A 5-year-old boy was admitted to the hospital for evaluation and treatment of an infected dog bite to the face and lip.

He sustained what was described as an unprovoked bite by a neighbor’s German shepard to the right side of his face five days earlier and was immediately taken to a local emergency room.

James H. Brien, DO

Pediatric Infectious Disease, Scott and White’s Children’s Health Center and Associate Professor of Pediatrics,
Texas A&M University, College of Medicine, Temple, Texas.
e-mail:jhbrien@aol.com

There, the face wound was cleaned, irrigated and glued closed with Dermabond (Ethicon). The small, full-thickness lip injury was cleaned and left open. He was sent home with amoxicillin-clavulanate to take at a dose of 200 mg twice per day for infection prophylaxis. The next day, he began running fever and was seen by his primary provider, but since his wound did not appear to be infected, he was continued on the amoxicillin-clavulanate and told to return the next day. At that visit, the bite site was still glued closed, swollen with erythema, and he was sent for admission.

The patient was a 5-year-old boy in mild distress with painful swelling of the left cheek with erythema. Photos courtesy of James H. Brien and the Jim Bass collection

During this time, the dog was taken to their local veterinarian where his rabies immunizations were documented up to date and detained for evaluation per protocol.

The patient’s past medical history is positive only for having had an orchiopexy a year earlier and bilateral inguinal herniorrhaphies four years earlier.

When admitted to the hospital, the wound was still glued closed, and therefore no discharge was seen.

His immunizations were documented to be up to date for his age.

His review of systems was unremarkable except for the chief complaint and the surgeries noted above.

Examination revealed normal vital signs on arrival to the hospital, but he had a documented fever of 102.5° F in the clinic.

General appearance was that of a normal 5-year-old boy in mild distress with painful swelling of the left cheek with erythema (Figures 1 & 2). The wound was still glued closed, and therefore no discharge was seen (Figure 3). He was also found to have a through-and-through injury to his lower lip that was healing well (Figures 4 and 5). The remainder of his examination was otherwise completely normal.

The patient was also found to have a through-and-through injury to his lower lip that was healing well.

His lab tests revealed a normal CBC and a blood culture is pending.

Later on the day of admission, Plastic Surgery was consulted, who then took him for incision and drainage, revealing a small amount of pus, which revealed no organisms on Gram stain, and culture is pending.

How would you treat pending culture results?

1. Continue oral amoxicillin- clavulanate
2. IV Unasyn (ampicillin + Sulbactam)
3. IV Vancomycin
4. IV Clindamycin + Unasyn

Case Discussion

Your choice may be none of the above, and be perfectly correct, but my choice was “D, IV clindamycin plus Unasyn” (Ampicillin + Sulbactam); the clindamycin for the possibility of methicillin-resistant Staphyloccus aureus and the Unasyn for other human and dog mouth organisms, such as Pasteurella multocida, group A strep, Eikenella corrodens and other anaerobes.

This patient’s culture grew three organisms; (1) Eikenella corrodens, (2) an oxidase-positive, pan-sensitive Gram-negative rod that the lab was unable to speciate and (3) a Neisseria species, which all sounds more like a human bite than a dog bite infection.

It is most likely that this mixed infection represents organisms from both the dog’s mouth and the child’s face skin. In either case, the child improved rapidly after the incision and drainage, and was sent home on Amoxicillin-clavulanate about 36 hours after admission, to follow up in the plastic surgery clinic six days later. At that time, he had no evidence of residual infection, and he was dismissed back to his primary provider.

There are several teaching points with this case:

(1) Wound management in the emergency department – It is widely agreed that primary repair, preferably by a plastic surgeon, is reasonable on bite wounds to the face, if done within the first eight hours. However, many experts recommend using sutures rather than tissue glue for bite wound closure in general, because of the increased risk of infection, to allow for drainage through the sutures in the event that it gets infected. Also, puncture wounds should not be sutured or glued.

(2) Tetanus risk – Following the guidelines from the Infectious Diseases Committee of the AAP (RedBook), as long as the child has had at least three doses of tetanus toxoid and it has been less than five years since the last dose, another dose at this time is not needed.

(3) Rabies risk – As long as the dog is known and the veterinarian can document immunizations and the dog can be watched in quarantine for at least 10 days, rabies prophylaxis (rabies immune globulin and vaccine) is not needed. The issue of “unprovoked” attacks is oftentimes questionable. When thoroughly explored, it usually turns out that the dog was provoked by the child by being too close to the dog’s food dish, getting in to the dog’s face or some other activity that causes the dog to snap at the child. A truly unprovoked attack is one when the dog goes out of its way to get to the child, which does not necessarily mean the dog is rabid but may just be an aggressive dog. A rabid dog will almost always act strange (to those who know him), even in the first few days of rabies, then will become aggressive and unpredictable, biting at anything nearby before dying of respiratory failure. However, having said that, you only get one chance to make the right decision with rabies prophylaxis.

Image of a cat bite, infected due to Pasteurella multocida.

Image of a dog bite, where the tissue is more likely to be torn or ripped.

(4) Antimicrobial prophylaxis – Even though the infection turned out to be due to organisms that are sensitive to Amoxicillin -clavulanate, this points out the limitation of prophylaxis in general. It relies on several factors, such as compliance, absorption from the gut, and sensitivity of the organisms contaminating the wound. Even under the best of circumstances, sometimes prophylaxis fails. However, it is generally recommended for all human, cat and dog bites, even though there’s not much evidence for benefit. As a rule, the cat bite is more likely to get infected because of the penetrating nature of the cat bite (Figure 6), as opposed to the dog bite, which is often a tearing or ripping injury (Figure 7). However, the dog bite can result in a puncture-type wound also, leading to infection (Figure 8).

