Use Of Linezolid Research Articles

Comparison of incidence of hyponatremia between linezolid and vancomycin in neonates and infants

A previous study reported that the incidence of hyponatremia after linezolid (LZD) use was higher than that with vancomycin (VCM) use in adults. However, hyponatremia due to LZD in neonates and infants was not investigated. This study aimed to compare the incidence of hyponatremia between LZD and VCM use in neonates and infants.The retrospective study was conducted at the Aichi Medical University Hospital. All patients who were cared for in NICU or GCU and received ≥3 days of LZD or VCM were included in this study. Hyponatremia was defined as serum sodium level ≤134 mEq/L and ≥5 % decrease from baseline after administration of LZD or VCM.A total of 76 patients (LZD, N = 36; VCM, N = 37) were included. There was no significant difference in the incidence of hyponatremia between the two groups (19.4 % vs 16.2 %, p = 0.72). The proportion of patients with a minimum value of serum sodium ≤134 mEq/L during treatment was 47.3 % in the LZD group and 35.1 % in the VCM group (p = 0.29), and the decrease in serum sodium level from baseline to the minimum value was 80.5 % and 78.4 %, respectively (p = 0.85).In conclusion, there was no significant difference in the incidence of hyponatremia between the LZD and VCM groups. Therefore, it is not necessary to avoid LZD use in neonates and infants because of the risk of hyponatremia.

New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?

Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens.

Risk factors and outcome associated with the acquisition of MDR linezolid-resistant Enterococcus faecium: a report from tertiary care centre.

The aim of the study was to determine the resistance profile of linezolid-resistant Enterococcus faecium (LREfm) and to investigate risk factors and outcomes associated with LREfm infections. A prospective case-control study was undertaken (2019 to 2022) and included 202 patients with LREfm infections (cases) and 200 controls with LSEfm infections. Clinical data was prospectively collected and analysed for risk factors and outcomes. Antimicrobial susceptibility was performed, and resistance profile was studied using WHOnet. Risk factors associated with LREfm infection were site of infection UTI (OR 5.87, 95% CI 2.59-13.29, p ≤ 0.001), prior use of carbapenem (OR 2.85 95% CI 1.62-5.02, p ≤ 0.001) and linezolid (OR 10.13, 95% CI 4.13-24.82, p ≤ 0.001), use of central line (OR 5.54, 95% CI 2.35-13.09, p ≤ 0.001), urinary catheter (OR 0.29, 95% CI 0.12-0.70, p ≤ 0.001) and ventilation (OR 14.87, 95% CI 7.86-28.11, p ≤ 0.007). The hospital stay 8-14 days (< 0.001) prior to infection and the mortality rate (p = 0.003) were also significantly high among patients with LREfm infections. Linezolid and vancomycin resistance coexisted; further, MDR, XDR and PDR phenotypes were significantly higher among LREfm. This study provided insight into epidemiology of MDR LREfm in a setting where linezolid use is high. The main drivers of infections with LREfm are multiple, including use of carbapenems and linezolid. Invasive procedures and increased hospital stay facilitate spread through breach in infection control practises. As therapeutic options are limited, ongoing surveillance of LREfm and VRE is critical to guide appropriate use of linezolid and infection control policies.

Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database.

Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the "primary suspected" drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.

Optic Neuropathy Secondary to Linezolid for Multidrug-resistant Mycobacterial Tuberculosis

Abstract&#x0D; Introduction : Toxic optic neuropathy is well known side effect of medications, including linezolid in patients with MDR-TB. We present 2 cases of patients with linezolid associated ON.&#x0D; Case Illustration : A 28 year pld man (case 1) and a 50 year old woman complained bilateral progressive visual loss after long term use of linezolid (both 8 months). On initial visit, case 1 presented with 0.1 visual acuity and case 2 presented with counting finger visual acuity. Both have hyperemic optic disc. OCT showed optic disc edema. Both patients showed generalized visual field defect on the Humphrey test. We immediately stopped the linezolid treatment.&#x0D; Discussion : The exact mechanism of linezolid induced ON is still unclear. It may be caused by impaired mitochondrial function for adenosine triphosphate (ATP) synthesis within retinal nerve fiber layer. Duration of linezolid therapy affects the prognosis for linezolid ON.&#x0D; Conclusion : Both Ophthalmologist and Physicians must be aware that visual function monitoring and early recognition of toxicity linezolid. Immediate cessation of linezolid has favorable visual recovery

Exploring the Synergy between Nano-Formulated Linezolid and Polymyxin B as a Gram-Negative Effective Antibiotic Delivery System Based on Mesoporous Silica Nanoparticles.

