Linezolid Therapy Research Articles

Exploring the impact of baseline platelet count on linezolid-induced thrombocytopenia: a retrospective single-center observation study.

Patients treated with linezolid (LZD) frequently develop thrombocytopenia, and previous studies have identified the risk factors for this condition. However, the relationship between the development of LZD-induced thrombocytopenia and baseline platelet count has varied according to different reports. To explore the relationship between platelet count and the development of LZD-induced thrombocytopenia. Patients who underwent LZD at Hokkaido University Hospital in Japan from September 2008 to March 2023 were included. We collected data on patient characteristics and platelet counts at baseline and during LZD therapy from the electronic medical records. Thrombocytopenia was defined as a decrease in platelet count by 30% or more from baseline, or a platelet level < 100,000/µL. Two hundred and ninety-five patients who received LZD were included in this study, of whom 34.9% developed thrombocytopenia. In the early days of LZD treatment, the thrombocytopenia group showed a nearly 5% decrease in platelet count, while the non-thrombocytopenia group exhibited an increase of over 5%. Additionally, focusing on early onset thrombocytopenia (within 5 days), a baseline platelet count of < 150,000/µL was identified as a risk factor for early thrombocytopenia. Conversely, it was also observed that 24.7% of patients with a baseline platelet count ≥ 150,000/µL still developed early thrombocytopenia. Our findings suggest that while a baseline platelet count of < 150,000/µL is a risk factor for the early onset of thrombocytopenia, vigilant monitoring of platelet counts by clinical pharmacists in the early stages of LZD treatment is essential, regardless of baseline platelet levels.

Thrombocytopenia risks in ARDS COVID-19 patients treated with high-dose linezolid during vvECMO therapy: an observational study.

Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD. An LZD trough concentration of 8mg/L was set as the cutoff value for thrombocytopenia occurrence among critically ill patients who received parenteral LZD therapy at a dose of 600mg every 8h during ECMO. Eleven patients were included in this prospective observational study. Median LZD trough concentrations were 7.85 (interquartile range (IQR), 1.95-11) mg/L. Thrombocytopenia was found in 81.8% of patients. Based on the median LZD trough concentrations cutoff value, patients were divided into two groups, 1.95 (IQR, 0.91-3.6) and 10.3 (IQR, 9.7-11.7) mg/L, respectively. Median platelet values differed significantly between groups on admission, ECMO day 0, ECMO day 1, and LZD sampling day [194 and 152.5, (p < 0.05)], [113 and 214, (p < 0.05)], [76 and 147.5, (p < 0.01)], and [26 and 96.5, (p < 0.01)], respectively. Duration of LZD therapy was similar between the groups. Significant platelet reduction was observed in both groups, emphasizing the need for closer monitoring to prevent LZD-associated thrombocytopenia.

Association of clinical factors with thrombocytopenia in patients receiving linezolid treatment: a retrospective study.

Linezolid (LZD) plays an important role in the treatment of severe infections caused by Gram-positive bacteria. Thrombocytopenia is regarded as one of the most common side effects of linezolid, which results from the destruction of platelets or myelosuppression. The study aimed to identify the risk factors associated with the development of thrombocytopenia in Vietnamese patients. This retrospective, descriptive cross-sectional study was performed on adult patients who received parenteral LZD therapy (1,200 mg/day) in at least 3 days between January 2020 and June 2021 at a tertiary referral hospital in Vietnam. Thrombocytopenia was defined as either a final platelet count of less than 100 G/L or a 25% decrease in platelet count from baseline. Multivariate logistic regression analysis was applied to predict risk factors associated with LZD-induced thrombocytopenia. In the 208 patients included in the study, the average age was 69 and males accounted for 73.1%. LZD-induced thrombocytopenia occurred in 37% of patients. LZD-induced thrombocytopenia was significantly associated with shock (HR = 8.26, 95% CI 3.82 - 17.84, p < 0.001), baseline creatinine clearance (HR = 1.02, 95% CI [1.01 - 1.03], p = 0.002), and duration of LZD treatment of at least 14 days (HR = 4.45, 95% CI [1.83 - 11.05], p = 0.001). The results showed that thrombocytopenia was fairly common in patients using linezolid. Shock, renal failure, and duration of linezolid therapy of at least 14 days were significant risk factors for the incidence of linezolid-induced thrombocytopenia.

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

Comparative analysis of linezolid, vancomycin, and hyperbaric oxygen therapies in a rat model of ventriculoperitoneal shunt infection.