Dog bites can sometimes be puncture wounds as well.

(5) Timing of infection manifestations – As a general rule, Pasteurella multocida and group A strep infections tend to occur very early in these injuries, whereas Staphylococcus aureus and other less common organisms tend to appear a bit later/slower. The child in figure 9 had an infected dog bite within the first 24 hours and grew Pasteurella multocida. She was treated with IV antibiotics for several days and then oral Amoxicillin-clavulanate, with a good outcome (Figure 10) a couple of weeks later. The patient in figure 6 was also seeking care within 24 hours of the cat bite.

Image of an infected dog bite that grew Pasteurella multocida within the first 24 hours.

The patient was treated with IV antibiotics for several days and then oral Augmentin, with a good outcome.

2009 Award for Quality winners are:

• SSM DePaul Health Center – Bridgeton, Mo.
• St. Elizabeth Health Center – Youngstown, Ohio
• Hoag Memorial Hospital – Newport Beach, Calif.
• Memorial Regional Hospital – Hollywood, Fla.
• Winchester Hospital – Winchester, Mass.
• Hackensack University Medical Center – Hackensack, N.J.
• Good Samaritan Hospital – Cincinnati
• Saint Vincent Health Center – Erie, Pa.
• Albert Einstein Medical Center – Philadelphia
• Allegiance Health – Jackson, Mich.
• Mercy General Hospital – Sacramento, Calif.
• Beth Israel Deaconess Medical Center – Boston
• Sound Shore Medical Center of Westchester – New Rochelle, N.Y.
• Joint Township District Memorial Hospital – Saint Marys, Ohio
• St. Vincent Charity Hospital – Cleveland
• Lakewood Hospital – Lakewood, Ohio
• The Western Pennsylvania Hospital – Pittsburgh
• Memorial Hospital – Colorado Springs, Colo.
• Penrose/St. Francis Healthcare – Colorado Springs, Colo.
• Rush University Medical Center – Chicago
• Paoli Memorial Hospital – Paoli, Pa.
• Medical University of South Carolina – Charleston, S.C.
• Maury Regional Hospital – Columbia, Tenn.

HealthDay ,  6/16/09:  

U.S. health officials on Tuesday warned consumers to stop using Zicam nasal cold remedy products because they can cause the loss of a sense of smell.

The specific products contained in the warning include Zicam Cold Remedy Nasal Gel, Zicam Cold Remedy Nasal Swabs, and Zicam Cold Remedy Swabs Kids’ Size.

“These products claim to reduce the duration of the common cold and severity of cold symptoms,” Deborah M. Autor, director of the Office of Compliance at the Center for Drug Evaluation and Research (CDER) in the U.S. Food and Drug Administration, said during a morning teleconference Tuesday. “Consumers should stop using these products immediately.”

The kids’ products have been discontinued, but consumers may still have them in their households and are advised to discard or return them, officials said.

The products’ manufacturer, Matrixx Initiatives, also received a warning letter and “must provide FDA with a plan on how it will remove existing inventory from the marketplace,” Autor said.

“We have asked Matrixx in a warning letter to stop marketing the products, and we intend to work with them to address the products on the market and, at the same time, warn consumers to stop using and discard or return them,” Autor continued. “We expect to hear a plan from the company.”

According to Autor, the products have been marketed as homeopathic remedies and, therefore, have not needed FDA approval as long as the company complied with certain labeling and manufacturing requirements.

Now, the FDA is essentially asking Matrixx to take the unusual step of recalling the product, and then filing for new drug approval.

“The next step is for the company to come in and seek FDA approval if they want to continue marketing the products,” Autor said.

“While the company has done trials involving small numbers of patients, we believe there have not been enough patients exposed in those trials to detect infrequent adverse events,” she said.

According to Dr. Charles E. Lee, medical officer in the division of New Drugs and Labeling Compliance in CDER’s Office of Compliance, the agency has received more than 130 reports from people using one of these zinc-containing products about the loss of a sense of smell, also known as anosmia.

“The loss of the sense of smell is potentially life-threatening and may be permanent,” Lee said. “People without the sense may not be able to detect dangerous situations such as gas leaks, something burning in the house, or if food is spoiled before eating it. It also has a life-limiting effect, and can affect the livelihood of people in occupations where the sense of smell or taste is a crucial component.”

Lee pointed out that, while the rate of adverse events seen here may not seem high, adverse events reports for over-the-counter drugs are historically low because consumers typically file their complaints with companies, not the FDA.

Until 2007, there was no requirement for makers of over-the-counter products to provide adverse event reports to the agency.

All reports of the latest problem have come from consumers and health-care providers, and Autor said the company has more than 800 adverse event reports related to the loss of sense of smell it has been asked to turn over to the FDA.

She declined to elaborate further on these reports, simply saying, “They have not been provided to the agency at this time.”

Lee said the first reports of something amiss came in 1999, but seemed to speed up after 2004.

In 2006, Matrixx agreed to pay $12 million to settle several hundred lawsuits from consumers who claimed the zinc products had stripped them of their sense of smell. At the time, Matrixx said the settlements were not an admission of liability, the Washington Post reported.

According to Lee, both animal studies and historical medical literature indicate that zinc is actually toxic to the nerve receptors in the nose. Zinc was apparently used in the 1930s to try to prevent polio infection, he said.

