J. Richard Hebel

Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America (IDSA) through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of two specific types of urinary tract infections (UTIs): uncomplicated, acute, symptomatic bacterial cystitis and acute pyelonephritis in women. The guideline does not contain recommendations for asymptomatic bacteriuria, complicated UTIs, Foley catheter-associated infections, UTIs in men or children, or prostatitis. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent women. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members represented experts in adult infectious diseases and urology. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendation and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council, the sponsor and supporter of the guideline. The American Urologic Association and the European Society of Clinical Microbiology and Infectious Diseases have endorsed it. An executive summary and tables highlight the major recommendations. Performance measures are described to aid in monitoring compliance with the guideline. The guideline will be listed on the IDSA home page at http://www.idsociety.org It will be evaluated for updating in 2 years.

PREGNANCY AND THE RISK OF STROKE

BACKGROUND It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk. METHODS We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the womens medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child. RESULTS Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, adjusted age and race, was 0.7 (95 percent confidence interval, 0.3 to 1.6), but it increased to 8.7 for the postpartum period (after a live birth or stillbirth) (95 percent confidence interval, 4.6 to 16.7). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy (95 percent confidence interval, 1.0 to 6.4) but 28.3 for the postpartum period (95 percent confidence interval, 13.0 to 61.4). Overall, for either type of stroke during or within six weeks after pregnancy, the adjusted relative risk was 2.4 (95 percent confidence interval, 1.6 to 3.6), and the attributable, or excess, risk was 8.1 strokes per 100,000 pregnancies (95 percent confidence interval, 6.4 to 9.7). CONCLUSIONS The risks of both cerebral infarction and intracerebral hemorrhage are increased in the six weeks after delivery but not during pregnancy itself.

Percutaneous Vertebroplasty for Osteoporotic Compression Fractures: Quantitative Prospective Evaluation of Long-term Outcomes

PURPOSE Osteoporotic vertebral compression fractures may cause debilitating pain that lasts for weeks or months, and which is often neither quickly nor completely relieved by conventional conservative therapy. Previous retrospective studies have suggested significant and nearly immediate pain relief, as well as rapid and sustained functional recovery, after percutaneous polymethylmethacrylate vertebroplasty (PPV). This prospective, quantitative study with long-term follow-up was designed to evaluate the safety and efficacy of PPV as a new treatment for patients with osteoporotic vertebral body compression fractures of the lumbar and thoracic spine. MATERIALS AND METHODS PPV was performed in 30 patients with 54 symptomatic osteoporotic vertebral compression fractures who had a less-than-satisfactory response to conventional therapy. All procedures were performed by a single operator with significant experience in performing PPV. The Musculoskeletal Outcomes Data Evaluation and Management Scale (MODEMS) spinal intervention questionnaire, which includes the SF-36, was administered to all patients before intervention and exactly 2 weeks after the final PPV procedure. Pain and disability, treatment expectations and satisfaction, mental function, and quality of life were evaluated by four specialized modules, and responses to questionnaires preceding treatment were compared to those obtained at follow-up. Results of a long-term follow-up questionnaire were collected 15-18 months after the final vertebroplasty treatment. RESULTS Our population consisted of three men and 27 women, with a mean age of 79 years. Fifty-four PPV procedures were performed for compression fractures in these 30 patients. Significant postprocedural improvement in all four MODEMS modules was demonstrated at 2 weeks (treatment score, P <.0001; pain and disability, P <.0001; physical function, P =.0004; and mental function, P =.0009). A small epidural leak of polymethylmethacrylate in one patient was asymptomatic and did not require intervention. At long-term follow-up (15-18 mo), 22 of 23 patients responding remained satisfied with the outcome of therapy and believed that the procedure had provided durable pain relief. Verbal pain scores documented significantly diminished back pain at 2 weeks (P <.0001) and again at long-term follow-up when compared to baseline (P <.0001). CONCLUSIONS PPV is a safe and efficacious procedure for the relief of pain and disability after osteoporotic vertebral compression fractures. Patient satisfaction is high and persists when compared to preprocedural expectations; durable pain relief is provided.

Dementia as a risk factor for falls and fall injuries among nursing home residents.

Objectives: To compare rates of falling between nursing home residents with and without dementia and to examine dementia as an independent risk factor for falls and fall injuries.

Nursing home facility risk factors for infection and hospitalization: importance of registered nurse turnover, administration, and social factors.

OBJECTIVES: Determine the relationship between a broad array of structure and process elements of nursing home care and (a) resident infection and (b) hospitalization for infection.

