martes, 22 de abril de 2014

CDC - NIOSH Science Blog – Semi-Autonomous Motor Vehicles: What Are the Implications for Work-related Road Safety?

CDC - NIOSH Science Blog – Semi-Autonomous Motor Vehicles: What Are the Implications for Work-related Road Safety?

Semi-Autonomous Motor Vehicles: What Are the Implications for Work-related Road Safety?

Vehicles communicating with each other and with the road infrastructure. Graphic courtesy of University of Michigan Mobility Transformation Center.
Motor vehicles that are semi-autonomous – in other words, those that can operate for extended periods with little human input – are no longer just a product of science fiction. Semi-autonomous vehicles (Level 3 automation as defined below) are expected to reach the market within five years, and employers that buy or lease vehicles will need to consider the effects of this major technological change on their transportation policies and operations.
Defining the issue: The National Highway Traffic Safety Administration (NHTSA) has defined five different levels of vehicle automation ranging from Level 0 (no automation) to Level 4 (fully automated).  These are defined as follows:
  • Level 0 is No Automation.
  • Level 1 automation is Function-Specific Automation such as cruise control and automatic braking or lane-keeping. These features are widely available in vehicles on the market today.  
  • Level 2 automation is Combined Function Automation, which means that at least two primary control functions are designed to work together, for example, adaptive cruise control in combination with lane centering. The driver cedes active primary control in certain limited driving situations, but is still responsible for monitoring the roadway and safe operation and is expected to be available for control at all times and on short notice.
  • Level 3 automation is Limited Self-Driving Automation. Vehicles at this level of automation enable the driver to cede full control of all safety-critical functions under certain traffic or environmental conditions. In these situations, the driver relies heavily on the vehicle to monitor for changes that require a transition back to driver control.
  • Level 4 automation is Full Self-Driving Automation, which means the vehicle is designed to perform all safety-critical driving functions and monitor roadway conditions for an entire trip. The only human input at this level is to provide the destination for the vehicle and the vehicle does the rest – the system is fully responsible for the safe operation of the vehicle.[1]
Potential benefits for employers
  • Crash reduction: For many employers, motor vehicle crashes are a significant source of injury, lost work time, asset damage, and liability. By reducing the potential for human error, the major promixate cause of crashes, automated vehicles are expected to lead to substantial improvements in safety for all road users. 
  • Improved efficiency and productivity: Once they become a large enough share of the overall vehicle fleet, semi-autonomous vehicles may eventually reduce congestion and increase highway capacity because the system will be able to safely accommodate shorter following distances. Goods and services can be delivered more quickly and efficiently.
  • Reduced fuel consumption: Semi-autonomous vehicles will be more fuel-efficient because they can accelerate and decelerate more efficiently than a human driver, and because travel time and idling time will be less. In addition to the obvious benefits to operational costs, reductions in fuel use and carbon monoxide emissions will contribute to environmental or sustainability goals.
Policy implications for employers
Semi-autonomous vehicles (Level 3 automation) are expected to lead to improved safety, efficiency, and fuel consumption. However, with this revolutionary new technology come policy issues that employers will need to consider. Here are some examples:
  • Driver training and licensing: Drivers of semi-autonomous vehicles will need to learn about the capabilities and limitations of these vehicles. It remains to be seen whether states will require special tests or certifications to operate these vehicles, similar to a motorcycle endorsement on a driver’s license, or whether it will be left to consumers to educate themselves. In any event, employers who furnish highly-automated vehicles to workers for business or personal use may consider whether they should provide additional training.
  • Distracted driving: Drivers of semi-autonomous vehicles will be able to cede control of the vehicle for extended periods of time. This raises the possibility that the vehicle can be transformed into a legitimate workplace during those times, with the worker engaged in business meetings or interacting with various types of technology. Employers will need to consider these new possibilities in light of their current policies related to distracted driving.
  • Liability: The availability of highly-automated vehicles raises a number of questions about liability. If a semi-autonomous vehicle is under the full control of automated functions at the time of a crash, who is responsible, the manufacturer, the driver, or the driver’s employer? How will the courts determine who is liable, and how will insurers conceptualize fault? Until highly-automated vehicles become more widely available and legal precedents are established, it is difficult to predict how this will play out.
Questions for our readers: The introduction of semi-autonomous vehicles is expected to result in substantial safety and economic benefits throughout the transportation system. We at the NIOSH Center for Motor Vehicle Safety  want to develop research projects and resources that address the risks and opportunities posed by the introduction of these new technologies in the workplace.  We’d like to start a conversation about the implications of semi-autonomous vehicles for work-related road safety and motor vehicle fleet operations:
  • Are employers planning to become early adopters of semi-automated vehicles as these become available?
  • Are they thinking about how the sweeping changes that are expected to accompany the introduction of these vehicles will affect their current fleet safety management policies?
  • We’ve identified some potential safety and policy issues here. What other issues should we consider?
  • Finally, what kinds of research might NIOSH and our partners undertake to assess the impact of increasingly autonomous vehicles on road safety in the workplace and fleet operations?
We welcome readers’ responses to these questions and any other comments on this topic.
Stephanie Pratt, PhD and Kwame Boafo, MPH
Dr. Pratt is Coordinator of the NIOSH Center for Motor Vehicle Safety, and is based in the NIOSH Division of Safety Research.
Mr. Boafo is an Association of Schools and Programs of Public Health (ASPPH) Fellow based in the NIOSH Division of Safety Research.

[1] National Highway Traffic Safety Administration (NHTSA) [2013]. Preliminary Statement of Policy Concerning Automated Vehicles. Washington, DC: NHTSA.

