Empiric antimicrobial management of sepsis

This topic will discuss the empiric antimicrobial management of sepsis...
Abdelwahab Ward, BS Pharm, PharmD

DEFINITIONS ã…¡ Bacteremia is simply the presence of bacteria in the blood. Systemic inflammatory response syndrome (SIRS) is denoted by two or more of the following clinical symptoms, (1) Body temperature > 38°C or < 36°C, (2) heart rate > 90 beats per minute, (3) respiratory rate > 20 breaths per minute or PaCO2 (partial pressure of carbon dioxide in arterial blood) < 32 mmHg, (4) WBC count > 12,000 or < 4,000 or bands > 10%.

Sepsis may be defined as an infection with a positive systemic response (SIRS). Multiple organ dysfunction syndrome (MODS) refers to a condition in which homeostasis cannot be maintained independently in an acutely ill patient with altered organ function. Sepsis may be further categorized as severe sepsis or septic shock. Sepsis occurring in combination with MODS or hypoperfusion is termed severe sepsis. Septic shock refers to sepsis-induced hypoperfusion despite adequate fluid resuscitation.

SITE, SOURCE OF INFECTION

SITE OF INFECTION ã…¡ The most common site of sepsis is the respiratory tract, accounting for 30% to 60% of infections. The bloodstream is the second most common site of infection, followed by the genitourinary tract and then the abdomen.

SOURCE OF INFECTION ã…¡ Sepsis acquired in the ICU is more likely to have a mixed microbial etiology. Gram-positive and gram-negative bacteria are currently in competition for the role of most causative pathogen of infection; anaerobic bacteria and fungi are less commonly implicated.

  • Gram-Positive Bacteria: Gram-positive bacteria have emerged as the pathogen most commonly associated with sepsis. Gram-positive bacteria now account for nearly 50% of all sepsis cases. Among these, Staphylococcus species (namely Staphylococcus aureus) are seen most often, with 14% of cultures isolating methicillin-resistant S aureus (MRSA).

    Gram-Negative Bacteria: The second most common causative organism in sepsis is typically shown to be gram-negative pathogens. Pseudomonas species and Escherichia coli are the major organisms behind gram-negative–associated sepsis.

    Anaerobic Bacteria: Anaerobic bacteria have also been implicated as causative organisms in sepsis infections, but at a rate of only around 4%. The most commonly associated anaerobic bacteria are gram-negative bacilli, mainly Bacteroides fragilis.

INFECTION MANAGEMENT

RECOMMENDATIONS ã…¡ Current guidelines recommend that antimicrobial therapy be initiated within 1 hour of identification of septic shock. Antibiotics should not be delayed if cultures cannot be obtained in a timely manner. Current guidelines recommend continuation of antibiotics for 7 to 10 days; however, if the source is found to be noninfectious, antimicrobial therapy should be promptly discontinued.

  • NOTE...!
    Monotherapy versus Combination Therapy..
     The efficacy of carbapenem monotherapy has been demonstrated to be equal to the combination of a beta-lactam plus an aminoglycoside. Equal efficacy was demonstrated for extended-spectrum penicillins with or without a beta-lactamase inhibitor compared with amoxicillin-clavulanate, piperacillin-tazobactam, or clindamycin in combination with an aminoglycoside.

Empiric antimicrobial therapy. The choice of antimicrobial agent can sometimes be daunting. Consideration should be given to the origin (i.e., community- or health care–acquired), site, and source of infection. Recently used antibiotics should be avoided if possible, and local susceptibilities should be considered. Broad-spectrum antibiotics are ideal for empiric therapy, as they provide coverage of multiple organisms. Empiric coverage of MRSA is important, as higher mortality rates have been associated with inappropriate antibiotic therapy. Vancomycin is often utilized as empiric therapy for suspected MRSA infections. If not, alternative MRSA-susceptible antibiotic therapies (e.g. linezolid, tigecycline, ceftaroline, or daptomycin) should be considered.

SITES OF INFECTION ã…¡ For lung, If the site of suspected infection is the lung, the origin of the infection must be considered. If the infection is community-acquired, likely pathogens include Streptococcus pneumoniae, Haemophilus influenzae, Legionella species, and Mycoplasma pneumoniae. Respiratory fluoroquinolones as monotherapy or a macrolide antimicrobial, in addition to a beta-lactam (such as a third- or fourth-generation cephalosporin), are good empiric options for community-acquired respiratory infections. Health care–acquired or –associated infections are often caused by Pseudomonas species, MRSA, Klebsiella species, and anaerobic bacteria. It can be empirically treated with the combination of a carbapenem or piperacillin-tazobactam, in addition to levofloxacin or ciprofloxacin, plus vancomycin.

IV Catheter–Related Bloodstream Infections. Common bacteria associated with IV catheter–related infections include Staphylococcus epidermidis, S aureus, aerobic gram-negative bacilli, and Candida species. Vancomycin plus piperacillin-tazobactam is one option for empiric therapy. If Candida is suspected, antifungal therapy should be considered.

Urinary Tract. Urinary pathogens include aerobic gram-negative bacilli, such as E coli, Proteus species, Pseudomonas species, and Enterococcus species. For community-acquired urinary infections, empiric treatment with ciprofloxacin or levofloxacin is a good choice, as is treatment with amoxicillin-clavulanate. For urinary infections that are health care–acquired or –associated, empiric treatment with ciprofloxacin or levofloxacin may be considered, as might treatment with piperacillin-tazobactam or cefepime. Pathogens to empirically cover for health care–acquired or –associated infections include Pseudomonas species, MRSA, Klebsiella species, and anaerobes. If MRSA is suspected, vancomycin should be added to the empiric regimen.

Abdomen. Aerobic gram-negative bacilli, anaerobes, and Candida species are commonly associated with intra-abdominal infections. May be empirically treated with a carbapenem or piperacillin-tazobactam with or without an aminoglycoside. Antifungal therapy should be considered. For suspected B fragilis or other bacteria that may be resistant to penicillins, the use of a carbapenem, metronidazole, or a combination penicillin and beta-lactamase inhibitor should be considered.

Unclear Source. If the source of infection is unknown or difficult to determine, empiric treatment options include carbapenems plus vancomycin. These drugs cover a wide array of bacteria, including aerobic gram-negative bacilli, S aureus, and streptococci.

REFERENCES

Abdelwahab Ward, BS Pharm, PharmD