Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

Acinetobacter baumannii: Emergence of a Successful Pathogen

We may soon be facing the end of the “antibiotic era.” The initial and seemingly unstoppable success of antibiotics, the fruit of human ingenuity, has been countered by an escalation of resistance mechanisms in bacteria. This crisis has been described as an “unwinnable war” (www.wellcome.org). The statistics compiled as a result of surveillance efforts illustrate the emergence of many genera of bacteria that are resistant to all antibiotics (57, 60). The genus Acinetobacter epitomizes this trend and deserves close attention. Acinetobacter spp. display mechanisms of resistance to all existing antibiotic classes as well as a prodigious capacity to acquire new determinants of resistance (7). The increasing recovery in the clinic of multidrug-resistant (MDR) Acinetobacter baumannii is a frightening reality (112). This review summarizes the worldwide emergence of antibiotic-resistant A. baumannii as a nosocomial pathogen and focuses on its mechanisms of resistance against selected antibiotics. It concludes with a summary of current strategies in the treatment of MDR A. baumannii and offers perspectives on the control of this global public health threat.

Global Challenge of Multidrug-Resistant Acinetobacter baumannii

Resistance to macrolides and lincosamides is increasingly reported in clinical isolates of gram-positive bacteria. The multiplicity of mechanisms of resistance, which include ribosomal modification, efflux of the antibiotic, and drug inactivation, results in a variety of phenotypes of resistance. There is controversy concerning the clinical relevance of in vitro macrolide resistance. Recent data, however, have shown that eradication of bacteria correlates with clinical outcome of acute otitis media in children and that macrolide therapy results in delayed eradication of macrolide-resistant pneumococci. These results support the need for in vitro detection of macrolide resistance and correct interpretation of susceptibility tests to guide therapy.

Mechanisms of Resistance to Macrolides and Lincosamides: Nature of the Resistance Elements and Their Clinical Implications

After they were first identified in the mid-1980s, vancomycin-resistant enterococci (VRE) spread rapidly and became a major problem in many institutions both in Europe and the United States. Since VRE have intrinsic resistance to most of the commonly used antibiotics and the ability to acquire resistance to most of the current available antibiotics, either by mutation or by receipt of foreign genetic material, they have a selective advantage over other microorganisms in the intestinal flora and pose a major therapeutic challenge. The possibility of transfer of vancomycin resistance genes to other gram-positive organisms raises significant concerns about the emergence of vancomycin-resistant Staphylococcus aureus. We review VRE, including their history, mechanisms of resistance, epidemiology, control measures, and treatment.

Vancomycin-resistant enterococci.

Attempts to optimize quality of life in woman with epilepsy should include a reliable method for birth control, including oral contraceptives (OC). One of these methods is hormonal oral contraception. The classic antiepileptic drugs (AEDs)--Phenytoin, Phenobarbital, Ethosuximide and Carbamazepine induce hepatic microsomal enzymes and decrease the production of estradiol and progesterone, that may be compromise the effects of OC. Recommendation for women taking OC include possible use of noninducing AEDs (Valproic acid), new AEDs--Lamotrigine, Gabapentin, Topiramate, Tiagabine or for patients taking inducing AEDs use of an OC containing > or = 50 micrograms. estrogen. Patients should be warned that midcycle bleeding indicates possible OC failure and that the absence of such bleeding is not an indication of OC effectiveness. Additional contraceptive methods are also advised. The authors report their own experience in 12 women taking AEDs and OC.

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Antimicrobial drug resistance in pathogens causing nosocomial infections at a university hospital in Taiwan, 1981-1999.

Clinical infections caused by Flavobacterium indologenes have never been documented. Thirteen isolates derived from seven patients with indwelling device-associated F. indologenes infections were identified from 1 April through 30 November 1995. The antimicrobial susceptibilities to 20 antimicrobial agents of the isolates, the cellular fatty acid chromatograms for the isolates, and the random amplified polymorphic DNA (RAPD) patterns generated by arbitrarily primed PCR of the isolates were studied. The antibiotypes and RAPD patterns differed among the isolates recovered from different patients. However, both antibiotypes and RAPD patterns were identical among the five isolates from one patient with multiple episodes of central venous catheter-associated bacteremia within a 1.5-month period and between the two isolates from another patient suffering from two episodes of catheter-related bacteriuria at an interval of 14 days. It is documented that the recurrent infections in each of these two patients were caused by a single F. indologenes clone, respectively. Identical antibiotypes and RAPD patterns were also demonstrated between two isolates from a patient with ventilator-associated pneumonia, one recovered from an endotracheal aspirate and the other derived from a blood specimen 10 days later, indicating the invasive nature of F. indologenes. Two cellular fatty acid chromatograms were identified among these isolates. All of the isolates showed in vitro resistance to cephalothin, cefotaxime, ceftriaxone, moxalactam, aztreonam, aminoglycosides, erythromycin, clindamycin, vancomycin, and teicoplanin. F. indologenes should be included as an etiologic agent of infections associated with the use of indwelling devices.