CDC - Infertility FAQs - Reproductive Health

CDC - Infertility FAQs - Reproductive Health

Infertility FAQs

lotus flower

What is infertility?

In general, infertility is defined as not being able to get pregnant (conceive) after one year of unprotected sex. Women who do not have regular menstrual cycles, or are older than 35 years and have not conceived during a 6-month period of trying, should consider making an appointment with a reproductive endocrinologist—an infertility specialist. These doctors may also be able to help women with recurrent pregnancy loss—2 or more spontaneous miscarriages. 

Pregnancy is the result of a process that has many steps.

To get pregnant—
  • A woman’s body must release an egg from one of her ovariesExternal Web Site Icon (ovulation).
  • A man's sperm must join with the egg along the way (fertilize).
  • The fertilized egg must go through a fallopian tubeExternal Web Site Icon toward the uterusExternal Web Site Icon (womb).
  • The fertilized egg must attach to the inside of the uterus (implantation).
Infertility may result from a problem with any or several of these steps. 

Impaired fecundity is a condition related to infertility and refers to women who have difficulty getting pregnant or carrying a pregnancy to term.

Is infertility a common problem?

Yes. About 6% of married women 15–44 years of age in the United States are unable to get pregnant after one year of unprotected sex (infertility).
Also, about 11% of women 15–44 years of age in the United States have difficulty getting pregnant or carrying a pregnancy to term, regardless of marital status (impaired fecundity).

Is infertility just a woman's problem?

No, infertility is not always a woman's problem. Both men and women contribute to infertility.
Many couples struggle with infertility and seek help to become pregnant; however, it is often thought of as only a women’s condition. A CDC study analyzed data from the 2002 National Survey of Family Growth and found that 7.5% of all sexually experienced men younger than age 45 reported seeing a fertility doctor during their lifetime—this equals 3.3–4.7 million men. Of men who sought help, 18% were diagnosed with a male-related infertility problem, including sperm or semen problems (14%) and varicocele (6%).

What causes infertility in men?

Infertility in men can be caused by different factors and is typically evaluated by a semen analysis. A specialist will evaluate the number of sperm (concentration), motility (movement), and morphology (shape). A slightly abnormal semen analysis does not mean that a man is necessarily infertile. Instead, a semen analysis helps determine if and how male factors are contributing to infertility.
Conditions that can contribute to abnormal semen analyses include—

  • Varicoceles, a condition in which the veins on a man’s testicles are large and cause them to overheat. The heat may affect the number or shape of the sperm.
  • Medical conditions or exposures such as diabetes, cystic fibrosis, trauma, infection, testicular failure, or treatment with chemotherapy or radiation.
  • Unhealthy habits such as heavy alcohol use, testosterone supplementation, smoking, anabolic steroid use, and illicit drug use.
  • Environmental toxins including exposure to pesticides and lead.

What causes infertility in women?

Women need functioning ovariesExternal Web Site Iconfallopian tubesExternal Web Site Icon, and a uterusExternal Web Site Icon to get pregnant. Conditions affecting any one of these organs can contribute to female infertility. Some of these conditions are listed below and can be evaluated using a number of different tests.
Ovarian Function (presence or absence of ovulation and effects of ovarian “age”):
  • OvulationExternal Web Site Icon. Regular predictable periods that occur every 24–32 days likely reflect ovulation. Ovulation can be predicted by using an ovulation predictor kit and can be confirmed by a blood test to see the woman’s progesterone level. A woman’s menstrual cycleExternal Web Site Icon is, on average, 28 days long. Day 1 is defined as the first day of “full flow.”
  • A woman with irregular periods is likely not ovulating. This may be because of several conditions and warrants an evaluation by a doctor. Potential causes of anovulation include the following:
    • Polycystic ovary syndrome (PCOS).External Web Site Icon PCOS is a hormone imbalance problem that can interfere with normal ovulation. PCOS is the most common cause of female infertility.
    • Functional hypothalamic amenorrhea (FHA). FHA relates to excessive physical or emotional stress that results in amenorrhea (absent periods).
    • Diminished ovarian reserveExternal Web Site Icon (DOR). This occurs when the ability of the ovary to produce eggs is reduced because of congenital, medical, surgical, or unexplained causes. Ovarian reserves naturally decline with age.
    • Premature ovarian insufficiencyExternal Web Site Icon (POI). POI occurs when a woman’s ovaries fail before she is 40 years of age. It is similar to premature (early) menopause.
    • Menopause External Web Site Icon. Menopause is an age-appropriate decline in ovarian function that usually occurs around age 50. It is often associated with hot-flashes and irregular periods.
  • Ovarian functionSeveral tests exist to evaluate a woman’s ovarian function.
  • No single test is a perfect predictor of fertility.
  • The most commonly used markers of ovarian function include follicle stimulating hormone (FSH) value on day 3–5 of the menstrual cycle, anti-mullerian hormone value (AMH), and antral follicle count (AFC) using a transvaginal ultrasound.
Tubal Patency (whether fallopian tubes are open, blocked, or swollen):
  • Risk factors for blocked fallopian tubesExternal Web Site Icon (tubal occlusion) can include a history of pelvic infection, history of ruptured appendicitis, history of gonorrhea or chlamydia, knownendometriosis External Web Site Icon, or a history of abdominal surgery.
  • Tubal evaluation may be performed using an X-ray which is called a hysterosalpingogram (HSG), or by chromopertubation (CP) in the operating room at time of laparoscopy, a surgical procedure in which a small incision is made and a viewing tube called a laparoscope is inserted.
    • Hysterosalpingogram (HSG) is an X-ray of the uterus and fallopian tubes. A radiologist injects dye into the uterus through the cervix and simultaneously takes X-ray pictures to see if the dye moves freely through fallopian tubes. This helps evaluate tubal caliber (diameter) and patency.
    • Chromopertubation is similar to an HSG but is done in the operating room at the time of a laparoscopy. Blue-colored dye is passed through the cervix into the uterus and spillage and tubal caliber (shape) is evaluated.
Uterine Contour (physical characteristics of the uterus):
  • Depending on a woman’s symptoms, the uterusExternal Web Site Icon may be evaluated by transvaginal ultrasound to look for fibroidsExternal Web Site Icon or other anatomic abnormalities. If suspicion exists that the fibroids may be entering the endometrial cavity, a sonohystogram (SHG) or hysteroscopy (HSC) may be performed to further evaluate the uterine environment.

