How Should We Treat Hospital-Acquired and Ventilator-Associated Pneumonia Caused by Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae?

Abstract

Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) due to extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) represent a growing problem. Indeed, ESBL-PE is endemic in many countries, and 5 to 25% of intensive care unit (ICU) patients are ESBL-PE carrier on ICU admission. ESBL-PE HAP/VAP is associated with a higher mortality than HAP/VAP due to susceptible Enterobacteriaceae because the resistance profile decreases the adequacy rate of empiric therapy. ESBL-PE should be considered in the empirical treatment in case of the high burden of ESBL-PE in the unit, in the case of previous ESBL-PE colonization, when the HAP/VAP occurs late, and in patients with shock. A negative active systematic surveillance culture on rectal swab reduced the risk of ESBL-PE VAP to less than 1%. Rapid diagnostic tests are now able to confirm the presence of ESBL-PE in VAP within 24 hours; new molecular methods will provide results within few hours.Adequate treatment usually required carbapenems. The alternative β-lactams such as β-lactams/β-lactamases inhibitor combinations could be proposed as a step-down therapy according to the antibiotic susceptibility result. Optimization of pharmacokinetics requires high dosage and continuous or prolonged infusions for β-lactams. When the patient is stabilized, a therapy of duration 7 to 8 days is recommended.

Antibacterial effect evaluation of moxalactam against extended-spectrum &beta;-lactamase-producing <em>Escherichia coli</em> and <em>Klebsiella pneumoniae </em>with in vitro pharmacokinetics/pharmacodynamics simulation

“… 2 Carbapenems are recognized as the first-line therapeutic agents to manage ESBL-producing Enterobacteriaceae infections. 2 , 3 However, the increased use of carbapenems may generate selection pressure for carbapenem-resistant isolates, resulting in their evolution and dissemination. Thus, the prudent use of anti-microbials in the clinic is crucial, as is finding alternatives of carbapenems to treat infections caused by ESBL-producing isolates and avoid exacerbation of the spreading of ESBLs.…”

Emerging strategies for the noninvasive diagnosis of nosocomial pneumonia

“…Invasive techniques, such as bronchoalveolar lavage (BAL) or protected specimen brush with quantitative culture, require qualified clinicians. Less invasive strategies, such as endotracheal aspirates or nasotracheal suctioning, can lead to an overidentification of bacteria [9,10]. Current guidance from the American Thoracic Society and Infectious Diseases Society of America therefore states that there is limited evidence to support invasive techniques to obtain respiratory samples in patients with HAP/VAP, instead recommending noninvasive sampling and semiquantitative cultures for most patients [6].…”

“…Interest has increased in gram-negative pathogens over recent years because they are associated with a higher mortality [6,7]. Moreover, patients treated in intensive care units (ICUs) with an MDR pathogen prevalence of >25% have an increased risk of developing MDR VAP, regardless of other risk factors [7][8][9]. For this reason, determining the frequency of MDR pathogens in ICUs is essential [3,5].…”

Update on ventilator-associated pneumonia

“…However, more recent reports 25 – 29 have identified similar rates of etiologies in patients with early- versus late-onset VAP. This may be related to the worldwide rise in MDR pathogens; it emphasizes that the local ICU ecology 30 is the most important risk factor for acquiring MDR pathogens, irrespective of the length of intubation. In early-onset pneumonia, the initial VAP severity—that is, the presence of sepsis or septic shock (odds ratio [OR] = 3.7)—and pneumonia that developed in a center with a prevalence of resistant pathogens greater than 25% were independently associated with the presence of resistant pathogens (OR = 11.3) 26 .…”

“…Concerning extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), carbapenems remain the first-line agents despite leading to the risk of emergence and spread of carbapenemase-producing Enterobacteriaceae 90 . Other options such as piperacillin/tazobactam or a high dose of third-generation cephalosporins administered by continuous infusion could be considered, especially as step-down therapy for ESBL-PE with low MICs 30 . New compounds such as ceftolozane/tazobactam and ceftazidime/avibactam have recently been released; however, against HAP/VAP, only the latter was non-inferior to meropenem in a recent randomized trial (REPROVE NCT01808092; results available on ClinicalTrials.gov, not yet published).…”