Clinical Professor, Medicine - Infectious Diseases
Infective endocarditis is an uncommon manifestation of infection with Histoplasma capsulatum. The diagnosis is frequently missed, and outcomes historically have been poor. We present 14 cases of Histoplasma endocarditis seen in the last decade at medical centers throughout the United States. All patients were men, and 10 of the 14 had an infected prosthetic aortic valve. One patient had an infected left atrial myxoma. Symptoms were present a median of 7 weeks before the diagnosis was established. Blood cultures yielded H. capsulatum in only 6 (43%) patients. Histoplasma antigen was present in urine and/or serum in all but 3 of the patients and provided the first clue to the diagnosis of histoplasmosis for several patients. Antibody testing was positive for H. capsulatum in 6 of 8 patients in whom the test was performed.Eleven patients underwent surgery for valve replacement or myxoma removal. Large, friable vegetations were noted at surgery in most patients, confirming the preoperative transesophageal echocardiography findings. Histopathologic examination of valve tissue and the myxoma revealed granulomatous inflammation and large numbers of organisms in most specimens. Four of the excised valves and the atrial myxoma showed a mixture of both yeast and hyphal forms on histopathology.A lipid formulation of amphotericin B, administered for a median of 29 days, was the initial therapy in 11 of the 14 patients. This was followed by oral itraconazole therapy, in all but 2 patients. The length of itraconazole suppressive therapy ranged from 11 months to lifelong administration. Three patients (21%) died within 3 months of the date of diagnosis. All 3 deaths were in patients who had received either no or minimal (1 day and 1 week) amphotericin B.
View details for DOI 10.1097/MD.0000000000000034
View details for PubMedID 25181311
The continuing emergence of infections due to multidrug resistant bacteria is a serious public health problem. Klebsiella pneumoniae, which commonly acquires resistance encoded on mobile genetic elements, including ones that encode carbapenemases, is a prime example. K. pneumoniae carrying such genetic material, including both blaKPC and genes encoding metallo-β-lactamases, have spread globally. Many carbapenemase-producing K. pneumoniae are resistant to multiple antibiotic classes beyond β-lactams, including tetracyclines, aminoglycosides, and fluoroquinolones. The optimal treatment, if any, for infections due to these organisms is unclear but, paradoxically, appears to often require the inclusion of an optimally administered carbapenem.
View details for DOI 10.12703/P6-80
View details for PubMedID 25343037
Emerging viral pathogens include newly discovered viruses as well as previously known viruses that are either increasing, or threatening to increase in incidence. While often first identified in the general population, they may affect transplant recipients, in whom their manifestations may be atypical or more severe. Enhanced molecular methods have increased the rate of viral discovery but have not overcome the problem of demonstrating pathogenicity. At the same time, improved clinical diagnostic methods have increased the detection of re-emerging viruses in immunocompromised patients. In this review, we first discuss viral diagnostics and the developing field of viral discovery and then focus on rare and emerging viruses in the transplant population: HTLV-1; HEV; bocavirus; KI and WU polyomaviruses; coronaviruses HKU1 and NL63; influenza, H1N1; measles; dengue; rabies; and LCMV. Detection and reporting of such rare pathogens in transplant recipients is critical to patient care and improving our understanding of post-transplant infections.
View details for DOI 10.1093/cid/cit456
View details for Web of Science ID 000325168100022
Objectives: To describe and discuss the utility and potential pitfalls of ribosomal RNA locus sequencing for direct identification of invasive fungi from fresh and formalin-fixed, paraffin-embedded specimens. Methods: DNA was extracted from fresh and formalin-fixed, paraffin-embedded tissue and subjected to real-time polymerase chain reaction (PCR) targeting ITS2 and D2 regions of fungal ribosomal RNA locus. Cycle sequencing was performed on PCR products, and the identity of sequences was determined using a public database. Results: Four clinical cases of invasive fungal infection are presented to illustrate the utility of DNA sequencing for determining etiology when microbiological culture is negative, for shortening the time to identification of slow-growing fungi, for guiding antifungal therapy, and for shedding light on the pathogenesis of disseminated fungal infection. Conclusions: Fungal ribosomal RNA locus sequencing from fresh or formalin-fixed, paraffin-embedded specimens is a powerful tool for rapid and accurate diagnosis of patients with culture-negative or uncultured invasive mycosis.
View details for DOI 10.1309/AJCPNSU2SDZD9WPW
View details for Web of Science ID 000322149600010
Vancomycin is often combined with a second antibiotic, most often rifampin or gentamicin, for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Published data from experiments evaluating these and other vancomycin-based combinations, both in vitro and in animal models of infection, often yield inconsistent results, however. More importantly, no data are available from randomized clinical trials to support their use, and some regimens are known to have potential toxicities. Clinicians should carefully reconsider the use of vancomycin-based combination therapies for the treatment of infection due to methicillin-resistant S. aureus.
View details for DOI 10.1086/605572
View details for Web of Science ID 000269672300013
View details for PubMedID 19725789
Inadvertent exposure to Coccidioides species by laboratory staff and others as a result of a mishap is not an uncommon cause of infection in clinical microbiology laboratories. These types of infection may occur in laboratories outside the endemic areas, because the etiologic agent is unexpected in the submitted specimens and because personnel may be unfamiliar with the hazards of dealing with Coccidioides species in the laboratory. Coccidioidal infections are often difficult to treat, and outcomes can be poor. Here, we emphasize prevention and an approach to a laboratory accident that minimizes the risk of exposure to laboratory staff and staff in adjacent areas. On the basis of an artificially large exposure to arthroconidia that may occur as a result of a laboratory accident, a conservative approach of close observation and early treatment of exposed staff is discussed.
View details for DOI 10.1086/605441
View details for Web of Science ID 000269145100014
View details for PubMedID 19663562
Ceftobiprole is among the first of a new generation of cephalosporins with activity against aerobic Gram-negative bacilli, which extends to cefepime-sensitive Pseudomonas aeruginosa, and activity against Gram-positive organisms, which includes methicillin-resistant Staphylococcus aureus. Ceftobiprole is currently undergoing evaluation by the US FDA for the treatment of complicated skin and skin structure infections, with a decision pending further evaluation of study site monitoring. It is also being evaluated for the treatment of community-acquired and healthcare-associated pneumonia. Two Phase III multicenter trials have demonstrated noninferiority in complicated skin and skin structure infections when tested against vancomycin in primarily Gram-positive bacterial infections, and when tested against vancomycin plus ceftazidime in Gram-positive and Gram-negative bacterial infections. It is well tolerated, with the most common side effects being nausea and dysgeusia. Ceftobiprole is likely to prove useful as an empiric as well as directed monotherapy in patients with complicated skin and skin structure infections, in which both Gram-positive pathogens including methicillin-resistant S. aureus and Gram-negative pathogens including cefepime-sensitive P. aeruginosa may be involved.