What things increase a woman's risk of infertility?

Female fertility is known to decline with—
  • Age. Many women are waiting until their 30s and 40s to have children. In fact, about 20% of women in the United States now have their first child after age 35, and this leads to age becoming a growing cause of fertility problems. About one-third of couples in which the woman is older than 35 years have fertility problems. Aging not only decreases a woman's chances of having a baby but also increases her chances of miscarriageExternal Web Site Icon and of having a child with a genetic abnormality. 

    Aging decreases a woman's chances of having a baby in the following ways—
    • Her ovaries become less able to release eggs.
    • She has a smaller number of eggs left.
    • Her eggs are not as healthy.
    • She is more likely to have health conditions that can cause fertility problems.
    • She is more likely to have a miscarriage.
  • Smoking.
  • Excessive alcohol use.
  • Extreme weight gain or loss.
  • Excessive physical or emotional stress that results in amenorrhea (absent periods).

How long should women try to get pregnant before calling their doctors?

Most experts suggest at least one year for women younger than age 35. However, women aged 35 years or older should see a health care provider after 6 months of trying unsuccessfully. A woman's chances of having a baby decrease rapidly every year after the age of 30.
Some health problems also increase the risk of infertility. So, women should talk to a health care provider if they have—
It is a good idea for any woman and her partner to talk to a health care provider before trying to get pregnant. They can help you get your body ready for a healthy baby, and can also answer questions on fertility and give tips on conceiving. Learn more at the CDC's Preconception Health Web site.
Women with timer

How will doctors find out if a woman and her partner have fertility problems?

Doctors will begin by collecting a medical and sexual history from both partners. The initial evaluation usually includes a semen analysis, atubal evaluation, and ovarian reserve testing.

How do doctors treat infertility?

Infertility can be treated with medicine, surgery, intra-uterine insemination, or assisted reproductive technology. Many times these treatments are combined. Doctors recommend specific treatments for infertility based on—
  • The factors contributing to the infertility.
  • The duration of the infertility.
  • The age of the female.
  • The couple’s treatment preference after counseling about success rates, risks, and benefits of each treatment option.

What are some of the specific treatments for male infertility?

Male infertility may be treated with medical, surgical, or assisted reproductive therapies depending on the underlying cause. Medical and surgical therapies are usually managed by an urologist who specializes in infertility. A reproductive endocrinologist may offer intrauterine inseminations (IUIs) or in vitro fertilization (IVF) to help overcome male factor infertility.

What medicines are used to treat infertility in women?

Some common medicines used to treat infertility in women include—
  • Clomiphene citrate (Clomid®*) is a medicine that causes ovulation by acting on the pituitary gland. It is often used in women who have polycystic ovarian syndrome (PCOS)External Web Site Icon or other problems with ovulation. This medicine is taken by mouth.
  • Human menopausal gonadotropin or hMG (Repronex®*; Pergonal®*) are medicines often used for women who don't ovulate because of problems with their pituitary gland—hMG acts directly on the ovaries to stimulate ovulation. It is an injected medicine.
  • Follicle-stimulating hormone or FSH (Gonal-F®*; Follistim®*) are medicines that work much like hMG. It causes the ovaries to begin the process of ovulation. These medicines are usually injected.
  • Gonadotropin-releasing hormone (Gn-RH) analog are medicines often used for women who don't ovulate regularly each month. Women who ovulate before the egg is ready can also use these medicines. Gn-RH analogs act on the pituitary gland to change when the body ovulates. These medicines are usually injected or given with a nasal spray.
  • Metformin (Glucophage®*) is a medicine doctors use for women who have insulin resistance and/or PCOSExternal Web Site Icon. This drug helps lower the high levels of male hormones in women with these conditions. This helps the body to ovulate. Sometimes clomiphene citrate or FSH is combined with metformin. This medicine is usually taken by mouth.
  • Bromocriptine (Parlodel®*) is a medicine used for women with ovulation problems because of high levels of prolactin. ProlactinExternal Web Site Icon is a hormone that causes milk production.
*Note: Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
Many fertility drugs increase a woman's chance of having twins, triplets, or other multiples. Women who are pregnant with multiple fetuses have more problems during pregnancy. Multiple fetuses have a high risk of being born prematurely (too early). Premature babies are at a higher risk of health and developmental problems.

What is intrauterine insemination (IUI)?

Intrauterine insemination (IUI) is an infertility treatment that is often called artificial insemination. In this procedure, specially prepared sperm are inserted into the woman’s uterus. Sometimes the woman is also treated with medicines that stimulate ovulation before IUI.
IUI is often used to treat—
  • Mild male factor infertility.
  • Couples with unexplained infertility.

What is assisted reproductive technology (ART)?

Assisted reproductive technology (ART) includes all fertility treatments in which both eggs and sperm are handled outside of the body. In general, ART procedures involve surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman. The main type of ART is in vitro fertilization (IVF).

How often is assisted reproductive technology (ART) successful?

