Aim:
To review the effect of group B streptococcus in both pregnant women and their newly born baby. With the tests for identification and to find the appropriate treatment and protection mechanism “prophylaxis”.
Introduction:
Hundred research conduct that Group B Strep is the first leading cause to severe bacterial infection associated with illness and death among newly born babies (Ahmadzia and Heine, 2014).
In newborn, they are the most common cause of severe early-onset (0–6 days) infection and a significant cause of serious late-onset (7–90 days) infection in infants. Some of those infected babies recover from their GBS infection, some are stillborn, and more die in the first weeks of life and others suffer lifelong disability (Burns and Plumb, 2013).
Group B streptococcus:
Group B streptococcus (GBS) or streptococcus agalactiae is a gram-positive coccus that arranged in chains. It is a beta-hemolytic, catalase-negative, facultative anaerobe, and below group B of lancefield classification (Stevens and Kaplan, 2000).
Like many bacteria able to causing disease, Group B Strep has abundant number of virulence factors that are critical for its pathogenicity. The most important of them are the pore-forming toxins, sialic acid-rich capsular polysaccharide (CPS), also ten capsular serotypes (Ia, Ib, II–IX) (Rajagopal, 2009).
Their normal habitat:
Group B strep lives in the intestines and migrates down to rectum, vagina, and urinary tract. 10-30% of pregnant women are “colonized” with or carries group B strep in their bodies normally (Johri et al. 2006).
In developing countries, the average rate of maternal group B Strep colonization is 12.7%.3. this Colonization can be transient, intermittent, or chronic (Ahmadzia and Heine, 2014).
Using a swab of the rectum and vagina, women can test positive for group B strep on-and-off, temporarily, or persistently.
Being colonized with group B strep does not mean that a woman will develop a group B strep infection. Most women with this bacteria do not have any infections or symptoms. However, group B strep can cause urinary tract infections and infections in the women and newborn in certain cases. Although, women those were have preterm births “significantly shorter than normal, especially after no more than 37 weeks of pregnancy” there are 1.7 times more likely to be colonized with Group B Strep during labor than women who do not have preterm births (CDC, 2010).
Transmission:
In early-onset disease Group B strep bacteria are passed from mother to her baby; most often during or shortly before time of birth (Cdc.gov, 2016).
A study was done of 148,000 infants born between 2000 and 2008, among those infant almost 94 infants who developed early Group B Strep infection were diagnosed within an hour after birth. Suggesting that early-onset Group B Strep infection probably begins before birth when the baby still in the uterus during delivery (Tudela et al. 2012).
Late-onset disease can be caused by passing of the bacteria from mother to newborn, but sometimes caused by bacteria come from another source. For a baby whose mother does not test positive for Group B Strep, the source of infection for late-onset disease almost all time can be hard to figure out and is often unknown (Cdc.gov, 2016).
Risk Factors:
Some factors increase the risk for having Group B Strep in young (less than 20 years old), non-pregnant women like if they have multiple sexual partners, Tampon use, African –American, and Infrequent hand washing (Feigin, Cherry et al. 2009).
For infant there are some factors increase the chance of having Group B strep disease. Like if the mother is a carrier of that bacteria, the baby is born prematurely (earlier than 37 weeks),The mother’s water breaks 18 hours or more before delivery, if Group B strep bacteria have been detected in the mother’s urine (bacteriuria) during pregnancy ,and if mother previously delivered an infant with group B strep disease.
However adult become susceptible for this type of infection in certain cases such as if they have medical condition that impair the immune system and in elderly more than 65 years old (Dekker, 2013).
Colonization of group B strep in pregnant women:
Group B streptococcus is found in around 30% of normal healthy women as normal flora. It is associated with pathogenicity in immunocompromised, elderly and more common in pregnant women and neonate as it can develop very serious disease (Chukwu et al., 2015).
Maternal colonization rate may vary with population characteristics such as age, parity, socio-economic status, geographic location, presence of sexually transmitted diseases and sexual behavior (Rocchetti et al., 2010).
Most common maternal infection in association with group B strep colonization are symptomatic and asymptomatic urinary tract infection, pyelonephritis, bacteremia or sepsis (Kalin et al., 2015).
Maternal streptococcal colonization is also associated with increased risk of pregnancy complications, such as endometritis and chorioamnionitis ,premature delivery and intrauterine death (Rocchetti et al., 2010).
Colonization in late pregnancy is a risk factor for poor pregnancy outcome because Group B Strep has the ability to penetrate the intact amniotic membrane causing amnionitis then it is infecting the fetus in uterus which could lead to miscarriage (Chukwu et al., 2015).
