Antimicrobial therapy sepsis

Harbarth S, Garbino J, Pugin J, et al. Inappropriate initial antimicrobial therapy and its effects on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 2003 115 529-535. 

The CSFs should not be used routinely for treatment of febrile neutropenia in conjunction with antimicrobial therapy.5 However, the use of CSFs in certain high-risk patients with hypotension, documented fungal infection, pneumonia, or sepsis is reasonable. A recent meta-analysis demonstrated that hospitalization and neutrophil recovery are shortened and that infection-related mortality is marginally improved.14 As with prophylactic use of these agents, cost considerations limit their use to high-risk patients. 

The average duration of antimicrobial therapy in the normal host with sepsis is 10 to 14 days. 

Children are also susceptible to opportunistic infection, notably Y. enterocolitica sepsis (142). In 10 children receiving intravenous deferoxamine (25 mg/kg) there were unexpected infections in four three had episodes of fever and S. aureus in blood cultures, and one had Y. enterocolitica sepsis (128). Because of the possibility of septicemic dissemination secondary to digestive Y. enterocolitica infection, the occurrence of febrile diarrhea in a child with thalassemia is a reason for immediate withdrawal of deferoxamine and the administration of antimicrobial therapy (co-trimoxazole) (142). 

Leukocytosis is a normal host defense to infection and is an important adjunct to antimicrobial therapy. Unfortunately, bacterial infection is a common complication of neutropenia from cancer chemotherapy. These patients are incapable of increasing their WBCs in response to infection. In fact, susceptibility to infection in these patients is highly dependent on their WBC status. Patients with neutrophil counts of less than 500 cells/mm are at high risk for the development of bacterial or fungal infections. The absence of leukocytosis also occurs in the elderly and in severe cases of sepsis. ... 

In a study evaluating 904 patients with microbiologically confirmed severe sepsis or septic shock, appropriate initial antimicrobial therapy was an important determinant of survival. The 28-day mortality was 24% in patients who received appropriate initial antimicrobial treatment versus 39% in those who received inappropriate initial treatment. 

The average duration of antimicrobial therapy in the normal host with sepsis is 10 to 14 days. " However, the duration may vary depending on the site of the infection, as well as the overall response to therapy. After the patient is stable hemodynamically, has been afebrile for 48 to 72 hours, has a normalizing white blood cell (WBC) count, and is able to take oral medications, then a step-down from parenteral to oral antibiotics can be considered for the remaining duration of therapy. Treatment may continue considerably longer if the infection is persistent. In a neutropenic patient, therapy usually is continued until the patient is no longer neutropenic and has been afebrile for at least 72 hours. 

D) Empiric antimicrobial therapy of abdominal sepsis should always include a third-generation cephalosporin... 

Raymond et al. reported on a rotation study in a surgical intensive care unit with a different twist.Patients were stratified as either having sepsis/peritonitis or pneumonia, and empiric therapy was cycled every 3 months by syndrome. Fourteen hundred fifty-six admissions and 540 infections were treated over a 2-year period. With similar severity of illness during the before and after periods (mean APACHE II = 19), the authors demonstrated a reduction of length of stay from a mean of 62 days to 39 days, a reduction of vancomycin-resistant enterococcal and methicillin-resistant staphylococcal infection from 14 per 100 admissions to 8 per 100 admissions and death due to any cause dropped from 25 in the before period to 18 in the rotation period. Antimicrobial susceptibility and several other key parameters needed to evaluate the effectiveness of this program were not reported. 

Antimicrobial combination therapy is used frequently to treat serious infections. Combination therapy may be used prior to knowing the pathogen or antibiotic susceptibility for the treatment of infections in neutropenic patients and in patients with enterococcal endocarditis or bacteremia, sepsis, or pneumonia caused by P. aeruginosa. In these cases, it is important to know whether the combination will have beneficial (or detrimental) effects on the overall antibacterial activity of the regimen. For example, the combination may result in activity that is... 

---