Infectious disease

Novel Strategy for Preventing CDI.

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Antigermination therapy prevented disease in mice challenged with massive inocula of C. difficile spores.

Spore germination is necessary for the development of symptomatic Clostridium difficile infection (CDI). Recent investigations have yielded novel nonantibiotic agents that inhibit spore germination mediated by taurocholate, a bile salt. To determine whether CamSA — a taurocholate analog that inhibits germination in vitro — might prevent CDIs, researchers conducted experiments using a mouse model.

Mice received an antibiotic “cocktail” in their drinking water for 3 days, and then a single dose of intraperitoneally administered clindamycin on day 4. The animals, in groups of five, each received 0 mg/kg, 5 mg/kg, 25 mg/kg, or 50 mg/kg of CamSA by oral gavage, followed on day 5 by gavage challenge with a massive dose of C. difficile spores and additional doses of CamSA 1 and 24 hours thereafter. The mice were then monitored for clinical evidence of CDI, and disease signs were scored. Some animals in each group were sacrificed and underwent postmortem examination of the gastrointestinal tract.

All animals that received 0 mg/kg of CamSA developed severe CDI within 48 hours of spore inoculation. In contrast, those that received 50 mg/kg showed no clinical or histopathologic evidence of CDI. Animals that received either 5 mg/kg or 25 mg/kg had a delayed onset of CDI and a reduction in disease severity. The excretion of cells and spores in feces also correlated with CamSA dose: Vegetative cells predominated in animals in the untreated (0-mg/kg) and 5-mg/kg groups, whereas spores predominated in those in the 25-mg/kg and 50-mg/kg groups.

Although CamSA (3 doses at 50 mg/kg) was protective in mice challenged with spores, it was ineffective in preventing CDI in animals challenged with vegetative cells.

Comment: These findings in a murine model deserve special attention. The novel, nonantibiotic strategy studied could be a “game changer” as we consider potential approaches for CDI management. As the authors note, patients determined to be at risk for CDI could receive CamSA before initiating antibiotics, then additional doses as needed until the intestinal microbiota has recovered.

Source: Journal Watch Infectious Diseases

 

Outbreak of Shigellosis Showed Decreased Susceptibility to Azithromycin.

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An outbreak of shigellosis that occurred in Los Angeles last year is the first known transmission in the U.S. of Shigella sonnei with resistance to azithromycin, according to MMWR.

Of 43 cases of shigellosis associated with a private bridge club, 14 were confirmed by culture. Four isolates had elevated azithromycin minimum inhibitory concentrations (MICs) of >16 μg/mL and a plasmid-encoded macrolide resistance gene.

The authors write: “Guidelines for azithromycin susceptibility testing and criteria for interpretation of MICs for Shigella species have not been published. Clinicians are urged to report azithromycin treatment failure among shigellosis patients to public health authorities and to retain Shigella isolates from such cases for further analysis.”

Source: MMWR

Treating Skin Infections.

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A noninferiority study of tedizolid phosphate provides information on this new antibiotic, as well as insights into both study design and treatment duration for skin infections.

Given the detrimental effects of antimicrobial therapy both in promoting antibiotic resistance and in altering the microbiome, shortening the duration of treatment for common infections is potentially beneficial. In a recent manufacturer-sponsored, multinational, phase III, double-blind, double-dummy trial, researchers compared a 6-day course of tedizolid phosphate — a novel oxazolidinone — with a 10-day course of linezolid for acute bacterial skin and skin-structure infections (ABSSSIs).

A total of 667 adults with ABSSSIs were randomized to receive 200 mg of oral tedizolid once daily for 6 days or 600 mg of oral linezolid twice daily for 10 days. In intent-to-treat analysis, tedizolid was noninferior to linezolid as determined at 48- to 72-hour clinical assessment (the primary efficacy outcome; 79.5% vs. 79.4%), as well as at the end of therapy (day 11; 69.3% vs. 71.9%) and 7 to 14 days later (85.5% vs. 86.0%). The posttherapy clinical response rate was high (85%) and similar between groups in the 178 patients (26.7%) with infections caused by methicillin-resistant Staphylococcus aureus.

Comment: As noted by the authors and editorialists, this study provides information both on tedizolid phosphate and on new FDA guidelines for assessing the efficacy of antibiotic therapy for ABSSSIs. It also highlights the need for clinical trials of currently approved agents to determine what treatment duration is really necessary for such infections.

Source: Journal Watch Infectious Diseases.

 

Recurrent Erythema Migrans Represents New Lyme Infection.

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In a study involving 17 patients with recurrent erythema migrans, the implicated strains of Borrelia burgdorferi differed between the first and second episodes.

