Retreatment of Hepatitis C Infection With Direct-Acting Antivirals.

BACKGROUND: Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) results in sustained virologic response (SVR) in > 90% of patients. However, some patients required retreatment with newer DAA options. Treatment was selected after consultation with a clinical pharmacy specialist. METHODS: A retrospective chart review of patients at the West Palm Beach Veterans Affairs Medical Center (WPBVAMC) in Florida retreated from January 2015 to December 2019 was conducted. Data collected included HCV genotype, previous therapy, newly prescribed medications, and treatment outcomes. RESULTS: Since 2015, > 900 patients have been treated at WPBVAMC, including 22 patients who had previously failed interferon combined with DAA regimens and 46 patients who needed retreatment after failure with an all-oral therapy. This review documents the outcomes of retreatment with DAA after initial failure to achieve SVR Of 28 patients treated with a boceprevir-based regimen, 10 ended in failure. All 10 were retreated, and all achieved SVR with ledipasvir/sofosbuvir. Of 53 patients treated with a sofosbuvir-based interferon regimen, 12 failed treatment. All 12 were retreated and all achieved SVR. Thirty patients were retreated after failure with an all-oral DAA. Of 27 tested, 21 achieved SVR. All patients who failed therapy again had cirrhosis. CONCLUSIONS: Veterans retreated with DAAs for HCV infection had a high success rate. Repeat failures of DAAs were rare, but cirrhosis seems to be common among these patients.

Pharmacotherapy for methicillin-resistant Staphylococcus aureus nosocomial pneumonia.

OBJECTIVE: To review the evidence for pharmacologic agents available in the treatment of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. DATA SOURCES: A search of PubMed (1975-July 2012) was conducted using a combination of the terms methicillin-resistant Staphylococcus aureus, pneumonia, nosocomial, vancomycin, linezolid, telavancin, ceftaroline, tigecycline, and quinupristin/dalfopristin. STUDY SELECTION AND DATA EXTRACTION: Randomized comparative clinical trials, meta-analyses, and review articles published in English were included. A manual review of the bibliographies of available literature was conducted and all relevant information was included. Observational and in vitro studies were incorporated as indicated. DATA SYNTHESIS: Pharmacotherapy for the treatment of nosocomial MRSA pneumonia is limited. Vancomycin has been the treatment of choice for several years. Linezolid has demonstrated similar efficacy to vancomycin in randomized clinical trials and recent data have suggested that it may be superior in some cases, although there are limitations to this conclusion. Telavancin has also demonstrated similar clinical efficacy to vancomycin; however, the drug is not commercially available in the US. Other agents with MRSA activity include ceftaroline, clindamycin, quinupristin/dalfopristin, and tigecycline, although the evidence for their use in nosocomial pneumonia is limited. CONCLUSIONS: Based on the currently available evidence and cost-effectiveness, vancomycin should continue to be the drug of choice for most patients with nosocomial MRSA pneumonia. Linezolid is a reasonable alternative for patients with treatment failure while receiving vancomycin, isolates with vancomycin minimum inhibitory concentrations over 2 µg/mL, allergic reactions, or vancomycin-induced nephrotoxicity.

Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis in patients without gastrointestinal bleeding.