View details for DOI 10.1586/eri.09.54
View details for PubMedID 19735220
Although bacteriophages have been used for the treatment of patients with bacterial infections in some regions of the world for >9 decades, adequate clinical trials of the safety and efficacy of the treatment have not been reported. The increasing problem of antibiotic resistance has, however, rekindled interest in this approach to therapy. Although potentially significant obstacles to systemic administration of phages exist, topical and oral administration of phages and/or phage products, such as lysins, are feasible in the short term. In addition to exploitation of the effects of native phages and phage products, bioengineering of phages will allow directed specificity and their use as delivery systems for antimicrobial and antivirulence molecules. This brief overview of the history and status of phage therapy, along with speculation about its future, provides a background for understanding of this imminent therapeutic modality.
View details for DOI 10.1086/597405
View details for Web of Science ID 000264307400010
View details for PubMedID 19275495
Vancomycin is frequently used as empirical therapy in patients with catheter-related bloodstream infections and for definitive therapy of such infections caused by meticillin-resistant Staphylococcus aureus. Evidence, however, indicates that as a consequence of decreasing activity of vancomycin against this organism, as well as with deficiencies in tissue penetration, vancomycin therapy of such infections frequently results in microbiological and clinical failure. The relative efficacy of alternative therapies requires urgent investigation in randomized clinical trials.
View details for DOI 10.1016/S0924-8579(09)70566-7
View details for PubMedID 19931817
Complicated skin and skin structure infections (cSSSIs) are common and are associated with significant health and economic costs. These infections are predominantly characterized by infection with Staphylococcus aureus, and SENTRY Surveillance data indicate that the occurrence of this pathogen in cSSSIs has increased and that almost half of the isolated pathogens are methicillin-resistant S. aureus (MRSA). Surveillance data also indicate that Gram-negative isolates are not uncommon in cSSSIs. In the past, empiric antimicrobial coverage of both Gram-positive and Gram-negative infections has generally necessitated the use of at least 2 antimicrobial agents. Ceftobiprole, a novel advanced-generation pyrrolidinone cephalosporin, is currently under review by the Food and Drug Administration as therapy for cSSSIs. This article presents a summary of the results of 2 recently published multicenter noninferiority trials involving approximately 1600 patients with a variety of cSSSIs. In the 1st trial, which included patients with Gram-positive cSSSI, the clinical cure rate at the test-of-cure (TOC) visit (the primary end point) among patients receiving ceftobiprole was 93.3%. The 2nd trial included a broad range of cSSSIs of varying pathogenicity. In this trial, the clinical cure rate among patients receiving ceftobiprole for S. aureus and MRSA infection was 94.6% and 91.8%, respectively. Ceftobiprole's capacity as a broad-spectrum agent was demonstrated in the 2nd trial, in which the clinical cure rate at TOC was 90.5% against a variety of infections and pathogens (including Gram negatives). In addition, the cure rate among patients with moderate to severe diabetic foot infection who received ceftobiprole was 86.2%, and these patients experienced a shorter length of stay in the hospital than those who received a comparator. This article also addresses the results of these trials in the context of the current medical need for safe broad-spectrum antimicrobial agents with MRSA coverage.
View details for DOI 10.1016/j.diagmicrobio.2008.03.004
View details for Web of Science ID 000255426000020
View details for PubMedID 18384998
The increasingly daunting problem of antimicrobial resistance has led to an intense focus on optimization of antibiotic therapy, with simultaneous goals of improving patient outcomes and minimizing the contribution of that therapy to making the available antibiotics obsolete. Although even appropriate antibiotic therapy drives resistance, inappropriate therapy may also have adverse effects on the individual patient, as well as on the bacterial ecology. Recent research has validated the benefit of intelligent utilization of both microbiological data and clinical assessment in the empirical selection of initial broad-spectrum therapy and in further guidance of therapeutic decisions throughout the course of illness by use of a systems approach. Thus, the optimal approach to the critically ill patient with infection involves the initiation of aggressive broad-spectrum empirical therapy followed by timely responses to microbiological and clinical results as they become available. An appropriate response to this information often involves de-escalation of therapy or even its discontinuation.
View details for DOI 10.1086/519472
View details for Web of Science ID 000248931300004
View details for PubMedID 17712744
The recognition of the shortcomings of vancomycin as an antistaphylococcal agent, together with the burgeoning availability of alternative effective antistaphylococcal antibiotics, has led to a reassessment of the role of this glycopeptide antimicrobial in clinical therapeutics. Evidence indicates that vancomycin is inferior to semisynthetic penicillins in the treatment of infections due to methicillin-susceptible Staphylococcus aureus. Additional evidence suggests that vancomycin may be inferior to some comparator agents in the treatment of infections due to methicillin-resistant S. aureus (MRSA). While high-level resistance remains rare, data from some centers suggest an evolutionary change in S. aureus, evidenced by reduced susceptibility to vancomycin. This, together with the problem of heteroresistance to vancomycin, as well as poor tissue penetration after its systemic administration, presents potential obstacles to the successful therapy of S. aureus infections with this glycopeptide. While it has been suggested that these problems may be overcome by administration of vancomycin in much higher doses, the efficacy and safety of this approach remains to be determined and will require randomized clinical trials for its demonstration. A number of novel agents with activity against MRSA have been introduced to clinical practice in the last 2 years and others are still in the investigational stage. Despite the fact that these newer agents have been compared with vancomycin in trials only designed to demonstrate noninferiority, some potential evidence of superiority over vancomycin has emerged. While the relative roles of each of these newer agents and vancomycin can only be determined definitively by performance of adequately powered randomized clinical trials, current evidence suggests that vancomycin may be an inferior therapeutic agent.
View details for DOI 10.1586/1478722.214.171.1243
View details for Web of Science ID 000250759800016
View details for PubMedID 17547504
The efficacy of vancomycin for the treatment of patients with infections due to Staphylococcus aureus is impaired by its poor tissue penetration and by its relatively weak antibacterial activity--an activity that is declining as S. aureus evolves. Neither dose escalation nor use of vancomycin in combination with other antibiotics that have antistaphylcoccal activity has been demonstrated to safely enhance its therapeutic efficacy. Although no clinical trials suggest superiority of vancomycin over any comparator, some have provided evidence of its inferiority. Strong consideration should be given to the use of alternative agents in the treatment of serious S. aureus infections.