More information

The National Library of Medicine has more on anosmia.

SOURCES: June 16, 2009, teleconference with: Deborah M. Autor, director, Office of Compliance, Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration; and Charles E. Lee, M.D., medical officer, Division of New Drugs and Labeling Compliance, Office of Compliance, Center for Drug Evaluation and Research, FDA; Jan. 30, 2006, Washington Post

Toxic Shock Syndrome and Rhinosinusitis in Children

Kenny H. Chan, MD; Tania L. Kraai, MD; Gresham T. Richter, MD; Sharon Wetherall, MD; James K. Todd, MD

Arch Otolaryngol Head Neck Surg. 2009;135(6):538-542.

Objective  To determine the association between toxic shock syndrome (TSS) and rhinosinusitis in children.
Author Affiliations: Departments of Otolaryngology (Drs Chan, Kraai, Richter, and Wetherall) and Pediatrics (Dr Todd), University of Colorado School of Medicine and The Children’s Hospital of Denver; Division of Otolaryngology–Head and Neck Surgery, University of New Mexico, Albuquerque (Dr Kraai); Division of Pediatric Otolaryngology, Arkansas Children’s Hospital, Little Rock (Dr Richter); and Department of Anesthesia, Brigham and Women’s Hospital, Boston, Massachusetts (Dr Wetherall).

Design  Eighteen-year retrospective review of medical records.

Setting  Tertiary children’s hospital.

Patients  A total of 76 patients were identified as having TSS. Twenty-three of them were also diagnosed as having either acute or chronic rhinosinusitis, with no other source of infection in 17 cases.

Interventions  Of the 23 patients with TSS and rhinosinusitis, 10 were admitted to the intensive care unit, 4 required pressors, and 6 received surgical intervention. Surgical intervention for sinus disease included bilateral antral lavage in 5 patients and bilateral maxillary antrostomy and ethmoidectomy in 1 patient.

Main Outcome Measures  Patients with TSS and rhinosinusitis were identified using a rigorous set of definitions and detailed data pertaining to history, imaging studies, microbiologic studies, and hospital course.

Results  Correlation of the data revealed 4 patients who met the criteria for proven TSS and proven rhinosinusitis, 2 patients who met the criteria for probable TSS and proven rhinosinusitis, 7 patients who met the criteria for proven TSS and possible rhinosinusitis, and 3 patients who met the criteria for probable TSS and possible rhinosinusitis.

Conclusions  Rhinosinusitis was found to be the primary cause of TSS 21% of the time in this series. Rhinosinusitis should be considered the primary cause of TSS when another site of infection has not been identified. Once the link is made, prompt otolaryngology consultation and sinus lavage should be considered.

Note:  The perfusion device consists of a column containing polymyxin B, which has a high affinity for endotoxin, bound to polystyrene fibers.

Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock

The EUPHAS Randomized Controlled Trial

Dinna N. Cruz, MD, MPH; Massimo Antonelli, MD; Roberto Fumagalli, MD; Francesca Foltran, MD; Nicola Brienza, MD, PhD; Abele Donati, MD; Vincenzo Malcangi, MD; Flavia Petrini, MD; Giada Volta, MD; Franco M. Bobbio Pallavicini, MD; Federica Rottoli, MD; Francesco Giunta, MD; Claudio Ronco, MD

JAMA. 2009;301(23):2445-2452.

Context  Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative–induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with polymyxin B hemoperfusion could potentially improve patient clinical outcomes.

Objective  To determine whether polymyxin B hemoperfusion added to conventional medical therapy improves clinical outcomes (mean arterial pressure [MAP], vasopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone.

Design, Setting, and Patients  A prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) conducted at 10 Italian tertiary care intensive care units between December 2004 and December 2007. Sixty-four patients were enrolled with severe sepsis or septic shock who underwent emergency surgery for intra-abdominal infection.

Intervention  Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34).

Main Outcome Measures  Primary outcome was change in MAP and vasopressor requirement, and secondary outcomes were PaO₂/FIO₂ (fraction of inspired oxygen) ratio, change in organ dysfunction measured using Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality.

Results  MAP increased (76 to 84 mm Hg; P = .001) and vasopressor requirement decreased (inotropic score, 29.9 to 6.8; P < .001) at 72 hours in the polymyxin B group but not in the conventional therapy group (MAP, 74 to 77 mm Hg; P = .37; inotropic score, 28.6 to 22.4; P = .14). The PaO₂/FIO₂ ratio increased slightly (235 to 264; P = .049) in the polymyxin B group but not in the conventional therapy group (217 to 228; P = .79). SOFA scores improved in the polymyxin B group but not in the conventional therapy group (change in SOFA, –3.4 vs –0.1; P < .001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20-0.94; adjusted HR, 0.36; 95% CI, 0.16-0.80).

Conclusion  In this preliminary study, polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal gram-negative infections.

Trial Registration  clinicaltrials.gov Identifier: NCT00629382

ABSTRACT

Background On April 15 and April 17, 2009, novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in specimens obtained from two epidemiologically unlinked patients in the United States. The same strain of the virus was identified in Mexico, Canada, and elsewhere. We describe 642 confirmed cases of human S-OIV infection identified from the rapidly evolving U.S. outbreak.

Methods Enhanced surveillance was implemented in the United States for human infection with influenza A viruses that could not be subtyped. Specimens were sent to the Centers for Disease Control and Prevention for real-time reverse-transcriptase–polymerase-chain-reaction confirmatory testing for S-OIV.