OBJECTIVE: To review relevant studies for both primary and secondary antibiotic prophylaxis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis without gastrointestinal bleeding. DATA SOURCES: A search of PubMed (1980-July 2010) was conducted using the terms prophylaxis, SBP, and antibiotics. A manual review of bibliographies was conducted for inclusion of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Prospective studies and meta-analyses published in English were included. DATA SYNTHESIS: Ten trials and 3 meta-analyses were included. Of the 10 trials, 2 examined the use of secondary prophylaxis for prevention of subsequent episodes of SBP, 4 examined the use of primary prophylaxis to prevent an initial SBP episode, and 4 examined the use of antibiotic prophylaxis in a mixed population. Seven trials evaluated the use of an antibiotic compared to placebo or no treatment. Only 1 trial evaluated norfloxacin versus trimethoprim/sulfamethoxazole. Trial duration varied from 24 days to 12 months. In general, trials examining norfloxacin as secondary prophylaxis found significantly decreased occurrence of SBP but no significant difference in mortality rates. Primary prophylaxis studies found no significant difference in the incidence of infections, including SBP, with norfloxacin or ciprofloxacin treatment but significantly lower incidence of gram-negative infections. Mixed population studies found a significantly decreased incidence of SBP but no significant difference in mortality. In the 3 meta-analyses, a significant decrease in mortality and an overall decrease in SBP incidence in the treatment groups were noted. CONCLUSIONS: Based on currently available data, the use of prophylactic antibiotic therapy is warranted for the prevention of recurrent SBP in patients with cirrhosis and ascites. In patients with low ascetic fluid protein and at least 1 more risk factor, primary prophylaxis may be considered. Further studies with improved methodology are needed to determine whether prophylactic antibiotic therapy has an impact on mortality.

Population mobility, globalization, and antimicrobial drug resistance.

Population mobility is a main factor in globalization of public health threats and risks, specifically distribution of antimicrobial drug-resistant organisms. Drug resistance is a major risk in healthcare settings and is emerging as a problem in community-acquired infections. Traditional health policy approaches have focused on diseases of global public health significance such as tuberculosis, yellow fever, and cholera; however, new diseases and resistant organisms challenge existing approaches. Clinical implications and health policy challenges associated with movement of persons across barriers permeable to products, pathogens, and toxins (e.g., geopolitical borders, patient care environments) are complex. Outcomes are complicated by high numbers of persons who move across disparate and diverse settings of disease threat and risk. Existing policies and processes lack design and capacity to prevent or mitigate adverse health outcomes. We propose an approach to global public health risk management that integrates population factors with effective and timely application of policies and processes.

Antibiotic prophylaxis in acute necrotizing pancreatitis revisited.

OBJECTIVE: To review studies of antibiotic prophylaxis in acute necrotizing pancreatitis published in the last decade and update recommendations. DATA SOURCES: A search of PubMed (1998-July 2009) was conducted using the terms necrotizing pancreatitis, antibiotics, prophylaxis, and treatment. Clinical studies, meta-analyses, and review articles published in English were included. Additional references were obtained from article bibliographies. Randomized trials published before 1998 were included if indicated. STUDY SELECTION AND DATA EXTRACTION: Relevant studies or meta-analyses on antibiotic prophylaxis since our previous review in 1998 were evaluated; older data were included if still relevant. DATA SYNTHESIS: Since our previous review, 4 more randomized trials, including 2 double-blind trials, have been conducted. The blinded studies found no significant difference in mortality with antibiotic prophylaxis compared with placebo, while the unblinded studies found a significant decrease in infections. Given these disparate results, available guidelines and meta-analyses provide different conclusions, usually based on exclusion or inclusion of a single trial. Based on all available data, antibiotic prophylaxis should not be used in patients with necrotizing pancreatitis. Instead, a more measured, on-demand use of antibiotics is preferred. Antibiotics should be added if signs and symptoms of infection are present (eg, fever, leukocytosis, positive results of cultures). Given improvements in intensive care and nutritional support, recent trials have found a lower incidence of infected necrotizing pancreatitis than before. Therefore, future trials are likely to need higher numbers of patients. CONCLUSIONS: Use of antibiotic prophylaxis for patients with necrotizing pancreatitis is not indicated, based on 2 blinded trials. Instead, on-demand use of antibiotics appears to be appropriate. Given progress in intensive care and the high crossover rate in studies, the need for antibiotic prophylaxis may continue to be debated for decades.

Recommendations for training and certification for pharmacists practicing, mentoring, and educating in infectious diseases pharmacotherapy.

