Current Guidelines for the Treatment of Severe Pneumonia and Sepsis

Abstract

Infections in intensive care unit (ICU) patients like severe pneumonia, e.g. nosocomial (NP) and community-acquired pneumonia (CAP), or septicemia must be treated promptly and effectively because of the ensuing high mortality. Treatment is thus empirical and starts before the results of microbiological cultures are known. The risk factors affecting mortality include severity of illness, virulence of etiologic pathogens and the use of inappropriate antibiotic therapy. Several studies have shown that modifying initially inadequate therapy, according to microbiological results, does not result in a better outcome. Due to this, antibiotic treatment requires agents which have an appropriate spectrum covering the likely pathogens causing these infections. In critically ill patients, the need for empirical first-line treatment covering a broad spectrum of Gram-negative and Gram-positive bacteria, as recommended in international guidelines (e.g. those of the American Thoracic Society or the Infectious Diseases Society of America), is justified in the presence of resistant organisms commonly documented in these patients. To choose an appropriate, initial antibiotic regimen, local and national resistance data have to be considered. With respect to new German resistance trends in Gram-negative and Gram-positive bacteria, the Paul Ehrlich Society of Chemotherapy has recently published guidelines for the treatment of infections in hospitalized patients. Especially in ICU patients with severe pneumonia (NP or CAP) or septicemia and risk factors like underlying diseases, antibiotic pretreatment or mechanical ventilation, agents with an appropriate spectrum encompassing Pseudomonas aeruginosa as well as other Gram-negative bacteria like Escherichia coli, Klebsiella spp., Enterobacter spp. and Gram-positive bacteria (e.g. Staphylococcus aureus, pneumococci and streptococci) are recommended as treatment of choice. Combination therapy with an anti-pseudomonal β-lactam and a fluoroquinolone or an aminoglycoside are recommended for these patients to provide the necessary spectrum of activity and to prevent the emergence of resistant organisms. On the other hand, clinical trials and meta-analyses have shown the efficacy, tolerability and cost-effectiveness of monotherapy regimens even in critically ill and immunocompromised patients. Conclusion: Appropriate β-lactam antibiotics recommended in international and German guidelines for the treatment of severe CAP, NP and septicemia, either as monotherapy or as combination therapy, are the 4th generation cephalosporin cefepime, the carbapenems imipenem and meropenem, and the acylamino-β-lactamase inhibitor combination piperacillin-tazobactam.

A Beneficial Interaction between Imipenem and Piperacillin Possibly through Their Renal Excretory Process

“…The combination therapy of an appropriate b-lactam antibiotic and an aminoglycoside or a fluoroquinolone is generally recommended for sepsis. 1) On the other hand, a recent review has suggested that the combination therapy of an aminoglycoside and a b-lactam antibiotic is discouraged for sepsis and, in fact, increases the risk of nephrotoxicity.…”

In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains isolated from the lower respiratory tract of Intensive Care Unit patients with nosocomial pneumonia and receiving antipseudomonal therapy

“…One of its preferential niches is the respiratory tract of Intensive Care Unit (ICU) patients with severe co-morbidities and receiving antibiotic treatment(s), resulting in so-called hospital-acquired pneumonia (HAP), especially in patients with impaired host defences [2][3][4][5]. The need for early appropriate antibiotic treatment in these patients [6] is substantiated by the observation of a direct correlation between increase in mortality rates and the delay with which such treatment is initiated [7][8][9]. Pseudomonas aeruginosa has a remarkable ability to develop resistance to most antimicrobial agents through multiple mechanisms.…”

In Vivo Pharmacodynamic Activity of Tomopenem (formerly CS-023) against Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus in a Murine Thigh Infection Model

“…Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) are well known as difficult-to-treat pathogens in nosocomial infections (5,9,19). Carbapenems are often used for empirical treatments, including those for P. aeruginosa infections.…”