Antimicrobial resistance is a current silent pandemic that needs new types of antimicrobial agents different from the classic antibiotics that are known to lose efficiency over time. Encapsulation of antibiotics inside nano-delivery systems could be a promising, effective strategy that is able to delay the capability of pathogens to develop resistance mechanisms against antimicrobials. These systems can be adapted to deliver already discovered antibiotics to specific infection sites in a more successful way. Herein, mesoporous silica nanomaterials are used for an efficient delivery of a linezolid gram-positive antibiotic that acts synergistically with gram-negative antimicrobial polymyxin B. For this purpose, linezolid is encapsulated in the pores of the mesoporous silica, whose outer surface is coated with a polymyxin B membrane disruptor. The nanomaterial showed a good controlled-release performance in the presence of lipopolysaccharide, found in bacteria cell membranes, and the complete bacteria E. coli DH5α. The performed studies demonstrate that when the novel formulation is near bacteria, polymyxin B interacts with the cell membrane, thereby promoting its permeation. After this step, linezolid can easily penetrate the bacteria and act with efficacy to kill the microorganism. The nano-delivery system presents a highly increased antimicrobial efficacy against gram-negative bacteria, where the use of free linezolid is not effective, with a fractional inhibitory concentration index of 0.0063 for E. coli. Moreover, enhanced toxicity against gram-positive bacteria was confirmed thanks to the combination of both antibiotics in the same nanoparticles. Although this new nanomaterial should be further studied to reach clinical practice, the obtained results pave the way to the development of new nanoformulations which could help in the fight against bacterial infections.

Current Review of the Use of Linezolid in the Treatment of Multidrug-Resistant Tuberculosis: Effectiveness and Management of Side Effects

Current Review of the Use of Linezolid in the Treatment of Multidrug-Resistant Tuberculosis: Effectiveness and Management of Side Effects

The effectiveness of chemotherapy regimens with the inclusion of linezolid in children and teenagers with tuberculosis

Purpose. To evaluate the effectiveness of anti-tuberculosis chemotherapy regimens with the inclusion of linezolid in children and teenagers.Materials and methods. The results of treatment of 55 children and adolescents with tuberculosis when using linezolid in anti-tuberculosis therapy regimens were analyzed. Bacterial excretion was detected in 12.7% of patients at the start of therapy. All children and teenagers included in the study received at least 85% of the daily doses of anti-tuberculosis drugs.Results. All children and teenagers included in the study showed positive clinical and radiological dynamics at different periods of chemotherapy. Cessation of bacterial excretion was registered in all bacterial isolators by the end of the first month of treatment. The frequency of adverse reactions associated with the use of linezolid was 5.4%; all of them were reversible.

Evaluation of Rational Use of Linezolid in Hospitalized Patient in Shahid Chamran Hospital in Isfahan City during the Second Six Months of the 2021

Introduction: The rational use of drugs is one of the main elements of achieving the best pharmacotherapy method for patients. Linezolid is used for infections caused by gram-positive bacteria, including vancomycin-resistant staphylococci and vancomycin-resistant enterococci, but the inappropriate use of this drug has led to the emergence of linezolid-resistant strains. The purpose of this study was to investigate the manner of Linezolid prescription in Shahid Chamran Hospital of Isfahan City in 2021.&#x0D; Methods: This cross sectional study was conducted during a period of 6 months (From September 1, 2021 to February 31, 2022) on 102 patients admitted to Shahid Chamran Hospital in Isfahan City. Patient information such as demographic information, indication and dosages of drugs, the basis of drug prescription, side effects and drug interactions, etc. were extracted from the medical records of patients and hospital systems and recorded in designed forms. After matching the information with the relevant guidelines, statistical analysis was performed using SPSS-16 software.&#x0D; Results: Out of the 102 patients, who received linezolid, 75.1% were men and the rest were women. 99% of the cases were prescribed experimentally and 1% was based on culture. In 40.2% of the patients, drugs were prescribed irrationally in terms of prescription indications. In 84.3% of the cases, a change in treatment regimen was observed after receiving the culture results.&#x0D; Conclusion: A large percentage of cases of linezolid drug prescription was not done correctly. Furthermore, it has not been attention to the side effects caused by the drug, especially thrombocytopenia.

Shorter TB treatment regimens should be safer as well.

