Current Drug Safety - Current Issue

The objective of this systematic review is to evaluate the patterns of post-surgical site infections, pre-surgical antibiotics prophylaxis, and related clinical outcomes in the recently published literature.

This systematic review is registered with PROSPERO registration number CRD42023398963. Several databases and individual journal websites were used to collect data from PubMed/Medline, TRIP, SCOPUS, Elsevier, Springer, ProQuest, and EMBASE. The established criteria of inclusion were RCTs, retrospective, prospective, and cross-sectional studies with patients who had a recent surgical procedure. Excluded from the study designs were systematic reviews, prospective studies, data on pediatrics, and data on disabilities. Quality assessment analysis of the results for randomized controlled trials (RCT) used CONSORT guidelines and STROBE guidelines for cross-sectional and cohort studies.

A total of 328 articles were identified from different databases. Among them, 15 studies were included for data extraction and qualitative analysis. A total of 33,193 patients with an average rate of 11.5% (surgical site infections- SSIs) were identified in these studies during 2008-2022. The mean rate of SSIs among the total number of immunocompromised patients/procedures was 10.2%. The SSI on patients undergoing major surgical procedures with visible incisions was 26.0%. The majority of the studies reported the use of pre-surgical antibiotic prophylaxis. Cefazolin was mostly prescribed antibiotics and administered in 90% of patients. Other antibiotics included ceftriaxone (4%), cloxacillin (3%), and vancomycin (4%). The mean reported rate of SSIs with combination antibiotic prophylaxis therapy was 22.8%.

This systematic review concluded the limited reported data on surgical site infections (SSIs). The overuse of pre-surgical antibiotic prophylaxis has been reported in several studies. This study recommended developing standardized guidelines on the use of antibiotics related to surgical cases rather than co-morbidities.

The COVID-19 pandemic has called for the rapid development and use of antiviral drugs to effectively control the disease. Nirmatrelvir/Ritonavir (Paxlovid), Molnupiravir, and Remdesivir have been pivotal in therapeutic approaches, although they raise concerns regarding adverse drug reactions (ADRs).

This study aimed to thoroughly assess the ADRs associated with these drugs by utilizing the Adverse Event Reporting System (FAERS) database of the Food and Drug Administration (FDA).

ADR reports for Paxlovid, Molnupiravir, and Remdesivir throughout the period of January 2022 to May 2023 were extracted and classified according to the severity, type of reaction, and demographic variables. Reporting Odds Ratios (RORs) with 95% confidence intervals were calculated to evaluate the relationship between antiviral medications and various ADRs.

The study established notable correlations between Paxlovid and the recurrence of the disease (40.08%) and dysgeusia (16.29%). Molnupiravir was linked to gastrointestinal (16.73%) and skin reactions (9.47%), while Remdesivir had impairments in the liver (25.21%) and kidneys (13.34%). ADRs were more commonly observed in female patients treated with Paxlovid (57.95%) and Molnupiravir (49.40%), whereas Remdesivir ADRs were mostly reported in males (58.56%). Paxlovid and Remdesivir ADRs were frequently reported in adults between the ages of 18 and 64 (46.01% and 45.01%), while Molnupiravir ADRs were more common in older individuals aged 65 to 85 (40.38%).

This thorough assessment emphasizes the importance of careful surveillance and control of ADRs linked to COVID-19 antiviral therapies. It is essential to customize treatments by considering specific patient histories, particularly for pre-existing diseases.

For surgical procedures of the upper limbs, ultrasound-guided supraclavicular brachial plexus block (SCBPB) represents a safe substitute for general anesthesia. The present study evaluated the effectiveness and safety of incorporating 1µg/kg dexmedetomidine (DEX) into 20 ml bupivacaine, as opposed to using 20 ml and 30 ml bupivacaine without additives, in SCBPB.

This randomized, controlled, double-blind study included 75 patients assigned to elective upper-limb surgery under the mid-humerus level. Patients were randomized into three equal groups to receive US-guided SCBPB with 20 ml bupivacaine 0.5% + 1 μg/kg DEX in group BD, 20 ml bupivacaine 0.5% without additives in group B20, and 30 ml bupivacaine 0.5% in group B30 (control).

Compared to group B20, groups BD and B30 had significantly quicker onset times for sensory and motor blocks. Groups BD and B30 had a more significant block duration than group B20. Group BD experienced considerably lower intraoperative hemodynamics than groups B20 and B30. Groups BD and B30 had a significantly delayed time to first rescue analgesia and consumed less pethidine than group B20. Compared to group B20, the pain score was significantly reduced in groups BD and B30. Comparable levels of pain score, rescue analgesia time, total pethidine consumption, and motor and sensory block onset and duration were seen in the BD and B30 groups.

DEX with a lower volume (20 ml) of bupivacaine reaches the same result as a higher volume of bupivacaine (30 ml) in managing perioperative pain and hemodynamic stability without the risk of the high volume of bupivacaine. Further, adding DEX to small dose of bupivacaine (20 ml) is more effective than small dose of bupivacaine (20 ml) alone without additives in prolonging the duration of sensory and motor block, reducing pain intensity, and delaying the need for rescue analgesia.

