Vancomycin-treated Group Research Articles

Protective Effects of Huo Xiang Zheng Qi Liquid on Clostridioides difficile Infection on C57BL/6 Mice.

Clostridioides difficile-associated disease (CDAD) is a major healthcare-associated infection. New treatment options for CDAD are needed. A traditional Chinese medicinal formula, Huo Xiang Zheng Qi (HXZQ), was chosen to test against CDAD in a mouse model. C57BL/6 mice were challenged with C difficile (ATCC 43255) orally; then received saline; vancomycin 25 mg/kg; or HXZQ in two different concentrations twice daily for 5 days. The animals' body weight; clinical signs; and survival rates were registered daily. Fecal pellets from each animal were taken for PCR analysis as a control of infection. 50% of the mice receiving saline died; 85.7% of the mice receiving vancomycin survived; 75% of the mice receiving HXZQ survived; and 87.5% of the mice receiving a 1:1 saline dilution of HXZQ survived. The HXZQ-treated groups were C. difficile PCR positive with loads less than that of the untreated mice. The weight loss in the vancomycin plus HXZQ 1:1 treated group; the vancomycin-treated group; and the untreated group were 3.08%, 4.06%, and 9.62%, respectively. our results showed that HXZQ can protect mice from CDAD-related death as effectively as vancomycin and the combination of vancomycin and HXZQ may give even better protection.

Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats.

Background: Vancomycin is a glycopeptide antibiotic with a high risk of acute liver injury. Resveratrol is believed to protect the liver against toxicity. Aim: To investigate the ability of resveratrol to attenuate vancomycin-induced liver toxicity in rats injected with vancomycin. Method: Twenty-four adult male Wistar rats were distributed into three groups. The control group received only a vehicle, while the treated group received either vancomycin 200 (mg/kg, i. p.) only or vancomycin (200mg/kg, i. p.) with resveratrol (20mg/kg, oral gavage). All groups received their dose once daily for 7days. Hepatic damage was assessed by measuring biochemical parameter levels in serum, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Also, antioxidants and inflammation biomarkers such as Interleukin-6 (IL-6), malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) were measured. Furthermore, the vancomycin-induced pathological changes in the liver were evaluated by histopathological studies. Results: In the vancomycin-treated group, hepatic serum biomarkers such as AST, ALT, ALP, IL-6, and MDA were elevated, while NO and GSH were depleted. However, resveratrol co-treatment with vancomycin prevented the elevation of AST, ALT, ALP, IL-6, and MDA and it protected the liver from NO and GSH depletion. Also, regarding vancomycin-induced degeneration of hepatocytes, resveratrol co-treatment with vancomycin prevented such degeneration and improved mononuclear cells in the liver. Conclusion: The results showed that oral administration of resveratrol has a significant hepatoprotective effect against vancomycin-induced hepatotoxicity.

Effectiveness of melatonin in preventing vancomycin-induced nephrotoxicity: an experimental study

Purpose: The aim of the study explores probable toxic effects of vancomycin on kidney and analysis of the probable protective effects of melatonin.
 Materials and Methods: In this study, rats were randomly divided into 4 groups: the control group; the melatonin (10 mg/kg/day) group; the vancomycin-treated (200 mg/kg) group; and the vancomycin (200 mg/kg) + melatonin (10 mg/kg/day) group. Rats in the treatment group were given two doses of vancomycin a day with an interval of seven consecutive days and melatonin (10 mg/kg/day) once daily for seven consecutive days. The experiment was continued for 15 days. In each group, seven rats were grouped together. 15 days after the experiment, the rats were sacrificed under anesthesia and among all groups. Kidney tissues were collected and processed for further TNF- expression analysis, as well as histological analyses such as hematoxylin and eosin (H&E), Masson's tricrom, and Periodic acid schiff (PAS) staining to assess pathological severity. In addition, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis.
 Results: While vancomycin upregulated TNF-α expression, melatonin reduced levels of TNF-α immunoreactivity intensity and clearly improved pathological severity in rat kidneys. Further, melatonin significantly inhibited vancomycin-induced TUNEL-positive cell numbers. 
 Conclusion: Melatonin has protective activity against vancomycin-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves kidney function.

