Fixed drug eruptions - the common and novel culprits since 2000.

A fixed drug eruption (FDE) is a common cutaneous adverse drug reaction which occurs following administration of an offending drug. The aim of this review is to provide an update on the list of drugs causing FDE, with a focus on emerging drug culprits reported since the start of the century. Across published literature, triggers for FDE are widely varied. The most frequently implicated drugs include analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs] and paracetamol) and antibiotics. Co-trimoxazole is perhaps the most well described single agent. Since the start of the century there have been over 200 drugs named in case reports on FDE. Newer, novel agents of note include cyclooxygenase-2 specific inhibitors, fluconazole, and phosphodiesterase 5 inhibitors. Other implicated drugs include vaccines, such as various SARS-CoV-2 vaccines. Drugs incriminated in FDE vary based on the geographical region studied and prescribing patterns at a given time. Newer drugs continue to enter the market and are playing an increasing role in the field of FDE. Awareness of rarer culprits and emerging novel agents can help identify a trigger, allowing for prompt withdrawal of the causative agent, preventing recurrence.

Pneumocystis jirovecii Pneumonia with a Normal Early Chest Radiography and Complicated with Drug-Induced Immune Hemolytic Anemia: A Case Report.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that commonly occurs in immunocompromised patients, especially those with HIV. Early diagnosis and prompt treatment are important because PJP is a potentially life-threatening infection. However, the diagnosis of PJP in the early stage can be challenging due to various factors. Furthermore, the early presentation of PJP, which includes normal chest radiograph and examination findings along with the subacute presentation of PJP in patients with HIV, makes an early diagnosis of the disease even more challenging for doctors. CASE REPORT In this case report, we present the case of a 39-year-old man who had normal chest X-ray findings during the initial stage of his presentation. Coupled with non-disclosure of HIV status, these led to a delay in PJP diagnosis. The diagnosis of PJP with underlying HIV was later supported by the patient's clinical features, initial blood investigations, and presence of high-risk sexual activity. The diagnosis was confirmed when the PJP polymerase chain reaction test from the respiratory sample was positive. He was successfully treated with oral trimethoprim-sulfamethoxazole. However, he subsequently developed rare adverse effects of drug-induced immune hemolytic anemia, which was diagnosed based on the presence of hemolytic anemia and recent exposure to a new drug. Trimethoprim-sulfamethoxazole was promptly discontinued, which resulted in symptom improvement. CONCLUSIONS This case report aims to create awareness among primary care doctors to be vigilant of the PJP diagnosis and its nonspecific presentations as well as to the rare adverse effects of medications to treat PJP.

Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial.

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. Objective: To assess the effect of antimicrobial therapy on clinical outcomes. Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020). Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group. Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality. Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%). Conclusions and Relevance: Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease. Trial Registration: ClinicalTrials.gov Identifier: NCT02759120.

Renal Transplant Recipient with Concurrent COVID-19 and Stenotrophomonas maltophilia Pneumonia Treated with Trimethoprim/Sulfamethoxazole Leading to Acute Kidney Injury: A Therapeutic Dilemma.

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.