Mycophenolate mofetil (MMF) is an immunosuppressant commonly used for treating autoimmune diseases.

We report a diagnostically challenging case of MMF-induced colitis in a patient after 3 years of initiation of MMF therapy. A 76-year-old Caucasian female with a history of chronic inflammatory demyelinating polyneuropathy receiving MMF presented to the hospital with a 7-weeks history of watery diarrhoea and crampy abdominal pains. Routine blood investigations, CMV-PCR, stool culture, viral PCR, Colonoscopy, and CT scan of the abdomen were broadly within normal limits. Histopathological changes were not significantly diagnostic apart from ischaemic-type changes. Finally, the reduction of the MMF dose caused the cessation of diarrhoea. Diagnosing MMF-induced colitis can be challenging, especially in patients on immunosuppressive medications. Further, long latency periods and non-specific colonoscopic and histopathologic changes add to the diagnostic dilemma.

MMF-induced diarrhoea should be part of the clinician’s differentials, and the decision to reduce the dose of MMF needs to be considered once infection and other causes have been ruled out.

Clomipramine, a Tricyclic Antidepressant (TCA), is known for its efficacy in treating Obsessive-Compulsive Disorder (OCD). However, it is associated with several side effects, including urinary retention. This case report discusses the case of a 20-year-old male with OCD who developed urinary retention following clomipramine administration.

A 20-year-old male with a one-year history of OCD with psychotic features was admitted to SIR-T Hospital, Bhavnagar, due to worsening symptoms. He was prescribed clomipramine along with other psychotropic medications. On the 16th day of hospitalization, the patient experienced acute urinary retention, necessitating catheterization. Clomipramine dosage was subsequently reduced, resulting in the resolution of urinary retention. The patient was discharged after 29 days with no further urinary complications.

The causality assessment suggested a probable link between clomipramine and urinary retention, supported by the Naranjo Scale, WHO-UMC criteria, and literature. The anticholinergic properties of clomipramine likely contributed to the condition. Despite its side effects, clomipramine remains a valuable treatment for OCD, requiring careful dose management to mitigate adverse effects.

Clinicians should be vigilant for urinary retention in patients receiving clomipramine, especially at higher doses. Regular monitoring and dose adjustments are crucial for managing this side effect without compromising the therapeutic benefits for OCD.

Tumor necrosis factor alpha (TNF-α) inhibitors, such as adalimumab, have significantly advanced the treatment of inflammatory diseases. However, these therapies are associated with various cutaneous adverse reactions.

We describe two rare instances of isolated facial hyperpigmentation induced by adalimumab. Both patients presented with asymptomatic, isolated brown macules on the cheeks following adalimumab treatment for ankylosing spondylitis. The hyperpigmentation appeared shortly after starting the medication in both cases. In one case, the hyperpigmentation persisted despite stopping the medication, while in the second case, it completely resolved within one month after discontinuation. However, in the second patient, the hyperpigmentation recurred after switching to certolizumab, another TNF-α inhibitor. No skin biopsies were performed, and both patients were otherwise healthy, with normal laboratory evaluations.

Hyperpigmentation is an uncommon adverse reaction of this class of drugs, with only a few reported cases in the literature. The recurrence of hyperpigmentation after switching to another TNF-α agent, certolizumab, further suggests that this reaction may be a class effect, adding new insights into the spectrum of cutaneous side effects associated with TNF-α inhibitors. Clinicians should consider this potential side effect in patients presenting with hyperpigmentation, and sun protection should be recommended as a preventive measure.

Although diuretic-induced Acute Pancreatitis (AP) cases are typically mild to moderate, severe and potentially fatal occurrences can arise.

We have, herein, presented a series of diuretic-induced AP cases from March 2018 to February 2024 of a 54-year-old woman treated with chlorthalidone, a 45-year-old male treated with hydrochlorothiazide, and a 48-year-old male treated with frusemide. The literature search has identified 26 cases published to date, 10 from frusemide and 16 from thiazide diuretics. The Naranjo adverse reaction probability scale has categorized all three drugs as “probable”. All cases have responded to conservative treatment and cessation of the offending drug. Various mechanisms, such as hypersensitization, ischemia, direct cytotoxic effects, hypercalcemia, and dose-dependent idiosyncrasy, have been found to lead to intrapancreatic activation of pancreatic enzymes, resulting in drug-induced AP.

Further research into the mechanisms and genetic factors contributing to diuretic-induced AP is essential for enabling early diagnosis and management of diuretic-induced AP.

The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a serious adverse reaction that occurs weeks after the onset of drug exposure. DRESS syndrome is commonly associated with antiseizure drugs, sulfa drugs, and antibiotics.

This was a case report of a 20-year-old female who suffered from DRESS due to vancomycin with symptoms similar to the Redman syndrome. The patient was a case of Infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin was intravenously administered. On the 18^th day, during the administration of vancomycin, the patient developed sudden severe flushing over the face and trunk. The offending drug was suspended and treated with antihistamines in view of Redman syndrome. Later, the patient developed uncontrolled fever, desquamating rash all over the body, severe pruritis, and eosinophilia. On applying the RegiScar score, a probable case of DRESS was diagnosed. The patient was managed symptomatically and discharged.