Recently created guidelines for the development of institutional antimicrobial stewardship programs recommend that a pharmacist with infectious diseases training be included as a core member of the antimicrobial stewardship team. However, training and certification requirements for infectious diseases-trained clinical pharmacists have not been established. Although pharmacists have nurtured their interest in infectious diseases by self-directed learning or on-the-job experiences, this mode of training is not considered feasible or sufficient for reliable training of future clinical specialists in infectious diseases. This document, therefore, is forward looking and provides overarching recommendations for future training and certification of pharmacists practicing, mentoring, and educating in infectious diseases pharmacotherapy, with the recognition that full implementation may take several years. We recommend that future pharmacists wishing to obtain a clinical position as an infectious diseases-trained pharmacist should complete a postgraduate year (PGY) 1 residency and a PGY2 residency in infectious diseases, that practitioners become board-certified pharmacotherapy specialists, that a certification examination in infectious diseases be developed, that practitioners maintain a portfolio of educational experiences to maintain qualifications, that current nonaccredited training programs seek accreditation, and that employers and academicians recognize the desirability of these qualifications in hiring decisions.

Manifestations, diagnosis, and treatment of Strongyloides stercoralis infection.

OBJECTIVE: To summarize current literature on the manifestations, diagnosis, and treatment of Strongyloides stercoralis infection. DATA SOURCES: A search was conducted of PubMed (1970-August 2007). Search terms included Strongyloides stercoralis, hyperinfection, prevention, and treatment. Reviews, studies, and recent case reports were included. Additional references were obtained from article bibliographies. STUDY SELECTION AND DATA EXTRACTION: All studies or review articles published in English from 1970 to August 2007 and case reports of hyperinfection or disseminated disease published since 2000 were evaluated. DATA SYNTHESIS: Strongyloidiasis is a parasitic infection endemic to tropical, subtropical, and temperate areas including the Appalachian region of the southern US. Prevalence rates vary widely. Patients may present with infection decades after original exposure. Diagnosis can be achieved by identifying the larvae in the stool; usually, more than one sample is needed. Most patients are asymptomatic. However, in immunosuppressed patients, a hyperinfection syndrome or disseminated disease may occur due to the ability of the parasite to reproduce within the host. The most common risk factors for these complications are immunosuppression caused by corticosteroids and infection with human T lymphotropic virus type 1. Treatment options for uncomplicated disease include thiabendazole, ivermectin, and albendazole. Thiabendazole has been replaced by ivermectin as treatment of choice due to better tolerance. These antihelminthics have been used to treat hyperinfection or disseminated disease alone or in combination, but data are limited to case reports or case series. Prevention of disease is mainly achieved by wearing shoes in endemic areas to avoid contact with infected soil. CONCLUSIONS: Strongyloides is a unique parasite that can cause a hyperinfection syndrome and disseminated infection several years after exposure. Treatment options include ivermectin, thiabendazole, or albendazole. Information on the best treatment for disseminated disease and hyperinfection is limited.

Probiotics for Clostridium difficile-associated diarrhea: focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii.

OBJECTIVE: To review the literature on the use of probiotics to treat or prevent recurrences of Clostridium difficile-associated diarrhea (CDAD) by replacing normal gastric flora. DATA SOURCES: PubMed (1970-March 2007) was searched using the terms probiotics, Clostridium difficile, colitis, diarrhea, prevention, and treatment. STUDY SELECTION AND DATA EXTRACTION: Case reports, case series, and clinical trials describing the use of probiotics in the treatment or prevention of recurrences of CDAD as primary outcome were included. DATA SYNTHESIS: A variety of controlled trials, case series, and case reports have evaluated probiotics to treat first or recurrent episodes of CDAD. In addition, a meta-analysis has been conducted to try to determine the role of probiotics in CDAD. In general, most case series and case reports have shown favorable results with Lactobacillus rhamnosus GG or Saccharomyces boulardii. However, other reports have shown lack of benefit. The meta-analysis showed that these probiotics may be useful in treating or preventing recurrences of CDAD. Nonetheless, the heterogeneity of the studies makes definite conclusions difficult. In addition, several cases of bacteremia or fungemia associated with probiotic use have been reported, particularly in the last decade. Patients most commonly affected by these complications are immunosuppressed. Unfortunately, these are also the patients more likely to have severe CDAD or are at risk for recurrences. CONCLUSIONS: Additional experience with and study of probiotics are warranted due to numerous unanswered questions. Given the potential for complications in debilitated and immunosuppressed patients, the risks may outweigh benefits, and rational antibiotic use may be a better option to prevent a first episode or recurrence of CDAD.