Success rates vary and depend on many factors, including the clinic performing the procedure, the infertility diagnosis, and the age of the woman undergoing the procedure. This last factor—the woman’s age—is especially important.
CDC collects success rates on ART for some fertility clinics. According to the CDC’s 2011 Preliminary ART Success Rates, the average percentage of fresh, nondonor ART cycles that led to a live birth were—
  • 40% in women younger than 35 years of age.
  • 32% in women aged 35–37 years.
  • 22% in women aged 38–40 years.
  • 12% in women aged 41–42 years.
  • 5% in women aged 43–44 years.
  • 1% in women aged 44 years and older.
Success rates also vary from clinic to clinic and with different infertility diagnoses.
ART can be expensive and time-consuming, but it has allowed many couples to have children that otherwise would not have been conceived. The most common complication of ART is a multiple fetus pregnancy. This is a problem that can be prevented or minimized by limiting the number of embryos that are transferred back to the uterus. For example, transfer of a single embryo, rather than multiple embryos, greatly reduces the chances of a multiple fetus pregnancy and its risks such as preterm birth.

What are the different types of assisted reproductive technology (ART)?

Common methods of ART include—
  • In vitro fertilization (IVF), meaning fertilization outside of the body. IVF is the most effective and the most common form of ART.
  • Zygote intrafallopian transfer (ZIFT) or tubal embryo transfer. This is similar to IVF. Fertilization occurs in the laboratory. Then the very young embryo is transferred to the fallopian tube instead of the uterus.
  • Gamete intrafallopian transfer (GIFT), involves transferring eggs and sperm into the woman's fallopian tube. Fertilization occurs in the woman's body. Few practices offer GIFT as an option.
  • Intracytoplasmic sperm injection (ICSI) is often used for couples with male factor infertility. Sometimes it is also used for older couples or for those with failed IVF attempts. In ICSI, a single sperm is injected into a mature egg as opposed to “conventional” fertilization where the egg and sperm are placed in a petri dish together and the sperm fertilizes an egg on its own.
ART procedures sometimes involve the use of donor eggs (eggs from another woman), donor sperm, or previously frozen embryos. Donor eggs are sometimes used for women who cannot produce eggs. Also, donor eggs or donor sperm are sometimes used when the woman or man has a genetic disease that can be passed on to the baby. An infertile woman or couple may also use donor embryos. These are embryos that were either created by couples in infertility treatment or were created from donor sperm and donor eggs. The donated embryo is transferred to the uterus. The child will not be genetically related to either parent.
Women with no eggs or unhealthy eggs might also want to consider surrogacy. A surrogate is a woman who agrees to become pregnant using the man's sperm and her own egg. The child will be genetically related to the surrogate and the male partner.
Gestational Carrier
Women with ovaries but no uterus may be able to use a gestational carrier. This may also be an option for women who shouldn't become pregnant because of a serious health problem. In this case, a woman uses her own egg. It is fertilized by her partner’s sperm and the embryo is placed inside the carrier's uterus.

Related Links

  • How Do I Know If I Have an Infertility Problem?External Web Site Icon (Resolve: The National Infertility Association)
  • Trying to Get Pregnant?External Web Site Icon (March of Dimes)
  • InfertilityExternal Web Site Icon (MedlinePlus)
  • American Fertility AssociationExternal Web Site Icon The American Fertility Association (AFA) is a national consumer organization that offers support for men and women dealing with infertility. Their purpose is to educate the public about reproductive disease, and support families during struggles with infertility and adoption.
  • RESOLVE: The National Infertility AssociationExternal Web Site Icon RESOLVE is a national consumer organization that offers support for men and women dealing with infertility. Their purpose is to provide timely, compassionate support and information to people who are experiencing infertility and to increase awareness of infertility issues through public education and advocacy.
  • Fertile HopeExternal Web Site Icon Fertile Hope is a national nonprofit organization dedicated to providing reproductive information, support, and hope to cancer patients whose medical treatments present the risk of infertility.
  • American Society for Reproductive MedicineExternal Web Site Icon The American Society for Reproductive Medicine (ASRM) is a multidisciplinary organization that provides information, education, advocacy, and standards in reproductive medicine.
  • Society for Assisted Reproductive TechnologyExternal Web Site Icon The Society for Assisted Reproductive Technology (SART) promotes and advances the standards for the practice of assisted reproductive technology to the benefit of patients, members, and society at large.
  • Human Cell, Tissues and Cellular and Tissue-Based ProductsExternal Web Site Icon Listing of ART clinics registered with FDA.

Join CDC Tomorrow for a Twitter Chat on Infertility

Join CDC Tomorrow for a Twitter Chat on Infertility

Join CDC Tomorrow for a Twitter Chat on Infertility

For National Infertility Awareness Week, this April 20–26, the NICHD joins the U.S. Department of Health and Human Services' Office on Women’s Health (OWH), the Centers for Disease Control and Prevention’sNational Center for Chronic Disease Prevention and Health Promotion (CDC NCCDPHP), the American Society for Reproductive Medicine (ASRM), and RESOLVE: The National Infertility Association for a Twitter chat on infertility.
Did you know that infertility is about as common as diabetes in the United States? Yet myths and misperceptions about this condition abound. Join us to learn the facts about infertility and about new research that is helping us understand infertility—and that may one day provide for better treatments.
When: Wednesday, April 23, 2–3 p.m. EDT
Who: We welcome everyone—including couples, health care providers, students, and researchers. 

Follow the #InfertilityChat hashtag.
Co-hosts: The chat will be hosted by:

This chat is for educational purposes only and does not take the place of a medical consultation or diagnosis. If you have inquiries about personal health care issues or needs, please contact a health care provider.

