Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections.

The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections.

The Impact of the COVID-19 Pandemic on Antimicrobial Resistance and Management of Bloodstream Infections.

INTRODUCTION: The pressure of the COVID-19 pandemic on healthcare systems led to limited roles of infectious diseases services, increased rates of irrational use of antimicrobials, and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during the COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). MATERIALS AND METHODS: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram-positive and -negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the intensive care unit (ICU). Additionally, bloodstream infections with requested infectious disease consultations were reported (n = 400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization, and clinical outcome were analyzed. RESULTS: A total of 4569 strains of Gram-positive and -negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious disease consultations were carried out, while during the period 2020-2022, the number was 154, with the percentage of telephone consultations 15% and 76%, respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic, and 28-day mortality was significantly reduced in cases with bedside consultations. CONCLUSION: The empowering of infectious disease surveillance programs and committees, rational use of antimicrobials agents, and bedside infectious disease consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.

The Antiviral Effect of Nirmatrelvir/Ritonavir during COVID-19 Pandemic Real-World Data.

INTRODUCTION: Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent the severe progression of COVID-19 in vulnerable patients with comorbidities. PATIENTS AND METHODS: Adults with confirmed SARS-CoV-2 infection were included in a matched-pair retrospective study based on age, gender, comorbidities and vaccination status. They were divided into two groups: group A (n = 200) consisted of outpatients at increased risk of severe clinical progress who were treated with nirmatrelvir/ritonavir and group B (n = 200) consisted of non-hospitalized patients who did not receive antiviral treatment. Demographic data, clinical outcome (death, intubation), days of hospitalization, time for recovery, adverse events and treatment compliance were reported. RESULTS: The median age (75.24 ± 13.12 years in the study group and 76.91 ± 14.02 years in the comparison group) and the proportion of males (59% vs. 60.5%, respectively) were similar between the two groups. A total of 6.5% of patients in group A and 10.5% in group B were unvaccinated against SARS-CoV-2. Three patients from group A (1.5%) and one hundred eleven (55.5%) from group B required hospitalization. The duration of hospitalization (3 days vs. 10 days in group B, p < 0.001) and the total time needed for recovery (5 days vs. 9 days, p < 0.001) was shorter in the study group. A rebound of SARS-CoV-2 infection within 8-12 days after diagnosis was documented in 6.5% of patients in group A and 8% of patients in group B. CONCLUSION: Oral treatment with nirmatrelvir/ritonavir in high-risk non-hospitalized patients was safe and effective in preventing the severe clinical progress of COVID-19 pneumonia. Early administration of antiviral agents in vulnerable outpatients combined with a full vaccination scheme is significant in order to avoid hospitalization and severe clinical outcomes.

Proposed amendments regarding the definitions of multidrug-resistant and extensively drug-resistant bacteria.

INTRODUCTION: It is fortunate that an international panel of experts proposed definitions for multidrug-resistant (MDR) and extensively drug-resistant (XDR) in the past. AREAS COVERED: In our opinion, these definitions need amendments in order to be semantically more accurate. EXPERT OPINION: We suggest for the MDR definition to add to 'MDR is defined as non-susceptibility to at least one agent in three or more antimicrobial categories' that this non-susceptibility is at most to the total number of all antimicrobial categories minus two, so that the definition reads: MDR is defined as non-susceptibility to at least one agent in three or more antimicrobial categories and up to (and including) the total number of all antimicrobial categories minus two. We suggest that the experts' definition of XDR as 'non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories)' has to be modified regarding the content of the parenthesis to: (i.e. bacterial isolates remain susceptible to only one or two or even none antimicrobial category [in this latter setting bacterial isolates are resistant to at least one antimicrobial agent in all antimicrobial categories and concurrently there is at least one antimicrobial agent to which the isolate is susceptible to]).

The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality.

BACKGROUND: Activins are members of the transforming growth factor-ß superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (COVID-19), we hypothesized that activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology. METHODS: Activin-A, activin-B, and follistatin were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters. Optimal scaling with ridge regression was used to screen variables and establish a prediction model. RESULT: The activin/follistatin axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a scoring system incorporating follistatin, activin-A, activin-B, C-reactive protein, lactate dehydrogenase, intensive care unit admission, neutrophil/lymphocyte ratio, age, comorbidities, and D-dimers, efficiently predicted fatal outcome (area under the curve [AUC], 0.951; 95% confidence interval, .919-.983; P <10-6). Two validation cohorts indicated similar AUC values. CONCLUSIONS: This study demonstrates a link between activin/follistatin axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.

Impact of SARS-CoV-2 on pregnancy outcomes (Review).

The impact of the pandemic outbreak associated with coronavirus 2019 disease (COVID-19) on pregnant women is of interest to obstetricians and gynecologists due to the vulnerability of this target group. In pregnant women and their infants, an exceptional clinical management is warranted. Current epidemiological findings provide information regarding the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnant patients and potential adverse perinatal outcomes. Overall, these findings are a strong indication that an increased antenatal surveillance for pregnant patients infected with COVID-19 is warranted. The aim of the present narrative review was to summarize the data obtained to date regarding the health of women during pregnancy, as well as that of the fetus associated with the risk of severe infection due to COVID-19. The present review aimed to provide further insight into the effects of this pandemic on pregnancy, also providing the experience of the authors on this matter as an example.

Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis.

Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.

Benefits of prolonged infusion of beta-lactam antibiotics in patients with sepsis: personal perspectives.

INTRODUCTION: In the current era of relatively scarce antibiotic production and significant levels of antimicrobial resistance, optimization of pharmacokinetics and pharmacodynamics of antibiotic therapy is mandatory. Prolonged infusion of beta-lactam antibiotics in comparison to the intermittent infusion has the theoretical advantage of better patient outcomes. Apparently, conflicting data in the literature possibly underestimate the benefits of prolonged infusion of antibiotic treatment. AREAS COVERED: We provide our perspective on the subject based on our experience and by critically evaluating literature data. EXPERT OPINION COMMENTARY: In our opinion, the available data are suggestive of the beneficial role of prolonged infusion of beta-lactams in regard to piperacillin/tazobactam and carbapenems after administering a loading dose. While more data from randomized controlled trials are necessary to solidify or negate the evident benefits of prolonged infusion of the aforementioned antibiotics, clinicians should strongly consider this mode of administration of relevant antibiotics, especially in patients with severe infections.

Addressing clinical safety of antimicrobial resistance: personal perspectives.

Introduction: Antimicrobial resistance is an important challenge for patients, societies, practicing physicians and health care organizations worldwide. Predictions in regard to the morbidity and mortality of antimicrobial resistance are grave especially in the setting of an era where the pipeline of production of antimicrobial agents is relatively dry.Areas covered: Herein, a viewpoint will be provided regarding antimicrobial bacterial resistance as a clinical safety need based on personal experience and data from the literature.Expert opinion: A variety of antibiotics has been produced during the last decade but novelty regarding truly new antimicrobial agents is rather little, as these new antibiotics are mainly based on modifications of known pharmaceutical molecules. Therefore, as there is still a desperate need to address optimal clinical safety in regard to antimicrobial resistance, we believe that strong financial incentives and rewards to producers of antimicrobial agents (especially new in concept) are necessary. Furthermore, global surveillance of antimicrobial resistance as suggested by the World Health Organization, coordination of measures of justified and appropriate use of antibiotics and application of strict infection control principles are needed to lessen the negative clinical impact of antimicrobial resistance.

Impact of oseltamivir use on the reduction of complications in patients with influenza: a prospective study.

To evaluate the factors associated with oseltamivir prescription and to study the effectiveness of oseltamivir in reducing influenza-related complications. A prospective cohort study using the SOS Doctors (a network of physicians who perform house-call visits in Attica, Greece). Patients with confirmed or clinically suspected influenza were followed up to 14 days during the 2011-2012 influenza period. 410 patients with confirmed or suspected influenza were included. Healthy adults were mainly enrolled, with a median age of 44 years. Influenza diagnosis was mainly based on clinical criteria (65.8 % of patients). Oseltamivir was prescribed for 45.4 % of them. In a multivariate analysis, prescription of oseltamivir was associated with the attending physician (p < 0.001), positive influenza test (p < 0.001) and diabetes (p = 0.027). Data on complications were available for 351 patients, and 50 (15.8 %) of them reported at least one. Seven patients required hospitalization. Types of complications (pneumonia, bronchitis, etc.) were not significantly different between patients receiving and those not receiving oseltamivir. In the multivariate analysis, higher oseltamivir prescription rate was associated with fewer complications (p < 0.001). Bearing in mind the limitations of a non-randomized study, in a real-life setting, oseltamivir prescription and the rate of complications in patients with influenza were associated with the attending physician, underlying diseases and diagnostic tests. Overall, when the frequency of oseltamivir prescription increased, the influenza-related complications decreased.

Options for treating carbapenem-resistant Enterobacteriaceae.

PURPOSE OF REVIEW: To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months. RECENT FINDINGS: Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations. SUMMARY: Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.

Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence.

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Frequency of the off-label use of monoclonal antibodies in clinical practice: a systematic review of the literature.

BACKGROUND: The monoclonal antibodies represent novel therapeutic options for many clinical entities. This study aimed to study the frequency of the off-label use to total use of different monoclonal antibodies in clinical practice. METHODS: This study systematically searched the PubMed and Scopus databases for relevant studies. RESULTS: Fifteen studies were considered eligible for inclusion in this review. Eight of the included studies referred to the off-label use of anti-neoplastic monoclonal antibodies, three referred to immunosuppressive ones, and four to other types of monoclonal antibodies. The most studied anti-neoplastic monoclonal antibody was rituximab; which was prescribed off-label at a frequency varying between 16-75%, mostly for an unapproved diagnosis. Bevacizumab was prescribed off-label for age-related macular degeneration more often than ranibizumab, the approved monoclonal antibody for this condition. Of the immunosuppressive monoclonal antibodies, infliximab was used off-label in an average of 15.4% (range=2.8-25%) and adalimumab in 10.5% (range=0-15.4% in different years). CONCLUSION: The frequency of off-label use of different types of monoclonal antibodies varies, but appears to be considerably high for specific monoclonal antibodies or indications. In certain examples, this might reflect implementation into clinical practice of relevant scientific data, albeit not of the strength or quality that suffices for receipt of regulatory approval. In others, it might relate to the sub-optimal effectiveness and considerable toxicity of the conventional therapies. Still, the clinician should bear in mind the potential costs and toxicity that can be associated with off-label use of monoclonal antibodies.