Effect of NZ2114 against Streptococcus dysgalactiae biofilms and its application in murine mastitis model.

Bovine mastitis caused by Streptococcus dysgalactiae (S. dysgalactiae) is usually treated with antibiotics, which may potentially increase drug resistance as the abuse. NZ2114, a variant of fungal defensin plectasin, displayed a potent antibacterial activity against S. dysgalactiae. The inhibition/eradication effect of the antimicrobial peptide NZ2114 on the early/mature biofilm of S. dysgalactiae CVCC 3938 was evaluated, as well as the elimination of bacteria in mature biofilms. In this study, NZ2114 displayed potent antibacterial activity against S. dysgalactiae CVCC 3938 and three clinical isolated S. dysgalactiae strains (0.11-0.45 μM). The early biofilm inhibition of S. dysgalactiae CVCC 3938 was 55.5–85.9% after treatment with NZ2114 at concentrations of 1–16 × MIC, which was better than that of vancomycin at the same concentration. The mature biofilm eradication rate was up to 92.7–97.6% with the increasing concentration (2–16 × MIC) of NZ2114, and the eradication rate did not change significantly with further increase of NZ2114 concentration, while the biofilm eradication rate of vancomycin-treated group at the same concentration remained at 92.5%. NZ2114 reduced the number of persister bacteria in biofilm. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) further demonstrated that NZ2114 could effectively reduce the biofilm thickness and bacterial number of S. dysgalactiae CVCC 3938. In vivo therapeutic effect of NZ2114 on murine mastitis model showed that NZ2114 was better than vancomycin in alleviating mammary gland inflammation by regulating cytokines production, inhibiting bacterial proliferation, and reducing the number of mammary gland bacteria. These data suggested that NZ2114 is a potential peptide candidate for the treatment of mastitis.

The neuroprotective effect of melatonin in preventing vancomycin-induced neurotoxicity

Vancomycin is a commonly used antibiotic with potent activity against Gram-positive organisms, but prolonged use and high doses can lead to toxicity. While vancomycin-associated nephrotoxicity is widely reported, few cases of neurotoxicity have been described. Presupplementation with melatonin, a powerful antioxidant for nervous tissues, protects the sciatic nerve against all of the changes. Melatonin, a neurosecretory product of the pineal gland, functions as an antioxidant in vivo and in vitro. Therefore, in this study the effect of melatonin in rats treated with vancomycin on the sciatic nerve was investigated. 28 wistar albino female rats were divided into four groups, each containing 7 rats. The first group was used as a control. The second group, melatonin (10 mg/kg/day) was injected intraperitoneally into rats for 7 days, respectively. The rats in the third group were injected with vancomycin (200 mg/kg) for 7 days, respectively. The fourth group, vancomycin (200 mg/kg)+melatonin (10 mg/kg/day) were received vancomycin for 7 days and than melatonin into rats for 7 days, respectively. The experiment was continued for 15 days. The sciatic nerve tissues were examined under light microscopes. According to our findings, S100 expression was lowest in the vancomycin-treated group. In addition, the immunoreactivity intensity of S100 was significantly increased in the vancomycin+melatonin group, compared to the vancomycin group (p < 0.01). However, the immunoreactivity intensity of UCHL in the vancomycin group was no statistically significantly than the immunoreactivity intensity of UCHL in the other groups (p > 0.05). In this study, it was found that melatonin treatment effects positively regeneration of sciatic nerve injury caused by vancomycin in the sciatic nerve of rats.

Alteration of Intestinal Microbiome of Clostridioides difficile-Infected Hamsters during the Treatment with Specific Cow Antibodies.

Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to the standard application of nonspecific antibiotics. To gain a deeper understanding of the role of the microbiome in the treatment of CDI with bovine antibodies, stool and intestinal fluid samples of hamsters were collected in large quantities from various treatments (>400 samples). The results show that the regeneration of the microbiome instantly begins with the start of the antibody treatment, in contrast to the Vancomycin-treated group where the diversity decreased significantly during the treatment duration. All antibody-treated hamsters that survived the initial phase also survived the entire study period. The results also show that the regeneration of the microbiome was not an antibody-induced regeneration, but a natural regeneration that occurred because no microbiota-inactivating substances were administered. In conclusion, the treatment with bovine antibodies is a functional therapy for both the acute treatment and the prevention of recurrence in hamsters and could meet the urgent need for CDI treatment alternatives in humans.