Most ongoing and planned TB therapeutic trials are focused on shortening the duration of treatment while giving less consideration to other aspects of TB care that are important to people with TB. Here we argue that other variables besides duration of TB treatment should also be considered when developing new TB treatment regimens, including drug toxicity, time spent in monitoring and overall quality of life while on therapy. We examine the specific use of linezolid in treatment-shortening trials for drug-susceptible TB and propose additional endpoints that should be prioritised in TB treatment studies.

Prolonged use of linezolid in bone and joint infections: a retrospective analysis of adverse effects.

Antibiotic treatment for bone and joint infections generally lasts for 6 weeks or longer. Linezolid may be a good option for treating bone and joint infections, but there is an increased risk of potential serious adverse drug events (ADEs) when used for more than 28 days. The aim of this study was to obtain detailed information on the type and time to occurrence of the patient-reported ADEs, the dynamics of haematopoiesis over time, and the reasons for early discontinuation of linezolid when used for an intended maximum duration of 12 weeks. This single-centre retrospective study was conducted at the Sint Maartenskliniek in The Netherlands. Patients were included if they were planned to use linezolid for more than 28 days. The main reason for discontinuation of linezolid, the ADE according to the Naranjo score, and the time to occurrence of ADEs were analysed. Among 78 patients, drug toxicity led to early discontinuation of linezolid in 11 (14%) patients before and nine (12%) after 28 days of therapy. The median treatment duration was 42 days. Gastrointestinal intolerance (42%) and malaise (32%) were the most common ADEs. In 75% of the cases the ADE occurred within 28 days of therapy. Sixty-seven patients were able to continue linezolid beyond 28 days, 87% of whom completed therapy as scheduled. Severe cytopenia, according to the Common Terminology Criteria for Adverse events (CTCA), was observed in four patients and was reversible after discontinuation of linezolid. One patient suffered optic neuropathy related to linezolid use. Linezolid could be considered an alternative option to the current standard of IV glycopeptides for the treatment of bone and joint infection for up to 12 weeks. If patients pass the first 28 days of therapy, the likelihood of successful completion of therapy is high with a low risk of serious ADEs.

Linezolid-Induced Pancreatitis Associated with Lactic Acidosis and Relative Hypoglycemia: A Rare Case Report.

Linezolid is known to cause side effects, including nausea, diarrhea, and headaches of short duration. As extended use of linezolid is becoming more common, additional rare side effects should be considered. A 68-year-old man hospitalized for osteomyelitis developed severe abdominal pain and altered mental status following five weeks of linezolid therapy. Laboratory studies showed very high lipase levels, lactic acidosis not responding to resuscitation, and relative hypoglycemia. All common causes of pancreatitis were ruled out, and a trial of linezolid withdrawal was done resulting in drastic improvement in the patient's clinical status. For patients on extended course of linezolid who develop abdominal pain, drug-induced pancreatitis should be considered as a side effect, and a trial of withdrawal of linezolid should be undertaken. Linezolid can be associated with a rare but serious triad of adverse effects of pancreatitis, hypoglycemia, and lactic acidosis.Possible risk factors include a prolonged course of linezolid, renal dysfunction, and sepsis.

Impact of common comorbidities on antimicrobial consumption and mortality amongst critically ill COVID-19 patients: A retrospective two center study in Saudi Arabia.

To determine the association between common comorbidities, ICU mortality and antimicrobial consumption among critically ill COVID 19 patients in Saudi Arabia. A retrospective observational study of patients admitted to the ICU from March 1st, 2020, through August 31st, 2021. We excluded patients who stayed <24h in the ICU and with no confirmed COVID-19 PCR testing. Of the 976 screened ICU patients, 848 were included. While there was no difference in mortality between patients with and without comorbidities, those with at least one comorbidity had a higher severity of illness (p=0.013). Compared to survivors, non-survivors were more likely to require mechanical ventilation and vasopressor support (P<0.001). Almost all patients received at least one antimicrobial therapy. Predictors independently associated with ICU mortality were: older age (adjusted odds ratio [AOR], 1.03; 95% confidence interval [CI], 1.01-1.04), vancomycin use (AOR, 2.69; 95% [CI], 1.65-4.37), linezolid use (AOR, 2.65; 95% [CI], 1.65-4.04), sepsis or septic shock (AOR, 6.39; 95% [CI], 3.68-11.08), Acute Kidney Injury (AKI) (AOR, 2.51; 95% [CI], 1.61-3.92) and Acute Respiratory Distress Syndrome (ARDS) (AOR, 2.03; 95% [CI], 1.61-3.92). Older age, vancomycin and linezolid use, sepsis/septic shock, AKI, and ARDS were negative prognostic factors in critically ill COVID-19 patients. More studies are needed to evaluate the outcomes of survived critically ill patients in relation to their vaccination status.