Lyme disease — infection with the tickborne spirochete Borrelia burgdorferi — is becoming more common, and its geographic zone is enlarging. The infection has protean manifestations and has been blamed for chronic symptoms of arthritis and fatigue. The most common initial symptom is erythema migrans (EM), a target-like lesion. Some patients, despite appropriate antibiotic treatment, experience recurrent EM. Distinguishing reinfection from relapse in these individuals can be difficult, and the issue remains controversial.

To explore this matter, researchers compared B. burgdorferi isolates from the skin or blood of adults with recurrent EM (17 patients, 22 paired consecutive episodes). All patients were treated with standard courses of antibiotics during each episode, with subsequent resolution of lesions.

Molecular typing of the isolated strains of B. burgdorferi, including analysis of the gene governing an outer-surface protein, revealed that in all of the paired EM episodes, the two episodes were associated with different strains. All repeat episodes were due to reinfection rather than relapse.

Comment: As noted by an editorialist, this study adds to the evidence that in antibiotic-treated patients, recurrent EM is caused by reinfection rather than by relapse of the original infection. The findings offer no real surprises: EM generally appears days to weeks after the offending tick bite. However, many patients with proven Lyme disease never experience (or notice) EM, and this study does not resolve the question of relapse or new infection in individuals with recurrent systemic symptoms.

Source: Journal Watch Infectious Diseases

 

 

 

 

Understanding the Effect of Healthcare Workers’ Hand Hygiene.

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Using a novel method, investigators revealed marked heterogeneity in healthcare worker interactions and in the potential consequences of their hand hygiene.

Attempts to understand disease transmission in healthcare settings have generally assumed that healthcare workers (HCWs) move and interact uniformly. However, observational studies have suggested the possibility of peripatetic “superspreaders” who have greater-than-average mobility and interactivity — and thus more opportunity to spread infection. In a recent study conducted in the medical intensive care unit of a university hospital, researchers assessed this possibility.

The researchers used small electronic badges worn by HCWs, together with fixed-position beacons, to determine patterns of HCW movement and interactions within this 20-bed unit. They then used these data to mathematically model the effect of HCW hand hygiene on pathogen transmission.

During the 48-hour period of analysis, the average number of contacts (HCW–HCW and HCW–patient) per HCW was 80.1 for day shifts and 76.1 for night shifts. However, a few HCWs were responsible for a disproportionately large share of the contacts. Modeling the effect of hand-hygiene activity on disease transmission showed that spread of a pathogen would be significantly greater with noncompliance of a few high-contact staff members than with noncompliance of an equal number of low-contact workers.

Comment: Hand hygiene is a central tenet of infection control, yet since the original work of Semmelweis, there has been relatively little research on the direct effects of hand-hygiene behavior on disease transmission. Hornbeck and colleagues have provided new insights into HCW contacts, which can help us to understand the role of hand hygiene in preventing nosocomial spread of pathogens and thus to develop more-sophisticated approaches for improving its efficacy.

Source: Journal Watch Infectious Diseases

 

 

 

 

 

 

 

 

 

Antibiotic Stewardship Program Reduces C. difficile Infection Rates.

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Restricted cephalosporin, fluoroquinolone, and clindamycin use was associated with reduced antibiotic consumption and a decline in the incidence trend of Clostridium difficile infection.

Use of cephalosporins, fluoroquinolones, and clindamycin has repeatedly been associated with increased risk for Clostridium difficile infection (CDI). However, little is known about how CDI rates are affected by antibiotic stewardship programs aimed at decreasing the administration of such “high-risk” antibiotics.

Researchers recently described their experience with a restriction policy for second- and third-generation cephalosporins, fluoroquinolones, and clindamycin at a hospital in Northern Ireland that became effective in January 2008, after a major CDI outbreak in other, affiliated institutions. The policy was devised based on a time-series analysis involving one of these affiliated institutions for the period February 2002 through March 2007, which suggested that treatment of 14 patients with second-generation cephalosporins or 8 with third-generation cephalosporins — versus 94 with amoxicillin/clavulanic acid or 78 with macrolides — would result in one CDI case (Antimicrob Agents Chemother 2009; 53:2082).

Cephalosporins, quinolones, and clindamycin were prescribed significantly less frequently during the study period following implementation of the restriction policy (January 2008–June 2010) than during the 4-year preimplementation period; the use of other antibiotics remained unchanged. The intervention resulted in an overall reduction in antibiotic use and a reversal of the increasing trend for antibiotic consumption. These changes were associated with a significant decline in the incidence trend for CDI (rate decrease, 0.047/1000 bed-days per month). Variations in CDI incidence were affected by the Charlson patient comorbidity index, with a lag of 1 month.

