Successful treatment of a left ventricular assist device infection with daptomycin non-susceptible methicillin-resistant Staphylococcus aureus: case report and review of the literature.

Recipients of left ventricular assist devices (LVADs) are highly susceptible to the development of infections with multidrug-resistant (MDR) organisms. We describe the case of a patient with an LVAD who developed a device-related, daptomycin non-susceptible, methicillin-resistant Staphylococcus aureus infection, highlighting this patient population as highly vulnerable to the development of such antimicrobial resistance. This report includes a thorough review of the literature on the mechanisms of development of daptomycin non-susceptibility and suggests ways to prevent its emergence. We also provide and underscore the appropriate guidelines to abide by when attempting to control infections with such resistant isolates. This case also demonstrates the importance of definitive treatment with LVAD removal and transplantation as a component of appropriate management of invasive LVAD infections. In addition, we suggest that even infections with MDR organisms may not adversely affect post-transplant outcomes.

Acute (ascending) cholangitis.

Cholangitis is an infection of an obstructed biliary system, most commonly due to common bile duct stones. Bacteria reach the biliary system either by ascent from the intestine or by the portal venous system. Once the biliary system is colonized, biliary stasis allows bacterial multiplication, and increased biliary pressures enable the bacteria to penetrate cellular barriers and enter the bloodstream. Patients with cholangitis are febrile, often have abdominal pain, and are jaundiced. A minority of patients present in shock with hypotension and altered mentation. There is usually a leukocytosis, and the alkaline phosphatase and bilirubin levels are generally elevated. Noninvasive diagnostic techniques include sonography, which is the recommended initial imaging modality. Standard CT, helical CT cholangiography, and magnetic resonance cholangiography often add important information regarding the type and level of obstruction. Endoscopic sonography is a more invasive means of obtaining high-quality imaging, and endoscopic or percutaneous cholangiography offers the opportunity to perform a therapeutic procedure at the time of diagnostic imaging. Endoscopic modalities currently are favored over percutaneous procedures because of a lower risk of complication. Treatment includes fluid resuscitation and antimicrobial agents that cover enteric flora. Biliary decompression is required when patients do not rapidly respond to conservative therapy. Definitive therapy can be performed by a surgical, percutaneous, or endoscopic route; the last is favored because it is the least invasive and has the lowest complication rate. Overall prognosis depends on the severity of the illness at the time of presentation and the cause of the biliary obstruction.

Effect of highly active antiretroviral therapy on the incidence of HIV-associated malignancies at an urban medical center.

The widespread use of highly active antiretroviral therapy (HAART) since 1996 has led to a substantial decline in morbidity and mortality in patients infected with HIV, although its effect on the incidence of HIV-associated malignancies is unknown. We retrospectively reviewed the annual number of outpatient visits to our HIV clinic, inpatient admissions for HIV disease, and first admissions for patients with cancer and HIV disease at our center between 1990 and 1997. Between 1990 and 1995, there was a progressive increase in the annual number of admissions for HIV disease and HIV-associated cancers that paralleled the increasing HIV clinic volume. In 1997, however, the annual number of first admissions for Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma compared with 1995 decreased by 36% and 63%, respectively, despite a continued increase in the annual number of HIV clinic visits. Similar declines were also noted in the number of new cases of biopsy-confirmed KS and primary central nervous system (CNS) lymphoma. In contrast, there was no decrease in the number of first admissions for patients with HIV infection and other cancers not typically associated with HIV infection. These findings suggest a declining incidence of HIV-associated malignancies since the introduction of HAART.

Opportunistic infection and immunologic function in patients with human immunodeficiency virus-associated non-Hodgkin's lymphoma treated with chemotherapy.

