Origin of Antimicrobial Therapy.

Medical historians typically situate the origins of the antimicrobial era during the early germ period at the turn of the 20th century. They have regarded the development of chemical compounds designed to treat infectious diseases by killing their causative germ as the beginning of the antimicrobial era. Scholars, however, had been speculating about the causal relationship between germs and diseases for centuries beforehand.

Efforts to regulate antibiotic misuse in hospitals: A history.

Today, most hospitals have implemented regulatory programs designed to curtail the antimicrobial misuse that has fueled resistance. In this paper, I trace the history of resistance and efforts to mitigate antibiotic overuse in the hospital. Medical investigators in the 1950s argued that the difficulties posed by resistant bacteria in the hospital were even more worrisome than the problems that antibiotics were intended to solve.

Polio, AIDS, and Ebola: A Recurrent Ethical Dilemma.

During the 2014 West African outbreak, a dilemma emerged about the ethics of conducting randomized placebo-controlled trials in the midst of a rapidly spreading, devastating epidemic for which there was no effective treatment. The dilemma has in fact has deep historic roots; it has appeared in several previous fearsome epidemics-during the poliomyelitis epidemic in the 1930s-1950s, and again during the AIDS epidemic in the1980s-1990s. Moreover, ethical and social questions characterizing each of these epidemics-the increased risks of withholding potentially life-saving drugs for people assigned to a control arm and the damaging effect on eroding community trust-were conceptualized beforehand in the 1925 novel Arrowsmith.

The Short-Lived Epidemic of Botulism From Commercially Canned Foods in the United States, 1919 to 1925.

In 1919, three deadly outbreaks of botulism caused by consumption of canned olives packed in California captured national headlines. In all of the outbreaks, which occurred in separate locales, unsuspecting people died after consuming tainted food during a banquet or family meal. The press's sensational portrayal of canned food as hazardous aroused alarm among consumers at a time when commercial canning was becoming more common.

Historical and contemporary features of infections due to Clostridium novyi.

Clostridium novyi is an anaerobic bacterium that resides in the soil in nature and that may cause severe clinical infections in humans. It is named after Frederick Novy, who incidentally discovered the anaerobic organism responsible for septicemia in rabbits. In this paper, we explore the circumstances surrounding the identification of the organism.

Ebola in Antiquity?

This article addresses whether Ebola may have been present in an urban setting in Athens in 430 bce and explores the historical importance of the ancient outbreak. New knowledge from today's West African epidemic allows a more accurate assessment of whether Ebola may have caused the Athenian outbreak than was once possible. The Athenian disease, whose etiology remains unknown, developed abruptly with fevers, abdominal pain, vomiting, diarrhea, dehydration, and hemorrhage.

The AIDS pandemic in historic perspective.

Potent antiretroviral drugs (ART) have changed the nature of AIDS, a once deadly disease, into a manageable illness and offer the promise of reducing the spread of HIV. But the pandemic continues to expand and cause significant morbidity and devastation to families and nations as ART cannot be distributed worldwide to all who need the drugs to treat their infections, prevent HIV transmission, or serve as prophylaxis. Furthermore, conventional behavioral prevention efforts based on theories that individuals can be taught to modify risky behaviors if they have the knowledge to do so have been ineffective.

Frederick Novy and the 1901 San Francisco plague commission investigation.

The 1900 San Francisco plague is a significant event in which citizens, physicians, and public health officials denied a diagnosis of plague on economic, political, and social grounds. To resolve the controversy, Surgeon General Walter Wyman appointed an independent federal commission of university-based experts to investigate whether plague was present. I use the activities of Frederick Novy, the commission bacteriologist and professor at the University of Michigan, to explore one circumstance in which bacteriology attempted to redefine traditional conceptions of disease during the early germ era.

Lifelong curiosity: Frederick Novy and the rat virus.

Frederick Novy (1864-1957) was a U.S. physician, medical researcher, and influential microbiologist of the early 20th century who devised culture techniques to visualize anaerobic bacteria, parasites, and spirochetes.

Mycobacterium avium complex immune reconstitution inflammatory syndrome: long term outcomes.

Background: To describe long term outcomes of Mycobacterium avium complex (MAC) immune reconstitution inflammatory syndrome (IRIS).

Methods: Cases of MAC IRIS were retrospectively identified at four HIV clinics (Michigan, Maryland, Rhode Island, and Indiana) from 1996-2004. Patients were included if they were initially diagnosed with AIDS and found to have evidence of focal MAC infection documented by tissue culture or PCR after initiating HAART, and at least 6 months of follow up.

Long-term immunologic and virologic responses in patients with highly resistant HIV infection who are treated with an incompletely suppressive antiretroviral regimen.

Background: Some treatment-experienced patients with highly drug-resistant human immunodeficiency virus (HIV) infection have no option but to continue to receive an incompletely suppressive regimen (ISR). We performed a study to determine their long-term immunologic and virologic responses to ISR, to investigate risks for immunologic or virologic failure, and to examine for the occurrence of new drug-resistance mutations.

Methods: Antiretroviral treatment-experienced HIV-infected patients with a genotype sensitivity score < or = 1, an HIV load > 1000 copies/mL, and no available optimized regimen were included in the study.

Long-term efficacy and safety of tipranavir boosted with ritonavir in HIV-1-infected patients failing multiple protease inhibitor regimens: 80-week data from a phase 2 study.

