Trends in Sexually Transmitted Infections.

Sexually transmitted infections have increased dramatically in the past 10 years. Rates are higher in Missouri than nationally, and higher in the large urban areas, in young adults, racial minority groups, among men having sex with men, and are associated with injection drug and methamphetamine use. Clinicians need to perform an appropriate sexual history and follow guidelines for screening and treatment. There is increasing concern for resistance among gonococcal isolates which limits future treatment options.

Staphylococcus aureus Bacteremia: Contemporary Management.

Staphylococcus aureus bacteremia (SAB) is a serious cause of bloodstream infection associated with significant morbidity and mortality. Complications include deep-seated foci of infection including infective endocarditis, device-associated infection, osteoarticular metastases, pleuropulmonary involvement, and recurrent infection. With the 30-day all-cause mortality being around 20%, a collaborative effort of early Infectious Diseases (ID) consultation and Antimicrobial Stewardship Program (ASP) involvement will show improved SAB outcomes and therapy optimization.1.

Disseminated histoplasmosis presenting as dental lesion in the absence of a vital organ, the thymus.

We present a case report of a patient who has rare anatomical anomalies and presented with an oral lesion that led to a diagnosis of disseminated histoplasmosis. The case brings forth important clinical considerations for a diagnosis of histoplasmosis.

Extragenital Gonorrhea and Chlamydia Among Men and Women According to Type of Sexual Exposure.

BACKGROUND: Current guidelines recommend screening for extragenital gonorrhea (GC) and chlamydia (CT) only among men having sex with men (MSM). Extragenital GC and CT is associated with treatment failure and disease transmission. The prevalence of extragenital GC/CT infections in women and in men having sex with women (MSW) are less well studied. We sought to determine the prevalence of extragenital CG and CT among all persons attending a sexually transmitted diseases clinic who engaged in extragenital sexual activity. METHODS: We examined demographic and clinical data of all patients who engaged in extragenital sexual activity between January 2012 and October 2014. Nucleic acid amplification testing for GC and CT was performed at sites of exposure among all men and women at pharyngeal, rectal, and urogenital sites. Multivariable logistic regression analyses were performed to determine the extent that age, race/ethnicity, and number of sexual partners predicted a positive test result. RESULTS: Pharyngeal GC was found in 3.1% of MSW, representing 35% of the GC infections in MSW. Thirty-six percent of MSW with pharyngeal GC tested negative at their urogenital site. Pharyngeal GC in MSW prevalence was higher among those with younger age or a higher number of sex partners. Pharyngeal GC, rectal GC, and rectal CT rates were 8.5%, 15.0%, and 16.5%, respectively, among MSM and 3.8%, 4.8%, and 11.8% among women having sex with men (WSM), respectively. CONCLUSIONS: Extragenital GC and CT rates of infection was highest among MSM but was also observed in WSM and MSW, representing an unrecognized disease burden.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Colovesical Fistula: An Unusual Complication of Cytomegalovirus Colitis.

Cytomegalovirus (CMV) is a double-stranded DNA virus that is associated with clinically significant disease in patients with advanced immunosuppression, particularly those with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). End-organ disease with CMV is classically associated with a CD4 cell count less than 50 cells/microliter. CMV colitis is the second most common manifestation of end-organ disease in this patient population. CMV-associated enteric fistula is a rare complication that has been described in only a few case reports in the literature. These cases describe gastrocolic, enterocutaneous, enterocolic, rectovaginal, and colocutaneous fistulae. However, colovesical fistula has not been described previously. Here, we report the first case of CMV-associated colovesical fistula in a patient with HIV infection and AIDS.

Cerebrospinal fluid Coccidioides antigen testing in the diagnosis and management of central nervous system coccidioidomycosis.

The goal of this study was to report on the potential utility of cerebrospinal fluid (CSF) Coccidioides antigen testing in the diagnosis and management of Coccidioides meningitis. We retrospectively reviewed medical records of seven patients with Coccidioides meningitis who had Coccidioides antigen tests performed on CSF. In two severely immunocompromised patients, CSF Coccidioides antigen testing was helpful in the diagnosis when other testing modalities were negative. Coccidioides antigen testing was also useful in the management of patients who had progression of disease due to non-adherence, development of resistance, failure of therapy and the presence of vasculitis. Changing antigen levels helped identify disease complications in three patients that led to alterations in therapy or management. On the basis of our review of these seven patients with Coccidioides meningitis, we concluded that the Coccidioides antigen test contributed to the diagnosis and management of patients with Coccidioides meningitis.

Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.

Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91-55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL. Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

A randomized controlled trial examining the efficacy of motivational counseling with observed therapy for antiretroviral therapy adherence.

This study determined whether motivational interviewing-based cognitive behavioral therapy (MI-CBT) adherence counseling combined with modified directly observed therapy (MI-CBT/mDOT) is more effective than MI-CBT counseling alone or standard care (SC) in increasing adherence over time. A three-armed randomized controlled 48-week trial with continuous electronic drug monitored adherence was conducted by randomly assigning 204 HIV-positive participants to either 10 sessions of MI-CBT counseling with mDOT for 24 weeks, 10 sessions of MI-CBT counseling alone, or SC. Poisson mixed effects regression models revealed significant interaction effects of intervention over time on non-adherence defined as percent of doses not-taken (IRR = 1.011, CI = 1.000-1.018) and percent of doses not-taken on time (IRR = 1.006, CI = 1.001-1.011) in the 30 days preceding each assessment. There were no significant differences between groups, but trends were observed for the MI-CBT/mDOT group to have greater 12 week on-time and worse 48 week adherence than the SC group. Findings of modest to null impact on adherence despite intensive interventions highlights the need for more effective interventions to maintain high adherence over time.

Nonengagement in HIV care: a descriptive and qualitative study in hospitalized patients and community-based analysis.

Nonengagement in HIV care is a major clinical and public health challenge. To identify the risk factors and reasons, we performed (1) a retrospective study of patients admitted to the hospital with advanced HIV disease, (2) a prospective qualitative study, and (3) a population-based area-wide telephone interview. In the retrospective study, clinic care engagement was associated with age (43.9 ± 9.1 years vs 37.9 ± 7.2 years, P = .005) and improved from 23% to 44% (P = .03) after hospitalization. Survival was higher (93% vs 73%, P = .03) among those who engaged in care. Twelve inpatients were interviewed in the qualitative study. Themes identified for nonengagement were social stigma, indifference, or lack of understanding of care needs/denial and life care issues. In the population-based study, 145 patients were interviewed. In all, 49 denied the need for HIV care and 28 denied their HIV status. Stigma, denial, and indifference or lack of understanding of need are significant barriers to care engagement.

Diagnosis, initial management, and prevention of meningitis.

Although the annual incidence of bacterial meningitis in the United States is declining, it remains a medical emer- gency with a potential for high morbidity and mortality. Clinical signs and symptoms are unreliable in distinguishing bacterial meningitis from the more common forms of aseptic meningitis; therefore, a lumbar puncture with cerebro- spinal fluid analysis is recommended. Empiric antimicrobial therapy based on age and risk factors must be started promptly in patients with bacterial meningitis. Empiric therapy should not be delayed, even if a lumbar puncture cannot be performed because results of a computed tomography scan are pending or because the patient is awaiting transfer. Concomitant therapy with dexamethasone initiated before or at the time of antimicrobial therapy has been demonstrated to improve morbidity and mortality in adults with Streptococcus pneumoniae infection. Within the United States, almost 30 percent of strains of pneumococci, the most common etiologic agent of bacterial meningitis, are not susceptible to penicillin. Among adults in developed countries, the mortality rate from bacterial meningitis is 21 percent. However, the use of conjugate vaccines has reduced the incidence of bacterial meningitis in children and adults.

Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: the potential role of daptomycin.

Staphylococcus aureus bacteremia is a common disease with a high risk of mortality and complications. An increasing proportion of cases are methicillin-resistant S.aureus (MRSA), and methicillin-resistance is being observed from both community-acquired bacteremias and in healthcare-associated infections. The duration of bacteremia and transesophageal echocardiographic findings are useful in predicting the likelihood of complications including endocarditis. Therapy with vancomycin has been the mainstay in the treatment of MRSA bacteremias, but is associated with a long duration of bacteremia on therapy and relapses. Loss of susceptibility to vancomycin, due to thickened cell walls and through the acquisition of the vanA gene, has been described. Daptomycin is newly approved lipopeptide that is highly bactericidal against most strains of MRSA. In a randomized trial, daptomycin was demonstrated to be effective in the treatment of S. aureus bacteremia and right-sided endocarditis. However treatment failures associated with isolates with daptomycin non-susceptibility are reported, and there is a correlation between isolates with reduced vancomycin susceptibility and reduced daptomycin susceptibility. Daptomycin is a useful alternative to vancomycin in the therapy of MRSA bacteremia and endocarditis. However the appropriate role of daptomycin in optimizing therapy with MRSA bacteremia and endocarditis remains to be elucidated.