Nutrition Update

Nutrition Update

Nutrition Update

New on the MedlinePlus Nutrition page:
04/16/2014 12:00 PM EDT

When study participants were thinking about calories, they ate more of the crunchier items, less of the soft
HealthDay news image

Source: HealthDay
04/18/2014 04:00 PM EDT

Making good meal choices is harder, researcher says
HealthDay news image

Source: HealthDay − HIV/AIDS Basics: A New App for iPad − HIV/AIDS Basics: A New App for iPad Blog Update Blog for U.S. Dept. of Health & Human Services.
This information has recently been updated, and is now available.
04/22/2014 02:56 PM EDT
HIV/AIDS Basics App 1
If you’ve visited before, you’re likely familiar with the array of HIV/AIDS content found on the site. Time and time again, our analytics and usability testing tell us that the HIV basics pages are among the most visited pages on the site. In tandem with this, the Pew Internet & American Life Project  has...

Persistence and Complex Evolution of Fluoroquinolone-Resistant Streptococcus pneumoniae Clone - Volume 20, Number 5—May 2014 - Emerging Infectious Disease journal - CDC


Persistence and Complex Evolution of Fluoroquinolone-Resistant Streptococcus pneumoniae Clone - Volume 20, Number 5—May 2014 - Emerging Infectious Disease journal - CDC

link to Volume 20, Number 5—May 2014

Volume 20, Number 5—May 2014


Persistence and Complex Evolution of Fluoroquinolone-Resistant Streptococcus pneumoniae Clone

Debby Ben-DavidComments to Author , Mitchell J. Schwaber, Amos Adler, Samira Masarwa, Rotem Edgar, Shiri Navon-Venezia, David Schwartz, Nurith Porat, Tali Kotlovsky, Nikolay Polivkin, Irina Weinberg, Avraham Lazary, Nissim Ohana, and Ron Dagan
Author affiliations: National Center for Infection Control, Tel Aviv, Israel (D. Ben-David, M.J. Schwaber, A. Adler, S. Masarwa, R. Edgar, S. Navon-Venezia)Sourasky Medical Center, Tel Aviv (D. Schwartz, N. Porat, T. Kotlovsky, R. Dagan)Ben-Gurion University of the Negev, Beer-Sheva (N. Porat, R. Dagan)Reuth Medical Center, Tel Aviv (N. Polivkin, I. Weinberg, A. Lazary, N. Ohana)


Prolonged outbreaks of multidrug-resistant Streptococcus pneumoniae in health care facilities are uncommon. We found persistent transmission of a fluroquinolone-resistant S. pneumoniae clone during 2006–2011 in a post–acute care facility in Israel, despite mandatory vaccination and fluoroquinolone restriction. Capsular switch and multiple antimicrobial nonsusceptibility mutations occurred within this single clone. The persistent transmission of fluoroquinolone-resistant S. pneumoniae during a 5-year period underscores the importance of long-term care facilities as potential reservoirs of multidrug-resistant streptococci.
Institutionalized persons, particularly those >65 years of age, are at high risk for pneumococcal infections (13). The rate of sporadic pneumococcal diseases for nursing home residents is almost 20 times higher than for elderly persons living in the community (1).
In September 2008 in Israel, after report of an invasive pneumococcal disease caused by a fluoroquinolone-resistant Streptococcus pneumoniae (FQRSP) strain in a patient who had been transferred from a post–acute care facility, an investigation led to discovery that this phenotype had been endemic in the facility for at least 2 years. In the index case-patient, an 81-year-old woman with dementia, bilateral pneumonia and acute respiratory failure developed while she was in a post-acute care facility. Because her condition rapidly deteriorated, she was transferred to a tertiary acute care facility and died within 48 hours. Blood cultures recovered FQRSP. Because fluoroquinolone resistance among S. pneumoniae strains is rare in Israel and was infrequently reported in previous pneumococcal outbreaks worldwide (4,5), we conducted an investigation and attempted to implement measures to limit the spread of the resistant strains. Here we describe prolonged endemicity of a FQRSP clone in the post–acute care facility, its molecular epidemiology, and the effect of infection control measures implemented. The analysis and reporting were approved by the jurisdictional institutional review board of Sourasky Medical Center (Tel Aviv, Israel).


