Trends in hospitalizations with antibiotic-resistant infections: U.S., 1997-2006

Objectives

Antibiotic resistance is a significant global problem, but the trends in prevalence and impact of antibiotic resistance in hospitalizations in the United States are unclear. We evaluated the trends in hospitalizations associated with antibiotic-resistant infections in U.S. hospitals from 1997 to 2006.

Methods

We analyzed the National Hospital Discharge Survey (NHDS) during 1997–2006 (unweighted n=3.3 million hospitalizations; weighted n=370.3 million hospitalizations) and examined trends in prevalence of hospitalizations with antibiotic-resistant infections, length of stay, and discharge status.

Results

The number of infection-related hospitalizations with antibiotic resistance increased 359% during the 10-year period, from 37,005 in 1997 to 169,985 in 2006. The steepest rise was seen among individuals <18 years of age. The mean age of individuals with infection-related hospitalizations that had antibiotic-resistant infections decreased substantially, from 65.7 years (standard error [SE] = 2.01) in 1997 to 44.2 years (SE=1.47) in 2006. As the proportion of patients with antibiotic-resistant infections who did not have insurance increased, the length of stay for those hospitalizations had a corresponding decrease (r=0.91, p<0.01).

Conclusions

Antibiotic-resistant infections are becoming increasingly commonplace in hospitalizations in the U.S., with a steady upward trend between 1997 and 2006. Antibiotic-resistant infections are increasingly being seen in younger patients and those without health insurance.Despite the clear benefits of antibiotic therapy for a variety of infectious diseases, the widespread use of these agents has facilitated the emergence of a variety of antibiotic-resistant pathogens.¹ Because of the significant impact antibiotic resistance has on morbidity and mortality, it is considered a threat to U.S. public health and national security by the Institute of Medicine and the Infectious Diseases Society of America.^2,3Since the 1990s in the United States, the prevalence of antibiotic resistance has increased for a variety of pathogens. Increased resistance has been found for Neisseria gonorrhoeae, Salmonella ser Typhi, Escherichia coli, and Mycobacterium tuberculosis.^4–7 In particular, the emergence of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) has raised serious questions about the ability to treat some of these new resistant pathogens.^8,9 At first, many of these resistant organisms were confined to hospitalized populations; however, in recent years the emergence of community-associated infections with these resistant organisms has become more common.^10,11 Community-associated MRSA is particularly important because it is not simply an extension of hospital-associated MRSA into the community, but rather a different strain.The purpose of this study was to describe the trends in hospitalizations and deaths associated with antibiotic-resistant infections in U.S. hospitals from 1997 to 2006.     

Intimate Partner Violence Among Men Having Sex with Men,Women, or Both: Early-Life Sexual and Physical Abuse as Antecedents

Little is known about the prevalence of intimate partner violence (IPV) among men who have sex with men (MSM) or about childhood adversity as a predictor of IPV among MSM. Studies have documented high rates of childhood sexual abuse among MSM. To evaluate associations of early-life sexual and physical abuse with IPV among African American heterosexual men or MSM, prevalence of early-life (≤21 years) sexual and physical abuse was measured among 703 nonmonogamous African American men. Men were classified as (1) MSM who disclosed male sex partners; (2) MSM who initially denied male sex partners but subsequently reported oral-genital and anal-genital behaviors with men; (3) non-MSM. MSM who initially disclosed male sex partners reported significantly (P < 0.0001) higher rates of early physical abuse (36%) and lifetime abuse (49%) compared with non-MSM (15 and 22%), respectively. These MSM reported significantly higher rates of sexual abuse by age 11, age 21, and over a lifetime compared with non-MSM (P < 0.0001). Being an MSM who initially disclosed male sex partners (OR: 2.1; 95% CI: 1.2, 3.6) and early-life sexual abuse (OR: 2.8; 95% CI: 1.8, 4.3) was associated with IPV victimization in current relationships. Similarly, being an MSM with early-life physical and sexual abuse was associated (0.0004 ≤ P ≤ 0.07) with IPV perpetration. Early-life physical and sexual abuse was higher among MSM who disclosed male sex partners compared with heterosexual men; however, all MSM who experienced early-life abuse were more likely to be IPV victims or perpetrators.     

Optimization of 3-(phenylthio)quinolinium compounds against opportunistic fungal pathogens

Ring-opened benzothieno[3,2-b]quinolinium salts (3) were designed and synthesized with substitution on the thiophene moiety. In vitro screenings were carried out against fungal pathogens including Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida krusei and Aspergillus fumigatus. In all, by replacing the N-methyl group (2) with N-ω-phenylpentyl or ω-cyclohexylpentyl group to form substituted 3-(phenylthio)quinolinium compounds produced remarkable potencies, as high as 300-fold (cf, cryptolepine (1) = 250 μg/mL vs 11p = 0.8 μg/mL for C. albicans) over the starting tetracyclic parent. In addition, all the N-ω-cyclohexylpentyl analogs produced superior activity against all the microorganisms tested than the N-ω-phenylpentyl substituted compounds. The potential of these compounds to induce toxicity in Vero cells was also investigated and the majority of them showed lower or no cytotoxicity at 10 μg/mL than amphotericin B, the gold standard in antifungal drug development. For instance, the trifluoromethyl substituted analogs (11n-p) have selectivity indices over 2-fold better than those of amphotericin B in C. neoformans. Overall, this ring-opened scafford of benzothienoquinolines, with substitution on the thiophenyl moiety, serves as a new lead for further development.     

Map: study sites in the special issue on structural vulnerability: Latino migrants in the United States

The map and index presented here accurately represent the places the authors involved in the special theme on structural vulnerability in Latino migrants in the United States (in Medical Anthropology, Volume 30, Numbers 4 and 5) have worked and undertaken research as pertains to the articles they wrote.     

Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy

Gene-corrected patient-specific induced pluripotent stem (iPS) cells offer a unique approach to gene therapy. Here, we begin to assess whether the mutational load acquired during gene correction of iPS cells is compatible with use in the treatment of genetic causes of retinal degenerative disease. We isolated iPS cells free of transgene sequences from a patient with gyrate atrophy caused by a point mutation in the gene encoding ornithine-δ-aminotransferase (OAT) and used homologous recombination to correct the genetic defect. Cytogenetic analysis, array comparative genomic hybridization (aCGH), and exome sequencing were performed to assess the genomic integrity of an iPS cell line after three sequential clonal events: initial reprogramming, gene targeting, and subsequent removal of a selection cassette. No abnormalities were detected after standard G-band metaphase analysis. However, aCGH and exome sequencing identified two deletions, one amplification, and nine mutations in protein coding regions in the initial iPS cell clone. Except for the targeted correction of the single nucleotide in the OAT locus and a single synonymous base-pair change, no additional mutations or copy number variation were identified in iPS cells after the two subsequent clonal events. These findings confirm that iPS cells themselves may carry a significant mutational load at initial isolation, but that the clonal events and prolonged cultured required for correction of a genetic defect can be accomplished without a substantial increase in mutational burden.