Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.

We describe the risk factors for the development, timing, and severity of doxycycline induced acute pancreatitis (DIAP) in two case reports and a review of prior published cases, to better understand DIAP. Clinicians must maintain a high level of suspicion for DIAP in patients presenting with acute pancreatitis, while on doxycycline therapy. The latency and severity of DIAP are variable, making diagnosis challenging. Treatment includes bowel rest, hydration, and discontinuation of doxycycline.

We report a case of acute pancreatitis that developed after four days of remdesivir therapy in a patient being treated for COVID-19. Despite improvement in patient's respiratory status, abdominal pain worsened and clinical signs and symptoms progressed to a diagnosis of acute pancreatitis 4 days after initiation of remdesivir therapy. Withdrawal of remdesivir paired with medical management of acute pancreatitis led to the resolution of pancreatitis within three days. To our knowledge, this is the first case report depicting remdesivir as a possible cause of acute pancreatitis.

With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has far-reaching impact well beyond. It has become increasingly recognized that drug-induced pancreatitis (DIP), despite accounting for less than 3% of all cases, represents an important and growing though often inconspicuous cause of acute pancreatitis. Nevertheless, knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents, especially for non-prescription medications. Indeed, the majority of available data is derived from case reports, case series, or case control studies. Furthermore, the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established (< 10% of cases). Several classification systems have been proposed, but no single system has been widely adopted, and periodic updates are required in light of ongoing pharmacologic expansion. Moreover, infrequently prescribed medications or those available over-the-counter (including herbal and other alternative remedies) are often overlooked as a potential culprit of acute pancreatitis. Herein, we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity. We believe this manuscript will aid in increasing both primary and secondary prevention of DIP, thus ultimately facilitating more expedient diagnosis and a decrease in DIP-related morbidity.

A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.

A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.

Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.

Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.

CRD42017060473.

To evaluate the actual incidence of both microlithiasis and acute cholecystitis during treatment with intravenous ceftriaxone in a new rabbit model.

New Zealand rabbits were treated with intravenous ceftriaxone or saline for 21 days. Ultrasound monitoring of the gallbladder was performed every seven days until the 21st day when histopathology, immunohistochemistry for proliferating cell nuclear antigen (PCNA), pro-caspase-3 and CD68, liver enzyme biochemistry, and chromatography analysis of the bile and sediments were also performed.

All animals treated with ceftriaxone developed acute cholecystitis, confirmed by histopathology (P<0.05) and biliary microlithiasis, except one that exhibited sediment precipitation. In the group treated with ceftriaxone there was an increase in pro-caspase-3, gamma-glutamyl transpeptidase concentration, PCNA expression and in the number of cells positive for anti-CD68 (P<0.05). In the ceftriaxone group, the cholesterol and lecithin concentrations increased in the bile and a high concentration of ceftriaxone was found in the microlithiasis.

Ceftriaxone administered intravenously at therapeutic doses causes a high predisposition for lithogenic bile formation and the development of acute lithiasic cholecystitis.

Drug toxicity is a well-known cause of acute pancreatitis (AP). Although many drugs have been associated with AP, the magnitude of the risk of most of them remains largely unknown.

To determine the pancreatotoxic risk of a wide range of drugs.

The hospital-based Berlin case-control surveillance study, including all 51 Berlin hospitals in a hospital network, ascertained 102 cases with idiopathic AP (IAP) and 750 controls between 2002 and 2011. Patients with IAP were thoroughly validated using anamnestic, clinical or laboratory data. Drug exposure was obtained in a face-to-face interview. Possible drug aetiology was assessed in individual patients through a standardised causality assessment applying the criteria of the World Health Organization. Drug risks were further quantified [odds ratios (OR) with 95% confidence intervals (CI)] in a case-control design with unconditional logistic regression analysis.

The pancreatotoxic risk of several drugs, including azathioprine (OR 5.1; 95% CI 1.9-13.5), fenofibrate (OR 12.2; 95% CI 2.3-69.1), mesalazine (OR 3.3; 95% CI 1.1-9.5) or angiotensin-converting enzyme inhibitors, was corroborated by case-control analysis and causality assessment. Causality assessment suggested a pancreatotoxic potential, among others, for mercaptopurine or the seldom reported leflunomide, and alluded to a novel risk for tocilizumab. Case-control analysis showed an increased risk for two phytotherapeutics: harpagophytum and valerian radix.

Our study quantified the pancreatotoxic risk of different drugs and phytotherapeutics. The findings corroborate previous results from the literature but also indicate risks for substances not previously reported, highlighting the need for further controlled studies on pancreatic toxicity.

We describe the first case of probable ceftriaxone-induced pancreatitis in a 2-year-old child. The patient was admitted to Santobono-pausilipon Children's Hospital with fever, vomiting and diarrhea and was treated with ceftriaxone 700 mg/day by intramuscular route. After the second administration of ceftriaxone, laboratory data revealed an increase in amylase. The patient's abdomen was mildly distended and diffusely painful. Drug-induced pancreatitis was considered and ceftriaxone was immediately discontinued, but after 24 hours laboratory data showed a further increase in amylase and an increase in lipase. Three days after interruption of ceftriaxone, the child's symptoms had improved. based on a) biochemical, clinical and instrumental parameters, b) criteria of drug-induced pancreas disorders and c) the Naranjo adverse drug reaction probability scale, we made a diagnosis of probable ceftriaxone-induced pancreatitis. To our knowledge, this is the first case report of probable primary ceftriaxone-induced pancreatitis in children.