The facility is a 307-bed, post–acute care hospital (273 adults, 34 children). Patients are grouped into the following wards: adults and children on long-term mechanical ventilation, rehabilitation, and skilled nursing care. Median duration of hospitalization is 48 days in the rehabilitation wards, 152 days in the skilled nursing wards, and 313 days in the long-term mechanical ventilation wards.
Outbreak Investigation
In September 2008, after report of the patient with FQRSP bloodstream infection, we reviewed the clinical microbiology database at Sourasky Medical Center from January 2006 onward. A clinical case was defined as FQNSP isolated from a clinical specimen from any source. Fifty-two clinical cases of FQRSP were identified, and an outbreak investigation was initiated. However, medical records were found only for 43 patients, and clinical documentation of physical examination and clinical assessment findings was sparse. We reviewed the medical records for clinical and epidemiologic data, including patients’ demographics, underlying diseases, and antimicrobial drug exposure, in the 3 months preceding the isolation.
The first intervention, vaccination, began in November 2008. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) was made mandatory for all patients >2 years of age who were admitted to the facility. In addition, all adult patients not previously vaccinated with PPV23 received 1 dose during November and December 2008. Hospitalized and newly admitted unvaccinated children <5 years of age received 1 dose of 7-valent pneumococcal polysaccharide vaccine (PPV7). In addition, children 2–4 years of age received 1 dose of PPV23.
The second intervention, fluoroquinolone restriction, was implemented from January 2010 through October 2011 in all wards. Under the restriction policy, fluoroquinolones were prescribed only after approval by a designated staff physician. Fluoroquinolones were not used for empirical therapy and were approved for definitive therapy only when other therapeutic options were unavailable.
Total fluoroquinolone use since January 2009 as recorded by the central pharmacy was aggregated for each ward into defined daily doses (DDDs) per 1,000 bed-days, as recommended by the World Health Organization (6). The study was divided into 3 periods: baseline period (January 2006–January 2009); phase 1: post–vaccination period (February 2009–December 2009); and phase 2: fluoroquinolone-restriction period (January 2010–October 2011).
Point-Prevalence Surveillances
To determine the extent of FQNSP spread among patients and staff members, point-prevalence surveillance was conducted during the baseline period in January 2009. A convenience sample of ≈10 patients from each of the 9 wards and 20 staff members from these wards were selected for screening. Oropharyngeal and nasopharyngeal swab samples were taken from all persons by using the Transwab Pernasal Amies Plain wire swabs (Medical Wire, Corsham, UK). Endotracheal aspirates were obtained by using a suction catheter introduced through tracheostomy tubes.
To evaluate the effects of vaccination and fluoroquinolone restriction on FQNSP, we conducted follow-up point-prevalence surveillances during December 2009–January 2010 and May–June 2011. In the second and third surveys we increased the sample size, screening all patients hospitalized in a convenience sample of 3 wards in addition to a sample of 10 patients from each of the other wards. These wards represented all types of wards in the facility.
Microbiological Methods
Pneumococcal Isolation, Identification, and Susceptibility Testing
Specimens were transported to the clinical laboratory at Sourasky Medical Center. Specimens were streaked onto either tryptic soy agar with 5% sheep blood and gentamicin (5 mg/L) (first and second surveys) or Streptococcal Select Agar plates (Hy-labs, Rehovot, Israel) (third survey) and incubated overnight at 37°C in 5% CO2; the 2 methods were validated in our laboratory. The selective plates were compared with tryptic soy agar–5% sheep blood and had similar ability to support the growth of S. pneumoniae (data not shown). Pneumococcal identification and antimicrobial susceptibility testing were performed with the VITEK-2 system by using the GP and AST-GP68 cards, respectively (bioMérieux, Marcy l’Etoile, France) according to Clinical and Laboratory Standards Institute guidelines (7). MICs of ofloxacin, levofloxacin, and moxifloxacin also were tested in representative isolates by Etest (AB Biodisk, Solna, Sweden). Pneumococci were defined as resistant to ofloxacin if the ofloxacin MIC was >8 μg/mL (FQRSP). Fluoroquinolone intermediately resistant S. pneumoniae (FQISP) was defined as MIC = 4 μg/mL. Penicillin-nonsusceptible strains were defined as those with penicillin MIC >2 μg/mL.
Clonal Analysis
Serogrouping and serotyping were performed by the quellung reaction using antiserum provided by Statens Serum Institute (Copenhagen, Denmark) (8). We determined the genetic relatedness of Spneumoniae strains by pulsed-field gel electrophoresis (PFGE) analysis, as described (9). Selected isolates representing all PFGE clusters were characterized by multilocus sequence typing (MLST) as described by Enright and Spratt (10). The sequences (alleles) at each locus were compared with those at the MLST website (www.mlst.netExternal Web Site Icon), and sequence types (STs) were assigned.
Mechanisms of Fluoroquinolone Resistance
Mutations in the quinolone resistance–determining regions (QRDR) of genes encoding subunits of topoisomerase IV and DNA gyrase were assessed. Representatives from each serotype in PFGE and resistance level were tested. Primers amplifying the QRDR (11) were designed for each of the 4 genes: parC primers, F-CAAAACATGTCCCTGGAGGA and R-GCAGCATCTATGACCTCAGC; parE primers, F-TCAAGTCTGCCATTACCAAGG and R-ACCCGCACCAATGGTATAAA; gyrA primers, F2-GACAAAGGAGATGAAGGCAAG and R2-GAAAATCTGGTCCAGGCAAG; gyrB primers, F-GGGAAATAGCGAAGTGGTCA and R-GTACGAATGTGGGCTCCAT. PCR on lysates with primers as above using Hot Star Taq (QIAGEN, Hilden, Germany) was performed as follows: 95°C for 15 min and 39 cycles of 94°C for 1 min, 56°C for 1 min, 72°C for 1 min, followed by an extension step of 72°C for 10 min, and the products were sequenced (HyLab, Rehovot, Israel). Sequences were analyzed by BLAST (http://blast.ncbi.nlm.nih.govExternal Web Site Icon) against 1 of the 2 identical sequenced pneumococcal strains in the database (NC_008533 Streptococcus pneumoniae D39 and AE007317).
Statistical Analysis
The effect of the intervention was assessed during the 3 periods: baseline period, phase 1 (February 2009–December 2009), and phase 2 (January 2010–October 2011). We assumed a lag time of 2–4 weeks for demonstrating vaccine efficacy and therefore defined the postvaccination period as beginning ≈1 month after vaccination. We used segmented Poisson regression analysis of interrupted time series to compare FQRSP incidence during the 3 periods. FQRSP incidence was measured as cases per 10,000 patient-days. A p value <0.05 was considered significant.