Staphylococcus epidermidis is the most common causative microorganism of ventriculoperitoneal shunt infections. This study aimed to compare linezolid and vancomycin treatments and to examine the effect of these antibiotics alone and combined with hyperbaric oxygen therapy on the amount of bacterial colonies in the experimental S. epidermidis shunt infection model. A shunt catheter was placed in the cisterna magna of 49 adult male Wistar albino rats. The rats were randomly divided into seven groups, as follows: sterile control, infected control, vancomycin, linezolid, hyperbaric oxygen, vancomycin + hyperbaric oxygen, linezolid + hyperbaric oxygen. In all groups except the sterile control group, 0.2ml 107CFU/mL S. epidermidis was inoculated to the cisterna magna. Parenteral vancomycin was administered 40mg/kg/day to the vancomycin groups, and 50mg/kg/day of enteral linezolid to the linezolid groups. Hyperbaric oxygen groups were given 100% oxygen at a pressure of 2.4 ATA for 50min a day. One day after the last treatment, colony quantities in the shunt catheters and CSF were analyzed. The number of CSF colonies in the linezolid group was significantly lower than in the vancomycin group (p < 0.05). The number of CSF colonies in the linezolid + HBO group was significantly lower than in the vancomycin + HBO group (p < 0.05). Linezolid treatment was found to be more effective than vancomycin in ventriculoperitoneal shunt infection caused by S. epidermidis. There was no statistical difference among other treatment groups. Hyperbaric oxygen therapy is shown to contribute to the sterilization of cultures.

Towards a better detection of patients at-risk of linezolid toxicity in clinical practice: a prospective study in three Belgian hospital centers.

Introduction: Linezolid is a last-resort antibiotic for infections caused by multidrug-resistant microorganisms. It is widely used for off-label indications and for longer than recommended treatment durations, exposing patients at higher risk of adverse drug reactions (ADRs), notably thrombocytopenia. This study aimed to investigate ADR incidence and risk factors, identify thrombocytopenia-related trough levels based on treatment duration, and evaluate the performance of predictive scores for ADR development. Methods: Adult in- and outpatients undergoing linezolid therapy were enrolled in three hospitals and ADRs and linezolid trough levels prospectively monitored over time. A population pharmacokinetic (pop-PK model) was used to estimate trough levels for blood samples collected at varying times. Results: A multivariate analysis based on 63 treatments identified treatment duration ≥10days and trough levels >8mg/L as independent risk factors of developing thrombocytopenia, with high trough values correlated with impaired renal function. Five patients treated for >28days did not develop thrombocytopenia but maintained trough values in the target range (<8mg/L). The Buzelé predictive score, which combines an age-adjusted Charlson comorbidity index with treatment duration, demonstrated 77% specificity and 67% sensitivity to predict the risk of ADR. Conclusion: Our work supports the necessity of establishing guidelines for dose adjustment in patients with renal insufficiency and the systematic use of TDM in patients at-risk in order to keep trough values ≤8mg/L. The Buzelé predictive score (if ≥7) may help to detect these at-risk patients, and pop-PK models can estimate trough levels based on plasma samples collected at varying times, reducing the logistical burden of TDM in clinical practice.

Nocardiosis ‘great imitator’: unusual disease with usual presentations at unusual site

Nocardia, an aerobic actinomycete, typically affects immunosuppressed individuals, commonly manifesting in the lungs. Cutaneous infections, particularly by N. pseudobrasiliensis, can occur, presenting as lympho-cutaneous, superficial, or mycetoma subtypes. Nocardia farcinica, resistant to third-generation cephalosporins, is particularly virulent. A 50-year-old female with type 2 diabetes presented with painful nodules, bullae, and recurrent discharge over the left wrist, mimicking cellulitis. Culture-sensitivity revealed Nocardia farcinica. Treatment involved debridement, De quervain release and prolonged Linezolid therapy for a complete cure. Cutaneous Nocardiosis can mimic cellulitis, posing diagnostic challenges due to slow growth and microbiological detection. N. farcinica demonstrated resistance to conventional antibiotics. This case emphasizes the importance of considering Nocardia infections in diverse clinical presentations, highlighting the need for a comprehensive diagnostic approach, especially in immunocompromised individuals.