Effectiveness and hepatotoxicity of statins in men seropositive for hepatitis C virus.

STUDY OBJECTIVE: To evaluate the effectiveness and hepatotoxicity of statins in patients who are seropositive for hepatitis C virus (HCV). DESIGN: Retrospective review of a registry of patients with HCV. SETTING: Veterans Affairs Medical Center. PATIENTS: One hundred forty-six male patients who were seropositive for HCV and had received statin therapy between January 1, 1995, and September 9, 2003. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected for each patient; lipid and alanine aminotransferase (ALT) levels at baseline (within 6 mo of starting a statin), at 3 and 6 months after starting a statin, and at long-term follow-up (mean 22 mo) were also recorded. The primary efficacy end point was a significant decrease from baseline to long-term follow-up low-density lipoprotein cholesterol (LDL) level; the primary safety end point was a significant increase from baseline in ALT level. The mean change in LDL level was a reduction of 22% (p<0.01). No significant increases in ALT levels were observed; only one patient discontinued therapy due to ALT level elevations greater than 3 times the upper limit of normal. CONCLUSION: In men seropositive for HCV, statins were effective in reducing LDL levels and did not result in significant increases in ALT levels from baseline. Thus, statin therapy should be considered for patients with HCV who are at risk for coronary heart disease and do not have significantly elevated serum transaminase levels at baseline.

Antibiotic lock technique: a review of the literature.

OBJECTIVE: To review the literature on the use of the antibiotic lock technique (ALT) as a treatment option for patients with highly needed catheters. DATA SOURCES: MEDLINE and International Pharmaceutical Abstracts were searched (1980-August 2004). Search terms included antibiotic lock, catheter infection, and topical treatment. STUDY SELECTION AND DATA EXTRACTION: Articles describing use of ALT in the treatment of catheter infections in humans and studies evaluating in vitro stability of antibiotics were included. DATA SYNTHESIS: ALT has been used in patients with highly needed catheters, usually for parenteral nutrition, cancer chemotherapy, or dialysis. Catheters are considered highly needed when removal is not feasible or desirable due to lack of alternative injection sites for required therapy. Success rates in saving the infected catheter have been variable and may depend on the infecting organism. In addition, there are conflicting data in terms of compatibility of antibiotics with heparin solutions. CONCLUSIONS: Consensus appears to be that the ALT can be tried for patients with highly needed catheters when infection with coagulase-negative staphylococci is documented and no systemic signs of sepsis, such as hypotension, are evident. Most of these patients are likely to need systemic therapy as well. Infection of the catheter associated with systemic gram-negative bacteremia or fungemia will most likely require removal of the catheter to prevent systemic complications. Additional research with the ALT is warranted given unanswered questions.

Probable vancomycin-induced neutropenia.