Clinical Cases of FQRSP during the Baseline Period
Before November 2008, pneumococcal vaccine was not administered at admission to the facility. Only 40 (13%) of 310 patients had received pneumococcal vaccine before hospitalization. During January 2006–December 2008, S. pneumoniae was isolated from 66 patients. Of these, 52 (79%) isolates were fluoroquinolone-resistant, 11 (17%) were fluoroquinolone-susceptible, and 3 (5%) were intermediate. FQRSP was isolated predominantly from sputum (51 of 52 isolates). Most (45 [87%] of 52) FQRSP isolates were nonsusceptible to penicillin. Resistance to erythromycin, tetracycline, and trimethoprim/sulfamethoxazole was found in 8%, 6%, and 13% of isolates, respectively. In contrast to the high FQRSP isolation rate in the facility, the same laboratory detected fluoroquinolone resistance in only 4 (2%) of 240 of pneumococcal isolates from sputum cultures from patients in a tertiary acute care facility during that period.
Medical records were available for 43 patients with FQRSP. Their median age was 59 years (range 20–94 years). Twenty-nine (67%) patients were male. The median length of stay at the facility before FQRSP isolation was 329 days (range 3 days–26 years). Antimicrobial drug use was high in this population: 51% of patients had received >1 antimicrobial agents in the 3 months preceding isolation. Only 5 (12%) of the 43 patients received fluoroquinolones in the 3 months preceding isolation. Symptoms associated with detection of FQRSP included fever (23 [53%] patients) and respiratory deterioration (27 [63%]).
Baseline Point-Prevalence Surveillance: Serotyping and Clonal Analysis
The baseline survey comprised 84 (93%) of the 90 eligible patients and 20 (4%) of 525 health care workers. Asymptomatic colonization with S. pneumoniae was detected among 20 patients (16 [23%] of 69 adults; 4 [27%] of 15 children) and 1 (5%) health care worker. Of the colonized patients, 12 (60%) had FQNSP. This represented 14% of the sampled patients: 10 (14%) of 69 adults, all with FQRSP; and 2 (13%) of 15 children, all with FQISP. The isolate from the health care worker was fluoroquinolone susceptible.
Figure 1
Thumbnail of Serotyping and clonal analysis of the first point-prevalence survey of Streptococcus pneumoniae infection in a post–acute care facility, Israel, 2006–2011. FQ fluoroquinolone; FQISP, fluoroquinolone-intermediate S. pneumoniae; FQRSP fluoroquinolone-resistant S. pneumoniae.
Figure 1. Serotyping and clonal analysis of the first point-prevalence survey ofStreptococcus pneumoniaeinfection in a post–acute care facility, Israel, 2006–2011FQ fluoroquinolone; ST, sequence type; FQISP, fluoroquinolone-intermediate Spneumoniae; FQRSP fluoroquinolone-resistant Spneumoniae.
The FQRSP isolates belonged to 2 different serotypes and 3 different PFGE types (Figure 1). All belonged to a single ST (ST156). The 3 FQISP isolates from children belonged to serotype 19F. All belonged to a single clone that was different from the adult clone.
Mechanism of Resistance
We sequenced 7 isolates representing each PFGE type and resistance profile (Table 1, Appendix). Four isolates from adults (nos. 109, 182, 129, 116) had identical mutations previously reported in quinolone resistance: S81F in gyrA and S79Y in parC. In addition, we observed 3 silent mutations in gyrB and 1 silent mutation in parC. The silent mutation in parC was common to all isolates, including those from the 2 children and the fluoroquinolone-susceptible reference isolate. The 2 isolates from children (nos. 177, 190) had mutations in parE; 1 silent mutation and an additional I460V mutation. Isolate no. 200, a susceptible reference, also had an I460V mutation. This mutation is not reported to yield fluoroquinolone resistance. Isolate no. 177, which had a higher degree of resistance to ciprofloxacin and levofloxacin than did isolate no. 190, had 2 additional mutations, E474K and A326V.
A total of 197 (83%) eligible patients received PPV23; the remaining 41 patients refused. Seventeen (93%) eligible patients received PCV7.
During 2009, the mean fluoroquinolone DDD in the facility was 36.1. After implementing fluoroquinolone restriction, the mean DDD decreased to 16.7 during 2010 but then increased again to 29.3 during 2011. Total antimicrobial drug use did not change during the entire follow up (DDD was 196, 182, and 208 during 2009, 2010, and 2011, respectively).
Effect of the Interventions
Figure 2
Thumbnail of Clinical isolates of FQ-resistant Streptococcus pneumoniae in a post–acute care facility, Israel, 2006–2011. FQ, fluoroquinolone.
Figure 2. Clinical isolates of FQ-resistantStreptococcus pneumoniae in a post–acute care facility, Israel, 2006–2011FQ, fluoroquinolone.
During the baseline period, the rate of new clinical cases decreased (−0.1021) (Table 2Figure 2). After implementation of mandatory vaccination, an additional decrease in incidence (−0.4675). However, after the restriction began on use of antimicrobial drugs, incidence again increased (0.5489).
In the second and third surveys, 154 (90%) of 172 and 165 (97%) of 171 eligible patients were included, respectively. The prevalence of FQRSP decreased from the initial survey to the second survey. Prevalence increased in the third survey (Table 3).