Efektivitas dan keamanan terapi dengan rejimen yang mengandung linezolid dalam pengobatan multidrug-resistant tuberculosis (MDR-TB): Kajian Sistematik

Objective: To systematically evaluate the existing evidence regarding the efficacy and safety of therapy with regimens containing linezolid in the treatment of Multidrug‐ resistant tuberculosis (MDR-TB). Data source: The search strategy was undertaken using PubMed, Cochrane, and ScienceDirect databases. Review method: Searching the literature without changing the type of research or year of publication in which articles published until March 14, 2021, are involved in this literature review. The search strategy undertaken using PubMed, Cochrane, and ScienceDirect with the keywords "linezolid", "treatment", "tuberculosis" and "multidrugresistant" which were combined with the use of a Boolean operator "AND". Results: A total of seven studies were included in the final study. Linezolid had efficacy in MDR-TB patients with a much higher level of treatment support in the linezolid therapy group than in the control group (not using linezolid). However, the side effects that occurred were categorized as hematologic, gastrointestinal, neurological, and dermatological which generally occurred after 278 days of use. Severe diarrhea and nausea shortly after starting treatment were felt in 12.5% of patients. The main side effects controlled with linezolid (anemia, thrombocytopenia, and/or polyneuropathy), which generally required discontinuation were reported in 1 study and required discontinuation in 27 (77%) cases. The most important side effect is peripheral neuropathy, necessary to monitor the report by the 5 articles included in the final study. Conclusion: Available evidence has shown linezolid therapy to be effective against MDR-TB treatment. Monitored for the incidence of major adverse neurotoxicity (peripheral or optic neuropathy). To follow side effects and improve clinical outcomes, a combined high dose (1200 mg daily) for the intensive phase followed by a lower dose (300-600 mg daily) for the continuous phase is recommended along with an effective patient to increase the current dose and monitoring.

384. Factors Potentiating the Risk of Linezolid-induced Thrombocytopenia in Patients without Haemato-oncologic Diseases: A Case-control Study

Abstract Background Thrombocytopenia is a major adverse effect of linezolid due to myelosuppression. Many studies assessed factors associated with this effect, but most included patients with haemato-oncologic diseases, which may confound the assessment of thrombocytopenia. Therefore, this study aimed to investigate risk factors for linezolid-induced thrombocytopenia in patients without haemato-oncologic diseases. Methods This was a multicenter retrospective case-control study of adults treated with linezolid 600 mg twice daily for ≥ 3 days. Cases were the patients who developed thrombocytopenia while controls are those who didn't develop it. Exclusion criteria were haemato-oncologic diseases, active COVID-19, active dengue fever, baseline platelet count &amp;lt; 100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, platelet transfusion within 7 days before linezolid therapy, and insufficient platelets data. Various factors were assessed for potential association with linezolid-induced thrombocytopenia (defined as drop in platelet count below 100 × 103/mm3). Results 142 patients were included, 31 cases and 111 controls. Patients in both groups had a median age of 62 years and received linezolid for a median of 8 days. Platelet counts significantly dropped in the cases (Figure 1). Figure 2 shows the trend of change in platelet count (the white square indicates the median duration to thrombocytopenia, 8 days). In the univariate analysis, serum creatinine, creatinine clearance, baseline hemoglobin, baseline platelet count, and bacteremia were significantly associated with thrombocytopenia. However, after adjusting for confounders in the multivariate analysis, only low baseline hemoglobin and bacteremia were associated with thrombocytopenia (adjOR = 0.71; 95% CI 0.53-0.95; P = 0.022 and adjOR = 17.02; 95% CI 1.15-251-71; P = 0.039, respectively). Among the cases, those who had a baseline platelet count of &amp;lt; 200 × 103/mm3 developed thrombocytopenia faster as early as 3 days (log-rank P = 0.002; figure 3). Figure 1 Rate of change in platelet count between the cases (thrombocytopenia) and controls (no thrombocytopenia) Figure 2 Trend of platelet counts over 14 days in the cases (thrombocytopenia) and controls (no thrombocytopenia) Figure 3 Kaplan-Meier curve for the development of thrombocytopenia depending on baseline platelet count Conclusion Patients without haemato-oncologic diseases are at risk of linezolid-induced thrombocytopenia. especially those with bacteremia and low hemoglobin level. Patients with low baseline platelet count should be monitored closely early in therapy. Disclosures All Authors: No reported disclosures

The Association of Serotonin Toxicity with Combination Linezolid-Serotonergic Agent Therapy: A Systematic Review and Meta-Analysis.

