eMedicine Specialties > Infectious Diseases > Bacterial Infections

Sepsis, Bacterial: Treatment & Medication

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Oct 19, 2009

Treatment

Medical Care

  • Offer supportive therapy aimed at maintaining organ perfusion.
  • Provide respiratory support, when necessary.

Consultations

  • Obtain a consultation with a surgeon for patients with presumed intra-abdominal or pelvic sepsis. Early surgical consultation and involvement by the surgical team is essential, since many causes of sepsis involve a perforated viscus, abscess, or obstructing process that requires surgical intervention for cure or resolution of the infection.
  • Obtain a consultation with an infectious disease specialist for all patients with sepsis included in the differential diagnoses.

Diet

  • Most patients are instructed to take nothing by mouth (NPO) and can tolerate a transient decrease in caloric intake over 1-2 weeks if their fluid and electrolyte balances are maintained.

Activity

  • Most patients are ill and require bed rest or admission to the ICU.

Medication

Appropriate antimicrobial therapy depends on adequate coverage of the resident flora of the organ system presumed to be the source of the septic process. Empiric monotherapy regimens include imipenem, meropenem, cefoperazone, piperacillin/tazobactam, or sulbactam/ampicillin. Combination therapeutic agents include clindamycin or metronidazole plus levofloxacin, aztreonam, trimethoprim/sulfamethoxazole (TMP-SMZ), or an aminoglycoside.

No single drug/regimen is superior to another. Alternative agents may be used alone or in combination provided they have a low reactive potential and a good adverse-effect profile.

Antibiotics

These agents are used to treat various types of infection.

Empiric therapy for intravenous-line infections

Since intravenous-line infections are most often due to Staphylococcus aureus (MSSA or MRSA) and less commonly due to aerobic gram-negative bacilli, the preferred empiric therapy for intravenous-line infections is meropenem, cefoperazone, or cefepime plus additional coverage for staphylococci. If MRSA is prevalent in the institution, add linezolid, vancomycin, or daptomycin.

If coagulase-negative staphylococci are recovered from the blood (high-level bacteremia, ie, 3/4 or 4/4 blood cultures positive), avoid vancomycin for empiric therapy if possible, since this is a low-virulence organism.

Treatment of coagulase-negative staphylococcal central-line infection requires removal of the line. Vancomycin may be given, but central line removal is essential. If the central line cannot be removed for clinical reasons in a patient with MRSA or coagulase-negative staphylococcal infection, empiric suppressive vancomycin therapy is acceptable.

Minimize the use of vancomycin in order to prevent the emergence of Enterococcus faecium, a vancomycin-resistant species.

Empiric therapy for biliary tract infections (cholecystitis/cholangitis)

The main biliary-tract pathogens include Escherichia coli, Klebsiella species, and Enterococcus faecalis. Coverage for staphylococci and anaerobes is not needed in the biliary tract. Anaerobes are important only in patients with diabetes who have Clostridium perfringens emphysematous cholecystitis. Preferred monotherapy for biliary-tract infections is with imipenem, meropenem, piperacillin, or cefoperazone.

Empiric therapy for intra-abdominal and pelvic infections

The main pathogens in the lower abdomen and pelvis include aerobic coliform gram-negative bacilli and B fragilis. Enterococci are permissive/opportunistic pathogens and do not require special coverage. Potent anti– B fragilis and aerobic gram-negative bacillary coverage are essential, in addition to surgical intervention when drainage or repair of intra-abdominal viscera is required.

Preferred monotherapy for intra-abdominal and pelvic infections is imipenem, meropenem, piperacillin/tazobactam, or ampicillin/sulbactam.

Preferred combination therapy for intra-abdominal and pelvic infections is clindamycin or metronidazole plus aztreonam, levofloxacin, or an aminoglycoside.

Empiric therapy for urosepsis

The primary uropathogens include gram-negative aerobic bacilli, eg, coliforms or enterococci (E faecalis, not E faecium vancomycin-resistant enterococci).

Pseudomonas aeruginosa, Enterobacter species, and Serratia species are rare uropathogens and are associated with urological instrumentation.

Preferred monotherapy for urosepsis due to aerobic gram-negative bacilli is with aztreonam, levofloxacin, third- or fourth-generation cephalosporins, or an aminoglycoside.

Preferred monotherapy for urosepsis due to enterococci (E faecalis) is with ampicillin or vancomycin (penicillin-allergic).

Empiric therapy for community-acquired urosepsis is levofloxacin, aztreonam, or an aminoglycoside plus ampicillin. For nosocomial urosepsis, piperacillin, imipenem, or meropenem monotherapy is preferred. 

