Bacterial Sepsis Medication

Updated: May 22, 2017
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

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Antibiotics, Other

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Imipenem/cilastatin (Primaxin IV)

Imipenem-cilastatin is a carbapenem with activity against most gram-positive organisms (except MRSA), gram-negative organisms, and anaerobes. It is used for treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated owing to their potential for toxicity.

Meropenem (Merrem)

Meropenem is a carbapenem with slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared with imipenem. It is less likely to cause seizures and has superior penetration of the blood-brain barrier compared with imipenem.

Piperacillin and tazobactam (Zosyn)

Piperacillin-tazobactam inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication. It has antipseudomonal activity.

Ampicillin and sulbactam (Unasyn)

Ampicillin and sulbactam is a drug combination of a beta-lactamase inhibitor with ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It is an alternative to amoxicillin if the patient is unable to take medications orally. It covers skin, enteric flora, and anaerobes and is not ideal for nosocomial pathogens.

Clindamycin (Cleocin)

Clindamycin is primarily used for its activity against anaerobes. It has some activity against Streptococcus species and methicillin-sensitive S aureus (MSSA).

Metronidazole (Flagyl, Metro)

Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is usually combined with other antimicrobial agents, except when used for Clostridium difficile enterocolitis, in which monotherapy is appropriate.

Cefepime (Maxipime)

Cefepime is a fourth-generation cephalosporin. It has gram-negative coverage comparable to ceftazidime but has better gram-positive coverage (comparable to ceftriaxone). Cefepime is active against Pseudomonas species. It has increased effectiveness against extended-spectrum beta-lactamase (ESBL)–producing organisms. Its poor capacity to cross blood-brain barrier precludes its use for treatment of meningitis.

Levofloxacin (Levaquin)

Levofloxacin is a fluoroquinolone with excellent gram-positive and gram-negative coverage. It is an excellent agent for pneumonia and has excellent abdominal coverage as well. High urine concentration necessitates reduced dosing in urinary tract infection.

Vancomycin

Vancomycin provides gram-positive coverage and good hospital-acquired MRSA coverage. It is now used more frequently because of the high incidence of MRSA. Vancomycin should be given to all septic patients with indwelling catheters or devices. It is advisable for skin and soft-tissue infections.

Trimethoprim/sulfamethoxazole (Bactrim DS, Septra DS)

The broad spectrum and action of trimethoprim and sulfamethoxazole (TMP-SMZ) against organisms found in patients with cystic fibrosis and the convenience of oral administration make this combination useful for treatment of milder infections in an outpatient setting.

Aztreonam (Azactam)

Aztreonam is a monobactam, not a beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. It is active against gram-negative bacilli but has very limited gram-positive activity and is not useful for anaerobes. Aztreonam lacks cross-sensitivity with beta-lactam antibiotics. It may be used in patients who are allergic to penicillins or cephalosporins.

The duration of therapy depends on the severity of infection and is continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Doses that are smaller than indicated should not be used.

Transient or persistent renal insufficiency may prolong serum levels. After the initial loading dose of 1 or 2 g, reduce the dose by one half for an estimated CrCl of 10-30 mL/min/1.73 m2. When only the serum creatinine concentration is available, the following formula (based on sex, weight, and age) can approximate CrCl (serum creatinine should represent a steady state of renal function):

• Males: CrCl = [(weight in kg)(140 - age)] divided by (72 X serum creatinine in mg/dL)

• Females: 0.85 X above value

In patients with severe renal failure (CrCl < 10 mL/min/1.73 m2), those supported by hemodialysis, a usual dose of 500 mg, 1 g, or 2 g is given initially.

The maintenance dose is one fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 hours. For serious or life-threatening infections, supplement maintenance doses with one eighth of the initial dose after each hemodialysis session.

Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by the kidneys, obtain estimates of CrCl and make appropriate dosage modifications. Insufficient data are available regarding intramuscular (IM) administration to pediatric patients or dosing in pediatric patients with renal impairment. Aztreonam is administered intravenously only to pediatric patients with normal renal function.

Linezolid (Zyvox)

Linezolid is used as an alternative drug in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci. It is also effective against MRSA and penicillin-susceptible S pneumoniae infections.

This agent is an oxazolidinone antibiotic that prevents formation of the functional 70S initiation complex, which is essential for the bacterial translation process. Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone is used for increasing prevalence of penicillinase-producing microorganisms. It inhibits bacterial cell wall synthesis by binding to 1 or more penicillin-binding proteins. Cell wall autolytic enzymes lyse bacteria, while cell wall assembly is arrested.

Daptomycin (Cubicin)

Daptomycin causes membrane depolarization by binding to components of the cell membrane of susceptible organisms. It inhibits DNA, RNA, and protein synthesis intracellularly. It is a bactericidal antibiotic.

Nafcillin (Nallpen)

Nafcillin is a broad-spectrum penicillin. It is used for methicillin-sensitive S aureus and is the initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. In severe infections, start with parenteral therapy and change to oral therapy as the condition warrants. Because of thrombophlebitis, particularly in elderly persons, administer parenterally for only 1-2 days; change to oral therapy as indicated clinically.

Rifampin (Rifadin)

Rifampin is for use in combination with at least 1 other antituberculosis drug. It inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription. Cross-resistance may occur.

Daptomycin (Cubicin)

This is the first of a new antibiotic class called cyclic lipopeptides. It binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis, and ultimately causing cell death. It is indicated for complicated skin and skin structure infections caused by S aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S dysgalactiae, and E faecalis (vancomycin-susceptible strains only).

Tigecycline (Tygacil)

Tigecycline is a glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. It inhibits bacterial protein translation by binding to the 30S ribosomal subunit, and it blocks the entry of amino-acyl tRNA molecules in ribosome A site. It is indicated for complicated skin and skin structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes and B fragilis.

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