No Decrease in Infection Rate with the Use of Local Vancomycin Powder After Partial Hip Replacement in Elderly Patients with Comorbidities.

IntroductionThe goal of this study was to evaluate the effects of local intra-wound vancomycin powder (VP) administration to decrease surgical site infections (SSIs), particularly in elderly patients with comorbidities, after having undergone partial hip replacement in the treatment of intertrochanteric (ITF) or femoral neck fractures (FNF).MethodsWe retrospectively reviewed patients who underwent partial hip replacement in the treatment of ITF or FNF in one year. We divided the patients into two groups. The non vancomycin-treated group received standard systemic prophylaxis only (1 gr cefazolin IV), while the vancomycin-treated group received 1 gr of VP in the surgical wound just before surgical closure in addition to the systemic prophylaxis. We included patients of 64 years or older who also had one or more comorbidities. We compared the post-operative SSI rates between the non vancomycin-treated group and the vancomycin-treated group.ResultsA total of 93 patients were included in the study. We detected post-operative wound infection in six patients (6.4%). The rate of SSI was found to be 5.7% in the vancomycin-treated group and 6.9% in the non vancomycin-treated group respectively, which showed no statistically significant difference (p:0.498). The incidence of SSI was statistically higher in the patients who had a follow-up in the post-operative intensive care unit than the patients who had not any follow-up in the intensive care unit.ConclusionLocal application of VP in the surgical wound was found to be ineffective in reducing the incidence of SSI after partial hip replacement in elderly patients with comorbidities.

Ceftaroline versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in an experimental MRSA meningitis model

ObjectivesThe aim of this study was to compare the antibacterial activity of ceftaroline versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in an experimental rabbit meningitis model. MethodsThe antibacterial activity of ceftaroline was compared with vancomycin in the treatment of meningitis induced by MRSA strain ATCC 43300 in an experimental rabbit meningitis model. Quantitative cerebrospinal fluid (CSF) cultures were performed at the beginning of antibiotic treatment and 24h and 73h after the first antibiotic dose. Furthermore, in vitro time–kill data were investigated at 0, 2, 4, 6, 8, 12 and 24h in sterile human serum. ResultsThe difference between the control group versus both treatment groups was significant when comparing the decrease in colony counts in CSF both at 24h and 73h after the first antibiotic dose (P<0.05). At the end of the experiment, there was a significant difference in survival between both the ceftaroline-treated group and the vancomycin-treated group versus the control group, but not between the two treatment groups. ConclusionThese results suggest that the antibacterial activity of both ceftaroline and vancomycin are similar in the treatment of MRSA meningitis in an experimental rabbit meningitis model.

Comparative Effectiveness of Vancomycin and Metronidazole for the Initial Episode of Nonsevere Clostridium Difficle Infection

The infection with Clostridium difficile (CDI), which appeared at epidemic level, after acquiring the germ of some fluoroquinolone resistance genes, initially considered nosocomial infection and adverse effect post-antibiotic therapy, is affecting more and more people without risk factors and extending into the community. This paper proposes an analysis of the two main antibiotics used in therapy: metronidazole and vancomycin, the evidence of efficacy in the literature and the chemical stability of antibiotics in simulated gastrointestinal fluid. Based on UV-Vis absorption spectra, it can be considered that there are no major changes in the chemical structure of the investigated drugs in the presence of gastro-duodenal conditions. Clinical impact of comparative treatment with metronidazole and vancomycin has also been studied, in a group of 720 CDI patients hospitalized during the period 1.01.2017-31.12.2018 in the Clinical Hospital St. Parascheva of Infectious Diseases Galati. From this group, two subgroups were selected, one of 284 patients receiving oral vancomycin treatment and one group of 62 patients receiving oral metronidazole for an initial nonsevere episode of CDI. The number of days from the beginning of the treatment until the normalization of the stool, the length of hospitalization, the number of days of antibiotic treatment and the percentage of relapses were comparable in the two groups, the percentage of deaths in the first 30 days from the episode of CDI was higher in the vancomycin-treated group, probably due mainly to the severe comorbidities of these patients. The conclusion of the study is that the treatments with metronidazole and vancomycin, of the initial episode, nonsevere of CDI are comparable as a therapeutic response, provided that the patients treated with metronidazole do not associate hepatic, renal or neurological impairment due to the risk of adverse reactions.