Empiric therapy for other causes of sepsis

S aureus sepsis is usually associated with infection caused by devices or acute bacterial endocarditis. Empiric therapy may be with nafcillin, an anti-staphylococcal, cephalosporin, a carbapenem, linezolid, or clindamycin with or without rifampin.

Pneumococcal or meningococcal sepsis may be treated with penicillin G or a beta-lactam. In patients with associated meningococcal meningitis, the antibiotic selected should penetrate the cerebrospinal fluid and should be given in meningeal doses.

Empiric therapy for sepsis of unknown origin

The usual sources of sepsis are from the distal GI tract, pelvis, or GU tract. For intravenous-line infections, see above.

Organisms that should be covered from the GI/GU tract and pelvis include aerobic gram-negative bacilli (coliforms) and B fragilis. Enterococci are important pathogens in biliary - tract sepsis and urosepsis.

Preferred empiric monotherapy includes meropenem, imipenem, piperacillin/tazobactam, or cefoperazone.

Empiric combination therapy includes (1) levofloxacin plus either clindamycin or metronidazole, (2) aztreonam, (3) cefepime plus either clindamycin or metronidazole, or (4) ceftriaxone or aminoglycoside plus metronidazole.


Imipenem (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity.

Adult

1 g IV q6h

Pediatric

<12 years: Not established; 15-25 mg/kg/dose IV q6h suggested
>12 years: Administer as in adults

Coadministration with cyclosporine may increase adverse CNS effects of both agents; coadministration with ganciclovir may result in generalized seizures

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal insufficiency; avoid use in children <12 y; avoid use in those with CNS disorders/seizures


Meropenem (Merrem)

Semisynthetic carbapenem antibiotic that inhibits bacterial cell wall synthesis.

Adult

1 g IV q8h

Pediatric

<10 years: Not established
>10 years: Administer as in adults

Probenecid increases serum levels

Documented hypersensitivity to carbapenem or beta-lactams; first trimester of pregnancy

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; pseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication


Cefoperazone (Cefobid)

Beta-lactam antibiotic that inhibits bacterial cell wall synthesis. A third-generation cephalosporin with antipseudomonal and antistaphylococcal activity. Only cephalosporin with anti-enterococcal (E faecalis) activity. Active against S aureus (MSSA), aerobic gram-negative bacilli, E faecalis, and B fragilis.

Adult

2 g IV q12h

Pediatric

<10 years: Not established
>10 years: Administer as in adults

Alcohol ingestion within 72 h induces disulfiramlike reaction

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May increase in PT or INR; may need prophylactic administration of AquaMEPHYTON 10 mg IM q1wk to all critically ill patients receiving any beta-lactam antibiotic


Levofloxacin (Levaquin)

A quinolone that exerts a bactericidal effect by interfering with DNA gyrase in bacterial cells; highly active against gram-negative and gram-positive organisms.

Adult

500 mg IV q24h

Pediatric

<10 years: Not established
>10 years: Administer as in adults

Antacids, iron, and zinc salts may reduce serum levels; administer antacids 1-2 h before or after taking

Documented hypersensitivity; pregnancy; breastfeeding

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Superinfections may occur with prolonged or repeated antibiotic therapy


Piperacillin/tazobactam (Zosyn)

Semisynthetic extended-spectrum penicillin that inhibits bacterial cell wall synthesis by binding to specific PBPs; most effective of the antipseudomonal penicillins.
Tazobactam increases piperacillin activity against S aureus, Klebsiella, Enterobacter, and Serratia species; (greatest increase in activity against B fragilis) but does not increase anti–P aeruginosa activity.
Intra-abdominal and pelvic infections: The main pathogens in the lower abdomen and pelvis are aerobic coliform gram-negative bacilli and B fragilis. Enterococci are permissive and opportunistic pathogens and do not require special coverage.

Adult

4.5 g IV q8h (piperacillin 4 g/tazobactam 0.5 g)

Pediatric

<10 years: Not established
>10 years: Administer as in adults

Probenecid increases piperacillin serum levels; synergistic effect with aminoglycosides; heparin increases risk of bleeding; may decrease efficacy of oral contraceptives; tetracycline may decrease effectiveness

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Renal impairment; may interfere with platelet function


Sulbactam/ampicillin (Unasyn)

A combination beta-lactam and beta-lactamase inhibitor that suppresses bacterial cell wall synthesis by binding to specific PBPs. Sulbactam increases effectiveness against beta-lactamase–producing microorganisms. Sulbactam increases the activity of ampicillin against S aureus, Klebsiella, Enterobacter, and Serratia species; greatest increase in activity against B fragilis.