Linezolid (LZD) has a longstanding reported association with the onset of serotonin toxicity (ST), secondary to drug-drug interactions with serotoninergic agents. There have been no conclusive data supporting the incidence or contributing risk factors to date. The study evaluated the incidence of ST in patients treated with LZD and serotonergic agents concomitantly versus LZD alone. The secondary objectives included a comparison of ST incidence in patients treated with one serotonergic agent + LZD versus two or more serotonergic agents + LZD. The studies used for this meta-analysis were retrieved from PubMed, Scopus, and Google Scholar. All studies including a comparison between LZD alone and LZD + a serotonergic agent published between 1 January 2000 and 1 October 2023 and meeting the quality standards were considered for inclusion. Fourteen studies were identified, with five meeting all inclusion and exclusion criteria with no significant heterogeneity. For the analysis of LZD monotherapy vs. SA combination therapy, four studies with 6025 patients total were analyzed and yielded an odds ratio of 1.78 (CI [1.04, 3.02]; I2 = 49%; GRADE certainty: low). Four studies and 2501 patients were included in the analysis of one versus more than one SA with an odds ratio of 5.18 (CI [1.05, 25.49]; I2 = 44.87; GRADE certainty: moderate). The Newcastle-Ottawa score, visual inspection of the funnel plot, and Egger's statistic were used to evaluate quality and heterogeneity. The Peto method was used to calculate the summary odds ratios. All analyses were performed using Comprehensive Meta-Analysis version 3.0 and R, while GRADE was used to evaluate the quality of the final recommendation. The number of concomitant serotonergic agents may play a role in the development of serotonin toxicity in patients prescribed linezolid. In patients requiring linezolid therapy and serotonergic agents, risk versus benefit analysis should pay attention to the number of interacting drugs.

Predictive value of methicillin-resistant staphylococcus aureus nasal swab in patients with COVID-19 pneumonia and secondary bacterial pneumonia

ObjectiveTo determine the performance measures of admission methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs for MRSA bacterial pneumonia in patients co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MethodsThe study included patients admitted with SARS-CoV-2-positive nasopharyngeal specimens, MRSA nasal screens, and bacterial cultures to assess secondary MRSA pneumonia. Results293 patients and 662 microbiological cultures evaluated. Overall, the specificity (91.8% [95% CI 88.6% to 95%]) and negative predictive value (NPV 97.4% [95% CI 95.4% – 99.3%]) of MRSA nasal swabs was high. However, the sensitivity (46.2%; 95% CI 19.1% to 73.3%) and positive predictive value (PPV 20.7%; 95% CI 59.5 – 35.4%) were low. Those patients in the MRSA nasal swab negative group had a shorter median duration of linezolid therapy. ConclusionsSARS-CoV-2 infection doesn't reduce the specificity or negative predictive value of MRSA nasal swabs for secondary MRSA pneumonia.

Evaluation of the impact of rifampicin on the plasma concentration of linezolid in tuberculosis co-infected patients.

Linezolid combined with rifampicin has shown excellent clinical outcomes against infection by multi-resistant Gram-positive bacteria. However, several studies have indicated that rifampicin reduces the plasma concentration of linezolid in patients with severe infection. Linezolid has been recommended for the treatment of patients with multidrug-resistant or extensively drug-resistant tuberculosis. However, studies on the interaction between linezolid and rifampicin in patients suffering from tuberculosis with infection are lacking. We evaluated the interaction between linezolid and rifampicin based on therapeutic drug monitoring (TDM). A retrospective analysis was undertaken for patients with tuberculosis and infection who were treated with linezolid and undergoing TDM. Patients were divided into the linezolid group and linezolid + rifampicin group. Data on demographic characteristics, disease, duration of linezolid therapy, and the plasma concentration of linezolid were used for statistical analyses. Eighty-eight patients with tuberculosis and infection were assessed. Values for the peak (Cmax) and trough (Cmin) concentrations of linezolid in plasma were available for 42 and 46 cases, respectively. Patients in the linezolid group had a significantly higher Cmax [15.76 (8.07-26.06) vs. 13.18 (7.48-23.64) mg/L, p = 0.048] and Cmin [8.38 (3.06-16.53) vs. 4.27 (0.45-10.47), p = 0.005] than those in the linezolid + rifampicin group. The plasma concentration of linezolid increased obviously in two patients after rifampicin discontinuation. However, the total efficiency and prevalence of hematologic adverse reactions were not significantly different in the linezolid group and linezolid + rifampin group. The plasma concentration of linezolid decreased upon combination with rifampicin, suggesting that TDM may aid avoidance of subtherapeutic levels of linezolid upon co-treatment with rifampicin.