Results From April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. Of patients with available data, 18% had recently traveled to Mexico, and 16% were identified from school outbreaks of S-OIV infection. The most common presenting symptoms were fever (94% of patients), cough (92%), and sore throat (66%); 25% of patients had diarrhea, and 25% had vomiting. Of the 399 patients for whom hospitalization status was known, 36 (9%) required hospitalization. Of 22 hospitalized patients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously.

Conclusions A novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred.

Mark A. Miller, M.D., Cecile Viboud, Ph.D., Marta Balinska, Ph.D., and Lone Simonsen, Ph.D.

Vast amounts of time and resources are being invested in planning for the next influenza pandemic, and one may indeed have already begun. Data from past pandemics can provide useful insights for current and future planning. Having conducted archeo-epidemiologic research, we can clarify certain “signature features” of three previous influenza pandemics — A/H1N1 from 1918 through 1919, A/H2N2 from 1957 through 1963, and A/H3N2 from 1968 through 1970 — that should inform both national plans for pandemic preparedness and required international collaborations.

Past pandemics were characterized by a shift in the virus subtype, shifts of the highest death rates to younger populations, successive pandemic waves, higher transmissibility than that of seasonal influenza, and differences in impact in different geographic regions. Although influenza pandemics are classically defined by the first of these features, the other four characteristics are frequently not considered in response plans.

Yet the second feature, the shift in mortality toward younger age groups, was the most striking characteristic of the 20th-century pandemics.^1,2 Exposure to influenza A/H1 subtypes before 1873 may have offered some protection to adults over 45 years of age during the pandemic of 1918 and 1919. A similar mechanism of antigen recycling might explain the partial protection against influenza-related death that was observed among people over 77 years of age during the 1968–1970 pandemic — a possibility supported by the prepandemic presence of antibodies to H3, which were isolated in people born before 1892.¹ Another possible mechanism is immune potentiation, leading to an increased likelihood of lethal outcomes after influenza infection in specific age groups. Still other hypotheses include the possibility of bacterial superinfection due to asymmetric carriage rates, given that higher rates were found among young people in 1918 and 1919.^1,2 Although the elderly frequently have the highest death rates during seasonal epidemics, their relative sparing during pandemics has not been generally appreciated. Advance knowledge of which subpopulations are most likely to be at increased risk for death can shape the optimization of control strategies.

The third feature, a pattern of multiple waves, characterized all three 20th-century pandemics, each of which caused increased mortality for 2 to 5 years (see chart).¹ The lethal wave in the autumn of 1918 was preceded by a first wave in the summer that led to substantial morbidity but relatively low mortality in both the United States and Europe. Recent studies suggest that these early mild outbreaks partially immunized the population, decreasing the mortality impact of the main pandemic wave in the fall of 1918.² In the United States, the 1957 influenza A/H2 pandemic had three waves in the United States, with notable excess mortality in the nonsuccessive winter seasons of 1959 and 1962 — the latter being 5 years after the initial emergence of the pandemic strain.¹ From 1968 through 1970, Eurasia had a mild first influenza season, with the full effects on morbidity and mortality occurring in the second season of pandemic-virus circulation. The reasons for multiple waves of varying impact are not precisely understood, but they probably include adaptation of the virus to its new host, demographic or geographic variation, seasonality, and the overall immunity of the population.^1,2 The occurrence of multiple waves potentially provides time for health authorities to implement control strategies for successive waves.

Increased transmissibility of influenza because of high susceptibility of the population, the fourth feature, has also been documented for all the past pandemics, although estimates of reproductive numbers — a measure of the average number of secondary infections caused by each individual case — vary considerably among studies and pandemics.^2,3 Recent studies suggest that during the early mild wave of the 1918–1919 pandemic, the reproductive number (i.e., the number of new cases attributable to a single established case) may have ranged between 2 and 5,^2,3 as compared with the average of 1.3 for seasonal influenza. Since models of containment and pandemic control assumed lower reproductive numbers for the current epidemic than those that have been historically observed, they are likely to be overly optimistic regarding the success of containment strategies.

Great heterogeneity among regions in terms of incidence and mortality is also a characteristic of pandemics. This variability is probably explained by the complex heterogeneity in the degree of immunity in local populations to the circulating influenza strains, as well as by transmission factors such as geographic conditions, social mixing, degree of viral infectiousness, and “seasonal forcing” (small seasonal changes in the effective transmission rate).⁴ The benefits of sharing data on all these variables provide major incentives for international collaboration.

Although the A/H5N1 influenza subtype has spread to avian populations in more than 30 countries and infected nearly 400 persons, with a case fatality rate above 50%, scientists disagree about its pandemic potential. Such a highly pathogenic virus does not usually adapt well to its host, since it tends to kill faster than it can be transmitted. Other avian subtypes are also considered to be pandemic threats. Although avian viruses have a different tropism for respiratory cellular receptors in birds than for those in humans, gradual viral mutations or gene-segment reassortments in a mammal “mixing vessel” could result in a novel viral clade or subtype that spreads rapidly in a population that has largely not previously been exposed to it. Such changes may have occurred in the current swine H1N1 circulating strain.

The death toll of a future pandemic depends not only on the virulence of the virus in question but also on the rapidity with which we are able to introduce effective preventive and therapeutic measures. Although A/H5N1 has been associated with a “cytokine-storm” phenomenon reminiscent of that observed in 1918 and 1919, new methods for the timely manufacture and administration of antiviral agents and influenza and pneumococcal vaccines could mitigate the effects of a pandemic.