Comparative Effectiveness of Vancomycin and Metronidazole for the Initial Episode of Nonsevere Clostridium Difficle Infection

The infection with Clostridium difficile (CDI), which appeared at epidemic level, after acquiring the germ of some fluoroquinolone resistance genes, initially considered nosocomial infection and adverse effect post-antibiotic therapy, is affecting more and more people without risk factors and extending into the community. This paper proposes an analysis of the two main antibiotics used in therapy: metronidazole and vancomycin, the evidence of efficacy in the literature and the chemical stability of antibiotics in simulated gastrointestinal fluid. Based on UV-Vis absorption spectra, it can be considered that there are no major changes in the chemical structure of the investigated drugs in the presence of gastro-duodenal conditions. Clinical impact of comparative treatment with metronidazole and vancomycin has also been studied, in a group of 720 CDI patients hospitalized during the period 1.01.2017-31.12.2018 in the Clinical Hospital St. Parascheva of Infectious Diseases Galati. From this group, two subgroups were selected, one of 284 patients receiving oral vancomycin treatment and one group of 62 patients receiving oral metronidazole for an initial nonsevere episode of CDI. The number of days from the beginning of the treatment until the normalization of the stool, the length of hospitalization, the number of days of antibiotic treatment and the percentage of relapses were comparable in the two groups, the percentage of deaths in the first 30 days from the episode of CDI was higher in the vancomycin-treated group, probably due mainly to the severe comorbidities of these patients. The conclusion of the study is that the treatments with metronidazole and vancomycin, of the initial episode, nonsevere of CDI are comparable as a therapeutic response, provided that the patients treated with metronidazole do not associate hepatic, renal or neurological impairment due to the risk of adverse reactions. Keywords: Clostridium difficile, metronidazole, vancomycine, chemical stability, UV-Vis spectra

A comparative study on the effects of vancomycin, enrofloxacin, and trimethoprim/sulfamethoxazole on methicillin-resistant Staphylococcus aureus osteomyelitis in an animal model

Osteomyelitis is a serious medical issue that is refractory to treatments. Methicillin-resistant Staphylococcus aureus (MRSA) is a major problem in cases with osteomyelitis. These S. aureus have recently developed a resistance to vancomycin, which is a choice antibiotic for osteomyelitis. Therefore, finding alternative antibiotics is highly essential for treatment of methicillin-resistant S. aureus osteomyelitis. Twenty-four New Zealand adult white rabbits were experimentally infected by the injection of 106 colony-forming unit of Staphylococcus aureus in diaphysis of the tibia. Two weeks after injection, the animals were checked by microbiological and radiological tests for osteomyelitis. All infected rabbits were randomly divided into four groups of 6 including control, vancomycin, enrofloxacin, and trimethoprim/sulfamethoxazole, and every 12 h were administered with 30, 15, and 20 mg/kg, for treatment groups, respectively. Body weight, body temperature, and heterophil/lymphocyte ratio were assessed before and after inducing osteomyelitis. Then, the animals were treated in experimental groups for 2 weeks post infection. All of the experiment and control groups were humanely sacrificed. Subsequently, the bone specimens were separated for microbiological tests. The groups treated with vancomycin and enrofloxacin had significantly lower colony counts, and lower heterophil/lymphocyte ratio than control groups after treatment (P < 0.05). In this study, enrofloxacin had comparable efficacy to that of the vancomycin-treated group. However, trimethoprim/sulfamethoxazole did not show such efficacy. It can be inferred that enrofloxacin can be an effective antibiotic for the treatment of acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus.