Adult

3 g IV q6h (ampicillin 2 g / sulbactam 1 g)

Pediatric

<10 years: Not established
>10 years: Administer as in adults

Probenecid increases serum levels; decreases effectiveness of oral contraceptives

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment


Metronidazole (Flagyl)

Binds to ribosomes in bacterial cells. Highly active against most anaerobes, including B fragilis, but not active against aerobic gram-positive or gram-negative organisms.
In intra-abdominal or pelvic infections, it must always be used in combination with another antibiotic active against aerobic gram-negative bacilli, which accompany B fragilis.

Adult

1 g IV q24h

Pediatric

<10 years: Not established
>10 years: Administer as in adults

Phenytoin and phenobarbital decrease serum levels; increases PT with warfarin; increases lithium levels and toxicity; cimetidine may increase serum levels

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Disulfiramlike reaction if taken within 72 h of alcohol consumption


Clindamycin (Cleocin)

Exerts a bacteriostatic effect by interfering with bacterial metabolism at the ribosomal level. It is highly active against all staphylococci except MRSA. Some strains of S epidermidis are resistant. It is excellent against B fragilis but is not active against aerobic gram-negative bacilli. In mixed intra-abdominal or pelvic infections, it must always be used in combination therapy with an antibiotic active against aerobic gram-negative bacilli. No antienterococcal activity.

Adult

600 mg IV q8h

Pediatric

<10 years: Not established
>10 years: Administer same as in adults

Increased neuromuscular blockade

Documented hypersensitivity; avoid in patients who have recently had C difficile diarrhea or colitis

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in advanced cirrhosis; avoid in patients with preexisting inflammatory bowel disease; discontinue if diarrhea or colitis occurs during therapy


Aztreonam (Azactam)

A monobactam that inhibits cell wall synthesis during bacterial growth. Active against gram-negative bacilli.

Adult

2 g IV q8h

Pediatric

90-120 mg/kg/d divided IV/IM q6-8h

Tetracyclines may reduce effects of this medication

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal insufficiency; not active against B fragilis or enterococci


Moxifloxacin (Avelox)

Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Adult

400 mg PO/IV qd

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS stimulating effect; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); ferrous sulfate decreases bioavailability (administer moxifloxacin 4 h prior or 8 h following ferrous sulfate); coadministration with drugs that prolong QTc interval (quinidine, procainamide, amiodarone, sotalol, erythromycin, tricyclic antidepressants) increase risk of life-threatening arrhythmia

Documented hypersensitivity; known QT prolongation; concurrent administration of drugs that cause QT prolongation

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in CNS disorders and have caused tendinitis or tendon rupture


Ertapenem (Invanz)

Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to PBPs. Stable against hydrolysis by various beta-lactamases, including penicillinases, cephalosporinases, and extended spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.

Adult

1 g qd for 14 d if IV and 7 d if IM; infuse over 30 min if IV
CrCl <30 mL/min/1.73 m2: 500 mg IV qd

Pediatric

<3 months: Not established
3 months to 12 years: 15 mg/kg IV q12h; not to exceed 1 g/d
>12 years: Administer as in adults

Probenecid may reduce renal clearance of ertapenem and increase half-life, but benefit is minimum and does not justify coadministration

Documented hypersensitivity to drug or amide type anesthetics

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Pseudomembranous colitis may occur; seizures and CNS adverse reactions may occur; when using with lidocaine to administer intramuscularly, avoid inadvertent injection into blood vessel; decrease dose in renal failure; serious and occasionally fatal hypersensitivity reactions may occur with beta-lactams, caution with previous hypersensitivity reactions to penicillin, cephalosporins, other beta-lactams, or other allergens; do not mix or coinfuse in same IV line as other medications; do not mix with dextrose-containing diluents

More on Sepsis, Bacterial

Overview: Sepsis, Bacterial
Differential Diagnoses & Workup: Sepsis, Bacterial
Treatment & Medication: Sepsis, Bacterial
Follow-up: Sepsis, Bacterial
References
Further Reading
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Further Reading

Additional resources on sepsis are available at Medscape's Sepsis Resource Center.

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Keywords

sepsis, bacterial sepsis, urosepsis, septic shock, bacteremia, symptomatic bacteremia, septicemia, leukocytosis, pseudosepsis, bacteruria

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Contributor Information and Disclosures

Author

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Pranatharthi Haran Chandrasekar, MD, Director of Infectious Disease Fellowship, Professor, Department of Internal Medicine, Harper Hospital, Wayne State University School of Medicine
Pranatharthi Haran Chandrasekar, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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