Elevated levels of proinflammatory cytokines in the semen of patients with chronic prostatitis/chronic pelvic pain syndrome ☆

OBJECTIVES Chronic prostatitis/chronic pelvic pain syndrome is a common diagnosis, but the disease is poorly understood. The diagnosis is based only on symptoms, and no measurable parameter can help in defining the presence of the disease, its severity, or its cause. Cytokines are soluble proteins secreted by cells of the immune system that principally regulate inflammatory and immune responses. To provide an objective measure of inflammation in the genital tract, we measured levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the semen of men with chronic prostatitis/chronic pelvic pain syndrome and compared these with levels in normal men. METHODS We obtained semen samples from 18 men with chronic prostatitis/chronic pelvic pain syndrome and from 8 normal male volunteers. Cytokine levels were measured in the seminal plasma by two-antibody enzyme-linked immunosorbent assay. RESULTS Men with prostatitis had higher mean levels of IL-1 beta and TNF-alpha in seminal plasma (mean +/-SEM) than normal men: TNF-alpha 98+/-39 versus 17+/-8; IL-1 beta 246+/-63 versus 27+/-10, respectively; P <0.05. There was a strong correlation between the levels of TNF-alpha and IL-1 beta in the semen of men with chronic prostatitis/chronic pelvic pain syndrome. There was no correlation between either TNF-alpha or IL-1 beta levels and the number of leukocytes per high power field in expressed prostatic secretions in patients. CONCLUSIONS Some men with chronic prostatitis/chronic pelvic pain syndrome have elevated levels of TNF-alpha and IL-1 beta in the semen. This suggests that inflammation of the genital tract is a feature of this disease, irrespective of the presence or absence of leukocytes in the expressed prostatic secretions. Seminal cytokine levels may provide an objective measure of disease in these patients and suggest specific therapeutic strategies to treat chronic prostatitis/chronic pelvic pain syndrome in such patients.

Cognitive impairment in hip fracture patients: timing of detection and longitudinal follow-up.

Objectives: To examine the prevalence, incidence, persistence, predictors, and outcomes of cognitive impairment after hip fracture.

Role of motility in the colonization of uropathogenic Escherichia coli in the urinary tract

ABSTRACT Uropathogenic Escherichia coli (UPEC) causes most uncomplicated urinary tract infections (UTIs) in humans. Flagellum-mediated motility and chemotaxis have been suggested to contribute to virulence by enabling UPEC to escape host immune responses and disperse to new sites within the urinary tract. To evaluate their contribution to virulence, six separate flagellar mutations were constructed in UPEC strain CFT073. The mutants constructed were shown to have four different flagellar phenotypes: fliA and fliC mutants do not produce flagella; the flgM mutant has similar levels of extracellular flagellin as the wild type but exhibits less motility than the wild type; the motAB mutant is nonmotile; and the cheW and cheY mutants are motile but nonchemotactic. Virulence was assessed by transurethral independent challenges and cochallenges of CBA mice with the wild type and each mutant. CFU/ml of urine or CFU/g bladder or kidney was determined 3 days postinoculation for the independent challenges and at 6, 16, 48, 60, and 72 h postinoculation for the cochallenges. While these mutants colonized the urinary tract during independent challenge, each of the mutants was outcompeted by the wild-type strain to various degrees at specific time points during cochallenge. Altogether, these results suggest that flagella and flagellum-mediated motility/chemotaxis may not be absolutely required for virulence but that these traits contribute to the fitness of UPEC and therefore significantly enhance the pathogenesis of UTIs caused by UPEC.

Proteus mirabilis Genes That Contribute to Pathogenesis of Urinary Tract Infection: Identification of 25 Signature-Tagged Mutants Attenuated at Least 100-Fold

ABSTRACT Proteus mirabilis, a common cause of urinary tract infections (UTI) in individuals with functional or structural abnormalities or with long-term catheterization, forms bladder and kidney stones as a consequence of urease-mediated urea hydrolysis. Known virulence factors, besides urease, are hemolysin, fimbriae, metalloproteases, and flagella. In this study we utilized the CBA mouse model of ascending UTI to evaluate the colonization of mutants of P. mirabilis HI4320 that were generated by signature-tagged mutagenesis. By performing primary screening of 2,088 P. mirabilis transposon mutants, we identified 502 mutants that ranged from slightly attenuated to unrecoverable. Secondary screening of these mutants revealed that 114 transposon mutants were reproducibly attenuated. Cochallenge of 84 of these single mutants with the parent strain in the mouse model resulted in identification of 37 consistently out-competed P. mirabilis transposon mutants, 25 of which were out-competed >100-fold for colonization of the bladder and/or kidneys by the parent strain. We determined the sequence flanking the site of transposon insertion in 29 attenuated mutants and identified genes affecting motility, iron acquisition, transcriptional regulation, phosphate transport, urease activity, cell surface structure, and key metabolic pathways as requirements for P. mirabilis infection of the urinary tract. Two mutations localized to a ∼42-kb plasmid present in the parent strain, suggesting that the plasmid is important for colonization. Isolation of disrupted genes encoding proteins with homologies to known bacterial virulence factors, especially the urease accessory protein UreF and the disulfide formation protein DsbA, showed that the CBA mouse model and mutant pools are a reliable source of attenuated mutants with mutations in virulence genes.

Gender differences in mortality after hip fracture: the role of infection.

Possible explanations for the observed gender difference in mortality after hip fracture were examined in a cohort of 804 men and women. Mortality during 2 years after fracture was identified from death certificates. Men were twice as likely as women to die, and deaths caused by pneumonia/influenza and septicemia showed the greatest increase.