Subhashis Mitra

Recurrent Urinary Tract Infections in Kidney Transplant Recipients

Urinary tract infections (UTIs) are the most common infectious complication after kidney transplantation (KT). Recurrent UTIs after KT can contribute to increased morbidity and may also be associated with graft loss and mortality. Though several risk factors like female gender, diabetes mellitus, presence of ureteric stents, native kidney disease with urological malformations and re-transplantation have been associated with recurrent UTIs after KT, vesicoureteric reflux appears to be a unique risk factor in this patient population. The emergence of drug-resistant pathogens as causative agents for post-transplant recurrent UTIs poses a significant therapeutic challenge. The use of pathogen-specific antibiotic therapy guided by culture and sensitivity data is warranted. The optimal duration of antimicrobial therapy for recurrent UTIs in renal transplant recipients remains uncertain.

Swallow Syncope: A Case Report and Review of the Literature

Swallow or deglutition syncope is a relatively rare syndrome. It is a vagally mediated syncope induced by swallowing. Swallow syncope may occur in all age groups and, when diagnosed, is treatable. A woman, aged 60 years, presented with an episode of a syncopal attack associated with swallowing a sandwich. She had a 6-month history of recurrent episodes of lightheadedness while eating solid foods. Telemetry monitoring demonstrated several episodes of severe bradycardia and complete atrioventricular block with up to a 7.0 second pause associated with meals. Computed tomography of the head and neck revealed no significant findings, and barium esophagram was normal. Echocardiogram was within normal limits. Her symptoms resolved after permanent pacemaker placement. Herein, we review the diagnosis, mechanism, and management of swallow syncope.

Gastric Antral Vascular Ectasia: Case Report and Review of the Literature

Gastric antral vascular ectasia is the source of up to 4% of nonvariceal upper gastrointestinal bleeding. It can present with occult bleeding requiring transfusions or with acute gastrointestinal bleeding. It is associated with significant morbidity and mortality and has been associated with such underlying chronic diseases as scleroderma, diabetes mellitus, and hypertension. Approximately 30% of cases are associated with cirrhosis. We report two cases of gastric antral vascular ectasia with two strikingly different endoscopic appearances. We further describe the clinical, endoscopic, histologic, and therapeutic aspects of this entity.

Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections.

Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA.

Diagnosis, treatment, and prevention of anal cancer.

Rare in the general population, anal cancer has reached epidemic proportions among HIV-infected men who have sex with men (MSM). These cancers are human papillomavirus (HPV)-associated, usually HPV type16, and are analogous to cervical cancer. At present, the rates of anal cancer in this group are 10-fold higher than that of cervical cancer occurring in women in the general population. Although there are no national guidelines for screening for anal intraepithelial dysplasia (AIN), many large HIV clinics are now performing anal cytologic screening in their at-risk patients. This paper outlines the current approach to screening for AIN and its management.

Immunogenicity of 13-Valent Conjugate Pneumococcal Vaccine in Patients 50 Years and Older with End-Stage Renal Disease and on Dialysis

ABSTRACT Patients with end-stage renal disease (ESRD) and on dialysis are at increased risk of pneumococcal disease. We evaluated the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in this population. Eligible patients with ESRD and on dialysis were given a single dose of PCV13. The concentrations of serum antibodies against 13 pneumococcal capsular polysaccharides were measured at the baseline and at 2 and 12 months postvaccination. A response to the vaccine was defined as a ≥2-fold increase in antibody concentration from that at the baseline and an absolute postvaccination value of at least 1 μg/ml. Seventeen patients completed the study. Increases in the concentrations of antibodies to the vaccine serotype were demonstrated 2 months after vaccination. The geometric mean antibody concentrations at 12 months postvaccination declined by 38% to 72% compared to those measured at 2 months postvaccination. A response to at least 1 serotype in the vaccine was seen in all patients at both 2 and 12 months postvaccination. The overall rate of the response to each individual vaccine serotype varied between 23.5% and 94.1% at 2 months postvaccination and 23.5% and 65% at 12 months postvaccination. Pain at the injection site was the most common local reaction. Vaccination with PCV13 induces antibody responses to vaccine serotypes in patients with ESRD and on dialysis at 2 months postvaccination. However, the decline in antibody concentrations at 12 months postvaccination with a conjugate pneumococcal vaccine requires further study. (This study has been registered at ClinicalTrials.gov under registration no. NCT01974817.)

