How to cite this article: Khilnani GC, Tiwari P, Mittal S. Author Response: Unanswered Questions and Contradictory Statements in the Antibiotics Prescription Guidelines. Indian J Crit Care Med 2024;28(7):717-718.

Background: Colistin is an effective therapy against multidrug-resistant gram-negative bacteria. However, nephrotoxicity is a major issue with its use. Objective: We aimed to evaluate the incidence and the potential risk factors of nephrotoxicity in colistin-treated patients. Methods: A retrospective cohort study was conducted. All adult patients aged 18 years and older who received colistin for ≥72 h were included in the study, while end-stage kidney disease patients requiring dialysis or had renal transplants were excluded. The incidence and severity of acute kidney injury (AKI) were assessed based on the Kidney Disease Improving Global Outcomes (KDIGO). Result: Out of 128 patients who received colistin, 51.56% of them have experienced AKI. The incidence was increased among oldest patients (above 80) and those who did not receive the appropriate dose (p-value = 0.0003). In addition, the median time until the AKI occurred was 10 days after receiving the colistin treatment. Rates of AKI in patients with previous AKI (71.7%) were three times higher than patients who did not previously experience AKI (HR = 2.97, 95% CI [1.8-4.8]). Conclusions: Nephrotoxicity is a significant issue among patients who receive colistin in the hospital, especially among older patients and those who did not receive the appropriate dose. As a result, healthcare providers should play a major role in colistin dosing, especially among the older adult population.

To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework.
A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS.
Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians.
Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction.
In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to.
This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post-operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%-53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end-stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug-resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri-operative antibiotic prophylaxis to minimize post-operative SSIs.

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of diarrhea in the pre- and post-transplant period. Diarrhea in an organ transplant recipient may result in significant morbidity including dehydration, increased toxicity of medications, and rejection. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common. Further, noninfectious causes including medication toxicity, inflammatory bowel disease, post-transplant lymphoproliferative disease, and malignancy can also result in diarrhea in the transplant population. Management of diarrhea in this population is directed at the cause of the diarrhea, instituting therapy where appropriate and maintaining proper hydration. Identification of the cause to the diarrhea needs to be timely and focused.

For effective antibacterial therapy, physicians require qualitative test results using susceptibility breakpoints provided by clinical microbiology laboratories. This article summarizes the key components used to establish the Clinical Laboratory Standards Institute (CLSI) breakpoints for tedizolid. First, in vitro studies using recent surveillance and clinical trial isolates ascertained minimal inhibitory concentration (MIC) distributions against pertinent organisms, including staphylococci, streptococci, and enterococci. Studies in animal models of infection determined rates of antibacterial efficacy and survival following administration of tedizolid phosphate at doses equivalent to those in humans. Pharmacokinetic and pharmacodynamic analyses examined the relationship between plasma concentrations and MICs against the target organism. Finally, clinical trials assessed clinical and microbiologic outcomes by MIC. All these data were evaluated and combined to obtain the ratified CLSI susceptibility criteria for tedizolid of ≤0.5μg/mL for Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Enterococcus faecalis and ≤0.25μg/mL for Streptococcus anginosus group.

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.