View details for DOI 10.1086/518452
View details for Web of Science ID 000246658200004
View details for PubMedID 17516396
Both alcoholism and HIV infection reduce health-related quality of life (HRQOL), and their co-occurrence is highly prevalent. We sought to determine whether comorbidity for both disorders further reduced HRQOL and what factors exacerbated or mitigated their effect.HRQOL, CD4 T-cell counts, lifetime alcohol consumption and length of sobriety, depressive symptoms (Beck Depression Inventory [BDI]-II), general cognitive status (Peabody Picture Vocabulary Test II), and other psychiatric comorbidities were assessed in patients with alcohol dependence or abuse (n = 44), HIV infection (n = 44), alcohol + HIV (n = 55), and healthy controls (n = 41).Alcohol + HIV patients had lower HRQOL and more psychiatric comorbidities compared with patients with only HIV or those with only alcohol dependence or abuse; however, they matched HIV patients with regard to CD4 counts and matched alcohol patients on lifetime alcohol consumption. Across patient groups, higher HRQOL was associated with lower BDI scores but was not associated with age, gender, lifetime alcohol use, or viral load. HRQOL was higher for alcoholics in remission than for those currently meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. In stepwise regression, BDI total score predicted 34% of HRQOL variance in alcohol, 52% in alcohol + HIV, and 55% in HIV groups. General cognitive status contributed an additional 4% to the prediction of HRQOL but only in the alcohol + HIV group.The superimposition of HIV infection onto alcoholism has a negative impact on HRQOL independent of the severity of either disease. Depression strongly predicts HRQOL, and general cognitive status plays a small role in enhancing quality of life for those at greatest clinical disadvantage.
View details for Web of Science ID 000248712600015
View details for PubMedID 17149525
Staphylococci are among the most frequently encountered pathogens in both the inpatient and the outpatient setting. Management of infections caused by these organisms is complicated by the increasingly common resistance of staphylococcal pathogens to commonly used antibacterials. As a consequence, novel approaches to prevention and treatment are urgently required. Such approaches include the development of vaccines and immunoglobulin preparations targeted at virulence factors expressed in vivo by staphylococci. This article reviews the biopharmaceutical progress made to date in this field and suggests approaches to further progress.
View details for Web of Science ID 000242086800002
View details for PubMedID 17040111
Methicillin-resistant Staphylococcus aureus, first identified just over 4 decades ago, has undergone rapid evolutionary changes and epidemiologic expansion. It has spread beyond the confines of health care facilities, emerging anew in the community, where it is rapidly becoming a dominant pathogen. This has led to an important change in the choice of antibiotics in the management of community-acquired infections and has also led to the development of novel antimicrobials.
View details for Web of Science ID 000227492600010
View details for PubMedID 15712079
Leptospirosis is a reemerging infectious disease in California. Leptospirosis is the most widespread zoonosis throughout the world, though it is infrequently diagnosed in the continental United States. From 1982 to 2001, most reported California cases occurred in previously healthy young adult white men after recreational exposures to contaminated freshwater. We report five recent cases of human leptospirosis acquired in California, including the first documented common-source outbreak of human leptospirosis acquired in this state, and describe the subsequent environmental investigation. Salient features in the California cases include high fever with uniform renal impairment and mild hepatitis. Because leptospirosis can progress rapidly if untreated, this reemerging infection deserves consideration in febrile patients with a history of recreational freshwater exposure, even in states with a low reported incidence of infection.
View details for Web of Science ID 000220079400004
View details for PubMedID 15109405
Tenofovir disoproxil fumarate (tenofovir DF) is a bioavailable prodrug of tenofovir, a potent nucleotide analogue reverse-transcriptase inhibitor with activity against human immunodeficiency virus (HIV) and hepatitis B virus. It is administered as a single 300-mg tablet once daily. It was approved for the treatment of HIV infection on the basis of data from clinical trials demonstrating activity in treatment-experienced patients, and it was subsequently shown to be effective when used as a component of initial therapy. Tenofovir DF is active against some nucleoside-resistant strains of HIV. However, cross-resistance is associated with multiple thymidine analogue mutations that include 41L or 210W. The signature mutation is the K65R mutation, which causes variable loss in susceptibility to tenofovir DF, didanosine, and abacavir. Tenofovir DF has been well tolerated in clinical trials with durations of follow-up up to 96 weeks. It is associated with more-favorable lipid profiles than stavudine and has not been associated with the mitochondrial toxicity attributed to other nucleoside analogues.
View details for Web of Science ID 000185677400012
View details for PubMedID 13130407
Caspofungin, the first inhibitor of fungal beta-1,3 glucan synthesis to receive approval by the United States Food and Drug Administration, is effective for the treatment of mucosal and invasive candidiasis and invasive aspergillosis. It is also active in vitro and in animal models against a number of other filamentous and dimorphic endemic fungi and in animal models of Pneumocystis carinii infection. In vitro studies and some animal studies almost always indicate an absence of antagonism when caspofungin is combined with azole or polyene antifungal agents. Caspofungin has an excellent safety profile. Caspofungin may prove to be useful in empirical therapy for suspected invasive fungal infections. Additional clinical trial data that expand our knowledge of the usefulness of caspofungin for these and other mycoses, including its administration in combination with other antifungal agents, is anticipated. Caspofungin is an important addition to the antifungal pharmacopoeia.
View details for Web of Science ID 000183126500015
View details for PubMedID 12766841
The safety and immunogenicity of inactivated hepatitis A (HepA) vaccine was assessed in 133 hepatitis A virus-seronegative, human immunodeficiency virus (HIV)-infected adults. Patients were randomly assigned to receive, in a blinded fashion, either 2 doses of vaccine (1440 enzyme-linked immunosorbent assay units) or placebo 6 months apart. Seroconversion at month 9 was observed in 68% of those with CD4 cell counts >/=200 cells/mm(3) but in only 9% of those with lower CD4 cell counts (P=.004). HepA vaccine was well tolerated and had no effect on the course of HIV infection or plasma HIV RNA load.
View details for Web of Science ID 000181972000021
View details for PubMedID 12696015
Recent studies have contributed to our understanding of risk factors for severe and potentially life-threatening infections with Coccidioides immitis, allowing a more rational approach to initiation of antifungal therapy for this infection, as well as determining its intensity and duration. A large randomized trial found that itraconazole and fluconazole had similar efficacies in the treatment of progressive nonmeningeal coccidioidomycosis. An animal model of coccidioidal meningitis suggested potential efficacy of systemically administered liposomal amphotericin B. Investigational agents that have activity against C. immitis include posaconazole, voriconazole, caspofungin, and sordarin derivatives.
View details for Web of Science ID 000172663200005
View details for PubMedID 11964886
A questionnaire regarding tolerability and adherence was administered for 5 days to hospital employees who received azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness. Analysis of the 239 responses from those having received prophylactic azithromycin determined that it was well tolerated and accounted for a minimal loss of days worked; 81.5% were fully adherent with the regimen.