Comment: This report on a successful antibiotic stewardship intervention is a nice example of the cause–effect relationship between antibiotic use and the occurrence of potentially serious nosocomial infections. The authors note that an antimicrobial-management team’s close surveillance of prescribing was key to successful implementation of the restriction policy.

Sourc: Journal Watch Infectious Disease.

 

Eradicating Infectious Disease: Consequences Of Hypothetical Universal Vaccines.

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Imagine a world with no HIV, no malaria, no tuberculosis, no flu and so on down to the absence of the common cold. With scientists chasing after cure-all anti-virus treatments and a universal flu vaccine in labs around the world, the eradication of infectious diseases certainly appears to be medical research’s ultimate (if remote) goal. But what if we actually got there?

As the Princeton mathematical epidemiologist Nim Arinaminpathy put it, “If we had a magic pill that got rid of all infectious diseases, period, would we really use it?” He isn’t sure. In all likelihood, purging humanity of infectious disease would not be a universally positive eventuality, but it wouldn’t trigger the immediate downfall of Homo sapiens, either.

Survival of the unfittest

First, consider what we’d be giving up. “Our evolutionary history has been a continual arms race against the pathogens that plague us,” said Vincent Racaniello, professor of microbiology and immunology at Columbia University. For eons, this battle has weeded out the weak, and in a less combative environment, standards for human survival would grow lax.

However, this is not quite as problematic as it might seem. In much of the West, “people are already kind of artificial animals,” Racaniello told Life’s Little Mysteries. “We have all these ways of intervening when people get sick, when otherwise they would have died and we would see some natural selection for people with more robust immune systems.” But as long as doctors keep having a way to render moot those diseases that used to kill us, natural immunity isn’t essential, he said.

And in fact, many diseases could be eradicated worldwide without any loss of evolutionary robustness. “With influenza, there isn’t any indication that this plays a role in human evolution,” said Arinaminpathy, who studies the evolutionary effects of flu vaccines. A pathogen can only impact human DNA if it tends to kill people before they have offspring. Otherwise, its victims have already passed on their genes to the next generation, regardless of whether those genes made them susceptible to the pathogen or not. The flu is most fatal to the elderly, who have typically already passed on their genes. [How Many Genetic Mutations Do I Have?]

Meanwhile, malaria does target the young, and it therefore molds the evolution of people in many tropical countries by killing children with feeble immune defenses (leaving behind those with malaria-resistant genes). But this “survival of the fittest” situation is not desirable; malaria has been largely eradicated in the United States with no obvious downsides. If the same were to happen in Africa and other afflicted regions, “the impact of reducing or removing malaria would go beyond public health,” Arinaminpathy said.

A healthy population

The malaria parasite is so rampant in Africa that many children are afflicted over and over in a nearly continuous cycle. “You can’t think clearly, you feel terrible, and it stops you from being able to go to school or have a productive life,” Racaniello said. Meanwhile, HIV is running amok in sub-Saharan Africa, similarly stifling development and productivity. [‘Superdrug’ Could Fight Both HIV and Malaria]

In short, disease ushers in poverty. “If you get rid of infectious diseases by vaccination,” Racaniello said, “you can make a big contribution to getting people out of poverty so they can have productive lives.”

And although wiping out malaria, tuberculosis, sleeping sickness, HIV and the other tropical plagues would mean significant population growth in just the areas that are already experiencing runaway birth rates and food crises, these socioeconomic problems would be far more tractable in a disease-free society. “If a good fraction of these individuals have productive careers they might come up with solutions,” he said.

These considerations all suggest eradicating infectious diseases would benefit humanity, on balance. But there’s one giant question left.

Good colds?

Does regularly getting the cold or the flu when we’re young help us later? These viruses might somehow aid in the growth and development of our metabolisms, or even our organs. Scientists aren’t sure, because they haven’t had the chance to study a virus-free human population, as they have with the bacteria- and parasite-lacking populations in the West.

“We’re just learning that the consequence of antibiotics is that when you get rid of the good bacteria in our guts, we can develop autoimmune diseases [such as allergies]. We’re not as advanced in our understanding of viruses. What do viruses do for us?” Racaniello said.

Allergies we can live with, but some of the benign viruses that hitch a ride in our bodies could be serving a much deeper role, Arinaminpathy said — as could a few of the slightly virulent ones with whom our relationship is “a bit fuzzy.” Would a world in which babies were permanently inoculated against the cold, the flu, HPV and everything else actually be better?

Like always, we should we careful what we wish for. Ridding the world of diseases would be “mostly a good thing,” Arinaminpathy said, “but there are these interesting questions when you scratch the surface of these illnesses.”

Source: http://www.huffingtonpost.com

 

 

 

Measuring Aerosol Production from Patients with Active TB.