OBJECTIVE: To report a case of vancomycin-induced neutropenia and provide a review of the literature. CASE SUMMARY: A 64-year-old white man was treated with intravenous vancomycin 1.5 g/day for finger osteomyelitis. He developed neutropenia after 21 days of vancomycin therapy. The absolute neutrophil count reached a nadir of 418 cells/mm(3) during vancomycin use and returned to normal 7 days after its discontinuation. The eosinophil count was also elevated during the neutropenic episode and probably related to vancomycin. Based on the Naranjo probability scale, the reaction was probably related to vancomycin use. DISCUSSION: Articles describing cases of vancomycin-induced neutropenia were identified. All patients developed neutropenia as a result of vancomycin therapy >/=12 days. Neutrophil counts generally increased following discontinuation of vancomycin. One article reported successful resolution of neutropenia and infection by switching the patient's therapy to the structurally related antibiotic agent teicoplanin. Other patients were continued on vancomycin therapy, and neutropenia was treated with moderate to good success with filgrastim. Rechallenge was not generally attempted. The mechanism of neutropenia caused by vancomycin is unclear, but appears to be immune-mediated. CONCLUSIONS: Vancomycin therapy should not be prolonged unless absolutely necessary, and therapy should be reserved for patients with clear indications for the drug, such as infections due to gram-positive organisms resistant to other therapies. Patients should have periodic assessment of white blood cell and neutrophil counts with consideration to discontinue vancomycin if neutropenia develops.

Valganciclovir: A new oral alternative for cytomegalovirus retinitis in human immunodeficiency virus-seropositive individuals.

Oral valganciclovir recently was approved by the Food and Drug Administration for treatment of cytomegalovirus (CMV) retinitis. We performed MEDLINE (June 1998-May 2002) and AIDSLINE (June 1998-December 2000) searches of available information on valganciclovir, and the drug's prescribing information was used to identify relevant articles. Additional studies, case reports, reviews, and abstracts were identified from references in the reviewed literature. Most of the information was obtained from abstracts or product labeling, since few trials have been published in the medical literature. Valganciclovir is a prodrug of ganciclovir and has been shown to have significantly higher oral absorption than ganciclovir capsules. One short-term study found valganciclovir to be as effective as intravenous ganciclovir in treating CMV retinitis. Recommended dosages for patients with normal renal function are valganciclovir 900 mg twice/day for induction and 900 mg once/day for maintenance. Side effects are similar to those of intravenous ganciclovir and require periodic monitoring of complete blood count and renal function. Given the need for lifelong therapy for CMV retinitis in some human immunodeficiency virus-positive patients, valganciclovir is a welcome alternative to long-term administration of intravenous antivirals.

Hyperlipidemia in HIV-positive patients receiving antiretrovirals.

OBJECTIVE: To assess the frequency of lipid abnormalities and treatment outcomes for hyperlipidemia in HIV-positive patients receiving antiretroviral (ARV) therapy as outpatients at a Veterans Affairs HIV clinic. METHODS: All patients monitored for at least 3 months were reviewed. Data collected included age, most recent CD4+ cell count and viral load, ARV history, and all fasting cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) values. The ARV therapy at the time of lipid readings was classified as including protease inhibitors (PI+) or not including them (PI-). Lipid values were compared with goals per national guidelines and risk factors. RESULTS: Male patients (n = 101) providing 210 lipid profiles were evaluated (median 2 per patient). Median age was 51 years. Fourteen patients were diabetic, 31 were hypertensive, and 6 patients had documented coronary disease. Mean cholesterol, triglycerides, and LDL values were significantly higher in PI+ (n = 50) compared with those of PI- patients (n = 51; p < 0.05). HDL values were not different between groups. Significantly more PI+ patients had lipid concentrations above recommended goals compared with PI- patients (17 vs. 7; p = 0.04). Six patients achieved lipid goals after following a low-fat diet (4 PI+). Fifteen subjects (11 PI+) were being treated with medications. Ten patients (67%) reached lipid goals, 2 had not reached goals (13%), and 3 (20%) were undergoing medication titration. CONCLUSIONS: Our HIV-infected patients had significantly higher cholesterol, triglyceride, and LDL values when PI+. In contrast to other reports, the majority of patients treated for lipid abnormalities achieved treatment goals.