View details for Web of Science ID 000173934800009
View details for PubMedID 11876458
Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection.Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks.HIV-infected, low GSH, CD4 T cells < 500 micro L(-1), no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors.Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.
View details for Web of Science ID 000090133200012
View details for PubMedID 11029607
This paper reviews a meeting at which basic pathophysiology of infections, mechanisms of action of hyperimmune products and pharmacokinetic and pharmacodynamic parameters, as well as currently available hyperimmunes and their potential new targets and uses, were discussed. A hyperimmune product was defined as either a monoclonal antibody or a polyclonal preparation enriched with antibody directed against one or more particular targets. A number of issues were emphasised, including: resistant bacterial pathogens, such as Staphylococcus aureus and Streptococcus pyogenes; the role of hyperimmune intravenous globulins in the prevention of sepsis in low birthweight infants; hepatitis B virus infection associated with liver transplantation; combination therapy; the potential role of hyperimmunes in the prevention and treatment of hepatitis C virus; and the use of immunoglobulins for the prophylaxis of Epstein-Barr virus-related lymphoproliferative disease. Routes of administration were also discussed. It was concluded that the development of hyperimmunes faces numerous obstacles. It was agreed that the use of hyperimmunes in clinical trials must be standardised; clinical trials must be large enough to have sufficient power to demonstrate efficacy with clear-cut end-points, and means need to be developed, in conjunction with regulatory agencies, for the feasible evaluation of combination products. However, progress in all these aspects will provide a wide range of hyperimmunes for future use.
View details for Web of Science ID 000090009300002
View details for PubMedID 18034567
Through the efforts of thousands of individuals, the World Wide Web has become a gold mine of information about HIV. In this article, we describe approximately 90 Web sites that are among the most useful to clinicians and researchers with regard to HIV. Web sites were classified according to their content and target audience and were judged according to their adherence to accepted standards of medical Internet publishing. Selected Web sites were categorized into the following groups: (1) sites with comprehensive coverage of HIV treatment and its management, (2) on-line peer-reviewed journals, (3) proceedings of scientific meetings, (4) sites with HIV-related textbooks, manuals, and guidelines, (5) government publications, (6) research databases, (7) information on clinical trials, (8) sites with comprehensive information for laypersons, and (9) sites with information related to specific medical complications of HIV infection.
View details for Web of Science ID 000089838700027
View details for PubMedID 10987723
To evaluate the effect of adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim, yeast-derived recombinant human GM-CSF) on incidence and time to opportunistic infection or death, plasma HIV-RNA, and CD4 cell count in patients with advanced HIV disease.This Phase III randomized, double-blind, placebo-controlled trial enrolled subjects with CD4 cell counts < or = 50 x 10(6)/l or < or = 100 x 10(6)/l with a prior AIDS-defining illness on stable antiretroviral therapy. Subjects were stratified by baseline HIV-RNA level (> or = or < 30,000 copies/ml) and randomized to receive subcutaneous injections of GM-CSF 250 microg or placebo three times per week for 24 weeks. Subjects were permitted to continue on blinded drug for up to 20 months. Subjects were evaluated for infections, plasma HIV-RNA, lymphocyte counts, changes in antiretroviral therapy, toxicity, and survival.Three-hundred and nine subjects received at least one dose of study drug, 70% completed 24 weeks of therapy. Groups were well matched at baseline. Significant increases in CD4 cell and neutrophil counts were observed at 1, 3, and 6 months in the GM-CSF group. GM-CSF significantly reduced the incidence of overall infections (78% placebo versus 67% GM-CSF; P = 0.03) and delayed time to first infection (56 days placebo versus 97 days GM-CSF; P = 0.04). No statistical difference in cumulative opportunistic infections was observed between groups; however, among subjects without an opportunistic infection prior to study, the GM-CSF group demonstrated a trend towards fewer subjects with an opportunistic infection on study (26% placebo versus 8% GM-CSF; P = 0.08). Change in HIV-RNA was not significantly different between groups, but significantly fewer GM-CSF subjects with baseline viral load < 30,000 copies/ml had changes in antiretroviral therapy for increased viral load (42% placebo versus 21% GM-CSF; P = 0.01). In patients with HIV-RNA levels below the limit of detection at baseline, more GM-CSF patients maintained an undetectable viral load at 24 weeks (54% placebo versus 83% GM-CSF; P = 0.02). GM-CSF was well tolerated.GM-CSF significantly increased CD4 cell count and decreased virological breakthrough and overall infection rate in subjects with advanced HIV disease.
View details for Web of Science ID 000086155800012
View details for PubMedID 10770541
Although mexiletine, an antiarrhythmic with local anesthetic properties, has been reported to relieve discomfort in diabetic neuropathy, its usefulness in the treatment of HIV-related painful peripheral neuropathy (PPN) has not been determined. The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were randomized to receive mexiletine (maximum dose, 600 mg/day) or placebo for 6 weeks, followed by the alternative intervention for 6 weeks after a 1-week washout period. The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug, 16 of whom were crossed-over to receive the alternate agent. No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo, irrespective of the order in which the agents were received. Comparing the mean individual daily pain scores for each phase of study, 5 patients (31%) had significantly less pain while receiving mexiletine compared with their response to placebo, 5 patients (31%) had significantly less pain while receiving placebo, and no difference was noted in 6 patients (38%). Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo. Dose-limiting adverse events occurred in 39% of those receiving mexiletine, but only 1 patient (5%) discontinued placebo. Mexiletine was only modestly well tolerated despite its relatively brief period of administration, and no evidence was found to support its benefit in HIV-related PPN. Although a first-drug effect was not demonstrated, a powerful placebo effect was seen in some patients.
View details for Web of Science ID 000077070300007
View details for PubMedID 9833745
View details for Web of Science ID 000077669800021
The impact of a standardized set of diagnostic interventions on the further management of 968 episodes of fever in neutropenic cancer patients who did not respond to initial therapy was assessed prospectively. At the onset of fever, 65% of patients had no additional signs of infection, whereas skin and soft tissue infections were present in 12%, and clinical sepsis and gastrointestinal infections in 8% each. After 72 h, 41% of the fevers still remained unexplained. New foci of infection emerged in 11% of the cases involving mainly the lungs, skin and soft tissues, and urinary tract. The presence of a lower respiratory tract infection or a microbiologically defined infection of any sort was associated with higher mortality than other types of infection were. Changes in initial antibiotic therapy were based on the results of the diagnostic measures specified in the protocol in only 15% of the cases.
