Complicated Intra-Abdominal Infections: The Old Antimicrobials and the New Players

Abstract

Complicated intra-abdominal infections (cIAIs) are an important cause of morbidity and mortality worldwide. They are diagnosed when the initial abdominal organ infection has spread into the peritoneal space. Successful treatment relies on adequate source control and appropriate empiric antimicrobial therapy. Inappropriate antimicrobial therapy may result in poor patient outcomes and increases in healthcare costs. Current guidelines recommend several single and combination antimicrobial regimens; however, empiric antimicrobial treatment has been complicated by the increasing rates of resistant organisms, especially the extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Additionally, the overuse of carbapenems to combat these resistant pathogens has contributed to the rise of carbapenemase-producing microorganisms, especially Klebsiella pneumoniae. This increasing resistance has prompted the development of novel antimicrobials like ceftazidime-avibactam and ceftolozane-tazobactam, whose activity extends to ESBL-producing microorganisms. Furthermore, the optimal duration of antimicrobial therapy is still unknown, and further research is necessary to find a definitive answer. This review will focus on antimicrobial therapies recommended by the current guidelines, the individual properties of these agents, appropriate duration of therapy, recent clinical trials, and place in therapy of the antimicrobial agents recently approved for the treatment of cIAIs.

Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection

“…However, simulations from a translational PK/PD model (24) suggest that higher concentrations of REL may be needed for efficacy against highly resistant strains of P. aeruginosa, which are identified at low frequency in surveillance studies of clinical isolates (25). Therefore, we evaluated the safety and efficacy of two REL dose levels, 125 mg and 250 mg, each given q6h with 500 mg IMI, for the treatment of complicated intra-abdominal infections (cIAI), an important area for new antimicrobial development because of their high prevalence, high morbidity and mortality, and the serious risk of clinical failure due to MDR Gram-negative bacilli (26,27).…”

Intra-abdominal infections: the role of different classifications on the selection of the best antibiotic treatment.

“…18,56,59 The misuse of antibiotics is a leading worldwide issue with an extensive economic influence on rising healthcare costs, due to the selection of MDR bacteria, culminating in extended hospital stay and a greater mortality, improving its use would probably lead to lower costs and better outcomes. 4,5,10,12,30,52…”

Intra-abdominal infections: the role of different classifications on the selection of the best antibiotic treatment.

“…cIAI, complicated intra-abdominal infection) Intra-abdominal infections (IAIs) include a large diversity of pathological conditions involving inflammatory processes and lesions of all the intra-abdominal organs in response to microorganisms, which may spread into the peritoneal space. [1][2][3][4][5] They include inflammation of single organs (such as cholecystitis, appendicitis, diverticulitis, cholangitis, pancreatitis, salpingitis, etc. ), peritonitis (classified as primary, secondary or tertiary) and intra-abdominal abscesses (classified by their location and anatomic configuration).…”

“…An optimal classification designed for clinicians' guidance in treatment should include: the origin of the source of infection, the anatomical extension, the supposed pathogens involved and risk factors for major resistance patterns, and the clinical condition of the patient. 3,5,10 Uncomplicated versus complicated intra-abdominal infections…”

“…13,18,20,28,30 IAI can be managed with single or combined antibiotic regimens, determined by the spectrum demands of antibiotic scope. 4,5,10,31 Ampicillin/sulbactam, cefoxitin, ertapenem, meropenem, moxifloxacin, ticarcillin/clavulanic acid and tigecycline are examples of antibiotic therapy licensed to be used as single agents. 10,14,31 2,6,14,32 Anticipating the microorganisms and promising resistance patterns of a particular infection initiates by determining the place of acquisition of the infection 4,13 (community-acquired, healthcareassociated or hospital-acquired).…”