Antigenic distribution of streptococcus agalactiae or group B strep that isolates from pregnant women:
Epidemiological studies of Group B Strep infections are based on capsular serotyping. Genotyping of the surface anchored protein genes “that act as antigenic markers in Group B Strep” is also becoming an important tool for that bacteria studies. Currently ten different GBS serotypes have been identified.
A study was performed to determine the prevalence of Group B Strep capsular types (CTs) and surface anchored protein genes that was isolates from colonized pregnant women attending antenatal clinic. The study population consisted of pregnant women with ages between 18-45 years, at the gestational period from 16 to 38 weeks. The women had not received antibiotic treatment for at least two weeks prior to recruitment into the study and sample collection. Specimen were a rectal and vaginal swabs and collected over the course of eleven months, from 413 pregnant women. Group B Strep was identified using different morphological and biochemical tests. Capsular typing was done using latex agglutination test and conventional polymerase chain reaction (PCR). Multiplex PCR with specific primers was used to detect the surface anchored protein genes. Results show that: 128 (30.9%) from those pregnant women were colonized with GBS. The capsular polysaccharide (CPS) typing test showed that CPS type III (29.7%) was the most prevalent capsular type and followed by CPS type Ia (25.8%), II (15.6%). Multiplex PCR revealed that the surface proteins genes were possessed by all the capsular types: rib (44.5%), bca (24.7%)(Table 3).
Finally, they include that The common capsular types found in this study were Ia, III, and II. And the most common protein genes identified were rib and bca (Chukwu et al., 2015).
Incidence rate of group B streptococcus infection in pregnant women in Saudi Arabia:
A study done in 2015 to determine number of asymptomatic bacteriuria in pregnant women due to Group B Strep infection. Result include that: the prevalence of asymptomatic bacteriuria due to group B strep was (2.1%) among pregnant women in Saudi Arabia. Among those (84.2%) had clinical and microbiological features consistent with cystitis “inflammation of the urinary bladder”, the other (15.8%) for pyelonephritis “inflammation in kidney tubules”. About (51.2%) of these women who had urine analysis positive results based on positive urinary leucocyte esterase and pyuria. Isolates showed that they were highly susceptible to Augmentin and linezolid. Thus they are not commonly resistant and can be treated by antibiotic to prevent their subsequent effect in the mother itself and the baby (Ahmad, 2016).
also a study done in King Abdul-Aziz University Hospital in Jeddah over one year (from 2009 to 2010) to determine the Prevalence rate of group B streptococcal colonization among women in labor. They collect the samples from 326 pregnant women in two interval. samples were Rectal and vaginal swabs in period around 33.5 ± 1.6 weeks gestational age and the second when they present in labor around 39.2 ± 2.5 weeks.Result show that: (31.6%) women had GBS colonization as shown in Table 1. (11.3%) of those women had only vaginal, (2.5%) women had only rectal and (17.8%) women had both vaginal and rectal colonization. Of the remaining women who had negative GBS cultures during pregnancy (14%) become positive when screened at labor. In this group, the positive cultures were distributed as follow:(1.2%) women had vaginal, (0.6%) had rectal and 39 (12%) women had both vaginal and rectal GBS colonization (Zamzami, Marzouki and Nasrat, 2010)
From the result they conclude that Group B strep colonization in pregnant women in Saudi Arabia almost present in high percentages. And the first screening is useful to identify the higher persent women who are having group B strep in that time of pregnancy. But in some cases who were negatively screening can be later coming colonized with that bacteria and the second screening which is during labor is effective to detect the bacteria and prevent its transmission by giving intrapartum antimicrobial prophylaxis.
For that the Screening of group B strep in pregnant women and specifically in that two period of time of gestation provide the best way of the detection even if the result in the first time screening was negative. (Zamzami, Marzouki and Nasrat, 2010)
Effect of group B streptococcus in new born:
Group B Strep is the leading infectious cause of morbidity and mortality among infants. And when it transmitted to new born one of two type of infection may occur, these are:
a) Early-Onset GBS Disease:
which occurs in the first 7 days after birth. Group B Strep has caused approximately 1,200 cases of early-onset invasive disease per year. Approximately more than 70% of cases are among babies born at term (≥37 weeks’ gestation). Infant with this infection usually present with respiratory distress, apnea, pneumonia, or other sign of sepsis within the first or second day of birth.