BACKGROUND: The incidence of systemic non-Hodgkin's lymphoma (NHL) is higher in the population infected with human immunodeficiency virus (HIV) than in the uninfected population. Standard treatment for this cancer involves the administration of systemic chemotherapy. PURPOSE: Our objective was to determine the relative risk (RR) of opportunistic infection and the relative change in immunologic function in a cohort of patients who had HIV-associated NHL and who were treated with combination chemotherapy and to compare them with those in a matched cohort of control subjects who had advanced HIV infection but no signs of NHL. METHODS: We performed a case-control study in which the clinical course of each patient with HIV-associated NHL (n = 43; case subjects) treated with infusional cyclophosphamide, doxorubicin, and etoposide was compared with that of two patients with HIV infection but without lymphoma who were matched for CD4 lymphocyte count and prior opportunistic infection (n = 86; control subjects). The patients' medical records were reviewed for all information related to acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections, survival, cause of death, and lymphocyte subset analyses. Univariate and multivariate analyses were performed to determine whether any of a number of confounding factors (e.g., age, sex, CD4 count, prior opportunistic infection, and prior antiretroviral therapy) could have influenced the risk of developing a first infectious event (defined as opportunistic infection or nonlymphoma death). All P values resulted from two-sided statistical tests. RESULTS: In the univariate analysis, a significantly greater risk for a first event was associated with being a case subject (RR = 1.8; 95% confidence intervals [CI] = 1.1-3.0; P < .05), having a low CD4 count (< 100/microL) (RR = 3.1; 95% CI = 1.8-5.4; P < .0001), being female (RR = 1.7; 95% CI = 1.1-3.3; P < .05), having prior Pneumocystis carinii pneumonia (RR = 3.5; 95% CI = 1.9-6.3; P < .0001), having any prior opportunistic infection (RR = 3.6; 95% CI = 2.1-6.4; P < .0001), and having prior antiretroviral therapy (RR = 1.9; 95% CI = 1.1-3.3; P < .05). In the multivariate analysis, however, being a case subject (RR = 2.1; 95% CI = 1.2-3.6; P < .01), having a low CD4 count (RR = 2.1; 95% CI = 1.2-3.9; P < .05), and being female (RR = 3.0; 95% CI = 1.8-5.6; P < .001) were the only characteristics associated with an increased risk of a first event. When the mean CD4 lymphocyte count at approximately 1 year was compared with that at baseline, there was a significantly greater decrease in the CD4 count among case subjects than among control subjects (mean decrease +/- standard deviation [SD] = 99/microL +/- 138/microL versus 29/microL +/- 100/microL; P = .03). CONCLUSIONS: Treatment of patients who have HIV-associated NHL with a non-steroid-containing chemotherapy regimen was associated with a significant and sustained reduction in the CD4 lymphocyte count and a twofold increase in the risk of developing opportunistic infection. IMPLICATIONS: Oncologists and other physicians who treat patients with HIV-associated NHL should be familiar with the prophylaxis, recognition, and management of opportunistic infection. In addition, there is a need to identify effective strategies for the amelioration of chemotherapy-induced immunosuppression in this population.

Mycobacterium marinum infection in a patient with the acquired immunodeficiency syndrome.

A variety of mycobacterial organisms may infect patients with acquired immunodeficiency syndrome. A patient with acquired immunodeficiency syndrome, lymphoma, and sporotrichoid Mycobacterium marinum is described. The patient responded completely to antimycobacterial therapy but relapsed when he discontinued his medications six months into his course. Disease persistence in spite of therapy had been noted in other immunocompromised states but not previously in acquired immunodeficiency syndrome. Patients with acquired immunodeficiency syndrome may require prolonged treatment or suppressive therapy for Mycobacterium marinum infections.

Z DNA and loop structures by immunoelectronmicroscopy of supercoiled pRW751, a plasmid containing left-handed helices.