Impact of Anti-Tuberculosis Drug Use on Treatment Outcomes in Patients with Pulmonary Fluoroquinolone-Resistant Multidrug-Resistant Tuberculosis: A Nationwide Retrospective Cohort Study with Propensity Score Matching.

Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

Serotonergic agents and linezolid: Impact of exposure to more than one agent concomitantly on risk of adverse effects

Background: The off-target effects linezolid have the potential to cause serotonin syndrome when given in conjunction with serotonergic agents. Despite package insert labeling as a contraindication, several postmarketing studies have demonstrated a low incidence of serotonin syndrome with the concomitant use of linezolid and other serotonergic agents. Linezolid provides a convenient oral option for gram-positive infections. However, due to concerns for serotonin syndrome, the use of linezolid is sometimes avoided. Methods: We performed a single-center, retrospective, medical record review of all adult inpatients from September 2021 to September 2022. Patients included had 1 administration of linezolid and 1 inpatient administration of a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) within 14 days. The primary outcome was the incidence of serotonin syndrome as defined by the Hunter serotonin toxicity criteria, which were retrospectively applied to each patient based on medical-record documentation. We compared patients receiving 1 versus multiple serotonergic agents. Secondary outcomes included duration of hospitalization and adverse outcomes based on concerns for serotonin syndrome such as need for rescue, ICU admission, or change in medication. Results: Of the 50 included patients from a convenience sample, 27 (54%) were on linezolid and &gt;1 serotonergic agent. Patients had similar baseline characteristics (Table 1). The most common concomitant agent used was an SSRI. Other agents that predispose patients to serotonin syndrome included opioid analgesics and other classes of antidepressants (Fig. 1). Serotonin syndrome occurred within 48 hours in 1 patient on an SNRI and a continuous fentanyl drip. There was no need for rescue or ICU admission due to serotonin syndrome. No patients were readmitted due to serotonin syndrome, and no differences were observed in hospital lengths of stay. Conclusions: Exposure to a single serotonergic agent combined with receipt of linezolid was not associated with any cases of serotonin syndrome. Exposure to multiple serotonergic agents was not associated with a high incidence of serotonin syndrome. This small series supports previous reports demonstrating relative safety of linezolid given with serotonergic agents and encourages review of interruptive drug–drug interaction alerts for linezolid within the electronic ordering system.Disclosures: None

Linezolid As An Add On Treatment In The Intensive Phase Of Tubercular Meningitis. A Randomized Controlled Pilot Trial. (S25.004)

<h3>Objective:</h3> To study whether administration of linezolid given for 4 weeks along with four drug standard weight-based Anti-Tubercular (ATT) regimen in intensive phase of tubercular meningitis (TBM) will help reduce mortality and morbidity. <h3>Background:</h3> Most agents used in the treatment of TBM have limited CNS penetration thereby limiting its efficacy. CSF penetration of linezolid is about 80–100 % and has been repurposed as a class C, core MDR-TB drug. <h3>Design/Methods:</h3> The study was a prospective, single center, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients fulfilling the eligibility criteria were randomized using computer generated numbers and permuted randomization block design in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD linezolid daily for 4 weeks along with standard ATT[rifampicin (10 mg/kg), isoniazid (5mg/kg), pyrazinamide (15–30 mg/kg, ethambutol (15 mg/kg) or streptomycin (0.75–1gm/day)]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. <h3>Results:</h3> A total of 29 patients (15 in intervention and 14 in the control arm) were recruited and 27 completed three months of follow up. There was no significant difference between two groups in mortality at one and three months with Odds ratio (95% CI) of 2[0.161 to 24.87] and p=1 at one month and 0.385[0.058 to 2.538] with p=value 0.39 at three months respectively. No major safety concerns were observed with the use of Linezolid. Favorable shift of mRS(modified Rankin Scale) at three months was observed in the Linezolid arm only (intra group p= 0.031with effect size (95% CI )1.667[0.353 to 7.875]. <h3>Conclusions:</h3> Linezolid was not effective in improving the mortality in TBM patients. Study with a larger sample size is desirable to demonstrate the benefits of Linezolid in TBM. <b>Disclosure:</b> Dr. Sahib has nothing to disclose. Dr. Bhatia has nothing to disclose. M.V. Padma Srivastava has nothing to disclose. Mamta Singh Bhushan has nothing to disclose. Vishnu VY has nothing to disclose. Roopa Rajan has received research support from DBT. Roopa Rajan has received research support from DST-SERB. The institution of Roopa Rajan has received research support from Michael J Fox Foundaton. The institution of Anu Gupta has received research support from ICMR. Dr. Srivastava has nothing to disclose.