Effect of Platelet Parameters on Linezolid-Related Thrombocytopenia in Hospitalized Patients.

Linezolid-induced thrombocytopenia incidence varies considerably. Linezolid-related thrombocytopenia in patients has received few studies which have investigated risk factors including platelet parameters except for platelet counts. The study aims to analyze the effect of platelet parameters, including mean platelet volume and platelet large cell ratio, on linezolid-related thrombocytopenia in patients. The effect of platelet parameters on linezolid-related thrombocytopenia was identified by univariate and multivariate logistic regressions. A Kaplan-Meier survival analysis was carried out to compare the survival of patients who developed linezolid-related thrombocytopenia with patients who did not. Thrombocytopenia occurred at a rate of 41.5% (66/159) after linezolid therapy in hospitalized patients. Platelet parameters, including the difference in mean platelet volume (MPV/fL=0.08 (-1.2-0.9)vs-0.5 (-1.5-0.3), (OR, 0.459; P = 0.001), the difference in platelet large cell ratio (PLCR/fL=0.9 (-5.1-6.2)vs-3.8 (-8.6-2.4), (OR, 1.156; P = 0.001), baseline platelet counts (OR, 0.995; P = 0.006) and duration of linezolid therapy≥10d (OR, 1.346; P = 0.007), were significantly associated with linezolid-related thrombocytopenia in hospitalized patients. In addition, other risk factors which also are associated with linezolid-related thrombocytopenia include baseline red blood cells, co-medication with parecoxib and co-medication with caspofungin. Accumulated in-hospital mortality of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia during linezolid treatment (19.7% vs 8.6%, P = 0.003). The difference in mean platelet volume, the difference in large platelet ratio, baseline platelet counts and duration of linezolid therapy≥10d significantly affected the development of linezolid-related thrombocytopenia in hospitalized patients.

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.

Risk factors for thrombocytopenia in patients receiving linezolid therapy: a systematic review and meta-analysis.

The incidence of linezolid-induced thrombocytopenia (LIT) has been reported to vary widely across studies. We performed a meta-analysis to identify the risk factors for thrombocytopenia among patients who received linezolid treatment. The PubMed, Embase and Cochrane Library databases were searched from inception to November 2022 to identify eligible studies. Data on the potential predictors of incidence in LIT were pooled using a random effects model. Sensitivity analyses were performed to determine the robustness of the results when significant heterogeneity was observed. Forty observational studies involving 6454 patients treated with linezolid were included in the analysis. LIT was estimated to occur in 37% of patients. The following important factors were associated with the incidence of LIT: advanced age, body mass index, concurrent renal impairment or liver disease, abnormal laboratory parameters (including white blood cell count, serum creatinine, baseline platelet count, albumin, creatinine clearance rate, and estimated glomerular filtration rate), treatment durationand renal replacement therapy. A variety of risk factors related to the occurrence of LIT were revealed in our analysis. Early identification of these factors could help patients improve clinical outcomes.

Effect of linezolid on platelet count in critically ill patients with thrombocytopenia.

Linezolid (LZD) is one of the antibiotics used to treat methicillin-resistant Staphylococcus aureus. In Japan, the dose of LZD is not generally adjusted by renal function or therapeutic drug monitoring and is readily available for critically ill patients. The adverse effects of LZD include pancytopenia, especially thrombocytopenia. We investigated the effect of LZD on platelet counts in critically ill patients with thrombocytopenia during admission to the intensive care unit (ICU). Fifty-five critically ill patients with existing thrombocytopenia (platelet count < 100 ×103 /μL) who received LZD for five days or more during the period from January 2011 to October 2018 were included. Changes in platelet count and frequency of platelet concentrate (PC) transfusion were evaluated retrospectively. Mean (± standard error) platelet count prior to initiation of LZD was 47 ± 4 ×103 /uL, which increased significantly to 86 ± 13 ×103 /uL on day 15 (p<0.01). Median [interquartile range] duration of LZD therapy was 9 [8-12] days. Thirty-two patients (58.2%) required PC transfusion in the 15-day study period. The daily rate of PC transfusion decreased from 30.2% on days 1-5 to 18.2% on days 11-15. Similar tendencies were observed in patients with non-hematological and hematological disease. Thrombocytopenia in critically ill patients in the ICU did not worsen after initiation of LZD therapy, and may be considered for the treatment of MRSA in this setting.