Isolated reports of neonatal and infant deaths associated with ceftriaxone-calcium precipitation in the lungs and kidneys have prompted a recommendation from the US FDA in June 2007 advising that in patients of all ages, calcium-containing solutions should not be administered simultaneously or within 48 h of the last ceftriaxone dose.

To provide a comprehensive review of the literature surrounding the safety of ceftriaxone in the neonatal (< or = 28 days) and geriatric populations (> or = 65 years).

Multi-database literature search for original research articles, review articles and case reports pertaining to safety of ceftriaxone in the neonatal and geriatric populations.

Ceftriaxone should be avoided or significantly minimized in neonates (especially those treated concomitantly with intravenous calcium solutions and those with hyperbilirubinemia), and potentially restricted in the geriatric population treated concomitantly with intravenous calcium.

The diagnosis of drug-induced acute pancreatitis often is difficult to establish. Although some medications have been shown to cause acute pancreatitis with a large body of evidence, including rechallenge, some medications have been attributed as a cause of acute pancreatitis merely by a single published case report in which the investigators found no other cause. In addition, some medications reported to have caused acute pancreatitis have obvious patterns of presentation, including the time from initiation to the development of disease (latency). There also appear to be patterns in the severity of disease. After reviewing the literature, we have classified drugs that have been reported to cause acute pancreatitis based on the published weight of evidence for each agent and the pattern of clinical presentation. Based on our analysis of the level of evidence, 4 classes of drugs could be identified. Class I drugs include medications in which at least 1 case report described a recurrence of acute pancreatitis with a rechallenge with the drug. Class II drugs include drugs in which there is a consistent latency in 75% or more of the reported cases. Class III drugs include drugs that had 2 or more case reports published, but neither a rechallenge nor a consistent latency period. Class IV drugs were similar to class III drugs, but only 1 case report had been published. Our analysis allows an evidence-based approach when suspecting a drug as causing acute pancreatitis.

Ceftriaxone is a parenteral third-generation cephalosporin with a long elimination half-life which permits once-daily administration. It has good activity against Streptococcus pneumoniae, methicillin-susceptible staphylococci, Haemophilus influenzae, Moraxella catarrhalis and Neisseria spp. Although active against Enterobacteriaceae, the recent spread of derepressed mutants which hyperproduce chromosomal beta-lactamases and extended-spectrum beta-lactamases has diminished the activity of all third-generation cephalosporins against these pathogens necessitating careful attention to sensitivity studies. Extensive data from randomised clinical trials confirm the efficacy of ceftriaxone in serious and difficult-to-treat community-acquired infections including meningitis, pneumonia and nonresponsive acute otitis media. Ceftriaxone also has efficacy in other community-acquired infections including uncomplicated gonorrhoea, acute pyelonephritis and various infections in children. In the nosocomial setting, extensive data also confirm the efficacy of ceftriaxone with or without an aminoglycoside in serious Gram-negative infections, pneumonia, spontaneous bacterial peritonitis and as surgical prophylaxis. Outpatient use of ceftriaxone, either as part of a step-down regimen or parenterally, is a distinguishing feature of the data gathered on the agent over the last decade. The review focuses on new applications of the drug and its use in infections in which the causative pathogens or their resistance patterns have changed over the past decade. Ceftriaxone has a good tolerability profile, the most common events being diarrhoea, nausea, vomiting, candidiasis and rash. Ceftriaxone may cause reversible biliary pseudolithiasis, notably at higher dosages of the drug (>/=2 g/day); however, the incidence of true lithiasis is <0.1%. Injection site discomfort or phlebitis can occur after intramuscular or intravenous administration.

As a result of its strong activity against S. pneumoniae, ceftriaxone holds an important place, either alone or as part of a combination regimen, in the treatment of invasive pneumococcal infections, including those with reduced beta-lactam susceptibility. Its once-daily administration schedule allows simplification of otherwise complex regimens in a hospital setting and has also contributed to its popularity as a parenteral agent in an ambulatory setting. These properties, together with a well characterised tolerability profile, mean that ceftriaxone is likely to retain its place as an important third-generation cephalosporin in the treatment of serious community-acquired and nosocomial infections.

We report a case of acute pancreatitis complicating Salmonella enteritis. A 43-yr-old woman who was admitted to our department because of Salmonella enteritis developed clinical acute pancreatitis with laboratory and radiographic signs on the fourth hospital day. She was free from symptoms on the eighth hospital day, but her elevated serum amylase and lipase levels persisted for more than 2 m.o. In this case, clinical acute pancreatitis was a complication of bacterial enteritis caused by Salmonella enteritidis, and it was characterized by onset a few days after the onset of enteritis and by sustained elevation of serum pancreatic enzyme levels.

The authors report a case of biliary colic secondary to gallstones formed during a course of therapy with Ceftriaxone. Three weeks after cessation of therapy the gallstones dissolved.

The role of antibiotic prophylaxis in the initial management of patients with acute pancreatitis is an area of major controversy. Contrary to earlier clinical trials, recent experimental and clinical studies have accrued evidence that warrants reappraisal of current clinical practice. This article reviews these recent advances in knowledge.

All papers derived from a Medline search for the years 1990-1997 inclusive using the text words 'acute', 'pancreatitis', 'antibiotic' and 'antibiotics' were studied. Additional papers were derived from reference lists within papers identified by the Medline search. Only experimental and clinical papers relevant to the issue of prophylactic antibiotic therapy in acute pancreatitis are included in the review.

Current experimental evidence favours the use of prophylactic antibiotics in severe acute pancreatitis. The results of contemporary randomized clinical trials restricted to patients with prognostically severe acute pancreatitis have demonstrated improvement in outcome associated with antibiotic treatment.