The evidence of multiple waves in the 20th-century pandemics underlines the importance of active real-time viral surveillance on a global scale. Transnational collaborations are crucial for the effective exchange of genomic, clinical, and epidemiologic data that will make possible the development of vaccines and treatment protocols and the identification of the best population-based strategies. Although our ability to produce a vaccine in sufficient quantities to cover people who are exposed in a first pandemic wave is very limited with today’s technology, an interwave period would provide time to increase the production of biomedical tools and to vaccinate populations, thereby mitigating the morbidity and mortality associated with successive and potentially more lethal waves. This possibility, too, is a powerful incentive for international collaboration, since all would potentially share the benefits. If an effective vaccine had been available and used even a year after the emergence of the A/H3N2 viruses in 1968, most of the deaths in Europe and Asia could probably have been prevented.

The signature pandemic feature of shifts in age-specific mortality patterns should influence vaccination priorities.⁵ Given that the supplies of vaccine and antiviral agents are likely to be constrained, the efficient allocation necessary for reducing mortality will require consideration of local demography, expected shifts in age-specific incidence, direct and herd effects of vaccination in various age groups, and ethical issues regarding life expectancies and potential years of life saved in various groups. The indirect effects of reducing transmission also warrant further consideration. The role of preexisting antibodies in the elderly, their reduced immune response because of immune senescence, and greater transmission among children should prompt the targeting of younger age groups as the soundest policy in a 1918-like scenario. However, these attributes do not necessarily apply to other pandemics to the same extent.⁵

Nonmedical interventions — primarily social distancing — could be useful in staving off transmission. Simulation models suggest that such interventions would considerably decrease the incidence of infection only if the basic reproductive number was less than 2, a rate that is lower than that observed in past pandemics.³

Though the rapidity of transmission of influenza virus during pandemics necessitates immediate action, it can be hoped that close collaborations and lessons drawn from previous pandemics will contribute to reducing national and global mortality. The documented relevant signature features can help health authorities prioritize national strategies and aid international collaborators in addressing the initial and successive waves of illnesses and deaths.

Dr. Miller reports being named on a pending patent held by the National Institutes of Health on a novel influenza vaccine; and Dr. Simonsen, receiving consulting fees from Merck and research support from Wyeth. No other potential conflict of interest relevant to this article was reported.
Source Information

Dr. Miller is the associate director for research, Dr. Viboud a staff scientist, and Dr. Balinska a research associate at the Fogarty International Center of the National Institutes of Health, Bethesda, MD. Dr. Simonsen is an adjunct professor and research director of the Department of Global Health, George Washington University School of Public Health and Health Services, Washington, DC.

This article (10.1056/NEJMp0903906) was published on May 7, 2009 at NEJM.org.

References

1. Simonsen L, Olson DR, Viboud C, et al. Pandemic influenza and mortality: past evidence and projections for the future. In: Knobler SL, Mack A, Mahmoud A, Lemon SM, eds. The threat of pandemic influenza: are we ready? Workshop summary. Washington, DC: National Academies Press, 2005:89-114. 
2. Andreasen V, Viboud C, Simonsen L. Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies. J Infect Dis 2008;197:270-278. [CrossRef][ISI][Medline]
3. Viboud C, Tam T, Fleming D, Handel A, Miller MA, Simonsen L. Transmissibility and mortality impact of epidemic and pandemic influenza, with emphasis on the unusually deadly 1951 epidemic. Vaccine 2006;24:6701-6707. [CrossRef][ISI][Medline]
4. Richard SA, Sugaya N, Simonsen L, Miller MA, Viboud C. A comparative study of the 1918-1920 influenza pandemic in Japan, USA and UK: mortality impact and implications for pandemic planning. Epidemiol Infect 2009 February 12:1-11 (Epub ahead of print).
5. Miller MA, Viboud C, Olson DR, Grais RF, Rabaa MA, Simonsen L. Prioritization of influenza pandemic vaccination to minimize years of life lost. J Infect Dis 2008;198:305-311. [CrossRef][ISI][Medline]

Emergency Department Skull Trephination for Epidural Hematoma in Patients Who
Are Awake But Deteriorate Rapidly
Published online: 18 June 2009
Stephen W. Smith, Michael Clark, Jody Nelson, William Heegaard, Kirk C. Lufkin,
Ernest Ruiz
DOI: 10.1016/j.jemermed.2009.04.062
Journal of Emergency Medicine

Background: Blunt head trauma patients who have been alert but are deteriorating (talk and deteriorate [T&D]) due to a rapidly expanding epidural hematoma (EDH) usually have poor outcome if they must wait for hospital transfer for evacuation. We therefore have continued to teach skull trephination to emergency physicians (EPs). We are unaware of any literature on EP trephination for EDH in the age of computed tomography (CT) scanning.

Methods: Patients with EDH from blunt trauma, either in our institution or known to our graduate network, who were T&D with anisocoria despite intubation plus medical therapy, and who had pre-transfer EP trephination, were compared to those who were transferred without trephination.

Results: There were 5 patients with blunt trauma and CT-proven EDH who were T&D with anisocoria who underwent Emergency Department (ED) trephination at outlying hospitals before transfer. All 5 had improvement in condition and good outcomes. Three had complete recovery without disability and 2 others had mild disability with good cognitive function. None had complications. Two patients with T&D and anisocoria were transferred without trephination. Both had good neurologic outcomes. The mean time to pressure relief in the trephination group vs. transfer group was 55 vs. 207 min, respectively.