The impact of prophylactic intraoperative vancomycin powder on microbial profile, antibiotic regimen, length of stay, and reoperation rate in elective spine surgery

Background ContextThere is growing concern that the microbial profile of surgical site infection (SSI) in the setting of prophylactic vancomycin powder may favor more resistant and uncommon organisms. PurposeTo demonstrate the impact of prophylactic intraoperative vancomycin powder on microbial profile, antibiotic regimen, length of stay (LOS), and reoperation rate in spine surgical site infection. Study Design and/or SettingRetrospective cohort study. Patient Sample: the study included 115 postoperative spine patients who were required to return to the operating room for SSI. Outcome MeasuresThe outcome measures were microbial profile, reoperation rate, antibiotic regimen, and LOS for patients with postoperative spine infection who either did (treated) or did not (untreated) receive prophylactic vancomycin powder during their index procedure. MethodsA retrospective review of patients who underwent posterior thoracic and/or lumbar spine surgery between 2010 and 2017 was conducted. Those undergoing surgical treatment of SSI were identified, and patients were divided into two groups - those who were treated with intraoperative vancomycin (treated) and those who were not (untreated). The organism profile for each group was compared. The average LOS, reoperation rate, and number of patients requiring more than 1 antibiotic were calculated for each patient in both groups. ResultsThere were 5,909 procedures performed. One hundred and fifteen SSIs were identified, resulting in a 1.9% infection rate. Prophylactic vancomycin powder was used in the index procedure for 42 of those cases. 23.8% of cultures in the vancomycin group were polymicrobial and 16.7% were gram-negative compared with 9.6% (p=0.039) and 4.1% (p=0.021) in the untreated group, respectively. In the vancomycin-treated group, 26.1% of patients underwent repeat irrigation and debridement compared with 38.4% in the untreated group (p=0.184). The percentage of patients in the treatment and untreated group who required more than 1 antibiotic was 26.0% and 26.1%, respectively (p=0.984). Mean LOS in the treatment group was 8.0 versus 7.9 for the untreated group (p=0.945) ConclusionsIn this series, vancomycin powder was associated with a higher prevalence of gram-negative and polymicrobial organisms in patients that ultimately developed postoperative SSI. However, this did not adversely affect the need for multiple reoperations, antibiotic regimen, or LOS for these patients.

Treatment of Clostridium difficile infection in mice with vancomycin alone is as effective as treatment with vancomycin and metronidazole in combination

ObjectiveClostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in...

Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing.

Antibiotic treatment eliminates commensal bacteria and impairs mucosal innate immune defenses in the gut. However, whether oral antibiotic treatment could alter the composition of the microbiota on the skin surface and influence innate immune responses remains unclear. To test this, mice were treated with vancomycin for 7 days and then wounds were made on the back skin of the mice. Five days later, scar tissue from each mouse was collected for bacterial enumeration, the bacterial composition on the scar and unwounded skin was determined using 16S RNA gene-based pyrosequencing analysis, and skin around wounds was collected for RNA extraction. Compared with the control group, the overall density and composition of skin bacteria were altered, and the proportion of Staphylococcus-related sequences was reduced in the vancomycin-treated group. Moreover, vancomycin treatment decreased the expression of RegIIIγ and interleukin (IL)-17 in the wounded skin. Taken together, our data demonstrate that antibiotic treatment decreases the bacterial density and alters the bacterial composition in skin wounds, followed by a decrease in RegIIIγ expression, which may contribute to the delayed wound repair. Our findings also indicate that antibiotic therapy should be carefully considered in the treatment of skin injury.