Leveling Up: Evaluation of IV v. PO Linezolid Utilization and Cost after an Antimicrobial Stewardship Program Revision of IV to PO Conversion Criteria within a Healthcare System

The CDC's Core Elements of an Antimicrobial Stewardship Program (ASP) lists intravenous (IV) to oral (PO) conversion as an important pharmacy-based intervention. However, despite the existence of a pharmacist-driven IV to PO conversion protocol, conversion rates within our healthcare system remained low. We aimed to evaluate the impact of a revision to the current conversion protocol on conversion rates, using linezolid as a marker due to its high PO bioavailability and high IV cost. This retrospective, observational study was conducted within a healthcare system composed of five adult acute care facilities. The conversion eligibility criteria were evaluated and revised on 30 November 2021. The pre-intervention period started February 2021 and ended November 2021. The post-intervention period was December 2021 to March 2022. The primary objective of this study was to establish if there was a difference in PO linezolid utilization reported as days of therapy per 1000 days present (DOT/1000 DP) between the pre- and post-intervention periods. IV linezolid utilization and cost savings were investigated as secondary objectives. The average DOT/1000 DP for IV linezolid decreased from 52.1 to 35.4 in the pre- and post-intervention periods, respectively (p < 0.01). Inversely, the average DOT/1000 DP for PO linezolid increased from 38.9 in the pre-intervention to 58.8 for the post-intervention period, p < 0.01. This mirrored an increase in the average percentage of PO use from 42.9 to 62.4% for the pre- and post-intervention periods, respectively (p < 0.01). A system-wide cost savings analysis showed projected total annual cost savings of USD 85,096.09 for the system, with monthly post-intervention savings of USD 7091.34. The pre-intervention average monthly spend on IV linezolid at the academic flagship hospital was USD 17,008.10, which decreased to USD 11,623.57 post-intervention; a 32% reduction. PO linezolid spend pre-intervention was USD 664.97 and increased to USD 965.20 post-intervention. The average monthly spend on IV linezolid for the four non-academic hospitals was USD 946.36 pre-intervention, which decreased to USD 348.99 post-intervention; a 63.1% reduction (p < 0.01). Simultaneously, the average monthly spend for PO linezolid was USD 45.66 pre-intervention and increased to USD 71.19 post-intervention (p = 0.03) This study shows the significant impact that an ASP intervention had on IV to PO conversion rates and subsequent spend. By revising criteria for IV to PO conversion, tracking and reporting results, and educating pharmacists, this led to significantly more PO linezolid use and reduced the overall cost in a large healthcare system.

Effectiveness of a neonatal intensive care unit-specific antimicrobial stewardship program: A ten-year review.

To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP). Retrospective cohort study between January 1, 2010, and December 31,2019. The neonatal intensive care unit at British ColumbiaWomen's Hospital (Vancouver Canada), a tertiary-care center. Admitted neonates prescribed antibiotics. We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups. We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431-517) in period 1 to 405 (95% CI, 367-446) in period 2 to 313 (95% CI, 280-350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid. The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.

Increased copy number of 23S ribosomal RNA gene with point mutation in MRSA associated with linezolid resistance in a patient treated with long-term linezolid

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) infection is one of the most difficult infections we have to treat. Linezolid is one of the effective treatment options for refractory MRSA infections. There are cases where we are forced to use long-term linezolid treatment for refractory MRSA infections. ObjectiveTo discuss the evolution of Linezolid resistance factors in clinical isolates of MRSA. MethodsWe investigated 16 MRSA isolated from a patient treated with linezolid for a long period of 75 days. We performed antibiotic susceptibility test, 23S rRNA genes sequencing analysis, Pulsed-field gel electrophoresis. ResultsMRSA isolates were susceptible to linezolid before the start of treatment, but became less susceptible by prolonged treatment. The 23S rRNA sequencing analysis of linezolid-resistant strains that appeared 17 days after the start of treatment with linezolid revealed that all resistant MRSA had the G2576T substitution (Escherichia coli 23S rRNA gene number). The number of copies of this mutation increased with the use of linezolid. ConclusionLong-term use of linezolid in a patient or reuse of linezolid in a patient who has been previously treated with linezolid can lead to the emerging of linezolid-resistant MRSA in the host.

Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.