Conclusion: In T&D patients with CT-proven EDH and anisocoria, ED skull trephination before transfer resulted in uniformly good outcomes without complications. Time to relief of intracranial pressure was significantly shorter with trephination. Neurologic outcomes were not different.

Amlodipine toxicity in children less than 6 years of age: a dose-response
analysis using national poison data system data
Published online: 18 June 2009
Blaine E. Benson, Daniel A. Spyker, William G. Troutman, William A. Watson,
Ludmila N. Bakhireva
DOI: 10.1016/j.jemermed.2009.02.016
Journal of Emergency Medicine

Background: Amlodipine is a long-acting calcium channel blocker capable of producing hypotension and dysrhythmia in overdose. The toxic doses of amlodipine in children are unclear.

Objectives: The purposes of this study were to describe amlodipine poisoning in children and to determine whether a dose-response relationship could be detected in this population using standardized call data from United States (US) poison centers.

Patients and Methods: 1251 amlodipine-only ingestions in children < 6 years of age were reviewed. Cases with doses coded as “Exact” or “Estimated” and with dose, age, and medical outcome were analyzed (n = 678). Ingestions reported as a “taste or lick” (n = 53) were included as a dose of 1/10 of the dosage form involved. A clinically important response was defined as bradycardia, hypotension, dysrhythmia, conduction disturbance, or hyperglycemia. The risk of such responses was examined over four dosage intervals (< 2.5 mg, 2.5–5 mg, 5.1–10 mg, and > 10 mg).

Results: The median estimated dose ingested was 5 mg (range 0.25–200 mg). Clinically important responses developed in 27 patients (3.98%), and the prevalence of such response significantly increased from 0% for the lowest to 11.1% for the highest dose interval (p = 0.001). The smallest dose to produce a clinically important response was 2.5 mg (0.15 mg/kg). Children who ingested > 10 mg were 4.4 times more likely to develop clinically important responses than those ingesting ≤ 5 mg.

Conclusion: Hypotension may occur in children with amlodipine doses as low as 2.5 mg. The National Poison Data System might provide useful insights regarding dose-response.

WASHINGTON, June 17 (Reuters) – “An analysis by U.S. regulators found Bristol-Myers Squibb and Elan Corp’s antibiotic Maxipime was not associated with a higher rate of death compared with similar drugs, the Food and Drug Administration said on Wednesday.

Maxipime “remains an appropriate therapy for its approved” uses, the FDA said in a notice on its website.

The agency said in November 2007 it was reviewing a study that suggested there may be a higher death rate in patients treated with the drug, known generically as cefepime.

“FDA has determined that the data do not indicate a higher rate of death in cefepime-treated patients,” the agency said in its announcement.

The FDA will continue to review the safety of the drug, the agency said. Separate analyses from the agency and Bristol-Myers are ongoing, and results likely will be reported in one year.

Maxipime is approved to treat pneumonia and other infections. Elan distributes the drug in the United States under a license from Bristol-Myers.

Bristol-Myers said its own analysis also showed no increase in deaths with Maxipime when compared to similar drugs…”

The FDA notice was posted here.

                                                                                                                              MMWR

Weekly

June 19, 2009 / 58(23);641-645

Novel Influenza A (H1N1) Virus Infections Among Health-Care Personnel — United States, April–May 2009

Soon after identification of novel influenza A (H1N1) virus infections in the United States in mid-April 2009, CDC provided interim recommendations to reduce the risk for transmission in health-care settings. These included recommendations on use of personal protective equipment (PPE), management of health-care personnel (HCP) after unprotected exposures, and instruction of ill HCP not to report to work (1). To better understand the risk for acquiring infection with the virus among HCP and the impact of infection-control recommendations, CDC solicited reports of infected HCP from state health departments. As of May 13, CDC had received 48 reports of confirmed or probable infections with novel influenza A (H1N1) virus* (2); of these, 26 reports included detailed case reports with information regarding risk factors that might have led to infection. Of the 26 cases, 13 (50%) HCP were deemed to have acquired infection in a health-care setting, including one instance of probable HCP to HCP transmission and 12 instances of probable or possible patient to HCP transmission. Eleven HCP had probable or possible acquisition in the community, and two had no reported exposures in either health-care or community settings. Among 11 HCP with probable or possible patient to HCP acquisition and available information on PPE use, only three reported always using either a surgical mask or an N95 respirator. These findings suggest that transmission of novel influenza A (H1N1) virus to HCP is occurring in both health-care and community settings and that additional messages aimed at reinforcing current infection-control recommendations are needed.

After identifying the first two cases of novel influenza A (H1N1) infection in the United States on April 15, 2009, CDC requested that all state and local health departments implement enhanced surveillance for unsubtypable influenza A viruses (3). On May 4, CDC began distributing a data collection instrument to health departments to gather additional information on infected HCP. The instrument included questions on job type, facility type, contact with patients with novel influenza A (H1N1) infections or respiratory illness (i.e., pneumonia, upper respiratory tract infections, or influenza-like illness), and use of PPE (i.e., gloves, gowns, surgical masks, N95 respirators, or eye protection [goggles or face shield]). For this analysis, HCP were defined as employees, students, contractors, clinicians, or volunteers whose activities involved contact with patients in a health-care or laboratory setting. Only HCP with confirmed or probable novel influenza A (H1N1) infections were included in the analysis.