Neutrophil-anti-microbial interaction in the established infection: effect on Staphylococcus aureus.

OBJECTIVES: To determine if differences in drug-related Staphylococcus aureus killing, associated in vivo with neutropenia, is neutrophil-related in vitro, and the mechanisms of this interaction. METHODS: To evaluate the influence of living neutrophils on drug-S. aureus interactions, cell wall enzymes, the PBPs, were isolated and their binding to five (beta lactam and other) antibiotics was evaluated following incubation (or not) with neutrophils. S. aureus killing by the test drugs was assayed in growth media of sterile filtered abscess fluid, either neutropenic infected or normal infected. At MBCs for the test isolate, each drug or saline control was incubated with S. aureus 10(6)and dilution-plated. RESULTS: Neutrophil incubation with S. aureus eliminated the S. aureus PBP-2 band in all Western blots irrespective of the drug used to tag the PBPs. Time-kill of S. aureus grown in neutropenic or normal abscess fluid showed greater kill by all drugs in neutropenic abscess fluid (p=0.029 6h incubation). Killing difference between the media correlates with drug PBP-2 activity. CONCLUSIONS: Drug activity against S. aureus in vitro is changed by neutrophil incubation. The neutrophil-induced loss of S. aureus PBP-2 drug binding suggests novel host-bacterial interaction that may impinge on drug treatment of S. aureus infections.

Management of Staphylococcus aureus infections.

Because of high incidence, morbidity, and antimicrobial resistance, Staphylococcus aureus infections are a growing concern for family physicians. Strains of S. aureus that are resistant to vancomycin are now recognized. Increasing incidence of unrecognized community-acquired methicillin-resistant S. aureus infections pose a high risk for morbidity and mortality. Although the incidence of complex S. aureus infections is rising, new antimicrobial agents, including daptomycin and linezolid, are available as treatment. S. aureus is a common pathogen in skin, soft-tissue, catheter-related, bone, joint, pulmonary, and central nervous system infections. S. aureus bacteremias are particularly problematic because of the high incidence of associated complicated infections, including infective endocarditis. Adherence to precautions recommended by the Centers for Disease Control and Prevention, especially handwashing, is suboptimal.

Calcium-binding proteins MRP 8 and 14 in a Staphylococcus aureus infection model: role of therapy, inflammation, and infection persistence.

Concentrations of the calcium-binding proteins of the S100 family, myeloid-related proteins 8 and MRP 14 (MRP8/14), are elevated in chronic infections, yet the role of these proteins is not clearly defined. Using commercial and developed enzyme immunoassays, we assayed for MRP8/14 in sterile-filtered abscess fluid from tissue-cage-implanted rats and rabbits. Staphylococcus aureus abscesses were created 6 weeks after the intraperitoneal implantation of tissue cages. Leukocytes, bacteria, and non-protein-bound calcium and zinc were measured in the infection exudate at day 3 or 5 of infection and after 8 days of treatment with antimicrobials beta-lactams (18 rabbits, 35 rats) and fluoroquinolone-rifampin (6 rabbits). Half of the infected rats were depleted of neutrophils; these rats exhibited significantly lower MRP 8/14 concentrations on all days sampled, regardless of the level of infection. The level of abscess MRP 8/14 is high early in the course of infection but decreases with effective antimicrobial treatment by as much as 100-fold. Thirty-day-old abscesses with log 6 bacterial counts and low neutrophil counts showed low concentrations of MRP 8/14 in these models. In abscess fluid, interleukin-6, as a representative marker of inflammation, correlated with MRP8/14, whereas ionized calcium and zinc did not. Our data suggest that infection and inflammation are not equal stimuli for MRP 8/14. The neutrophil appears to be the main source of MRP8/14 in this model.

Anomalous role of tumor necrosis factor alpha in experimental enterococcal infection.