View details for Web of Science ID 000077315800001
View details for PubMedID 9861558
The seroprevalence of measles (rubeola) antibody in 619 human immunodeficiency virus (HIV)-infected adults was determined by a standard ELISA. Risk factors for a lack of antibody and presumed susceptibility to measles were examined. Whereas overall, 9.8% of patients (60) were found to lack antibody, 17.8% of those born within the United States in 1957 or later were antibody-negative. Multivariate analysis showed that absence of measles antibody was significantly associated with younger age (born in 1957 or later) (odds ratio [OR], 8.15; 95% confidence interval [CI], 3.7-21.5; P < .0001) and birth within the United States (OR, 4.72; 95% CI, 1.7-19.7; P = .0045). Neither minority status, stage of HIV infection, CD4 cell count, nor a history of opportunistic infection bore any relationship to the presence of antibody. While progression of HIV disease does not affect measles serostatus, younger HIV-infected patients, especially those born in the United States in 1957 or later, are at the greatest risk for measles.
View details for Web of Science ID 000076248000039
View details for PubMedID 9806055
Eight AIDS patients with Mycobacterium avium complex (MAC) bacteremia were randomized to receive azithromycin with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 weeks to examine the effect of GM-CSF administration on clearance of mycobacteremia and on monocyte function. Superoxide anion production was significantly increased ex vivo in monocytes from patients receiving GM-CSF but not in those from patients receiving azithromycin alone. Relative to monocytes obtained from untreated healthy controls, median differences in viable intracellular MAC at 2, 4, and 6 weeks were -0.76, -0.94, and -0.47 log10 cfu/mL of lysate for cells from patients receiving GM-CSF versus -0.15, -0.11, and -0.19 log10 cfu/mL for cells from patients receiving azithromycin alone. Although no effect on mycobacteremia was detected, the administration of GM-CSF to AIDS patients with MAC bacteremia resulted in activation of their blood monocytes, as evidenced by increased superoxide anion production and enhanced mycobactericidal activity. GM-CSF deserves further investigation in the treatment of mycobacterial infections.
View details for Web of Science ID 000072719400011
View details for PubMedID 9534963
Glutathione (GSH), a cysteine-containing tripeptide, is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggested a link between GSH depletion and HIV disease progression. Clinical studies presented here directly demonstrate that low GSH levels predict poor survival in otherwise indistinguishable HIV-infected subjects. Specifically, we show that GSH deficiency in CD4 T cells from such subjects is associated with markedly decreased survival 2-3 years after baseline data collection (Kaplan-Meier and logistic regression analyses, P < 0.0001 for both analyses). This finding, supported by evidence demonstrating that oral administration of the GSH prodrug N-acetylcysteine replenishes GSH in these subjects and suggesting that N-acetylcysteine administration can improve their survival, establishes GSH deficiency as a key determinant of survival in HIV disease. Further, it argues strongly that the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals.
View details for Web of Science ID A1997WM05900068
View details for PubMedID 9050888
We report a patient without immune compromise with infection of an automatic internal cardiac defibrillator patch due to Aspergillus fumigatus presenting 8 years after implantation. The mechanism of infection was unknown, but symptoms began 1 month after laser uvulopalatopharyngoplasty was performed for sleep apnea. The patches were surgically removed and the patient was treated sequentially with amphotericin B and itraconazole. He remains without evidence of infection 12 months after the completion of therapy.
View details for Web of Science ID A1996WA95000019
View details for PubMedID 8994959
The aim of this multicentre randomised trial was to determine whether it was possible to predict grampositive bacteraemia, and whether the empirical use of vancomycin would lead to reduced morbidity and mortality. 35 of 113 patients (31%; confidence interval, CI 8.5), who presented with a skin or soft tissue infection and had received empirical vancomycin in addition to either ceftazidime or piperacillin-tobramycin, had initial bacteraemia with a single gram-positive bacterium compared with 135 of the 784 (17%; CI 2.6), who presented with another infection and who had been given ceftazidime or piperacillin-tobramycin without vancomycin (P < 0.001). Empirical vancomycin resulted in a higher rate of eradication (P = 0.033, relative risk 1.2), but not a better clinical outcome and was associated with more toxicity (P = 0.042, relative risk 1.6). Irrespective of the initial treatment regimen, fever lasted an average of 8 days, the empirical regimen was modified in more than 50% of cases and mortality attributed to gram-positive infection was less than 2%. Incorporating vancomycin in the initial empirical antibiotic regimen for febrile neutropenic patients does not appear necessary, even for skin and soft tissue infections associated with gram-positive bacteraemia.
View details for Web of Science ID A1996VA83900019
View details for PubMedID 8869095
View details for Web of Science ID A1996UC68200008
To determine the predictive value of a standard murine model in the treatment of disseminated Myocardium avium complex (MAC) infection, beige mice were infected with MAC strains isolated from human immunodeficiency virus-infected patients and treated with the same antibiotic (ethambutol, clofazimine, or rifampin) that had been administered to the subject from whom that strain had been recovered. While ethambutol had the greatest bacteriologic efficacy in humans (mean decrease +/-SD, 1.0+/-0.5 log 10 cfu/mL of blood), clofazimine had the greatest bacteriostatic efficacy in mice (mean decrease +/- SD, 2.8 +/- 0.7 log(10) cfu/g of tissue). A linear correlation was not observed between bacteriostatic activity in mouse liver or spleen and the degree of bacteriologic response in humans (P > or = to .1). Odds ratios for a response in humans based on a bacteriologic response in mice were not significant for each agent (P > or = to .1, all cases).
View details for Web of Science ID A1996TW80600035
View details for PubMedID 8627046
The ability of various in vitro methods of antibiotic susceptibility testing to predict therapeutic outcome in patients infected with Mycobacterium avium complex (MAC) was evaluated. Pretreatment bloodstream MAC isolates from 38 patients with AIDS, previously treated in a randomized fashion with either ethambutol, rifampin, or clofazimine, were tested by three conventional methods using broth or agar, as well as by cocultivation with macrophages. The results obtained with each method were compared with the quantitatively determined bacteriologic response to the administration of the single agent in humans. None of the conventional in vitro susceptibility methods was predictive of therapeutic outcome, while the results of cocultivation with macrophages were of moderate predictive value. The positive predictive value of a response in humans based on a response in macrophages (defined by > or = to 1.0 log reduction in baseline colony counts after 5 days of treatment) was 74%. The negative predictive value was 82%.
View details for Web of Science ID A1996TW80600021
View details for PubMedID 8627032
Acanthamoeba infection has been described as an opportunistic infection in persons with AIDS. We report two cases of patients with AIDS and acanthamoeba infection and review the manifestations of this protozoan infection in patients infected with human immunodeficiency virus. The diagnosis of this infection requires a high index of suspicion because the clinical and histologic manifestations may be confused with those of disseminated fungal or algal disease. Clinicians and laboratory personnel should be aware of this potentially fatal condition so that appropriate diagnostic studies can be performed and treatment can be urgently administered. Early initiation of therapy may alter the clinical outcome of the disease.