Reports on HCP cases were reviewed by infection-control staff members at CDC. Cases were categorized, using criteria developed for this investigation, as having potential acquisition in the community or in a health-care setting.† The criteria used to determine the most likely source of acquisition were based on exposures indicated on the data collection instrument during the 7 days preceding symptom onset. PPE use was used to assign a level of certainty (probable or possible) to patient to HCP transmission, but PPE use was not used to distinguish between acquisition in community or health-care settings.

CDC received 48 reports of confirmed or probable novel influenza A (H1N1) infection among HCP from 18 states. Detailed information on health-care exposures was obtained for 26 cases (18 confirmed and eight probable) reported from 11 states (Table 1). Dates of illness onset ranged from April 23 to May 4. Job type was available for 25 HCP: five registered nurses (20%), four nursing assistants (16%), four physicians (16%), and 12 persons in 10 other occupations.§ Two (8%) of these infected HCP were hospitalized, one of whom reported having underlying medical conditions. Neither hospitalized HCP was admitted to an intensive-care unit; no HCP died. Among the 16 HCP for whom such information was available, eight had been vaccinated for seasonal influenza since September 2008.

Among the 26 infected HCP, 12 (46%) reported caring for a patient with either novel influenza A (H1N1) infection (six) or respiratory illness (six) (Table 2). Six HCP (23%) reported having a close contact or family member with either respiratory illness (three) or novel H1N1 infection (three); four (15%) reported recent travel to Mexico. By using the criteria for assessment of infection acquisition, 13 HCP (50%) were deemed to have been infected in a health-care setting, including five instances of probable patient to HCP transmission,¶ seven of possible patient to HCP transmission, and one of probable HCP to HCP transmission. Community transmission was deemed most likely for 11 HCP (42%); two HCP (8%) had no reported exposures in either health-care or community settings.

Of the 12 HCP with probable or possible patient to HCP acquisition, 11 reported information on their use of PPE when caring for the presumed source patient. Only three reported always using either a surgical mask (two) or an N95 respirator (one) (Table 2). Five reported always using gloves. None reported always using eye protection. None reported always using gloves, gown, and either surgical mask or N95 respirator.

Among the three HCP who reported always using either a surgical mask or N95 respirator, a physician with possible patient to HCP acquisition reported always using an N95 respirator when with the presumed source patient. However, the physician also reported never having had a fit test for the respirator, and information was not available on whether the physician used a gown or eye protection (Table 3). A nurse anesthetist with possible patient to HCP transmission reported always using gloves and a surgical mask with the presumed source patient, but sometimes using a gown, N95 respirator, and eye protection. In addition, a registered nurse with possible patient to HCP transmission (who was caring for a novel H1N1 patient on droplet precautions) reported always using a surgical mask and gloves with the presumed source patient but never using a gown, N95 respirator, or eye protection.

Editorial Note:

Routine infection-control recommendations to decrease the risk for transmission of seasonal influenza to HCP include vaccination, isolation of infected patients in single rooms, and use of standard precautions and droplet precautions (4,5). For infections with the novel influenza A (H1N1) virus, because of the lack of a vaccine and little initial information regarding the severity and transmissibility of the virus, CDC’s interim infection-control recommendations for the care of patients with such infections have included the use of fit-tested N95 respirators, eye protection, and contact precautions in addition to routine infection-control practices applied to seasonal influenza (1). In addition, CDC has recommended that aerosol-generating procedures (e.g., bronchoscopy) should be performed in an airborne infection–isolation room with negative pressure air handling. In this analysis, among the 11 HCP infected because of probable or possible patient to HCP transmission for whom information was available, none adhered to these recommended practices completely.

Although no data are available on why recommended practices often were not followed in these situations, similar nonadherence with recommended PPE by HCP caring for patients with febrile respiratory infections has been documented previously for influenza and other respiratory infections (6–8). Barriers to adherence can include 1) a belief that these practices are not necessary, inconvenient, or disruptive; 2) lack of availability of PPE; 3) inadequate training in infection control; 4) failure to establish effective, systematic approaches to HCP safety; and 5) failure to recognize patients and activities that warrant specific infection-control practices. In addition, some of the suboptimal practices described in this report might have occurred before CDC’s interim recommendations were first issued on April 25.

Most of the probable or possible patient to HCP transmissions in this report occurred in situations where the use of PPE was not in accordance with CDC recommendations. Among the three HCP who reported always using either a surgical mask or an N95 respirator while caring for a patient with either confirmed novel H1N1 infection or respiratory illness, one had not been fit-tested for the respirator, and none used all of the PPE recommended by CDC for infection control. Even so, these findings cannot definitively establish that patient to HCP transmission was related to nonuse of certain PPE, nor can the findings be used to determine the effectiveness of PPE in protecting HCP from infection with the novel influenza A (H1N1) virus.

Initial evidence suggests that HCP are not overrepresented among reported cases of persons infected with novel influenza A (H1N1) virus in the United States. Among confirmed and probable cases in adults aged 18–64 years and reported to CDC as of May 13, approximately 4% have occurred in HCP; approximately 9% of working adults in the United States are employed in health-care settings (9,10). However, this comparison is subject to several limitations, including that case reports are not geographically homogeneous, and substantial underreporting is likely. As data on additional novel influenza A (H1N1) cases are collected, the risk for infection among HCP might be better elucidated.

