Successful Treatment of UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Viremia in a Renal Transplant Recipient With Letermovir and Adjunct Hyperimmune Cytomegalovirus Immunoglobulin: A Case Report.

Letermovir is an antiviral agent indicated for primary prophylaxis of cytomegalovirus (CMV) infection and disease in adult allogeneic hematopoietic stem cell transplant recipients. In this case, UL97 mutation that conferred resistance to ganciclovir was seen in a patient 8 months after renal transplant. We report the off-label use of letermovir with adjunct hyperimmune CMV immunoglobulin in the successful treatment of CMV disease. This report is the first to use this combination for treatment of CMV infection with a high viral load. It contributes to the limited available literature supporting the use of letermovir in the treatment of resistant CMV, where current therapeutic options can be suboptimal due to adverse effects and the risk of cross-resistance.

Controversies in Treating Asymptomatic Bacteriuria and Urinary Tract Infection: A Case Based Review of Antibiotic Use in Renal Transplant Patients and its Impact on the Development of Resistance.

There is excessive use of both broad spectrum and niched antibiotics for urinary tract infections (UTIs) in hospital and ambulatory setting in spite of clear guidelines on appropriate use. Majority of antibiotics prescribed in United States for UTIs are for nonspecific indications such as positive urine cultures in the absence of symptoms, etc. For these conditions especially asymptomatic bacteriuria, a large proportion of the antibiotics prescribed are unlikely to provide clinical benefit to patients. Asymptomatic bacteriuria (ASB) is a common finding in healthy women and persons with underlying urological abnormalities. Guidelines from Infectious Diseases Society of America (IDSA) clearly define the use of antibiotics in ASB only in pregnant patients and in individuals prior to undergoing invasive urological procedures. IDSA updated the guidelines in 2019 on the use of antibiotics for UTI in special groups such as patients with neutropenia, solid organ transplants, and non-urologic surgery. Considering the implications of antibiotic resistance in the setting of indiscriminate use, there is definitely a need to improve their use in asymptomatic bacteriuria as well as in UTIs. In this review, we follow case-based approach to identify the barriers to appropriate antibiotic prescribing practices in renal transplant recipients.

Antibiotics: From the Beginning to the Future: Part 2.

We read, write, and discuss the option of adding new agents to the armamentarium of antibiotic therapy very frequently. However, the past and present has taught us that resistance is likely to develop to any and all kinds of antibiotics. Here we start with an overview of potential future antibiotics from novel sources and targets that may circumvent most known resistance mechanisms. The other future options for antibiotic discovery include antibiotic hybridization, harvesting, and modifying natural antimicrobial peptides from eukaryote and prokaryote organisms. Non bacteriostatic and bactericidal agents that have the potential of becoming therapeutic agents include bacterial attachment inhibitors, bacteriophages, and live microbial vectors. In this review, we have incorporated all the possible avenues that might be useful in the future. However, none is more important than relearning the judicious use of antibiotics based on microbiology, pharmacology, and genetics.

Antibiotics: From the Beginning to the Future: Part 1.

The first written record of intervention against what later came to be known as an infectious disease was in the early seventeenth century by a Buddhist nun. She dried 3 to 4 wk old scabs from patients with mild smallpox and asked well people to inhale the powder. More than a century later in 1796, Edward Jenner described vaccination against smallpox by using cowpox that later was found to be caused by cowpox virus which is non-pathogenic for humans. Another century later in 1890, Robert Koch published the Koch's Postulates allowing the study of pathogenic bacteria and subsequently the study of agents to fight them. The first chemical cure for disease was reported by Paul Erhlich in 1909 in the form of an arsenic compound to treat syphilis. One hundred and ten years since then a lot has happened in the area of preventing and treating infectious diseases with significant contribution to increase in human lifespan. This is the only area of medicine in which treatment (antimicrobial agent) is used to eradicate a replicating biological agent inside the human host. The potential of this second biological agent to mutate under the selection pressure of antibiotics making them resistant was recognized in the 1940s. But the indiscriminate use of antibiotics for over 70 y has led to the present crisis of resistance in major pathogens with increased morbidity and mortality. In this review, we have incorporated all the possible avenues that might be useful in the future. However, none is more important than relearning the judicious use of antibiotics based on microbiology, pharmacology, and genetics.