8 hrly
  • Reduce to ≤6 mg/kg/day IV as soon as clinically indicated usually w/ in 48 hr
c. Streptomycin
  • 1-2 g/day IM/IV in divided doses
d. Tobramycin
  • P aeruginosa: 8 mg/kg/day IM/IV 24 hrly


2. Antibacterial Combinations

  • Adverse Reactions:
    • GI effects (N/V, anorexia, diarrhea, rarely antibiotic- associated diarrhea/colitis, glossitis); Dermatologic effects (rash, pruritus, photosensitivity); Hypersensitivity reactions can range from mild (eg rash) to severe/life-threatening (eg Stevens-Johnson syndrome); Urogenital effect (crystallization in the urine)
    • Rarely hematologic effects which may be more common if given for long periods or w/ high doses; rarely hepatic effects, renal effects; aseptic meningitis has occurred
  • Special Instructions:
    • Maintain adequate fluid intake
    • Contraindicated in patients allergic to sulfonamides
    • Use w/ extreme caution or not at all in patients w/ hematological disorders esp megaloblastic anemia due to folic acid deficiency
    • Use w/ caution in patients w/ renal impairment or severe hepatic dysfunction & w/ caution in patients w/ folate deficiency (may consider administration of Folinic acid)
  • Dosage Guidelines:
a. Co-trimoxazole [Sulfamethoxazole (SMZ) & Trimethoprim (TM)]
  • 800 mg SMZ/160 mg TM PO 12 hrly
  • 8-10 mg TM/kg/day IV divided 6 hrly


3. Cephalosporins

  • Adverse Reactions:
    • Hypersensitivity reactions (urticaria, pruritus, rash, severe reactions eg anaphylaxis can occur); GI effects (diarrhea, N/V, rarely antibiotic-associated diarrhea/colitis); Other (Candidal infections)
    • High doses may be associated w/ CNS effects (encephalopathy, convulsions); rarely hematologic effects; hepatic & renal effects have occurred
    • Prolonged prothrombin time (PT), prolonged activated partial thromboplastin time (APTT), &/or hypoprothrombinemia (w/ or w/o bleeding) have been reported & occur most frequently w/ NMTT side chain-containing cephalosporins
  • Special Instructions:
    • May be taken w/ food to decrease gastric distress
    • Use w/ caution in patients allergic to Penicillin, there may be 10% chance of cross sensitivity
    • Use w/ caution in patients w/ renal impairmen
  • Dosage Guidelines:
3.1. Cephalosporins (1st Generation)
a. Cefalexin
  • 250-500 mg PO 6 hrly or 750 mg PO 12 hrly
b. Cefazolin
  • 1-3 g/day IM/IV divided 6-8 hrly
  • Max dose: 6 g/day
c. Cefradine (Cephradine)
  • 2-4 g/day IV divided 6 hrly
  • Max dose: 8 g/day
3.2. Cephalosporins (2nd Generation)
a. Cefoxitin
  • 2 g IV/IM 8 hrly
  • Max dose: 12 g/day
3.3. Cephalosporins (3rd Generation)
a. Cefoperazone
  • 1-2 g IV/IM 12 hrly
  • Max dose: 12 g/day
b. Cefotaxime
  • 1-2 g IV 8-12 hrly
  • Max dose: 12 g/day
c. Ceftazidime
  • 1-2 g IV/IM 8 hrly
  • Max dose: 6 g/day
d. Ceftizoxime
  • 0.5-2 g IV/IM divided 6-12 hrly
  • Max dose: 4 g/day
e. Ceftriaxone
  • 1-2 g IV/IM 24 hrly or divided 12 hrly
  • Max dose: 4 g/day
3.4. Cephalosporins (4th Generation)
a. Cefepime
  • 2 g IV 8-12 hrly


4. Macrolide

  • Adverse Reactions:
    • GI effects (N/V, abdominal discomfort, diarrhea & other GI disturbances, antibiotic-associated diarrhea/colitis); Other effect (Candidal infections)
    • Hypersensitivity reactions are uncommon (urticaria, pruritus, rash, rarely anaphylaxis); Rarely cardiotoxicity, hepatotoxicity; Dose-related tinnitus/hearing loss have occurred w/ some macrolides
  • Special Instructions:
    • May take w/ food to decrease gastric distress
    • Use w/ caution in patients w/ hepatic dysfunction
  • Dosage Guidelines:
a. Clarithromycin
  • Alternative to penicillin for prophylaxis of bacterial endocarditis: 500 mg PO 12 hrly


