The role of the surgeon in the management of intra-abdominal infections

The use of antimicrobial agents is very high and often improper in the management of intra-abdominal infections (IAIs) in the departments of general and emergency surgery and in the Intensive Care Units. Antibiotic Resistance (AR) is a direct consequence of the excessive and irrational use of antibiotics resulting from incorrect indication, spectrum, route, dose and/or duration of antimicrobial treatment, with limited therapeutic options in clinical practice because of the lack in the development of new and effective antimicrobial agents.

The surgeon has a starring role in the fight against improper use of antibiotics and the spreading of AR with his adequate and early treatment decisions.

Actually still too many mistakes are made in clinical practice in the management of IAIs.

Short Antibiotic prophylaxis 

Prolonged peri-operative antibiotic prophylaxis is associated with an increased risk of Clostridium difficile infection and side-effects; it does not reduce the number of wound infections (1).

Early Infectious source control and empiric broad spectrum therapy 

In uncomplicated IAIs, when the focus of infection is treated effectively by surgical excision of the involved tissue, the 24 short therapy may be sufficient, sometimes unnecessary beyond prophylaxis (it’s decision of the surgeon according to intra-abdominal features). In the treatment of complicated IAI, source control surgery and antibiotic therapy are mandatory and complex.

Sepsis Source control technique

It is based on 3 principles:

1. Drainage and lavage of the infected fluid,
2. Debridment of infected/necrotic tissue
3. Definitive and temporary measures derangements  and to restore optimal function.

It can be achieve by re-laparotomy strategies with temporary abdomen closure or open abdomen (2).

Open abdomen procedure (OA)

         OA is a therapeutical option to use in the management of patients with severe sepsis, with the aim to control any persistent source of infection, preventing abdominal compartment  syndrome and defer definitive intervention and anastomosis (3).

Time

to initiation of antibiotic treatment is the single strongest predictor of outcome; inappropriate and delayed initial empiric antibiotic therapy is associated with greater morbidity and mortality. (4-5).

Empiric antimicrobial therapy

Take into account the most frequently isolated germs, the local trend of antibiotic resistance and the international evidence-based guidelines. The antimicrobial regimen depends on the source of intra-abdominal infection, the risk factors for specific microorganisms, the resistance patterns and the clinical patient’s condition (World Society Emergency Surgeons Sepsis Severity Score;WSES-SSS) (6).

Microbiological culture of peritoneal fluid and necrotic tussues 

An antimicrobial regimen is adequate when all relevant pathogens isolated in one patient were susceptible to at least one of its components (5). Diagnostic microbiology of IAIs plays a relevant role in the therapeutic strategy of every patient, in the era of the broad spread of resistant microorganisms above all in nosocomial IAIs.

The etiology of IAIs is polimicrobial

The CIAOW Study showed that the major pathogens involved in community-acquired IAIs were found to be Enterobacteriaceae (especially E.Coli, Klebsiella Pneumoniae, Enterobacter), Streptococcus species, and certain anaerobes (particularly B. fragilis). Extended spectrum beta lactamase (ESBL) producers were the most commonly identified drug-resistant microorganism involved in IAIs. ESBL-producing Enterobacteriaceae are becoming increasingly common in community-acquired infections (2). Pseudomonas aeruginosa (non-fermenting gram negative bacterium) is one of the major nosocomial pathogens worldwide, intrinsically resistant to many drugs and it is able to become resistant to virtually any antimicrobial agent. (2). Enterococci (E. faecalis and E. faecium) were the most Gram positive facultative anaerobic isolates and they were more prevalent in nosocomial infections. Enterococci infections are difficult to treat because of both intrinsic and acquired resistance to many antibiotics. Furthermore, in the last years there has been a significant increase in the incidence of invasive infections due to Candida species (2, 4-5). Biliary infections are often caused by gram negative aerobes such as E. Coli, Klebsiella pneumoniae and anaerobes as Bacteroides fragilis. (4,7-8).

Community acquired IAIs etiology: the pathogens are generally predictable (Enterobacteriaceae such as E.Coli, Klebsiella pneumonia, Enterobacter; Streptococcus species, and B. fragilis) and antimicrobial agents with narrower spectrum of activity are preferred. (7, 10-12).

Nosocomial infections etiology: they are commonly caused by larger and more resistant flora such as ESBL producers, pseudomonas aeruginosa, methicillin resistant Staphylococcus aureus (MRSA), acinetobacter baumanii, vancomicyn resistant enterococcus, klebsiella pneumoniae carbapenemases, and for these infections, complex multi-drug regimens are always recommended.(7,10-12).

Empirical antifungal therapy in nosocomial infections 

 It is recommended for candida species (7).

Determination of serum levels drugs

The dosing of antibiotics has to be adequately adjusted in order to achieve an effective drug level above the minimum inhibition concentration but avoiding toxic side effects, above all in patients with acute kidney injury and continuous renal replacement therapy (9). In any case, a sufficiently high loading dose should be included (9). Lower than standard dosages of renally excreted drugs must be administered in the presence of impaired renal function, while higher than standard dosages of renally excreted drugs may be required for optimal exposure in patients with glomerular hyperfiltration (7).

World Society of Emergency Surgery Guidelines for the management of IAIs 

Antimicrobial therapy for community acquired extra-biliary IAIs: in stable non critical patients without ESBL associated risk factors, the first line antibiotic to be used is amoxicillin/clavulanate, or ciprofloxacin associated with metronidazole in allergic to beta lactams patients; for stable patients with risk of ESBL pathogens, ertapenem or tigecycline are indicated ; for critically ill patients with no ESBL  associated risk factors, piperacillin/tazobactam is the antimicrobial agent indicated, while in critically ill patients with risk of ESBL pathogens, meropenem or imipenem +/- fluconazole are indicated.

Treatment of biliary infections: for stable patients without ESBL associated risks factors amoxicilline/clavulanate or in presence of allergic patients ciprofloxacin+metronidazole are indicated; in patients with risk of ESBL pathogens, tigecycline is indicated; for critically ill patients with biliary infections piperacillin/tazobactam is indicated in case of no risk of ESBLs, and piperacillin+tigecycline+/-fluconazole, in case of ESBL pathogens.

Antimicrobials for nosocomial IAIs: in stable patients piperacillin+tigecycline+fluconazole are indicated; critically ill patients have to be treated with the association of piperacillin+tigecycline+echinocandin or meropenem, imipenem, doripenem+teicoplanin+echinocandin. (7).

 De-escalation strategy

 It refers to the replacement of empirical broad-spectrum antimicrobial treatment with a narrower antimicrobial therapy, by either changing the pharmacological agent or discontinuing a pharmacological combination according to the patient’s microbial culture results (10).

All antibiotic treatments start with an I.V. administration followed by oral switch when appropriate and possible (normal infection signs, normal infection laboratory parameters and resumption of oral feeding) (11).

Duration of antibiotic therapy

         In stable patients a short course of antimicrobial therapy (3-5 days) after adequate source control, depending on fever and leukocytosis, may be a reasonable option. In critically ill patients with severe sepsis and septic shock, an individualized approach is always mandatory and patient’s inflammatory response should be monitored regularly by the dosage of Procalcitonin (12).

Conclusions

Proper antimicrobial stewardship in selecting an appropriate antibiotic and optimizing its dose and duration to treat IAIs may prevent the emergence of AR and decrease costs for antibiotics.

A global cooperation to limit the spreading of AR avoiding common errors of clinical practice is necessary.

Belinda De Simone

References

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