JOURNAL OF GYNECOLOGIC SURGERY© Mary Ann Liebert, Inc.

Antimicrobial Use in Septic Shock

NEWTON G. OSBORNE, M.D., Ph.D.

SEPTIC SHOCK is a common clinical problem that requires management in an intensive care set-ting. The presence of bacteria in the bloodstream is, by definition, bacteremia. When mi-

croorganisms invade a normally sterile host tissue or if there is an inflammatory response to theirpresence, there is infection. Infected patients who manifest abnormal alterations in two or moreof four parameters (body temperature, heart rate, respiratory rate, or white blood cell count) are,by convention, septic. If there is, in addition, organ dysfunction, organ hypoperfusion, or hy-potension, then there is severe sepsis. Septic shock is the presence of severe sepsis associated withhypotension in spite of adequate fluid resuscitation.1

Septic shock occurs in hospitalized patients in the overwhelming majority of cases. The of-fending microorganisms almost always derive from the patient’s endogenous microbial flora orare acquired during hospitalization. Although septic shock may be associated with a wide rangeof microorganisms, in female patients whose septic shock originates with pelvic infections, it ismost commonly associated with endotoxin-producing Enterobacteriaceae. The principal pathogensassociated with septic shock in women are usually part of the normal flora of the genital tract.Escherichia coli is the offending organism in more than 50% of cases of septic shock in womenthat are associated with gram-negative facultative organisms. Species of Serratia, Klebsiella, andEnterobacter are associated with another 30% of gram-negative–induced septic shock. The re-maining cases are associated with infections caused by gram-positive organisms, such as staphy-lococci and streptococci and by obligate anaerobic bacteria, such as species of Bacteroides, Pre-votella, Peptostreptococcus, and Clostridium.2–4

The management of septic shock is complicated. The high mortality rate associated with sep-tic shock reflects the inadequacy of current therapeutic approaches. The health care team needsto keep the patient adequately oxygenated, maintain an adequate circulating volume, obtain per-tinent laboratory data, maximize cardiac performance with proper inotropic and vasoactive ther-apy, administer appropriate antibiotic therapy, and, when feasible, remove the focus of infectionby surgical intervention.

One of the early effects of endotoxin is activation of the Hageman factor, which, in turn, initi-ates the clotting cascade. Activation of the coagulation cascade leads to activation of the fibri-nolytic system. Activation of the coagulation cascade and of the fibrinolytic system eventuallyleads to disseminated intravascular coagulation (DIC) if not arrested early on. There is also acti-vation of the complement system. The chemotactic effect that results from complement activationattracts leukocytes that, with the release of leukotrienes, cause vasoconstriction and increased per-meability in the postcapillary venules.

The production of inflammatory mediators that results from DIC and the onset of vasocon-striction will eventually cause inflammatory and hypoxic injury to vital organs. If the hemody-

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Department of Obstetrics and Gynecology, Howard University College of Medicine, Washington, D.C.

Infectious Diseases

namic changes precipitated by sepsis are not corrected, compromise of coronary and cerebral bloodflow will eventually result in death.

Sepsis predisposes patients to develop acute respiratory distress syndrome (ARDS). ARDS leadsto a type of hypoxemia that is very difficult to treat. A shunting of blood away from areas of lowalveolar pO2 tension causes arterial hypoxemia.5 The health care team must take appropriate stepsto regulate pulmonary blood flow to increase the probability of survival in affected patients. In-tensivists must administer oxygen, monitor arterial blood gases frequently, and use mechanicalventilation with a volume-cycled respirator early on in the management of sepsis.

The team must also restore intravascular volume by means of large-bore intravenous cathetersand establish a reliable fluid intake and output monitoring system. The hypoperfusion of vital or-gans associated with septic shock must be controlled with pharmacologic doses of glucocorticoidsand dopamine. A bladder catheter must be used along with an arterial catheter to monitor urinaryoutput, blood pressure, and arterial oxygenation.6–10

Laboratory tests must include a complete blood count (CBC) with platelets, coagulation pro-file, arterial blood gases, electrolytes, urinalysis, kidney function tests, serum lactate, and chestX-ray, as well as blood, urine, and infected-wound or soft-tissue cultures.

Although all measures for the management of septic shock are important, eradication of the in-fecting organisms is of paramount importance.11,12 Pelvic infections are usually polymicrobial.Prompt administration of effective, wide-spectrum antibiotics, and removal of the focus of infec-tion, if applicable, are essential steps to improve the probability of survival.

Fortunately, there is an extensive pharmacopeia available for effective control of the microor-ganisms associated with pelvic infections. The use of the old triple-therapy workhorse (ampicillin,clindamycin, and gentamicin) is as effective as newer regimens such as imipenem-cilastatin sodiumin combination with vancomycin, ticarcillin, and tobramycin, or ceftriaxone with metronidazole.The usual dosages are one g of ampicillin every 4 hours plus 900 mg of clindamycin and 80 mgof gentamicin every 8 hours. If aminoglycosides are used, peak and trough levels must be ob-tained, because these critically ill patients are at greater risk of nephrotoxicity or ototoxicity.