Pharmacokinetic and Pharmacodynamic Analysis of Ceftazidime/Avibactam in Critically Ill Patients

BACKGROUND The pharmacokinetics, especially the volume of distribution (Vd), of ß-lactam antibiotics can be altered in critically ill patients. This can lead to decreased serum concentrations and a reduction in clinical cures. Ceftazidime/avibactam (CZA) is a new antimicrobial agent utilized in critically ill patients although its pharmacokinetics has not been well defined in these patients. PATIENTS AND METHODS In this study, the serum concentrations of CZA from adult patients treated in an intensive care unit (ICU) with standard dosing regimens were measured and both pharmacokinetic and pharmacodynamic parameters were computed. The pharmacodynamic analyses included Monte Carlo simulations to determine the probability of target attainment (PTA: free ceftazidime concentrations exceed the minimum inhibitory concentration [MIC] for 50% of the dosing interval; free avibactam concentrations exceed 1 mg/L over the dosing interval) and serum time-kill curves against multi-drug-resistant Enterobacteriaceae susceptible to CZA. Serum concentrations were measured in 10 critically ill patients at two, four, six, and eight hours after multiple doses (infused over two hours) of CZA. RESULTS A significant linear relation between creatinine clearance and total body clearance was identified for both ceftazidime (R = 0.91) and avibactam (R = 0.88). The mean clearance, volume of distribution, and half-life for ceftazidime were 6.1 ± 3.8 L/h, 35 ± 10.5 L, and 4.8 ± 2.15 h, respectively. For avibactam, these values were 11.1 ± 6.8 L/h, 50.8 ± 14.3 L, and 4.1 ± 2.1 h, respectively. Ceftazidime/avibactam achieved optimal PTA for bacteria with MICs of 16 mg/L or less. Furthermore, time-kill experiments revealed that serum concentrations of CZA, at each collection time, exhibited bactericidal (≥ 3 log10 CFU/mL reduction) activity against each of the study isolates. CONCLUSION In conclusion, our study results suggest that the current dosing regimens of CZA can provide effective antimicrobial activity in ICU patients against CZA-susceptible (MIC ≤8 mg/L) isolates.

Cytomegalovirus infection in immunocompetent adults: Is observation still the best strategy?

Cytomegalovirus (CMV) infection in immunocompetent patients generally resolves with few sequelae. However, it can cause severe and relapsing symptoms that can last for several weeks. Due to the self-limiting nature of CMV disease in immunocompetent individuals, criteria for specific antiviral therapy in this cohort are not well established. Additionally the adverse effect profile of currently available anti-CMV therapy limits its use in specific patient populations .We describe 3 immunocompetent adults who developed symptomatic CMV infection and were ill for several weeks. All patients had positive CMV viral assays and ultimately received anti-CMV therapy with significant improvement in symptoms within a few days of starting therapy. Choosing appropriate candidates for anti-CMV therapy, among mmunocompetent individuals, requires further research.

1103Immunogenicity of 13-valent conjugate pneumococcal vaccine in patients 50 years or older with end stage renal disease on dialysis

Patients with end-stage renal disease (ESRD) and on dialysis are at increased risk of pneumococcal disease. We evaluated the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in this population. Eligible patients with ESRD and on dialysis were given a single dose of PCV13. The concentrations of serum antibodies against 13 pneumococcal capsular polysaccharides were measured at the baseline and at 2 and 12 months postvaccination. A response to the vaccine was defined as a ≥2-fold increase in antibody concentration from that at the baseline and an absolute postvaccination value of at least 1 μg/ml. Seventeen patients completed the study. Increases in the concentrations of antibodies to the vaccine serotype were demonstrated 2 months after vaccination. The geometric mean antibody concentrations at 12 months postvaccination declined by 38% to 72% compared to those measured at 2 months postvaccination. A response to at least 1 serotype in the vaccine was seen in all patients at both 2 and 12 months postvaccination. The overall rate of the response to each individual vaccine serotype varied between 23.5% and 94.1% at 2 months postvaccination and 23.5% and 65% at 12 months postvaccination. Pain at the injection site was the most common local reaction. Vaccination with PCV13 induces antibody responses to vaccine serotypes in patients with ESRD and on dialysis at 2 months postvaccination. However, the decline in antibody concentrations at 12 months postvaccination with a conjugate pneumococcal vaccine requires further study. (This study has been registered at ClinicalTrials.gov under registration no. NCT01974817.).

Treatment of clostridium difficile infection with tigecycline proof of concept study

BackgroundCases of tigecycline treatment, as single or adjacent therapy, have been reported in patients with Clostridium difficile infection (CDI). At present, there have not been any controlled investigations of tigecycline in this patient population. MethodsTen hospitalized adult patients with CDI were treated with standard doses of intravenous tigecycline and oral vancomycin or metronidazole therapy. Susceptibility testing and polymerase chain reaction ribotyping of C difficile isolates were performed on initial fecal specimens. Blood and fecal concentrations of tigecycline were determined on day 3 of treatment by high-performance liquid chromatography. The efficacy and safety of treatment was assessed each day of hospitalization and for 30 days after discharge. ResultsThe C difficile isolates cultured from these patients exhibited similar minimum inhibitory concentrations (range, 0.125–0.25 mg/L) to tigecycline irrespective of ribotype. The mean ± SD fecal concentration of tigecycline (17.8 ± 23.8 &mgr;g/g) on day 3 of treatment was almost 100 times higher than the corresponding mean ± SD serum level (0.18 ± 0.14 mg/L). No serious untoward events occurred during this study, but 2 patients had mild nausea associated with tigecycline administration. In general, these patients did well after hospital discharge, but one had recurrent CDI and was hospitalized during the follow-up period. ConclusionsThe results from this investigation support further study of intravenous tigecycline in patients with CDI.