Background: BI 1182.2, an open-label, randomized, multicenter, phase 2 study, evaluated efficacy and tolerability of the protease inhibitor (PI) tipranavir (TPV; 500 mg twice daily or 1000 mg twice daily) administered with ritonavir (100 mg twice daily) in combination with 1 nucleoside reverse transcriptase inhibitor and 1 nonnucleoside reverse transcriptase inhibitor in multiple PI-experienced HIV-1-infected patients.

Methods: Forty-one patients were evaluated in 2 arms: low-dose (19 patients) or high-dose (22 patients) ritonavir-boosted tipranavir (TPV/r).

Use of a novel assay based on intact recombinant viruses expressing green (EGFP) or red (DsRed2) fluorescent proteins to examine the contribution of pol and env genes to overall HIV-1 replicative fitness.

Multiple studies have described a reduction in the replicative fitness of HIV-1 isolates harboring mutations that confer resistance to antiretroviral drugs. Contradictory results, however, have been obtained depending on the methodology used in each study (Quinones-Mateu, M.E.

Effect of maintaining highly active antiretroviral therapy on AIDS events among patients with late-stage HIV infection and inadequate response to therapy.

Background: We evaluated the effect of maintaining highly active antiretroviral therapy (HAART) on the development of new acquired immunodeficiency syndrome (AIDS)-related events in patients with late-stage human immunodeficiency virus (HIV) infection who had suboptimal CD4+ cell count and viral load responses to HIV therapy.

Methods: In patients with pretreatment CD4+ cell counts of <200 cells/mm3, incidence rates of new AIDS-related events occurring during HIV treatment were calculated during period 1 (pre-HAART era, 1990-1995; 88 patients) and period 2 (HAART era, 1996-2004; 214 patients) according to CD4+ cell count responses while receiving treatment. Cox multivariate model was used to compare rates of AIDS-related events from period 2 with those from period 1 according to specific CD4+ cell count response categories and rates of AIDS-related events for various viral load ranges within CD4+ cell count categories during period 2.

Viral load responses to HAART is an independent predictor of a new AIDS event in late stage HIV infected patients: prospective cohort study.

Background: A sizeable number of HIV-infected patients receiving HAART do not maintain prolonged virologic suppression. We evaluated long-term HIV viral load (VL) responses to HAART as a risk factor for AIDS events (AE) that is independent of CD4 responses.

Methods: A cohort of patients with pre-therapy CD4 < 200/mm3 who had CD4 and VL measurements for > one year after receiving HAART at a university clinic were prospectively enrolled.

Bacterial infections in adult HIV-infected patients.

Purpose: The purpose of this article is to critically review articles published from the pre-HAART era to the present on bacterial infections in adult HIV-infected patients.

Method: Literature search on bacterial infections in HIV-infected patients yields predominantly small case series from single centers, many of which are retrospectively collected.

Results: Variations in case selection limit the utility of these articles for assessing the epidemiology and clinical features of a particular infection.

Magnitude and duration of elevated gastric pH in patients infected with human immunodeficiency virus after administration of chewable, dispersible, buffered didanosine tablets.

Study Objectives: To test the hypothesis that gastric pH would be elevated above pH 3.0 for at least 2 hours after administration of chewable, dispersible, buffered didanosine tablets. Doses tested were 200 mg (two 100-mg tablets) and 400 mg (two 200-mg tablets).

Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii pneumonia.

A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.

Changing interest among physicians toward pneumococcal vaccination throughout the twentieth century.

Interest in using pneumococcal vaccination among physicians has come full circle since the early twentieth century. Interest first arose during an epidemic among South African gold miners when a potential therapeutic agent, ethylhydrocupreine, caused significant toxicities. When a safe and effective vaccine became available in 1946, interest in using it paradoxically waned as its introduction coincided with the advent of penicillin.

Sequencing-based detection of low-frequency human immunodeficiency virus type 1 drug-resistant mutants by an RNA/DNA heteroduplex generator-tracking assay.

Drug-resistant viruses may be present as minority variants during early treatment failures or following discontinuation of failed antiretroviral regimens. A limitation of the traditional direct PCR population sequencing method is its inability to detect human immunodeficiency virus type 1 (HIV-1) variants present at frequencies lower than 20%. A drug resistance genotyping assay based on the isolation and DNA sequencing of minority HIV protease variants is presented here.

Lack of good correlation of serum CC-chemokine levels with human immunodeficiency virus-1 disease stage and response to treatment.

Three CC-chemokines-MIP-1alpha (CCL3), MIP-1beta (CCL4), and RANTES (CCL5)-are natural ligands for the human immunodeficiency virus-1 (HIV-1) coreceptor CCR5. To determine correlations between CC-chemokines and HIV-1 disease stage or response to treatment, we examined serum levels of MIP-1alpha, MIP-1beta, and RANTES in 60 infected patients during 18 months while they were taking highly active antiretroviral therapy (HAART). Our results demonstrate that serum levels of MIP-1alpha and RANTES were increased in HIV-1-infected individuals compared with those in healthy controls.

Increase in prevalence of Pneumocystis carinii mutations in patients with AIDS and P. carinii pneumonia, in the United States and China.

This study of Pneumocystis carinii dihydropteroate synthase (DHPS) mutations in patients with AIDS who have P. carinii pneumonia compares the change in the prevalence of such mutations in the United States, where sulfa-drug prophylaxis is widespread, to that in China, where it is infrequent. The DHPS gene from 145 US patients presenting during 1983-2001 and from 15 Chinese patients presenting during 1998-2001 was amplified by polymerase chain reaction and was sequenced.