Antibiotics management in severe acute pancreatitis

Fu-Zheng To ,Rong-Lin Jing

a Intensive Care Unit,Taizhou Integrated Traditional Chinese and Western Medicine Hospital,Taizhou 310075,China

b Intensive Care Unit,the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310 0 06,China

Severe acute pancreatitis (SAP) is a common and critical disease.It is life-threatening at any time if multiple organ dysfunction occurs.SAP may develop secondary infection,often iatrogenic [1].To treat infected SAP,appropriate antibiotic use and nosocomial management is critical,along with adequate drainage of the infected foci and optimizing the immune function.Not only is the use of powerful antibiotics necessary to minimize mortality,but early use is also necessary to reduce the occurrence of drug-resistant bacteria.Therefore,antibiotic management is clinically important and requires careful attention.

The main causes of SAP are biliary diseases,high triglyceride and alcohol misuse at present.Biliary and alcoholic SAP are mainly caused by bile duct obstruction which leads to poor excretion of pancreatic juice early in the course of the disease.In hyperlipidemic SAP,pancreatic injury is usually due to the disturbance of pancreatic blood supply.Although infection is absent in the aforementioned etiologies of SAP,antibiotic use may still be beneficial due to the risk of secondary infection in the disease course [2,3].Nausea and vomiting associated with SAP may cause aspiration pneumonia.Pancreatic head swelling may compress the biliary tract,which may result in secondary infections including ascending cholangitis and infected pancreatic necrosis.SAP patients also often require many invasive procedures,such as endotracheal intubation,tracheostomy,central venous catheters,arterial line monitoring,and urinary catheters.These indwelling devices may become secondarily infected.Therefore,antibiotics can be used prophylactically to prevent or delay the occurrence of infected pancreatic necrosis and secondary extra-pancreatic infections due to local lesions within the pancreas and invasive therapies [4,5].

Bacteria,especially Gram-negative bacilli,most commonly cause secondary infections in SAP [6].Second and third generation cephalosporins or extended-spectrumβ-lactamase inhibitors are commonly used prophylactically in SAP.Generally speaking,fluoroquinolones and carbapenems are not appropriate for prophylactic use because of the risk of inducing multiple drug-resistant bacteria and fungal infections.The course of treatment often depends on the predisposing factors above.And once these factors are removed,the use of prophylactic antibiotics can be stopped.

If risk factors of secondary infection persist or the cause of SAP is obstructive cholangitis,close attention is needed to monitor for the development of infection and monitor trends in the white blood cell count,C-reactive protein,procalcitonin,liver function panel (including bilirubin),and body temperature.Additionally,B-ultrasound and computed tomography should be utilized to identify the presence of any biliary obstruction or air bubbles that would indicate a bacterial infection [7].If there is inflammation that cannot be explained by pancreatitis itself,it should be considered a secondary infection.If infection is suspected,strong antibiotics should be used in a timely fashion to avoid disease progression that may quickly become more complex and critical.

The initial antibiotic selection is usually empirical in accordance with the patient’s infection site,infection severity,and immune function.Gram-negative bacilli are common pathogens for biliary tract,peripancreatic infection,urinary tract infection and hospital-acquired/ventilator-associated pneumonia.In such cases,broad-spectrum antibiotics and combination of concurrent antibiotics including fluoroquinolones or carbapenems are appropriate.For catheter-related bloodstream infection,Gram-positive bacteria are dominant,followed by Gram-negative bacilli and fungi.Therefore,vancomycin,teicoplanin,and linezolid should be empirically added when catheter-related bloodstream infection is suspected.Before antibiotic initiation,foreign bodies such as central venous catheters and urinary catheters should be removed as early as possible.Cultures should be collected to guide antibiotic therapy.Once the pathogen is identified and antibiotic sensitivities are determined,targeted antibiotics should be used.All culture samples collected should undergo bacterial Gram staining,culture and drug sensitivity (including combined drug sensitivity),metagenomic next-generation sequencing,directed polymerase chain reaction detection of drug resistance enzymes [8,9].The antibiotic regimen is tailored using culture data combined with the condition of the patient,the severity of the disease,the accessibility of drugs and drug pharmacokinetics.In cases of multiple drugresistant bacteria,pan-drug-resistant and fully drug-resistant bacteria or fungi,combinations of extremely broad-spectrum antibiotics and antifungals can be considered,such as tigecycline,eravacycline,polymyxin,ceftazidime/avibactam sodium,caspofungin.

The course of antibiotic therapy should be adjusted comprehensively according to the patient’s clinical condition and immune function,drainage of bile duct obstruction or abscess,drug resistance data,and clinical response to treatment.Procalcitonin levels are helpful in guiding drug discontinuation.Antibiotics generally can be discontinued after procalcitonin falls to 10% of the peak or to <0.25 μg/L [10].Procalcitonin levels should continue to be closely monitored -if it rebounds,antibiotics need to be resumed.

The SAP patient is in a state of high metabolism due to strong inflammatory reaction.In addition,fluid resuscitation increases the effective volume of distribution of water-soluble antibiotics,capillary leakage makes some antibiotics extravasate,and blood purification causes the loss of some water-soluble antibiotics [11].Finally,in a hypoproteinemic state,antibiotics with a high affinity for protein are more quickly metabolized.Because of these factors,the dose or frequency of antibiotics should be increased appropriately.However,antibiotics metabolized by the kidneys or liver easily accumulate in patients with hepatorenal insufficiency,which necessitates decreasing the dose or frequency.Different antibiotics have different tissue distribution characteristics and metabolic pathways in different SAP patients,which determines that the pathophysiological and biochemical characteristics of SAP patients should be taken into consideration to make the strategy of application of antibiotics.The goal is to choose antibiotics that achieve higher concentrations in the target infection site and closely monitor the concentration of antibiotics in the blood to achieve a better clinical effect [12].

In summary,patients with SAP are often in critical condition and require early diagnosis and treatment.It is necessary to use appropriate preventive antibiotics because SAP is prone to secondary infection and infections due to invasive procedures.General principles of SAP management include identifying the source of infection,addressing risk factors including biliary duct obstructions or abscesses,removing unnecessary catheters,and restoring the normal immune function of the patients.For prevention,common antibiotics should be chosen.For suspected infections,empiric broad-spectrum antibiotics should be narrowed as quickly as possible after identifying the microorganisms and their drug resistance mechanisms.The antibiotic regimen should be tailored according to the disease characteristics of patients and the pharmacokinetics and pharmacodynamics of the antibiotics.Inflammation biomarkers and imaging findings can be used to evaluate the therapeutic effect and to determine the course of antibiotics.

Acknowledgments

None.

CRediTauthorshipcontributionstatement

Fu-ZhengTao: Data curation,Investigation,Writing -original draft.Rong-LinJiang: Conceptualization,Supervision,Writing -review &editing.

Funding

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Ethicalapproval

Not needed.

Competinginterest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.