5. Penicillins

  • Adverse Reactions:
    • Hypersensitivity reactions (rash, urticaria, pruritus, severe reactions eg anaphylaxis can occur); GI effects (diarrhea, N/V, rarely antibiotic-associated diarrhea/colitis); Other effect (Candidal infections)
    • Rarely hematologic effects; renal & hepatic effects have occurred; high doses may be associated w/ CNS effects (encephalopathy, convulsions)
  • Special Instructions:
    • Avoid in patients w/ Penicillin allergy
    • Use w/ caution in patients w/ renal impairment
  • Dosage Guidelines:
a. Benzylpenicillin (Penicillin G, Penicillin G Na, Penicillin G K)
  • 1.2 g IM/IV 4 hrly
5.1. Aminopenicillins w/ or w/o Beta-lactamase Inhibitors
a. Amoxicillin (Amoxycillin)
  • 500 mg IM/slow IV 8 hrly
  • High dose: 1 g slow IV/IV infusion 6 hrly
b. Amoxicillin/clavulanic acid (Co-amoxiclav, Amoxicillin/clavulanate)
  • 1.2 g IV 8 hrly
c. Ampicillin
  • 500 mg IM/IV 4-6 hrly
d. Ampicillin/sulbactam (Sultamicillin: Pro-drug of Ampicillin/sulbactam, the 2 drugs are linked chemically w/ a double ester)
  • 1.5-3 g IV 6-8 hrly
  • Max dose: Sulbactam 4 g/day
5.2. Antistaphylococcal Penicillins
a. Cloxacillin
  • 500 mg IM/IV 4-6 hrly
  • Max dose: 8 g/day
b. Flucloxacillin
  • 250-500 mg IM/slow IV/IV infusion 6 hrly
  • Max dose: Up to 12 g/day divided 4 hrly
c. Oxacillin
  • 500 mg-1 g IM/slow IV/IV infusion 4-6 hrly


6. Other Beta-Lactam

6.1. Carbapenem
  • Adverse Reactions:
    • GI effects (diarrhea, N/V, antibiotic-associated diarrhea/colitis, tongue/tooth discoloration, altered taste); Hypersensitivity reactions ranging from mild (eg rash) to severe (eg anaphylaxis) can occur; Other (Candidal infections)
    • CNS effects (mental disturbances, confusion; Imipenem/cilastatin: Seizures & convulsions have been reported esp in patients w/ a history of CNS lesions &/or renal dysfunction); Rarely severe dermatologic reactions (eg exfoliative dermatitis, Stevens-Johnson syndrome, etc); rarely hepatic effects
  • Special Instructions:
    • Use w/ caution in patients allergic to penicillins, cephalosporins or other beta-lactams
    • Use w/ caution in patients w/ CNS disorders (eg epilepsy), renal impairment
  • Dosage Guidelines:
a. Cilastatin/Imipenem
  • 1-2 g/day IV divided 6-8 hrly
  • Max dose: 4 g/day or 50 mg/kg/day


7. Quinolones

  • Adverse Reactions:
    • GI effects (N/V, diarrhea, abdominal pain, dyspepsia, diarrhea, rarely antibiotic-associated diarrhea/colitis); CNS effects (headache, dizziness, sleep disorders, restlessness, drowsiness); Dermatologic effects (rash, pruritus, photosensitivity); Hypersensitivity reactions can range from mild (eg rash) to severe/life-threatening (eg Stevens-Johnson syndrome)
    • Rarely hematologic effects, hepatic & renal effects
    • Some quinolones have the potential to prolong the QT interval
  • Special Instructions:
    • Administer at least 2 hr before or 3 hr after Al- or Mg-containing antacids, dietary supplements containing Zn or Fe or buffered ddl preparations
    • Avoid exposure to strong sunlight or tanning beds
    • Use w/ caution in patients w/ epilepsy or history of CNS disorders, in patients w/ impaired renal or hepatic function & in those w/ G6PD deficiency
  • Dosage Guidelines:
a. Ciprofloxacin
  • 500 mg PO 12 hrly or
  • 400 mg IV 12 hrly
b. Pefloxacin
  • 400 mg IV 12 hrly