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Twenty-eight of 101 patients with culture-confirmed pulmonary tuberculosis had culture-positive cough aerosols, suggesting infectiousness; likelihood of a culture-positive aerosol was directly correlated with degree of sputum-smear positivity.

Although tuberculosis (TB) is transmitted by aerosols of droplet nuclei <5 µm in diameter, determination of infectiousness has been based on microscopic examination of sputum for the presence of organisms (smear assessment) — a method that may be neither sensitive nor specific. The magnitude and particle-size distributions of the aerosols generated by patients with active TB are unknown.

In a study conducted in Uganda, researchers attempted to collect, quantify, and size the aerosols produced by voluntary coughing in patients with active pulmonary TB and to compare these findings with results from sputum smears and aerosol cultures. Patients with culture-confirmed TB were asked to cough in two 5-minute sessions into a custom-built chamber that analyzed and collected their cough aerosol. Plates within the chamber contained 7H11 agar for mycobacterial culture.

Among the 101 patients, 28 produced aerosols that grew Mycobacterium tuberculosis. The proportion of patients who generated culture-positive aerosols increased significantly as the sputum smear microscopy grade increased (P=0.03). All patients with a culture-positive aerosol were smear positive; none of those with a negative smear produced a culture-positive aerosol. More than 96% of the culturable particles collected were between 0.7 and 4.7 µm in diameter.

Comment: Although the authors conclude that cough aerosols might provide a better determination of infectiousness than smear assessment, the data indicate that smear results correlate well with aerosol culture results.

Source: Journal Watch Infectious Diseases

A New Tickborne Viral Infection in the U.S. Heartland.

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A novel phlebovirus caused a severe febrile illness in two patients in Missouri.

In 2011, a tickborne phlebovirus — so-called severe fever with thrombocytopenia syndrome virus (SFTSV) — was described as a cause of human disease in China. Now, illness closely resembling that caused by SFTSV has been reported in two men in northwestern Missouri.

The two patients had suffered tick bites 5 to 7 days before the onset of a severe febrile illness characterized by fatigue, diarrhea, thrombocytopenia, and leukopenia. Ehrlichiosis was the presumptive diagnosis in each case, but results from laboratory tests (serologic analysis, polymerase chain reaction assay, cell culture) were all negative. The men were hospitalized for 10 and 12 days.

Viral particles were isolated from the patients’ leukocytes in cell culture. Thin-section electron microscopy revealed characteristics of viruses in the Bunyaviridae family. Total RNA was recovered from the infected culture media and subjected to genomic sequencing; the resulting sequences were similar to those of phleboviruses in the Bunyaviridae family. Phylogenetic analysis demonstrated a distinct virus closely related to SFTSV. Enzyme-linked immunosorbent assay testing of serum samples collected from the patients >2 years after illness onset showed high titers of antibodies reactive to the novel virus (dubbed “Heartland” by the researchers).

Comment: Some patients who have been treated for anaplasmosis or ehrlichiosis may have had Heartland virus infection or coinfection. The list of tickborne illnesses in the U.S. and abroad continues to expand, as is evidenced by cases described in this article and other recent reports (JW Infect Dis Mar 16 2011 and Aug 3 2011).

Source: Journal Watch Infectious Diseases

Reducing the Rate of Active TB by Targeted Testing and Treatment.

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Such a program, initiated by the Tennessee Department of Health, prevented an estimated 184 cases of active tuberculosis during its first 5 years.

Although the overall number of new tuberculosis (TB) cases has declined in the U.S., the proportion of cases among foreign-born individuals has increased. Most such cases are due to reactivation of latent TB infection (LTBI).

To address this problem, the Tennessee Department of Health initiated a targeted tuberculin testing program in which individuals determined to have any risk factor for TB exposure (or for progression to active TB, once infected) are screened using the tuberculin skin test (TST), and those with positive test results receive treatment for LTBI. Now, researchers have evaluated the results of this program from its initiation, in March 2002, through December 2006.

After initial risk screening of 168,517 people, 125,200 individuals had a TST placed. Of these, 91,332 (73%) were considered to be high risk, including 21,680 (17%) who were foreign born. Among 102,709 recorded TST results, 9090 (9%) were positive. The positive TST rate was 33% for foreign-born persons, compared with 5% for high-risk, U.S.-born individuals and 1% for low-risk individuals. The number needed to test to identify one case of LTBI was 4 for foreign-born individuals, 24 for high-risk, U.S.-born persons, and 85 for low-risk persons. A total of 4780 individuals with positive TST results initiated LTBI therapy, and 1953 (54%) completed it. An estimated 184 cases of active TB were prevented.

Comment: These findings suggest that targeted testing and treatment of persons at high risk for TB, particularly those who are foreign born, can result in marked reductions in TB rates over time.

Source: Journal Watch Infectious Diseases