Use of Colistin in Critically Ill Patients.

Due to lack of better therapeutic options, colistin use for extensively drug-resistant Gram-negative organisms was revived in the past two decades, including in patients in intensive-care units (ICU). There are multiple knowledge gaps pertaining to the clinical use and utility of colistin in critically-ill patients, but due to lack of options, it is used in these high risk patients. In this chapter, we critically review the various topics pertaining to colistin use in critically-ill patients, while highlighting the (lack of) controlled evidence supporting common current practices pertaining to colistin use by clinicians.

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP).

The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.

Treatment of complicated urinary tract infections with an emphasis on drug-resistant gram-negative uropathogens.

Complicated urinary tract infection is a challenging infection, since cure is difficult and either persistence or recurrence is common. The challenge is frequently increased because complicated urinary tract infection is often caused by gram-negative bacilli resistant to multiple antimicrobial drugs. In this review, we approach the therapy of complicated urinary tract infection with an emphasis on those caused by antimicrobial drug-resistant gram-negative uropathogens.

Revisiting "older" antimicrobials in the era of multidrug resistance.

Infections due to multidrug-resistant (MDR) organisms continue to increase, and the antimicrobial pipeline remains unacceptably lean. Given this challenge, it is has become necessary to use older antimicrobials for treatment of MDR pathogens despite concerns regarding toxicity and the lack of clinical efficacy data. In some cases, older antimicrobials offer potential advantages compared with new agents, including lower cost and better in vitro activity. In this review, we focus on the pharmacology, in vitro activity, and clinical experience of older agents, including colistin, minocycline, trimethoprim-sulfamethoxazole, and fosfomycin. We also discuss some new antimicrobial agents that are used to treat MDR pathogens. As MDR pathogens continue to outpace the development of new antimicrobials, it will become imperative to develop strategies regarding the optimal use of older agents in terms of monotherapy versus combination therapy, dosing regimens, and treatment of invasive infections caused by these pathogens.

Current use for old antibacterial agents: polymyxins, rifamycins, and aminoglycosides.

This article reviews three classes of antibacterial agents that are uncommonly used in bacterial infections and therefore can be thought of as special-use agents. The polymyxins are reserved for gram-negative bacilli that are resistant to virtually all other classes of drugs. Rifampin is used therapeutically, occasionally as a companion drug in treatment of refractory gram-positive coccal infections, especially those involving foreign bodies. Rifaximin is a new rifamycin that is a strict enteric antibiotic approved for treatment of traveler's diarrhea and is showing promise as a possible agent for refractory Clostridium difficile infections. The aminoglycosides are used mainly as companion drugs for the treatment of resistant gram-negative bacillary infections and for gram-positive coccal endocarditis.

Antibacterial agents in the elderly.

Older patients disproportionately suffer the burden of infection in the community and in health care facilities. The rational approach to antimicrobial therapy for older patients with infection requires an appreciation and understanding of the complex immunologic, epidemiologic, pharmacologic, and microbiologic factors that influence the manifestations and consequences of infection in this group. Specific recommendations for common infectious syndromes must take into account the unique needs of older patients and should be tailored for each individual case.

Current use for old antibacterial agents: polymyxins, rifamycins, and aminoglycosides.

This article reviews three classes of antibacterial agents that are uncommonly used in bacterial infections and therefore can be thought of as special-use agents. The polymyxins are reserved for gram-negative bacilli that are resistant to virtually all other classes of drugs. Rifampin is used therapeutically, occasionally as a companion drug in treatment of refractory gram-positive coccal infections, especially those involving foreign bodies. Rifaximin is a new rifamycin that is a strict enteric antibiotic approved for treatment of traveler's diarrhea and is showing promise as a possible agent for refractory Clostridium difficile infections. The aminoglycosides are used mainly as companion drugs for the treatment of resistant gram-negative bacillary infections and for gram-positive coccal endocarditis.

Mortality and time to extubation in severe hospital-acquired pneumonia.

BACKGROUND: This study examined predictors of in-hospital mortality and time to extubation among patients with acute, severe hospital-acquired pneumonia (HAP) managed in the intensive care unit (ICU). METHODS: Patients with HAP prospectively identified between June 2001 and May 2003 were included in the study if they (1) met the Centers for Disease Control and Prevention's definition for HAP, (2) were treated in the ICU within 1 day of the HAP diagnosis, and (3) required intubation acutely or had a bloodstream infection within 48 hours of the HAP diagnosis. RESULTS: The cohort included 219 patients, 83 of whom died (37.9%). Independent predictors of mortality included cancer (odds ratio [OR] = 4.2; 95% confidence interval [CI] = 1.7 to 10.5), age over 60 years (OR = 2.7; 95% CI = 1.3 to 5.6), APACHE-II score >15 (OR = 2.0; 95% CI = 1.0 to 4.1), and receiving care in the medical ICU (OR = 3.0; 95% CI = 1.1 to 8.2). The following predictors were associated with an increased time to extubation: receipt of vancomycin (1.81-fold increase; P = .001), immunocompromised status (1.92-fold increase; P = .07), and treatment in the surgical or neurosurgical ICU (1.95-fold increase, P = .01; 1.83-fold increase, P = .03). CONCLUSION: Vancomycin was associated with increased time to extubation. Alternatives to vancomycin for treating patients with acute, severe HAP should be studied.