8. Tetracycline

  • Adverse Reactions:
    • GI effects (N/V, diarrhea, antibiotic-associated diarrhea/colitis has occurred, dysphagia, esophageal ulceration has occurred when taken w/ an insufficient amount of liqd); Dermatologic effect (photosensitivity); Other effects (Candidal infections, discoloration of teeth, interference w/ bone growth in young infants/pregnant women)
    • Rarely renal dysfunction, hepatotoxicity, hematologic effects, intracranial pressure w/ headache & visual disturbances; hypersensitivity reactions have occurred
  • Special Instructions:
    • Avoid long exposure to sunlight or tanning beds
      • Take w/ plenty of fluid while sitting or standing & well before retiring to bed
    • Avoid in children ≤8 yr & pregnant women; avoid in patients w/ SLE
    • Use w/ caution in renal or hepatic impairment
  • Dosage Guidelines:
a. Doxycycline
  • Loading dose: 200 mg PO/IV 24 hrly or divided 12 hrly
  • Maintenance dose: 100 mg PO/IV 24 hrly


9. Other Antibiotics

9.1. Cyclic Lipopeptide
  • Adverse Reactions:
    • GI effects (diarrhea, N/V, constipation); Hematologic effect (anemia)
    • Less common: CV effects (peripheral edema, chest pain, hypertension, hypotension); CNS effects (insomnia, headache); Dermatologic effects (rash, pruritus); Endocrine effects (hypokalemia, hyperkalemia); GUT effect [urinary tract infection (UTI)]; Musculoskeletal effects [increased creatine phosphokinase (CPK), limb pain, back pain, weakness]; Resp effects (pharyngolaryngeal pain, pleural effusion, cough, pneumonia, dyspnea); Misc effects (osteomyelitis, bacteremia, diaphoresis, sepsis, fungal infections, renal failure, inj site reaction)
  • Special Instructions:
    • Monitor CPK levels once wkly or more frequently in high-risk patients
    • Monitor for signs & symptoms of neuropathy
  • Dosage Guidelines:
a. Daptomycin
  • 6 mg/kg IV 24 hrly
9.2. Fusidate
  • Adverse Reactions:
    • GI effect (mild GI upset); Hepatic effects (jaundice & changes in liver function which return to normal once drug is discontinued)
  • Special Instructions:
    • Use w/ caution in patients w/ liver dysfunction & monitoring of hepatic function in these patients is recommended if on high or prolonged doses
  • Dosage Guidelines:
a. Fusidic acid (Na fusidate)
  • Na fusidate:
    • 500 mg slow IV 24 hrly
    • 500 mg PO 8 hrly
    • Max dose: 2 g/day
9.3. Glycopeptides
a. Teicoplanin
  • Adverse Reactions:
    • Fever, chills, skin rash, pruritus; occasionally, anaphylaxis or bronchospasm have been reported; generally better tolerated than Vancomycin
    • Other hypersensitivity reactions can occur (eg Stevens- Johnson syndrome); GI effect (GI disturbances); CNS effects (dizziness, headache); hematologic effects; hepatic effects; renal effect (renal impairment, but less often than w/ Vancomycin); ototoxic effects have occurred but less frequently than w/ Vancomycin
  • Special Instructions:
    • Use w/ caution in patients w/ preexisting renal dysfunction & monitor renal & auditory function if on prolonged therapy
    • Periodic monitoring of CBC & LFTs are advised
  • Dosage Guidelines:
  • Loading dose: 400 mg IV 12 hrly for 1st 3 doses
  • Maintenance dose: 400 mg IV 24 hrly
b. Vancomycin
  • Adverse Reactions:
    • “Red neck syndrome” which is usually related to too rapid infusion: Flushing, erythema, rash over face & upper torso, sometimes hypotension & shock-like symptoms also occur
    • Hypersensitivity reactions (can range from mild to severe eg anaphylactoid reactions, Stevens-Johnson syndrome); Hematologic effects have occurred; Renal effects (nephrotoxicity may occur esp at high doses or in patients w/ predisposing factors); Ototoxic effects (ototoxicity, which is more likely w/ high plasma conc or in renal impairment, may be irreversible; tinnitus may precede hearing loss & can be used as a sign to discontinue treatment)
  • Special Instructions:
    • Avoid in patients w/ a history of impaired hearing
    • Use w/ caution in patients w/ impaired renal function & in the elderly
    • Monitoring of serum conc may be done to help avoid renal & otic toxicity, monitoring of CBC & renal function during treatment is suggested along w/ monitoring of auditory function
  • Dosage Guidelines:
  • 500 mg IV 6 hrly or
  • 1 g IV 12 hrly
  • Max dose: 2 g/day
9.4. Lincosamide
  • Adverse Reactions:
    • GI effects (diarrhea, severe antibiotic-related pseudomembranous colitis, N/V, abdominal pain, metallic taste); Hypersensitivity reactions (rash, urticaria, rarely anaphylaxis); Severe dermatologic effects have occurred (erythema multiforme, exfoliative & vesiculobullous dermatitis); cardiac, hematologic & hepatic effects have occurred; Other effect (polyarthritis)
  • Special Instructions:
    • Use w/ caution in patients w/ GI disease esp w/ history of colitis, in atopic patients & in patients w/ renal or hepatic impairment
    • Discontinue if diarrhea occurs
  • Dosage Guidelines:
a. Clindamycin
  • Alternative to penicillin for prophylaxis of endocarditis: 150 mg PO 6 hrly or 600 mg PO/IV 1 hr before procedure
9.5. Oxazolidinone
  • Adverse Reactions:
    • GI effects (diarrhea, N/V, metallic taste, constipation, antibiotic-associated diarrhea/colitis can occur); CNS effects (headache, insomnia, dizziness); Hepatic effect (abnormal LFTs); Hematologic effects (reversible myelosuppression including leukopenia, anemia, pancytopenia, thrombocytopenia has occurred); Other (moniliasis infection)
  • Special Instructions:
    • Use w/ caution in patients w/ preexisting myelosuppression & in patients w/ severe renal dysfunction
    • Recommend monitoring of blood counts wkly
  • Dosage Guidelines:
a. Linezolid
  • 600 mg PO 12 hrly
  • 600 mg IV 12 hrly
9.6. Rifamycin
  • Adverse Reactions:
    • Generally well tolerated; GI effects (N/V, anorexia, diarrhea, GI distress, antibiotic-associated diarrhea/colitis has occurred); Discoloration of urine & body fluids
    • Rarely hepatic effects (transient abnormalities in liver function, hepatitis rarely occurs); Hematologic effects have occurred; Renal effects have been reported w/ intermittent therapy; CNS effects (headache, drowsiness, ataxia, etc)
  • Special Instructions:
    • Rifampicin accelerates the metabolism of drugs metabolized by the CYP450
    • Use w/ caution in patients w/ preexisting liver dysfunction, monitor liver function during therapy in these patients
  • Dosage Guidelines:
a. Rifampicin
  • 600 mg PO 12 hrly
  • 600 mg IV 12 hrly
9.7. Streptogramin
  • Adverse Reactions:
    • GI effects (N/V, diarrhea, antibiotic-associated diarrhea/colitis); CNS effect (headache); Hypersensitivity reactions (pruritus, rash, rarely anaphylaxis); Hematologic effects (anemia, eosinophilia, leukopenia, neutropenia); Musculoskeletal effects (myalgia, arthralgia have occurred & may improve w/ decreasing dose frequency); Hepatic effects have occurred
  • Special Instructions:
    • Contraindicated in severe hepatic impairment
    • Use w/ caution in patients w/ hepatic dysfunction
    • May cause prolongation of QT interval, use w/ caution in patients w/ cardiac arrhythmia
  • Dosage Guidelines:
a. Quinupristin/Dalfopristin
  • 7.5 mg/kg IV 8 hrly