Single and multiple loops were seen when the plasmid pRW751 was allowed to react with anti-Z-DNA or with a Z-specific cross-linking agent. Loop formation was dependent upon negative supercoiling and the presence of Z-specific antibody or cross-linking agent. Restriction enzyme mapping located 18 sites at the bottoms of loops, in addition to the two (dG-dC)n inserts of pRW751. No more than 5 loops were seen in any of the measured molecules; thus, not all potential Z-sites assume the Z conformation at any particular time. Stretches of alternating purine-pyrimidine sequences occur at all 20 sites. Almost all of the Z sites could be mapped to regions located at the beginnings or ends of reading frames or at various regulatory sites. Our findings support the concept that supercoiling brings distant sequences to within 5A of one another, allowing joint participation in regulatory processes controlled by DNA-binding proteins.

Intervening sequences in human fetal globin genes adopt left-handed Z helices.

The large intervening sequences ( IVS2 ) of three human fetal globin genes contain tracts of alternating purine-pyrimidine sequences approximately 40-60 base pairs in length which adopt left-handed Z DNA helices under the influence of negative supercoiling. The amount of negative supercoiling (approximately 0.045) required for the right- to left-handed transitions is within the physiological range. The structural aberrations between the right- and left-handed helices were mapped by sequencing the S1 nuclease cleavage sites. Two-dimensional gel electrophoretic analyses of the supercoil-induced relaxation served to characterize the type and length of left-handed structure. Furthermore, binding studies with several types of antibodies confirmed the presence of left-handed helices. Since these simple sequences appear to be hotspots for recombination and gene conversion, unusual DNA conformations may participate in genetic expression.

An immunochemical examination of acetylaminofluorene-modified poly(dG-dC) X poly(dG-dC) in the Z-conformation.

Immunization of rabbits with a complex of methylated bovine serum albumin and N-2-acetylaminofluorene (AAF)-modified poly(dG-dC) X poly(dG-dC), a polynucleotide that can assume the Z-DNA conformation, yielded several populations of antibodies specific for Z-DNA determinants. The Z-DNA determinants were analyzed by examination of the antisera and of antibody preparations purified on immunoadsorbents. The following was found: AAF-poly(dG-dC) X poly(dG-dC) shared Z-DNA determinants in common with poly(dG-dC) X poly(dG-dC) in 3.0 M NaCl, poly(dG-m5dC) X poly(dG-m5dC) in 1.5 M NaCl, and brominated poly(dG-dC) X poly(dG-dC) in 0.2, 1.5, and 3.0 M NaCl. Included among the antibodies induced by these determinants was a subpopulation whose reaction with brominated poly(dG-dC) X poly(dG-dC) was sensitive to increased ionic strength. Another distinct population of antibodies recognized determinants present on AAF-poly(dG-dC) X poly(dG-dC) but not on the other Z-DNAs. Only a small portion of this population was specific for the AAF moiety; the greater part appeared to recognize Z-DNA-associated conformational characteristics that were unique to AAF-poly(dG-dC) X poly(dG-dC). These findings are consistent with the existence of a continuum of Z-DNA determinants, which might be capable of functioning as recognition signals for regulatory DNA-binding proteins.

Stabilization of (dG-dC)n.(dG-dC)n in the Z conformation by a crosslinking reaction.

(dG-dC)n.(dG-dC) was converted to the Z conformer by heating in the presence of Mn++n. Reaction of this preparation with the crosslinking reagent, DL-diepoxybutane (DEB), stabilized this conformer so that it retained its structure even when returned to conditions that favored reversion to the B conformation. Treatment of the crosslinked Z conformer with periodate caused scission of the crosslink, allowing reversion to the B conformer. Reaction of (dG-dC)n.(dG-dC)n in the B conformation with DEB did not prevent conversion to the Z conformer in 4M NaC1; dialysis of the high salt solution against low ionic strength buffer allowed return to the B conformer. The Z in equilibrium B transitions were followed by circular dichroism studies and immunochemical procedures. The results suggest the feasibility of stabilizing Z sequences of DNA in chromatin by crosslinking, so that they could then be identified after DNA isolation.