Evaluation of ProMED-mail as an electronic early warning system for emerging animal diseases: 1996 to 2004.

OBJECTIVE: To identify emerging animal and zoonotic diseases and associated geographic distribution, disease agents, animal hosts, and seasonality of reporting in the Program for Monitoring Emerging Diseases (ProMED)-mail electronic early warning system. DESIGN: Retrospective study. SAMPLE POPULATION: 10,490 disease reports. PROCEDURES: Descriptive statistics were collated for all animal disease reports appearing on the ProMED-mail system from January 1, 1996, to December 31, 2004. RESULTS: Approximately 30% of reports concerned events in the United States; reports were next most common in the United Kingdom, Canada, Australia, Russia, and China. Rabies, bovine spongiform encephalopathy, and anthrax were reported consistently over the study period, whereas avian influenza, Ebola virus, and Hantavirus infection were reported frequently in approximately half of the study years. Reports concerning viral agents composed more than half of the postings. Humans affected by zoonotic disease accounted for a third of the subjects. Cattle were affected in 1,080 reports, and wildlife species were affected in 825 reports. For the 10,490 postings studied, there was a retraction rate of 0.01 and a correction rate of 0.02. CONCLUSIONS AND CLINICAL RELEVANCE: ProMED-mail provided global coverage, but gaps in coverage for individual countries were detected. The value of a global electronic reporting system for monitoring emerging diseases over a 9-year period illustrated how new technologies can augment disease surveillance strategies. The number of animal and zoonotic diseases highlights the importance of animals in the study of emerging diseases.

Avian influenza viruses and their implication for human health.

Widespread outbreaks of avian influenza in domestic fowl throughout eastern Asia have reawakened concern that avian influenza viruses may again cross species barriers to infect the human population and thereby initiate a new influenza pandemic. Simultaneous infection of humans (or swine) by avian influenza viruses in the presence of human influenza viruses could theoretically generate novel influenza viruses with pandemic potential as a result of reassortment of genome subunits between avian and mammalian influenza viruses. These hybrid viruses would have the potential to express surface antigens from avian viruses to which the human population has no preexisting immunity. This article reviews current knowledge of the routes of transmission of avian influenza A viruses to humans, places the risk of appearance of a new pandemic influenza virus in perspective, and describes the recently observed epidemiology and clinical syndromes of avian influenza in humans.

Principles of use of antibacterial agents.

The selection of an antimicrobial regimen is based on a number of factors, including the nature of the infection, the identity and susceptibility of the pathogens, host characteristics, and the pharmacokinetics and pharmacodynamics of antimicrobial agents. This article provides a comprehensive overview of these factors, with particular attention to pharmacokinetics and monitoring for efficacy and toxicity. A brief summary is also provided of some other topics discussed in detail elsewhere in this issue, such as susceptibility testing, pharmacodynamics, and pharmacokinetics-pharmacodynamics parameters.

Antibiotic agents in the elderly.

Diagnosis and treatment of infections in the elderly is challenging and complicated because of age-related physiologic changes and lack of classical clinical symptoms. Elderly patients are more vulnerable to infections because of their underlying diseases. This article reviews the pharmacologic issues in treating the elderly with antibiotics, the most frequently encountered infections in this patient population, and the suggested antibiotic regimens. The discussion also includes the special challenges of treating these most frequently encountered infections in the elderly who reside in long-term care facilities.

Current use for old antibacterial agents: polymyxins, rifampin, and aminoglycosides.

This article discusses three classes of antibacterial agents that are uncommonly used in bacterial infections (other than mycobacterial infections) and can be thought of as special-use agents. These are the polymyxins, rifampin, and the aminoglycosides.

Occipital neuralgia and twelfth nerve palsy from a chondromyxoid fibroma.

The purpose of this case report is to record the unusual combination of occipital neuralgia and hypoglossal nerve palsy causing dysarthria, dysphagia, and unilateral weakness of tongue protrusion, with no other neurological findings. The cause was a discrete tumor in the clivus and the right occipital condyle. Following surgical resection of the tumor, dysarthria and dysphagia persisted. These improved with therapy by a speech therapist, but deviation of the tongue persisted on protrusion. No similar case reports were found in the literature. In addition, the tumor was an unusual one, a chondromyxoid fibroma (CMF); these tumors uncommonly involve the skull base.