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Surgery

Surgery should be considered in the following:
  • NVE patients w/ acute aortic or mitral regurgitation & CHF
  • Evidence of perivalvular extension
  • Persistent infection after 7-10 days of adequate antimicrobial therapy
  • Relapsing infection ie recurrence of bacteremia following a complete antibiotic course & subsequently negative BCs w/ no known source of infection
  • Infection w/ microorganisms that have poor response to antibiotic therapy (eg fungi, Brucella sp, Coxiella sp, Staphylococcus lugdunensis, Enterococcus sp w/ high-level resistance to Gentamicin, gram-negative organisms)
    • Left-sided IE caused by S aureus, fungal, or highly resistant organisms
  • NVE patients w/ mobile vegetation >10 mm before or during the 1st wk of antibiotic therapy
  • Recurrent emboli despite appropriate antibiotic therapy
  • Obstructive or persistent vegetations
  • Early PVE
  • Hemodynamically significant prosthetic valve
  • IE complicated by annular or aortic abscess, destructive penetrating lesion, or heart block

All dosage recommendations are for non-pregnant & non-breastfeeding women, non-elderly adults w/ normal renal & hepatic function unless otherwise stated.

 

Not all products are available or approved for above use in all countries. 

 

Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information.


Click the link below for specific prescribing information of products available in respective countries.

Brands available in:   Hong Kong     Indonesia     Malaysia     Philippines     Singapore     Thailand     Vietnam

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