Clinical and microbiological characteristics of Flavobacterium indologenes infections associated with indwelling devices.

Arcobacter cryaerophilus group 1B, a gram-negative, curved or helical bacillus primarily known as a bovine and porcine pathogen, was isolated from the blood of a uremic patient with hematogenous pneumonia. The patient was treated successfully with ceftizoxime and tobramycin.

https://jcm.asm.org/content/jcm/35/2/489.full.pdf

Bacteremia caused by Arcobacter cryaerophilus 1B.

Objective:To describe the incidence and patterns of nosocomial fungal infection in a large teaching hospital in Taiwan.Design:Prospective, hospitalwide nosocomial surveillance data from 1981 through 1993 were analyzed to show the secular trend in nosocomial fungal infection rates and to identify the most common pathogens and sites of infection (other than skin) in this hospital.Setting and Patients:The National Taiwan University Hospital is a medical school-affiliated hospital in the city of Taipei, Taiwan, with a 1,200-bed capacity before 1991 and 1,500 beds since 1992. It provides both primary and tertiary medical care.Results:The overall nosocomial fungal infection rate rose from 0.9 infections per 1,000 discharges in 1981 to 6.6 per 1,000 discharges in 1993, with the highest rate at the medical intensive-care unit (26.5/1,000 discharges in 1993). This increase in infection rate was found at four major anatomic sites of infection, particularly including the bloodstream (0.08-2.19/1,000 discharges) and the urinary tract (0.36-2.95/1,000 discharges). Of 256 pathogens causing nosocomial fungemia from 1981 through 1993, Candida albicans was the most commonly isolated (50.8%), followed by Candida tropicalis (17.6%), Candida parapsilosis (11.7%), and Candida glabrata (8.2%). As compared to isolates from 1981 through 1988, the proportion of C parapsilosis and C glabrata isolated between 1989 and 1993 increased more than sixfold and fourfold, respectively. The increasing importance of fungal infections was confirmed further by the increased use of amphotericin B and azoles in this hospital.Conclusions:Candida species and other yeasts have become a prominent cause of nosocomial infections in this hospital. These fungal pathogens accounted for a higher proportion of nosocomial bloodstream and urinary infections than any single bacterial species. Therefore, it is important to conduct a prospective epidemiological study and to establish in vitro antifungal susceptibility testing to enhance efforts to control nosocomial fungal infections and to minimize the risk of emergence of antifungal resistance.

Secular trends in the epidemiology of nosocomial fungal infections at a teaching hospital in Taiwan, 1981 to 1993

The prevalence of drug-resistant bacterial pathogens is very high in Taiwan. Accordingly, there was great concern that the introduction of fluconazole would result in rapid emergence of drug-resistant yeasts. Thus, we recommended in 1991 that fluconazole be used for treatment only. To explore the impact of this policy fluconazole susceptibility of Candida species blood culture isolates and outcome of patients with noso- comial candidaemia were monitored prospectively at National Taiwan University Hospital during 1994-2000. The MICs of fluconazole were determined by the disc diffusion method. There were 1095 episodes of noso- comial candidaemia during 1994-2000. Candida albicans was the most common species (50.4%), followed by Candida tropicalis (20.5%), Candida parapsilosis (14.2%) and Candida glabrata (12.0%). There were 0-2 isolates of Candida krusei per year. The incidence of nosocomial candidaemia and the proportion of C. glabrata peaked in 1996 and decreased thereafter. Fluconazole susceptibility was determined for 552 Candida blood isolates. Only 0.7% of blood isolates were resistant to fluconazole. Fluconazole susceptibility was 94.0% in 1994-1995 and 97.9% in 1999-2000 (P = 0.06). Attributable mortality for patients with noso- comial candidaemia was 43.2% in 1994-1995 and was 25% in 2000 (P = 0.005). Despite an increase in the incidence of nosocomial fungal infection and increased consumption of fluconazole from 1994 to 2000, there was no significant change in the susceptibility to fluconazole for bloodstream isolates of Candida species. These findings appear to be attributed to several factors. These include low prevalence of C. krusei and C. glabrata, changing patterns of use of antifungal drugs and broad-spectrum antibiotics, and efforts to improve the rational use of antifungal agents at our hospital.

Wei-Chuan Hsieh

Papers

Antimicrobial drug resistance in pathogens causing nosocomial infections at a university hospital in Taiwan, 1981-1999.

Clinical and microbiological characteristics of Flavobacterium indologenes infections associated with indwelling devices.

Bacteremia caused by Arcobacter cryaerophilus 1B.

Secular trends in the epidemiology of nosocomial fungal infections at a teaching hospital in Taiwan, 1981 to 1993

Stable susceptibility of Candida blood isolates to fluconazole despite increasing use during the past 10 years