Whatever the risk for infection to HCP, much of that risk likely exists in the outpatient setting. As of May 31, only 653 (6%) of 10,053 patients reported with novel influenza A (H1N1) infection had been hospitalized. The findings in this report indicate that six of the 12 HCP with probable or possible patient to HCP acquisition reported working in outpatient settings during the week preceding symptom onset. Many interactions between HCP and infected patients likely occur in ambulatory-care settings and highlight the need for outpatient staff members to follow infection-control recommendations.

The findings in this report are subject to at least four limitations. First, the total number of infected HCP likely is underreported. Some HCP might not seek care for their symptoms; in addition, some states might not systematically collect data that allow them to identify HCP among persons with novel H1N1 infection. Second, detailed risk factor information was available for only 26 (54%) of the 48 reported cases, some information was missing, and data were not collected on a number of infection-control practices, including hand hygiene. Third, information collected on health-care and community exposures might have been subject to recall bias, and HCP might have had unrecognized exposures in either setting, which might have resulted in errors in identifying the source of acquisition. Finally, conclusions in this report were limited by the small number of HCP cases available for analysis.

These results highlight the need to maintain adherence to comprehensive infection-control strategies to prevent transmission of novel H1N1 in health-care settings. These strategies should include administrative controls (e.g., visitor policies and triage of potentially infectious patients), provision of infection-control resources, training in infection-control practices and correct use of PPE, identification of all ill HCP, and exclusion of ill HCP from work.

References

1. CDC. Interim guidance for infection control for care of patients with confirmed or suspected novel influenza A (H1N1) virus infection in a health-care setting. Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm.
2. CDC. Interim guidance on case definitions to be used for investigations of novel influenza A (H1N1) cases. Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/h1n1flu/casedef.htm.
3. Novel swine-origin influenza A (H1N1) virus investigation team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360:2605–15.
4. Siegel JD, Rhinehart E, Jackson M, Chiarello L; Health-care Infection Control Practices Advisory Committee. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health-care settings. Atlanta, GA: US Department of Health and Human Services, CDC; 2007. Available at http://www.cdc.gov/ncidod/dhqp/gl_isolation.html.
5. CDC. Guideline for preventing health-care-associated pneumonia. Atlanta, GA: US Department of Health and Human Services, CDC; 2004. Available at http://www.cdc.gov/ncidod/dhqp/gl_hcpneumonia.html.
6. Daugherty EL, Perl TM, Needham DM, Rubinson L, Bilderback A, Rand CS. The use of personal protective equipment for control of influenza among critical care clinicians: a survey study. Crit Care Med 2009;37:1210–6.
7. Swaminathan A, Martin R, Gamon S, et al. Personal protective equipment and antiviral drug use during hospitalization for suspected avian or pandemic influenza. Emerg Infect Dis 2007;13:1541–7.
8. Visentin LM, Bondy SJ, Schwartz B, Morrison LJ. Use of protective equipment during infectious disease outbreak and nonoutbreak conditions: a survey of emergency medical technicians. CJEM 2009;11:44–56.
9. The New York Center for Health Workforce Studies. The United States health workforce profile: October 2006. Rensselaer, NY: The New York Center for Health Workforce Studies; 2006. Available at http://www.albany.edu/news/pdf_files/U.S._Health_Workforce_Profile_October2006_11-09.pdf.
10. US Census Bureau. Annual estimates of the resident population by sex and selected age groups for the United States: April 1, 2000 to July 1, 2008 (NC-EST2008-02). Washington, DC: US Census Bureau; 2009. Available at http://www.census.gov/popest/national/asrh/NC-EST2008-sa.html.

Influenza A(H1N1) – update 50

Laboratory-confirmed cases of new influenza A(H1N1) as officially reported to WHO by States Parties to the International Health Regulations (2005)

The world’s number of novel H1N1 cases climbed to 39,620, including 167 deaths, the World Health Organization (WHO) reported yesterday.

Cumulative and new figures are subject to revision
17 June 2009 12:00 GMT

Chinese Taipei has reported 58 confirmed case of influenza A (H1N1) with 0 deaths. Cases from Chinese Taipei are included in the cumulative totals provided in the table above.

*The data has been revised on the basis of further laboratory confirmation

Abbreviations

UKOT: United Kingdom Overseas Territory
FOC: French Overseas Collectivity
OT: Overseas Territory

Posted on the Pediatric SuperSite on June 15, 2009

 OPAT discontinued in many pediatric patients due to adverse events

Adverse drug events have been reported in many children receiving outpatient parenteral antibiotic therapy, often leading to discontinuation of the antibiotic.

To determine which antibiotics are most commonly associated with an adverse event, researchers from the department of pediatrics at The State University of New York, Buffalo School of Medicine and Biomedical Sciences, and Women and Children’s Hospital of Buffalo, reviewed medical records of children who had received this type of therapy for osteomyelitis between 1986 and 2005.

The researchers identified 45 children who received OPAT. There were 26 male and 19 female patients, ranging in age from 5 months to 20 years. The researchers said Staphylococcus aureus caused most of the cases of osteomyelitis, followed by Pseudomonas aeruginosa, Escherichia coli, Enterobacta cloacae, Serratia marcesens and Streptococcus pneumoniae.

Half of the antibiotic courses were associated with an adverse drug event, and 32% of those courses were discontinued because of an adverse event. The researchers said the most commonly identified adverse event was leukopenia, followed by hepatitis and rash.

The researchers said that vancomycin was associated with the highest rate of adverse events at 85.7%, but ceftriaxone was associated with the highest discontinuation rate at 66.7%. About half of the oxacillin courses had to be discontinued because of an adverse drug event. – Erin Hopkins

PIDJ. 2009. 28 (6): 539-541.