The clinical presentation of DRESS includes skin rash, fever, eosinophilia, and organ involvement. But, in this case, there was a varied initial presentation of DRESS with severe flushing, which mimics the Redman syndrome due to vancomycin. Difficulty in establishing organ involvement remained a challenge in diagnosing DRESS.

DRESS can have a varied clinical presentation. Careful monitoring of all vital parameters is important in preventing the misdiagnosis of DRESS syndrome.

Ciprofloxacin is a fluoroquinolone antibiotic widely used in clinical practice with a fluorine atom in its chemical structure. Like other antibiotics, it can induce several adverse effects, such as tendinopathy, musculoskeletal toxicity, peripheral neuropathy, and cardiotoxicity, thereby causing relevant and irreversible health injuries. Ciprofloxacin fluoride's adverse toxicological effect associated with a urinary fluoride concentration above the reference value has not yet been reported.

This case report aimed to provide evidence of ciprofloxacin treatment intoxication, an antibiotic containing a fluorine atom in its chemical structure, associated with a fluoride urine concentration above the reference value.

A 32-year-old man developed tendinopathy and peripheral neuropathy on the third day’s night after initiating the ciprofloxacin doses, exhibiting symptoms comparable to a low-power electrical discharge and very intense motor agitation. After following habitual laboratory exams, a urinary fluoride measurement was performed by an ion-selective electrode. The urinary fluoride concentration was above the reference values in mg/g of creatinine.

This is the first study that has described an association among ciprofloxacin-fluoride, tendinopathies, and peripheral neuropathy. The patient's symptomatology has suggested a toxic effect related to fluoride. We consider the documented finding of a fluorine atom at the ciprofloxacin structure and its toxic potential neuropathies and tendinopathies as an issue of alert.

Parsonage-Turner Syndrome is an uncommon cause of shoulder pain.

Herein, we present the case of a male in his 40s, who was presented with a 3-month history of acute onset of intense shoulder pain, which decreased rapidly leaving behind a residual upper limb weakness. The diagnosis of Parsonage-Turner Syndrome following COVID-19 vaccination was made based on electroneuromyography and magnetic resonance imaging findings. The patient responded well to analgesics and rehabilitation.

A better knowledge of this disease and early recognition are crucial to prevent unnecessary tests and interventions.

This case study presents a rare and fatal instance of Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome in a 51-year-old male patient diagnosed with Rheumatoid Arthritis (RA).

The patient was initially treated with sulfasalazine, leflunomide, and hydroxychloroquine, following which he developed a rash, fever, and loose stools. Drug allergy was suspected, and the anti-rheumatic medications were withdrawn, following which, the patient improved. A subsequent attempt was made to treat the RA with methotrexate, prednisolone, and hydroxychloroquine, following which the rash returned along with an increase in severity, including detachment of the epidermis and mucosa, and systemic involvement, both hepatic and renal. The patient ultimately succumbed to multiple organ dysfunction syndrome and neutropenic sepsis.

This case highlights the possibility of DRESS syndrome and Stevens-Johnson Syndrome (SJS)/TEN following treatment with anti-rheumatic medications. Evidence of this is rare, with the exception of sulfasalazine. This case also considers that the signs of a moderately severe adverse drug reaction could be the early warning signs of DRESS syndrome, which can be difficult to manage and may turn fatal. Additionally, this case highlights the need for maintenance of quality health records in low- and middle-income countries due to the failure to identify hydroxychloroquine as a suspected drug inducing the initial adverse reaction that resulted in it being prescribed again, leading to a fatal outcome.

Rifampicin is a first-line anti-tuberculosis drug, but it may cause severe allergic adverse reactions.

This case report describes an unusual and severe adverse reaction to rifampicin in a 53-year-old male patient with pulmonary tuberculosis. The patient developed intense systemic pain within 4 hours of rifampicin administration, affecting multiple organs and joints, without typical allergic manifestations, such as fever or rash. The pain progressively worsened over three consecutive days of treatment, reaching its peak intensity (NRS score 8/10) on the third day with pain duration extending from 3 to 8 hours. The severe pain was characterized as sharp and burning in nature, significantly impacting the patient's daily activities and mobility. A subsequent rifampicin challenge test (single dose 0.45g) confirmed the causal relationship by reproducing identical severe pain symptoms. The Naranjo adverse drug reaction probability scale yielded a score of 7, indicating a “probable” causal relationship. Notably, the patient exhibited underlying autoimmune abnormalities (positive ANA and elevated ESR), which may have contributed to the severity of the reaction through enhanced inflammatory responses and altered pain mechanisms. The symptoms completely resolved upon rifampicin discontinuation, and alternative treatment with levofloxacin proved successful with no pain recurrence during the four-month follow-up period.

This case highlights a previously unreported presentation of rifampicin hypersensitivity and emphasizes the importance of careful risk assessment in patients with autoimmune features before initiating rifampicin therapy.