The ability of S. pneumoniae to cause outbreaks in long-term care facilities has been reported (2,12,13). Most reports have described invasive infections over a few weeks that involved on average 10–20 patients (2,12). Also well documented is the ability of multiresistance serotypes to spread internationally and to become predominant clones in multiple geographic areas (1416). However, outbreaks of FQRSP have rarely been reported (4,5). This study describes prolonged transmission of FQRSP in a post–acute care hospital during at least 5 years despite implementation of mandatory vaccination and fluoroquinolone restriction. The prolonged endemicity demonstrates the potential for FQRSP strains to persist within an institution for several years; undergo capsular switch; and in the process, acquire new resistance mutations to multiple antimicrobial drugs.
Most health care–associated S. pneumoniae infections are reported from long-term care facilities, and residence in a long-term care facility is an independent risk factor (2,3,17,18). In the study reported here, despite the persistence of FQRSP in the facility, we did not notice spread of FQRSP to other settings or health care facilities. During the 5-year follow-up, no FQRSP outbreaks were reported to the National Center for Infection Control from elsewhere in the country, suggesting a high fitness cost of the fluoroquinolone resistance. Despite the prolonged presence of FQRSP clones in the facility, most colonization did not progress to invasive disease. Indeed, the dominant serotypes, 19F and 23F, are not typically associated with invasive disease in adults (19). However, reduced virulence as a result of antimicrobial resistance cannot be ruled out. It was previously suggested that penicillin resistance is associated with decreased virulence (14,15,20). However, to the best of our knowledge, no clinical evidence of reduced virulence in FQRSP is available.
Despite the recommendation for PPV23 administration to persons at high risk for pneumococcal pneumonia (21), longstanding controversy exists over its efficacy in preventing noninvasive disease (22). A recent randomized controlled study demonstrated PPV23 efficacy in preventing pneumococcal pneumonia and reducing associated death in nursing home residents (23). Although most successful interventions in long-term care facilities included use of vaccinations (12,24,25), evidence is limited for effectiveness of PPV23 against pneumococcal pneumonia or nasopharyngeal colonization. Furthermore, PPV23 is not thought to reduce carriage and thus cannot be an effective tool to reduce transmission. Preliminary studies suggest that pneumococcal conjugate vaccines induce higher levels of immunity among adults than does PPV23 (26). However, further studies are needed to assess whether pneumococcal conjugate vaccines will be more effective in pneumonia prevention among the elderly.
In a recent review, interventions implemented in 28 cluster reports included vaccination, chemoprophylaxis, and infection control measures (27). Most studies have reported successful interventions. However, in most cases, outbreak duration and follow-up both were short (median 3 months). In the current study, after implementing mandatory vaccination, we observed an initial decrease in the incidence of FQRSP. However, a decreasing trend was demonstrated even before the intervention. During the prolonged follow-up, we noticed continuous spread of the resistant clones in the facility. Chemoprophylaxis was used in most reported interventions (27). However, this strategy might be associated with selection of new resistant strains or mechanisms. Specifically, FQRSP was detected in a long-term care facility, after a short chemoprophylaxis course with combination therapy (5). Furthermore, in the present outbreak, because of diversity of the antimicrobial resistance and multiresistance phenotypes, any chosen antimicrobial drug would have further selected and promoted the already prevalent resistant strains, explaining its prolonged persistence. Restriction of fluoroquinolones did not result in a sustained decrease in the incidence of FQRSP. Prior fluoroquinolone treatment was not common in the study population reported here, but the overall use of antimicrobial drugs was not reduced in the studied facility even after the interventions began. We are assessing the effect of antimicrobial drug stewardship and improved compliance with standard precautions on the control of the spread of FQRSP in the facility.
The current FQRSP clone (ST156) comprised 2 different serotypes, which suggests that capsular switch occurred somewhere after introduction of the clone to the facility. The capacity of pneumococci for transformation of capsular type has been described in several studies (28,29), but in the current study, the location of the event can be assumed with a high degree of certainty. Capsular switch events have been defined as 2 isolates identified by MLST as being closely related but expressing different serotypes. Acquisition of a new capsule may have provided an advantage against the host immune system.
During the past few years, FQRSP has been reported from several countries, although the prevalence remains low (16,30,31). Fluoroquinolone nonsusceptibility among pneumococci results mainly from point mutations in the QRDR topoisomerase genes (32). In the current study, identical mutations were found in different serotypes among the strains in adults. This finding suggests that the mutation occurred before capsular switch. Different mutations occurred among the children’s strains and were associated with intermediate resistance. The difference between children and adults might be due to low rates of fluoroquinlone use among children and the relative separation of the children from adults in the family.
Our study has several limitations. First, because microbiological data were not available before January 2006, we cannot determine when the resistant clone was introduced into the facility. Second, clinical isolates for 2006–2008 were not available for analysis. Therefore, we performed molecular characterization only for strains found in the point-prevalence survey. Consequently, we cannot determine the dynamics of resistance development in the facility. Third, we conducted point-prevalence surveys among a sample of hospitalized patients and not among all hospitalized patients. Because we used a convenience sample, selection bias, although unlikely, cannot be categorically excluded. We assessed the effect of both vaccination and fluoroquinolone restriction. However, because the second phase comprised 2 ongoing interventions, we cannot assess separately the effect of each intervention. Finally, we did not conduct a case–control study and therefore risk factors for FQRSP acquisition cannot be assessed.
The persistent transmission of FQRSP during a 5-year period underscores the importance of long-term care facilities as potential reservoir of multidrug resistant particularly FQRSP. Further work is needed to identify optimal strategies to prevent the emergence and spread of resistant pneumococcal strains in long-term care facilities, including potential use of pneumococcal conjugate vaccines, antimicrobial stewardship, and infection control interventions to interrupt transmission.
Dr Ben-David is a hospital epidemiologist at the National Center for Infection Control in Israel. Her research emphasis is multidrug-resistant pathogens.


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Suggested citation for this article: Ben-David D, Schwaber MJ, Adler A, Masarwa S, Edgar R, Navon-Venezia S, et al. Persistence and complex evolution of fluoroquinolone-resistantStreptococcus pneumoniae clone. Emerg Infect Dis [Internet]. 2014 May [date cited]. Web Site Icon
DOI: 10.3201/eid2005.130142