Vancomycin versus Linezolid in the Treatment of Methicillin-Resistant Staphylococcus aureus Meningitis

Vancomycin is the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) meningitis. However, successful outcomes with linezolid have not been reported in a large series of patients. We conducted a single-center retrospective cohort study to compare vancomycin with linezolid in the treatment of MRSA meningitis. We extracted data and outcomes for all adult patients (age >18 years) with culture-proved MRSA meningitis who received vancomycin or linezolid between January 2006 and June 2011. A definite diagnosis of meningitis was based on the isolation of MRSA in at least one cerebrospinal fluid (CSF) culture and findings in CSF that are typical of the infection. Linezolid was given intravenously (IV) at a dosage of 600 mg q12h and vancomycin IV at 500 mg q6h. A total of 8 patients with MRSA meningitis (5 male, 3 female; age [mean±SD] 61.6±13.2 years) received vancomycin and 9 patients (7 male, 2 female; age 59.1±15.6 years) received linezolid. All isolated strains of MRSA were susceptible to both vancomycin and linezolid. The rates of microbiologic success with linezolid or vancomycin, in terms of clearance of MRSA from CSF on day 5, were 7/9 and 2/8 (p=0.044, Fisher exact test). No severe adverse events occurred in either treatment arm of the study. One-month survival of the patients in whom treatment was successful microbiologically was 2/2 in the vancomycin-treated group and 4/7 in the linezolid-treated group. Minimum inhibitory concentration (MIC) data for vancomycin were available for 5/6 treatment failures with vancomycin, and vancomycin MIC values of these five strains were 2 mg/L. Analysis of the findings in the limited cohorts in our study suggests that linezolid is superior to vancomycin for treating MRSA meningitis, especially in cases in which there is a high MIC (2 mg/L) for vancomycin. A clinical study involving larger cohorts may increase the evidence available in relation to this question.

Staphylococcus aureus Infection Induced Oxidative Imbalance in Neutrophils: Possible Protective Role of Nanoconjugated Vancomycin.

Staphylococcus aureus infection causes oxidative stress in neutrophils. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was aimed to test the protective role of nanoconjugated vancomycin against vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection induced oxidative stress in neutrophils. VSSA- and VRSA-infection were developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was treated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, and nitrite generation and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative imbalance in neutrophils.

Amelioratory Effect of Nanoconjugated Vancomycin on Spleen during VRSA-Induced Oxidative Stress.

Objective. The aim of the present study was to evaluate the possible antioxidant effects of nanoconjugated vancomycin against VRSA infection on select makers of oxidative damage and antioxidant status in spleen. Methods. A coagulase-positive VRSA strain was used for this study. VRSA infection was developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. VRSA-infected mice were treated with nanoconjugated vancomycin at its effective dose for 10 days. After decapitation, blood was used for determination of viable bacteria count and spleen was excised from control and experimental groups, homogenized and used for different biochemical estimations. Results. Nitrate level, myeloperoxidase activity, lipid peroxidation, protein oxidation, oxidized glutathione, and DNA fragmentation level were increased significantly (P < 0.05) in spleen of VRSA-infected group as compared to control group, and reduced glutathione level, activity of SOD, CAT, GPx, GR, and GST were decreased significantly (P < 0.05); which were increased or decreased significantly (P < 0.05) near to normal in nanoconjugated vancomycin-treated group. Conclusion. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VRSA-infection-induced oxidative stress and DNA damage in spleen.