The murine D-galactosamine (D-gal) model of tumor necrosis factor alpha (TNF-alpha) hypersensitization was used as an initial tool to investigate the potential contribution of TNF-alpha to lethal intraperitoneal (i.p.) infection with Enterococcus faecalis. D-gal sensitized mice to lethal E. faecalis infection, whereas dexamethasone and neutralizing anti-TNF-alpha antibody protected D-gal-treated, E. faecalis-infected mice, implicating TNF-alpha in the lethal response to E. faecalis infection in D-gal-treated mice. Circulating TNF-alpha was undetectable for at least 8 h following i.p. E. faecalis infection, although low peritoneal levels of TNF-alpha were detected within 3 h, suggesting that localized TNF-alpha production contributed to the lethal response to E. faecalis infection in D-gal-treated mice. Although i.p. E. faecalis infection failed to induce a detectable systemic TNF-alpha response, circulating Interleukin-6 (IL-6) was detected within 3 h of infection. IL-6 was also detected in the peritoneum within an hour of infection, prior to the appearance of peritoneal TNF-alpha. In striking contrast to in vivo results, E. faecalis induced a potent and rapid TNF-alpha response from both mouse peritoneal macrophages and the RAW 264.7 cell line in vitro. This led us to hypothesize that TNF-alpha production in response to E. faecalis infection is suppressed by IL-6 in vivo. In vitro experiments demonstrated a statistically significant, but modest, inhibitory effect of IL-6 on TNF-alpha production by RAW cells stimulated with E. faecalis. Collectively, these data indicate that acute, lethal E. faecalis infection appears to induce an unusual cytokine response that differs in character from that previously described for most other gram-positive and gram-negative bacteria.

Effects of neutrophils on cefazolin activity and penicillin-binding proteins in Staphylococcus aureus abscesses.

Bacteria survive within abscesses despite antimicrobial therapy, usually necessitating drainage. Our previous work showed that bacterial killing is diminished within the neutrophils of animals with abscesses. To further assess the role of neutrophils in Staphylococcus aureus survival and the poor activities of beta-lactams in abscesses, tissue cage abscess-bearing rats were given polymorphonuclear leukocyte (PMN)-depleting antibody prior to and several times following inoculation of the tissue cages with S. aureus. Cefazolin (300 mg/kg of body weight/day) was administered to all animals in appropriately divided doses. After 7 days of antimicrobial therapy, the 17 animals that received anti-PMN serum had significantly fewer abscess neutrophils than the 18 controls and fewer abscess bacteria (5.55 versus 3.79 log(10) CFU/ml [P = 0.04]) than the 18 controls. The data were consistent with the premise that cefazolin is more effective in abscesses depleted of neutrophils. To investigate further, S. aureus was incubated with rat peritoneal neutrophils; and bacterial cell membrane proteins were isolated, labeled with biotinylated ampicillin, separated by electrophoresis, blotted onto nitrocellulose, and stained for biotin reactivity. PBP 2 expression was consistently and significantly decreased after a brief, nonkilling PMN exposure. These experiments showed that PMN depletion enhanced the activity of cefazolin in the abscess milieu. Furthermore, altered bacterial cell wall cefazolin targets may be the mechanism by which the PMN diminishes antimicrobial activity, suggesting the importance of the staphylococcus-PMN interaction in the outcome of established infections.

Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS.

BACKGROUND: In patients with moderate to severe histoplasmosis associated with AIDS, the preferred treatment has been the deoxycholate formulation of amphotericin B. However, serious side effects are associated with use of amphotericin B. OBJECTIVE: To compare amphotericin B with liposomal amphotericin B for induction therapy of moderate to severe disseminated histoplasmosis in patients with AIDS. DESIGN: Randomized, double-blind, multicenter clinical trial. SETTING: 21 sites of the U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group. PATIENTS: 81 patients with AIDS and moderate to severe disseminated histoplasmosis. MEASUREMENTS: Clinical success, conversion of baseline blood cultures to negative, and acute toxicities that necessitated discontinuation of treatment. RESULTS: Clinical success was achieved in 14 of 22 patients (64%) treated with amphotericin B compared with 45 of 51 patients (88%) receiving liposomal amphotericin B (difference, 24 percentage points [95% CI, 1 to 52 percentage points]). Culture conversion rates were similar. Three patients treated with amphotericin B and one treated with liposomal amphotericin B died during induction (P = 0.04). Infusion-related side effects were greater with amphotericin B (63%) than with liposomal amphotericin B (25%) (P = 0.002). Nephrotoxicity occurred in 37% of patients treated with amphotericin B and 9% of patients treated with liposomal amphotericin B (P = 0.003). CONCLUSION: Liposomal amphotericin B seems to be a less toxic alternative to amphotericin B and is associated with improved survival.

Osteomyelitis.

Preview Infection of bone remains difficult to treat, despite recent advances in antimicrobial therapy and refinements in surgical technique. To add to the challenge, studies have been inconclusive in establishing the best method of obtaining a culture specimen, comparing the effectiveness of one drug regimen versus another, and determining the proper duration of antibiotic therapy. Dr Bamberger summarizes his experience with hematogenous osteomyelitis and osteomyelitis secondary to a contiguous focus of infection.