Use of an extended spectrum cephalosporin along with an aminoglycoside is an acceptable al-ternative. Because there is a vast range of effective antimicrobials available, a regimen should beselected with an understanding of the sensitivity pattern of microorganisms associated with pelvicinfections at a given institution. A regimen of 1 g of ceftriaxone and 1 g of metronidazole every12 hours would cover the vast majority of pathogens involved in septic shock resulting from pelvicinfections. If the offending pathogen or pathogens are identified, then antibiotic therapy can betailored to eliminate the specific pathogens in question effectively.

In certain instances, immunocompromised neutropenic patients, patients with staphylococcal in-fections, or patients with pseudomonas infections for example, it may be necessary to use specialantibiotic combinations. If Staphylococcus aureus is isolated from the bloodstream, nafcillin orvancomycin therapy may be necessary.13 Isolation of Pseudomonas species may require amikacin.Immunocompromised patients with septic shock who harbor Pneumocystis carinii would requiretrimethoprim-sulfamethoxazole or pentamidine. It is also important to check on microbial sensi-tivity because, especially in the case of nosocomial infections, antibiotic resistance may emergein previously sensitive organisms.14

Surgical removal of the source of infection subsequent to the initiation of antibiotic therapy maybe the most important step in the necessary sequence to stabilize these critically ill patients. Itmay be necessary to drain abdominal or pelvic abscesses, remove infected products of concep-tion in the case of septic abortion, debride devitalized and infected tissue in cases of necrotizingfasciitis, or extirpate grossly infected pelvic organs.

It is essential that physicians recognize that the management of septic shock involves muchmore than the administration of antibiotics and surgical intervention. Prevention of septic shockis the best way to eliminate the high mortality rate associated with this disease. Prompt recogni-tion of the signs and symptoms of septic shock is essential to initiate therapy early in the sequence

Journal of Gynecologic Surgery30 Osborne

of events before the establishment of irreversible shock. Early surgical intervention and properuse of vasomotor drugs and corticosteroids may enhance survival. Complete familiarity with thepathophysiology of shock is necessary to treat these patients appropriately. Appropriate oxy-genation and prompt hemodynamic stability may be life saving. It may require sophisticated tech-nologies that most generalists are not fully acquainted with, unless such technologies are used ona regular basis.

There is renewed interest in pursuing new avenues in the management of septic shock.15 A newage of treating patients afflicted with septic shock is approaching. A multidrug approach is likelyto be used to interrupt the systemic inflammatory response to infection that will involve new an-tibiotics as well as new immune and inflammatory modulating therapies. Physicians need to up-date themselves constantly with new information to provide patients with the optimal care thatseptic shock demands. It is therefore advisable to consult the hospital infectious disease team earlyon if there is even a slight suspicion of impending septic shock.

REFERENCES

1. Bone RC, Balk RA, Cerra FR, et al. ACCP/SCCM consensus conference: Definitions for sepsis and organ failureand guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644.

2. Ledger WJ, Norman M, Gee C, Lewis W. Bacteremia on an obstetric–gynecologic service. Am J Obstet Gynecol1975;121:205.

3. Blanco JD, Gibbs RS, Castaneda YS. Bacteremia in obstetrics: Clinical course. Obstet Gynecol 1981;58:621.4. Gonik B. Septic shock in obstetrics. Clin Perinatol 1986;13:741.5. Bersten A, Sibbald WJ. Acute lung injury in septic shock. Crit Care Clin 1989;5:49.6. Freid MA, Vosti KL. The importance of underlying disease in patients with gram-negative bacteremia. Arch In-

tern Med 1968;121:418.7. Motsay GJ, Dietzman RH, Ersek RA, et al. Hemodynamic alterations and results of treatment in patients with gram-

negative septic shock. Surgery 1970;67:577.8. Parker MM, Parrillo JE. Septic shock: Hemodynamics and pathogenesis. JAMA 1983;250:3324.9. Christian R, Warszawski J, Anguel N, et al. Early use of pulmonary artery catheter and outcomes in patients with

shock and acute respiratory distress syndrome: A randomized controlled trial. JAMA 2003;290:2713.10. Fowler RA, Cook DJ. The arc of the pulmonary artery catheter. JAMA 2003;290:2732.11. Rackow EC, Weil MH. Recent trends in diagnosis and management of septic shock. Curr Surg 1983;40:181.12. Monif GRG, Osborne NG. Ciprofloxacin monotherapy for acute pelvic infections: A comparison with clindamycin

plus gentamicin. Obstet Gynecol 1992;79:639.13. Osborne NG. Vancomycin-resistant enterococci: The problem and the challenge. J Gynec Surg 1995;11:121.14. Osborne NG. Vancomycin-resistant Staphylococcus aureus. It’s here! J Gynecol Surg 2003;19:57.15. Crowley SR. The pathogenesis of septic shock. Heart Lung 1996;25:124.

Address reprint requests to:Newton G. Osborne, M.D., Ph.D.

Department of Obstetrics and GynecologyHoward University College of Medicine

2041 Georgia Avenue NWWashington, DC 20060

E-mail: NewtonOsborne@aol.com

Volume 20, Number 1, 2004 Antibiotic Use in Septic Shock 31