Reply to Tarchini

TO THE EDITOR—We appreciate the opportunity to respond to Dr. Tarchini regarding the important questions he poses in his letter. The following addresses each of his points in turn. First, as has been repeatedly demonstrated, achievement of vancomycin trough concentrations in the range of 15–20 mcg/mL does not necessarily result in improved outcomes (compared with lower trough concentrations). There have been several papers published showing just the opposite, similar, or worse clinical outcomes [1–3] with higher rates of nephrotoxicity associated with vancomycin trough concentrations >15 mcg/mL [1–6]. Importantly, this has been demonstrated using multivariate techniques to adjust for severity of illness and other risk factors [4, 5]. We performed a similar analysis using the data from the telavancin studies, wherein we examined outcome measures by vancomycin trough category (<10 mcg/mL, 10–14 mcg/mL, and ≥15 mcg/mL) and found lower clinical response rate, higher mortality, and higher rates of nephrotoxicity in the highest trough group [7]. Importantly, Acute Physiology and Chronic Health Evaluation (APACHE) scores at baseline were also similar across the three patient groups, and the findings held up after adjusting for important covariates that would predict poor outcomes. These observations, along with the mortality reported in the vancomycin arm of the Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia trials, suggest that inadequate dosing of vancomycin in these studies is unlikely. In addition, it is important to note that the support for the vancomycin trough concentration recommendations are graded as IIIB (moderate evidence for support and from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees), which is rather soft [8]. Unfortunately, there are no adequately controlled prospective studies to support the recommended trough concentrations. Finally, the studies were conducted as registrational studies. In the recent FDA guidance on conduct of registrational trials, the following recommendation was made: “The active comparator should be an antibacterial drug at the recommended dosage that is FDA-approved for the treatment of ‘nosocomial pneumonia’” [9]. In response to Dr. Tarchini's second question, there were only 20 patients (2.7% of 754 treated) who were switched from vancomycin to an antistaphylococcal penicillin (footnote Table 3, original report) [10]. Given that the efficacy and safety outcomes of this small cohort were similar to that of the entire vancomycin-treated group, their data were included with that of the larger population. With regard to the third question, all but 19 of 92 patients with baseline blood cultures containing a respiratory pathogen had the same pathogen in respiratory cultures. Only 5 of these 19 patients were included in the microbiologically evaluable population. Identity between the two sources was based on genus, species, and antimicrobial susceptibility pattern. More sophisticated techniques to determine identity were not carried out, so it is possible that some of these patients had other sources for their bacteremia. We sincerely hope that our responses reassure the readership of the validity and robustness of the telavancin clinical trial data.

Internalization ofStaphylococcus aureusin Lymphocytes Induces Oxidative Stress and DNA Fragmentation: Possible Ameliorative Role of Nanoconjugated Vancomycin

Staphylococcus aureus is the most frequently isolated pathogen causing bloodstream infections, skin and soft tissue infections and pneumonia. Lymphocyte is an important immune cell. The aim of the present paper was to test the ameliorative role of nanoconjugated vancomycin against Vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection-induced oxidative stress in lymphocytes. VSSA and VRSA infections were developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was adminstrated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was adminstrated to VSSA- and VRSA-infected mice at a similar dose, respectively, for 10 days. Vancomycin and nanoconjugated vancomycin were adminstrated to normal mice at their effective doses for 10 days. The result of this study reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, nitrite generation, nitrite release, and DNA damage and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group, which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VSSA and VRSA infection-induced oxidative stress in lymphocytes.

Protective Effects of Caffeic Acid Phenethyl Ester, Vitamin C, Vitamin E and N‐Acetylcysteine on Vancomycin‐Induced Nephrotoxicity in Rats

The objective of this study was to compare the beneficial effects of caffeic acid phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity. Thirty rats were randomly devided into six groups: (i) control; (ii) vancomycin, 200 mg/kg administrated via intraperitoneal route; (iii) vancomycin plus CAPE-vancomycin with 10 micromol/kg CAPE; (iv) vancomycin plus vitamin C-vancomycin (intraperitoneally) with 200 mg/dl vitamin C in drinking water; (v) vancomycin plus vitamin E-vancomycin with 1000 mg/kg body weight vitamin E (intramuscularly); and (vi) vancomycin plus N-acetylcysteine-vancomycin with 10 mg/kg body weight (intraperitoneally) of N-acetylcysteine. Vancomycin treatments were started 1 day after the first administrations of these agents and continued for 7 days. At the end of the experiments, catalase activity was significantly decreased by vancomycin in kidney homogenates (P < 0.05). Vitamin E, vitamin C, N-acetylcysteine and CAPE administrations decreased the blood urea nitrogen levels increased by vancomycin, although significant differences were detected only in the vitamins E and C groups (P < 0.05). Increased renal malondialdehyde and nitric oxide levels by vancomycin were significantly suppressed by agents used in the study (P < 0.05). Histopathological examination demonstrated prominent damages in the vancomycin-treated group. Vitamin E was the most beneficial agent on vancomycin-induced tubular damage, followed by vitamin C, N-acetylcysteine and CAPE treatments, respectively. The data suggest that vitamin E, as well as vitamin C, N-acetylcysteine and CAPE, could be useful for reducing the detrimental effects on vancomycin-induced toxicity in kidneys.