Antimicrobial activity and clinical effectiveness of sisomicin: an evaluation of the literature (1995-2011).

The authors sought to evaluate whether sisomicin has a place in the current therapeutic armamentarium. PubMed and Scopus databases were systematically searched. Ten cohort studies and 11 case reports and case series were included evaluating, in total, 383 Gram-positive and 83 Gram-negative isolates. Sisomicin was active in vitro against 41% of Enterococcus spp., 97% of Staphylococcus spp. and was the most active in vitro (74%) aminoglycoside against Stenotrophomonas maltophilia isolates in one study. Regarding clinical effectiveness, sisomicin topical cream was effective in all 290 patients with pyoderma in one study, while the intravenous formulation of sisomicin was effective as prophylaxis for the development of postoperative pneumonia in 91% of lung surgery patients in another. In conclusion, sisomicin may be useful against certain pathogens; however, clinical data are scarce. Further studies are needed and may shed additional light in this area.

Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug?

OBJECTIVE: To study the predictors of mortality among patients with multi-drug resistant Gram negative (MDRGN) infections and the role of MDRGN bacteria in the outcome of such patients. METHODS: PubMed and Scopus databases were searched (until June 30, 2012). Data were extracted and analyzed using the technique of meta-analysis. RESULTS: 30 studies (25 retrospective) were included in the analysis; 9 provided data on predictors of mortality for MDRGN infections only, while 21 provided data for MDRGN vs non-MDRGN infections. Acinetobacter spp were the most commonly studied bacteria followed by Pseudomonas aeruginosa and Enterobacteriaceae. Significant diversity was observed among studies regarding the evaluated predictors of mortality. Infection severity and underlying diseases were the most commonly reported independent predictors of mortality followed by multidrug resistance, inappropriate treatment and increasing age. In studies that included only patients with MDRGN infections, cancer (RR 1.65, 95% CI 1.13-2.39) and prior or current ICU stay (1.27, 1.02-1.56) were associated with mortality. In studies that included patients with MDRGN and non-MDRGN infections, septic shock (3.36, 2.47-4.57), ICU stay (2.15, 1.45-3.20), pneumonia (1.65, 1.09-2.52), isolation of MDRGN bacteria (1.49, 1.21-1.83), inappropriate definitive (2.05, 1.12-3.76) and empirical treatment (1.37, 1.25-1.51), and male gender (1.13, 1.05-1.21) were most commonly observed in patients who died than patients who survived. CONCLUSION: Significant diversity and statistical heterogeneity was observed. Beyond comorbidity and severity scores, MDR and inappropriate treatment were also identified as predictors of mortality.

Frequency of the off-label use of antibiotics in clinical practice: a systematic review.

Antibiotics constitute a major class among drugs commonly prescribed either empirically or for microbiologically documented infections in clinical practice. In addition, due to medical necessity physicians are forced, at times, to prescribe medications for off-label indications. The authors sought to record the frequency of the off-label use of antibiotics among both adult and pediatric patients. PubMed and Scopus databases were searched to identify relevant studies. A total of 25 studies met the inclusion criteria (725,124,505 prescriptions); 16 were prospective and nine retrospective. Fifteen studies reported on the pediatric population, seven on adults who had received a specific antibiotic, two on adult critical-care patients, and one on the general outpatient population. In the pediatric population, the percentage of off-label prescriptions varied from 1 to 94%. Off-label prescriptions varied from 19 to 43% in adult critical-care patients. Last, one study reporting on general outpatient care showed that 23% of prescriptions were off-label. Antibiotics are frequently prescribed as off-label among patient populations. The wide variation observed in the off-label use of antibiotics among pediatric patients might be attributed to the heterogeneity among the study populations regarding the age of children. Although this unapproved manner of prescribing cannot always be avoided, clinicians should only use unapproved drugs in cases when there are no effective alternatives are available and based on scientific evidence regarding safety and effectiveness.

Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression.

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1 mg/L but ≤2 mg/L) and 'low-VMIC' (VMIC≤1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.

Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis.

INTRODUCTION: The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens. OBJECTIVE: To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis. RESULTS: Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR] =1.10 [95% confidence intervals: 0.82-1.48]). Among patients with MRSA infection, telavancin showed higher eradication rates (OR=1.71 [1.08-2.70]) and a trend towards better clinical response (OR=1.55 [0.93-2.58]). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR=2.22 [1.38-3.57]), serious adverse events (OR=1.53 [1.05-2.24]), and adverse event-related withdrawals (OR=1.49 [1.14-1.95]) among telavancin recipients. CONCLUSION: Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.