View details for Web of Science ID A1995QY77100020
View details for PubMedID 7620001
Background: Little is known about the frequency and pattern of travel in the HIV-infected population. Method: A test questionnaire administered to patients cared for at a public hospital HIV clinic examined the frequency, destinations, and motivations for travel of persons with HIV disease. Results: Of 89 persons surveyed, 46% had traveled within the preceding 2 years within the United States for a minimum of 1 week, or to a foreign destination. Forty patients (45%) had traveled to a mean of 3.4 destinations within the United States for an average trip duration of 16 days. In addition, 18 patients (20%) had traveled to at least one foreign country for an average of 20 days. Of the 25 foreign destinations that were specified, 15 (60%) were in lesser developed countries. Patients stated that they undertook 30% of their trips because they thought it was their last chance to travel. At the time of completion of the survey, the majority of those patients who had traveled were severely immunosuppressed (median CD4+ count, 120/mm3). Conclusions: These data provide information by which the clinician can anticipate the health care needs of patients who travel and develop appropriate travel medicine guidelines. (J Travel Med 2:85-88, 1995)
View details for PubMedID 9815367
View details for Web of Science ID A1995VA90700006
View details for Web of Science ID A1994NR96500023
To compare piperacillin and tobramycin with ceftazidime alone for the empiric treatment of fever in the neutropenic patient without evidence of skin infections or anaerobic infections.A multicenter, randomized, controlled trial.876 febrile, neutropenic episodes in 696 patients (83% acute leukemia or bone marrow transplantation); 92 episodes were excluded from analysis because of protocol violation.Patients received either intravenous ceftazidime (2 g every 8 h) or piperacillin (12 to 18 g/d in 4 to 6 divided doses plus tobramycin (1.7 to 2.0 mg/kg body weight every 8 h). Treatment could be modified at any time at the discretion of the investigator.Percentage of satisfactory response, eradication of the infecting organism, development of superinfections, and occurrence of adverse events.As a single agent, ceftazidime was as effective as the combination of piperacillin and tobramycin (62.7% satisfactory responses compared with 61.1%; odds ratio, 1.07%; 95% Cl, 0.79 to 1.44; P > 0.2). Equivalent responses were also obtained in episodes of profound neutropenia (odds ratio, 0.76; Cl, 0.43 to 1.33; P > 0.2). Infectious mortality was 6% for ceftazidime and 8% for the combination therapy. Eradication of the infecting organisms was achieved in 79% of bacteremic episodes treated with ceftazidime compared with 68% of the episodes treated with the combination therapy (odds ratio, 1.76; Cl, 0.92 to 3.38; P = 0.08), and rates for gram-negative rod bacteremia were also similar (95% compared with 77%; odds ratio, 5.25; Cl, 1.0 to 27.5; P = 0.03). Superinfections developed in 38 episodes in each group. An adverse event occurred in 8% of episodes treated with ceftazidime compared with 20% of episodes treated with combination therapy (P < 0.001).Ceftazidime alone was as effective but safer than the combination of piperacillin and tobramycin for the empiric treatment of febrile, neutropenic patients, even those with profound and prolonged granulocytopenia.
View details for Web of Science ID A1994NK45800004
View details for PubMedID 8154643
Tracheobronchitis is an uncommon manifestation of infection due to Aspergillus species, occurring in < 7% of cases of pulmonary aspergillosis. At least 58 cases of invasive aspergillus tracheobronchitis have been described since 1962. We describe four patients with AIDS, all of whom were severely immunocompromised, who had ulcerative tracheobronchitis due to Aspergillus species demonstrated histologically. Three patients had received corticosteroids or were neutropenic at presentation. At bronchoscopy, three patients had some degree of diffuse tracheobronchitis, multiple ulcerative or "plaque-like" inflammatory lesions, and occasionally nodules involving the mainstem and segmental bronchi. The remaining patient had a single deep ulceration of the proximal trachea. Aspergillus was isolated from biopsy specimens from all four patients. There were varied degrees of invasion of the mucosa, submucosa, and cartilage on histological examination in three patients, one of whom had evidence of disseminated aspergillosis. Two patients subsequently developed pulmonary parenchymal disease due to Aspergillus. A review of aspergillus tracheobronchitis, including a discussion of airway disease in patients infected with human immunodeficiency virus, is presented.
View details for Web of Science ID A1993LW23700005
View details for PubMedID 8218674
While quantitative mycobacterial blood cultures have been accepted as the standard for evaluating response to various Mycobacterium avium complex (MAC) treatment regimens, variability in this methodology has not been evaluated in a rigorous fashion. We thus studied the reproducibility of quantitative MAC cultures by a lysis-centrifugation culture system within and among five institutions. To measure the intralaboratory variation in mycobacterial colony counts, colony counts from duplicate blood specimens collected from 52 AIDS patients with MAC bacteremia were determined. Colony counts ranged from 0 to 50,000 CFU/ml. Nonparametric analyses revealed there was no significant difference in colony counts between the 52 duplicate specimens. The agreement between the intralaboratory paired specimens, as measured by the intraclass correlation coefficient, was 0.997. To measure the interlaboratory variation, multiple 10-ml aliquots from 12 patients were distributed to five institutions and processed within 24 to 32 h by lysis-centrifugation. For the 12 specimens distributed to the five laboratories, two-way analysis of variance for repeated measures revealed no significant difference in an individual patient's colony counts between laboratories (P > 0.2). We conclude that quantitation of mycobacterial colony counts by the lysis-centrifugation system is reproducible within and between institutions. Clinical trials evaluating response to therapeutic interventions for MAC can use multiple laboratories for quantitation of mycobacteremia. Furthermore, a 24- to 32-h delay in processing appeared to have no impact on reproducibility.
View details for Web of Science ID A1993LJ20100022
View details for PubMedID 8349755
We describe the isolation and identification of a Helicobacter (Campylobacter)-like organism obtained from the blood of a 32-year-old homosexual man with a 10 months' history of AIDS and progressive mucocutaneous Kaposi sarcoma. Fever and bacteremia persisted despite sequential administration of ciprofloxacin and trimethoprim-sulfamethoxazole, antibiotics reported to be active against this organism in vitro. Facultative organisms like Campylobacter fennelliae and Campylobacter cinaedi which are difficult to isolate by standard techniques may be important but unrecognized causes of febrile illness in patients with human immunodeficiency virus infection. Laboratories should consider use of acridine orange staining and more extensive subculture protocols for blood cultures with progressive growth indices which appear negative by conventional staining and subculture technique.