Linezolid-associated serotonin toxicity: a systematic review.

This systematic review aims to evaluate the existing evidence associating linezolid to serotonin toxicity when used as monotherapy or when co-administered with other serotonergic agents. A systematic literature search using PubMed (till March 2023), IDWeek meetings (2003-2023), the European Congress of Clinical Microbiology and Infectious Disease Annual Meetings (2001-2023), and the American College of Clinical Pharmacy (1999-2023) identified studies and abstracts related to linezolid and serotonin toxicity. A total of 84 studies were included. The data collected in retrospective/observational studies compared the incidence of serotonin toxicity with linezolid monotherapy at 0.0050% and linezolid combination therapy at 0.0134%. All cases which discontinued linezolid and serotonergic agent/s at signs and symptoms of toxicity found symptom resolution; 75% of cases reported serotonin toxicity resolution within 24-48h after discontinuation. Linezolid therapy when optimal should not be deferred due to the risk of serotonin syndrome. The data collected reveals a low prevalence of serotonin toxicity in both linezolid monotherapy and linezolid concurrent with other serotonergic agents.

Targeted Antibiotics for Lower Respiratory Tract Infection with Corynebacterium striatum.

To assess the impact of targeted antibiotic therapy on clinical outcomes of patients with lower respiratory tract (LRT) infection with Corynebacterium striatum (C. striatum). A new propensity score-inverse probability of treatment weighting (IPTW) cohort study was conducted by using 10-year data. The study included LRT infection patients with respiratory secretions cultured positive for C. striatum simultaneously. The primary outcome was all-cause hospital mortality; the secondary outcomes included hospital stay, ICU stay and ventilation time. The safety outcomes were drug-related serum creatinine (Cr) increase and thrombocytopenia. A total of 339 patients were included in the cohort, and 84 (24.78%) initiated vancomycin or linezolid therapy. In the new IPTW cohort, targeted antibiotic therapy did not improve all-cause hospital mortality (P=0.632), and the OR (95% CI) was 0.879 (0.519-1.488). Moreover, targeted antibiotic therapy was not associated with hospital stay (P=0.415), ICU stay (P=0.945) or ventilation time (P=0.885). The side effects of drug-related higher serum Cr (P=0.044) and thrombocytopenic levels (P=0.038) cannot be ignored. Clinical benefits by vancomycin or linezolid targeted against LRT infection with C. striatum were limited and with drug-related side effects. A prospectively designed study is needed to further confirm the results.

A Rare Adverse Effect Following Prolonged Linezolid Therapy.

A Rare Adverse Effect Following Prolonged Linezolid Therapy.

LInezolid Monitoring to MInimise Toxicity (LIMMIT1): A multicentre retrospective review of patients receiving linezolid therapy and the impact of therapeutic drug monitoring

BackgroundLinezolid is a broad-spectrum antimicrobial with limited use due to toxicity. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity, including the impact of therapeutic drug monitoring (TDM). MethodsPatients administered linezolid between January 2017 and December 2019 were retrospectively reviewed. Data were collected on patient characteristics, linezolid therapy and outcomes. Descriptive statistics were performed on all patients, and statistical comparisons were undertaken between those who did and did not experience linezolid toxicity. A multivariable logistic regression model was constructed to identify any covariates that correlated with toxicity. ResultsLinezolid was administered to 1050 patients; of these, 381 did not meet the inclusion criteria and 47 were excluded as therapy ceased for non-toxicity reasons. There were 105 of 622 (16.9%) patients assessed to have linezolid toxicity. Patients who experienced toxicity displayed a higher baseline creatinine (96.5 µmol/L vs. 79 µmol/L; P = 0.025), lower baseline platelet count (225 × 109/L vs. 278.5 × 109/L; P = 0.002) and received a longer course (median 21 vs. 14 days; P < 0.001) than those who did not. Linezolid TDM was performed in 144 patients (23%). Multivariable logistic regression demonstrated that TDM-guided appropriate dose adjustment significantly reduced the odds of linezolid toxicity (aOR = 0.45; 95% CI 0.21–0.96; P = 0.038) and a treatment duration > 28 days was no longer significantly associated with toxicity. ConclusionsThis study confirmed that linezolid treatment-limiting toxicity remains a problem and suggests that TDM-guided dose optimisation may reduce the risk of toxicity and facilitate prolonged courses beyond 28 days.