View details for Web of Science ID A1993KH53000017
View details for PubMedID 8454896
View details for Web of Science ID A1992HV36800014
The authors have shown previously that intracellular glutathione (GSH) plays an important role in the regulation of human immunodeficiency virus (HIV) transcription and replication in vitro, through modulation of signal transduction by inflammatory cytokines. Moreover, intracellular GSH levels are known to regulate T-lymphocyte function. In multiparameter FACS studies presented here, we show that relative GSH levels in CD4+ and CD8+ T cells from HIV+ individuals are significantly lower than in corresponding subsets from uninfected controls. These studies define the relative intracellular glutathione (GSH) levels in CD4+ T cells, CD8+ T cells, B cells, and monocytes from 134 HIV-infected individuals and 31 uninfected controls. The greatest decreases in intracellular GSH occur in subsets of T cells in individuals in the later stages of the HIV infection. In AIDS patients, GSH levels are 63% of normal in CD4+ T cells (p less than 0.0001) and are 62% of normal in CD8+ T cells (p less than 0.0001). Similarly, in AIDS-related complex (ARC) patients, GSH levels are 66% of normal in CD4+ T cells (p less than 0.003) and are 69% of normal in CD8+ T cells (p less than 0.003). These findings suggest that low intracellular GSH levels may be an important factor in HIV infection and in the resulting immunodeficiency.
View details for Web of Science ID A1992HG48900025
View details for PubMedID 1540417
There are increasing expectations that community-based physicians who care for people with HIV infection will offer their patients opportunities to enroll in clinical trials. The information-management requirements of clinical investigation, however, make it unrealistic for most providers who do not practice in academic centers to participate in clinical research. Our T-HELPER computer system offers community-based physicians the possibility of enrolling patients in clinical trials as a component of primary care. T-HELPER facilitates data management for patients with HIV disease, and can offer patient-specific and situation-specific advice concerning new protocols for which patients may be eligible and the treatment required by those protocols in which patients currently are enrolled. We are installing T-HELPER at three county-operated AIDS clinics in the San Francisco Bay Area, and plan a comprehensive evaluation of the system and its influence on clinical research.
View details for PubMedID 1482965
A 27-year-old man presented with a 7-month history of debilitating recurrent fever and weight loss. Extensive clinical evaluation led to the discovery of splenomegaly and retroperitoneal lymphadenopathy. The patient underwent splenectomy as well as liver and lymph node biopsy. Histologic examination of the lymph nodes, but not the liver and spleen, revealed inflammatory pseudotumor of lymph nodes. The patient has remained asymptomatic for more than 3 years following the surgical procedure despite the absence of further intervention. Inflammatory pseudotumor of lymph nodes should be considered in the differential evaluation of prolonged or relapsing fever of unknown etiology.
View details for Web of Science ID A1991FG90500017
View details for PubMedID 2012094
View details for Web of Science ID A1991FK53300008
Opportunistic infection with the causative agent of cat scratch disease may be responsible for an unusual vascular proliferative lesion, referred to as bacillary epithelioid angiomatosis, previously described only in human immunodeficiency virus (HIV)-infected patients. We present a case of an HIV-infected patient with bacillary epithelioid angiomatosis involving the liver and bone marrow causing progressive hepatic failure. We also report a case of a cardiac transplant recipient with hepatic and splenic bacillary epithelioid angiomatosis manifesting as a fever of unknown origin, a previously unreported event in a non-HIV-infected patient. These cases represent the first documentation of bacillary epithelioid angiomatosis with visualization of cat scratch-like organisms involving internal organs.
View details for Web of Science ID A1990DT83100015
View details for PubMedID 2382668
Male golden Syrian hamsters were evaluated as a model for the pathogenesis of human infection with Mycobacterium avium complex. Intratracheal inoculation produced a chronic, nonfatal, pulmonary and disseminated infection (overall rate, 86%). The frequency of infection in hamsters that received 5 x 10(8) versus 1 x 10(8) colony forming units (cfu) was not significantly different (87% and 92%, respectively), but 1 x 10(7) cfu produced infection in only 78% of inoculated animals (P = .034). The percentage of animals developing pulmonary infection with M. avium complex did not differ between inoculum groups (77%-80%). Disseminated infection occurred significantly less frequently in the 1 x 10(7) group (46%) compared with the 5 x 10(8) (79%) and 1 x 10(8) (68%) groups (P = .001 and .056, respectively). After seven weeks, partial clearance of M. avium complex from the lungs coincided with an increased number of animals with splenic involvement. The hamster may be a useful model for human infection with M. avium complex.
View details for Web of Science ID A1989T266800027
View details for PubMedID 2644384
The efficacy and safety of norfloxacin were compared with those of placebo, vancomycin-polymyxin, and trimethoprim-sulfamethoxazole (TMP/SMX) for prophylaxis of bacterial infections in granulocytopenic patients. The study results showed that norfloxacin treatment, which was well tolerated and not associated with any serious systemic adverse effects, prevented acquisition of gram-negative bacillary organisms. Fewer norfloxacin-treated patients (38 of 108 patients, or 35 percent) experienced microbiologically documented infections compared with patients receiving placebo (27 of 40 patients, or 68 percent), vancomycin-polymyxin (16 of 30 patients, or 53 percent), or TMP/SMX (14 of 28 patients, or 50 percent). Gram-negative bacteremia developed in five of 108 norfloxacin-treated patients (5 percent), compared with 17 of 40 placebo-treated patients (43 percent), five of 30 treated with vancomycin-polymyxin (17 percent), and one of 28 patients treated with TMP/SMX (4 percent). The incidence of gram-positive bacteremia was similar in all study groups and was not affected by norfloxacin or any other oral prophylactic antibiotics. These results suggest that norfloxacin is both safe and effective for the prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive bacterial infections, however, is needed.
View details for Web of Science ID A1987J200700007
View details for PubMedID 3037899
Fulminant Aspergillus sinusitis is a disease of immunocompromised hosts strongly associated with neutropenia. A case of sinusitis due to Aspergillus flavus that developed in a patient with acute leukemia during the third week of treatment with amphotericin B is described. Indium 111-labeled white blood cell scanning demonstrated uptake of granulocytes into the involved sinuses. Thereafter, use of granulocyte transfusions was associated with stabilization of the patient's clinical course.
View details for Web of Science ID A1984RX91900034
View details for PubMedID 6419603
View details for Web of Science ID A1982ND18300008
Dissemination of fungal infection due to Coccidioides immitis has been previously shown to be related to hereditary factors. Two associations reported to date are race (e.g., Filipino and black ancestry) and HLA histocompatibility type (HLA-19). In the present study of 105 patients a significant association of blood group B and dissemination is demonstrated. C. immitis is known to possess antigens with blood group A activity. Previous epidemiologic studies have also shown HLA-A9 and blood group B are both more common in persons of black and Filipino ancestry. Further studies are needed to define whether these are independent variables, and may define subgroups at particularly high risk following coccidioidal infection.
View details for Web of Science ID A1979HM42400014
View details for PubMedID 531716
Phagocytosis of killed endospores by glass adherent peripheral human mononuclear cells was studied. Phagocytosis continued through 30 minutes of incubation. No difference in rates of ingestion could be detected when cells from coccidioidin-reactive and nonreactive subjects were compared although both groups ingested endospores more avidly than latex particles.
View details for Web of Science ID A1978FY53500010
View details for PubMedID 732866
The association of Pseudomonas maltophilia endocarditis in three patients with recent history of intravenous drug abuse is reported. All three patients had abnormal heart valves (two prosthetic and one rheumatic). A prominent characteristic of this uncommon pathogen is its in vitro resistance to the commonly used antimicrobials. Cure was achieved in all three cases. In two cases, synergistic antibiotic combinations were used. In one case, plasmid-mediated resistance to amikacin sulfate (Amikan, British; no comparable US product) emerged during therapy. The two patients with prosthetic valves received combined surgical and antibiotic therapy.
View details for Web of Science ID A1978FW27000017
View details for PubMedID 718316
Twelve patients with fungal meningitis (ten cases were due to Coccidioides immitis, two were from Cryptococcus neoformans) were treated with brief courses of intravenous (IV) miconazole. Eleven patients, including patients with severe, chronic disease, had been treated unsuccessfully with amphotericin B. Four patients also received miconazole injected directly into the CSF. The drug was well tolerated by any route, with mild reversible side effects. After IV administration the miconazole concentration in the CSF rarely exceeded the minimal inhibitory concentration (MIC) of the infecting organism. Intra-CSF administration of 20 mg generally produced levels above the MIC for 24 hours. Five of ten patients with coccidiodial meningitis responded clinically. Of these five, four received only IV miconazole; three relapsed after therapy was stopped. Miconazole appears promising as a treatment of fungal meningitis, but trials of longer duration might prevent relapse.
View details for Web of Science ID A1977DU44500016
View details for PubMedID 901086
View details for Web of Science ID A1977DN85100010
Fourteen patients with chronic coccidioidomycosis, many of whom had complicating concurrent diseases and/or had failed to respond to amphotericin therapy, were treated with intravenous miconazole, a synthetic imidazole drug previously shown to be effective in experimental murine coccidioidomycosis. Up to 3.6 g/day was given for up to three months. 7inimal inhibitory concentrations of mycelial and endospore phases of all clinical isolates of C. immitis were less than 2.0 mug/ml. Peak concentrations in the blood of up to 7.5 mug/ml (by assay against C. immitis in vitro) were achieved. Doses above 9 mg/kg or 350 mg/m2 were more efficacious in producing blood levels over 1 mug/ml. Serum protein binding, determined by several methods, was approximately 90 per cent. The disappearance of bioactive drug from blood after infusion has a rapid initial phase (t1/2 approximately 30 minutes) and a final plateau (t1/2 approximately 20 hours). Eight patients had objective evidence of response, three had slight or equivocal responses, two could not be evaluated, and one was a treatment failure. Side effects were generally uncommon, minor and transient except for phlebitis. Infusion into central venous catheters appears to circumvent this problem. Miconazole is a potentially useful drug in the treatment of coccidioidomycosis.
View details for Web of Science ID A1976BF07800004
View details for PubMedID 766623
To determine the frequency and clinical characteristics of infection with Coccidioides immitis in immunosuppressed patients at Stanford University Hospital, clinical records of 14 years were examined. Thirteen cases met the diagnostic criteria. Half had Hodgkin's disease. In six the infection was disseminated; five of the six died early in the course of their infectious illness, frequently without diagnosis. Conclusions include: 1. The occurrence of coccidioidomycosis in immunosuppressed patients seen at institutions in or adjacent to the endemic area is not as rare as the literature suggests. 2. Dissemination is frequently explosive and the radiographic appearance of pulmonary involvement may appear late. Widespread pulmonary dissemination may occur within 24 hours after a negative x-ray. 3. Although the skin test loses its diagnostic value, the serology remains valid. Thus immunosuppressed patients with febrile illnesses (with or without radiographically evident pulmonary involvement) who have a history of travel to an endemic area should have serological examinations. 4. Lymphocytopenia correlates with risk of dissemination of coccidioidomycosis. 5. The administration of immunsuppressive chemotherapy correlates with such risk while radiotherapy and the malignant or non-malignant nature of the disease do not.
View details for Web of Science ID A1975AR32100002
View details for PubMedID 1099399
View details for Web of Science ID A1975AV05800017
A patient with disseminated herpes simplex virus infection, documented by direct immunofluorescence, and untreated multiple myeloma with abnormal immunoglobulins is presented. Reports of infections with intracellular pathogens in myeloma patients are rare, whereas pyogenic infections have been amply documented. Partly in consequence of this, the untreated disease has been thought of as a relatively pure defect in humoral immunity. Review of present knowledge suggests that cell-mediated immunity is of paramount importance in combatting and containing infection with this virus. Thus, immune defects in multiple myeloma, and its infectious complications, may be more complex than appreciated by current concepts of this disease based on previously reported cases.
View details for Web of Science ID A1974AD35400006
View details for PubMedID 4218637
Development of an effective vaccine against Staphylococcus aureus would provide great potential public health benefit. We present a brief overview of the current knowledge in this field, with emphasis on present challenges and lessons learned, together with a summary of vaccines and immunoglobulin preparations currently under investigation.
View details for DOI 10.1086/655992
View details for Web of Science ID 000283841800013
View details for PubMedID 20929369
Both HIV infection and alcoholism can impair motor abilities involving manual dexterity and postural stability. Given the high prevalence of HIV and alcoholism comorbidity, we examined whether each disease selectively disrupts different components of upper and lower limb motor control and whether these impairments are compounded by disease comorbidity.Simple and complex upper (speed and finger dexterity) and lower (static posture) limb functions were tested in 31 men with HIV infection, 27 with alcoholism, 43 comorbid for HIV infection and alcoholism, and 22 normal healthy controls to assess whether comorbid patients would demonstrate greater motor impairment relative to those with a single diagnosis.Individuals with HIV infection and those with alcoholism had impaired upper and lower limb motor function. Disease comorbidity compounded deficits in speeded finger movement. Neither Beck Depression Inventory scores, self-reported peripheral neuropathy, nor HIV medication accounted for group differences. Lower limb motor composite scores with eyes open were correlated with upper limb motor scores in the alcoholism group.Overall, the observed impairment patterns indicate the presence of upper and lower limb motor impairment in both HIV infection and alcoholism and the relevance of alcoholism in exacerbating impairment in speeded fine finger movement, when it occurs in HIV infection.
View details for DOI 10.1111/j.1530-0277.2007.00385.x
View details for Web of Science ID 000246576500015
View details for PubMedID 17403062