Early infection is caused by direct transfer of group B strep from the mother to the baby, usually after the water breaks. The bacteria travel up from the vagina into the amniotic fluid, and the fetus may swallow some of the bacteria into the lungs—leading to an early group B strep infection. Babies can also get Group B Strep during birth on their body (skin and mucous membranes) as they travel down the birth canal (Cdc.gov, 2016).
Risk Factors for getting Early-Onset Group B Strep Disease:
Mothers colonization with group B strep is the primary risk for early-onset disease. Other risk factor in addition to maternal colonization with group B strep include: gestational age <37 completed weeks, long duration of membrane rupture, intra-amniotic infection, young maternal age, and black race. Previous delivery of infant with Group B strep invasive colonization consider as risk factor for subsequent deliveries to be colonized also (Cdc.gov, 2016).
Recent studies observe that; there is an association between early-onset group B strep disease and certain obstetric procedures, such as the use of internal fetal monitoring devices and more than five or six digital vaginal examinations after onset of labor or rupture of membranes (Adair et al, 2003).
Prevention of Early-Onset Group B Streptococcal Disease:
1)Intravenous Intrapartum Antibiotic Prophylaxis:
using intravenous intrapartum antibiotic prophylaxis to prevent early-onset group B strep disease in the infant was first studied in the 1980s (Cdc.gov, 2016).
surveillanve and well-designed observational studies found that intrapartum antibiotic prophylaxis reduced the vertical transmission “which is from the mother to baby” of group B strep, as measured by changing in numbers of infant colonization or by protection against early-onset disease (Easmon et al, 1983).
Subsequent observational studies found the effectiveness to be (86%-89%) among infants born to women who received intrapartum group B strep prophylaxis (Schrag et al, 2002).
2) Intrapartum Antibiotic Prophylaxis Agents:
The efficacy of penicillin and ampicillin as intravenously administered intrapartum agents for the prevention of early-onset neonatal Group B Strep disease was demonstrated in clinical trials (Boyer and Gotoff, 1987).
Beta-lactam antibiotics for GBS prophylaxis administered for ≥4 hours before delivery have been found to be highly effective at preventing vertical transmission of Group B Strep from the mother to fetus (Cdc.gov, 2016).
Maternal anaphylaxis associated with Group B Strep intrapartum chemoprophylaxis occurs but is sufficiently rare that any morbidity associated with it. Anaphylaxis is greatly reduced by reduction in the incidence of maternal and neonatal invasive group B strep disease.
Anaphylaxis-related mortality is likely to be rare event because the majority of women receiving intrapartum antibiotics will be in hospital settings and rapid intervention is readily available. Allergic reactions occur in an estimated ( 0.7%-4.0%) of all treatment courses with penicillin (Felitti, 2006).
In the center of disease control and prevention “CDC” samples of approximately 5,000 live births occurring during 1998—1999 having nonfatal anaphylactic reaction was noted among the 27% of deliveries in which intrapartum antibiotics were administered . In that case, a single dose of penicillin was administered approximately 4 hours before a delivery, and an anaphylactic reaction occurred shortly after the mother received a single dose of a cephalosporin following umbilical cord clamping (Cdc.gov, 2016).
There is no risk for anaphylaxis in the fetus or newborn resulting from intrapartum antibiotic prophylaxis. Because a fetus or newborn is unlikely to have a previous exposure to the antibiotic, and because specific maternal IgE antibodies are not transmitted across the placenta (Jaureguy et al, 2004).
b) late-onset group B strep disease:
Late-onset GBS disease occurs in babies over 1 week of age up to several months old. Babies can become infected with GBS by sources other than the mother most probably transmitted when babies are in contact with hands contaminated by the bacteria. There are currently no prevention method in place to help prevent late-onset GBS disease (Dekker, 2013).
Its presentation can vary greatly depend in the gestational age at which the infant was born. Because there are high differences in the presenting symptoms of late-onset disease between premature and mature infants. However , its systemic effect can be characterized by symptoms in varying body systems, which them make its diagnosis complicated (Cdc.gov, 2016).
late-onset group B strep disease symptoms is normally meningitis which causing fever, breathing difficulty, feeding problems and fits. Pneumonia caused by Group B Strep can be in early or late onset. (Medscape, 2016)
Screening and diagnosis for group b strep in pregnancy:
For maternal colonizing with Group B Strep bacteria there is a critical risk factor for early-onset disease in their newborn. Two strategies or ways used to prevent early-onset disease are: first, universal culture-based screening at 35- to 37-week gestation for all pregnant women with intrapartum antibiotic prophylaxis (usually penicillin) given to those with positive results. Second, a prophylactic antibiotics provided to all women with obstetric risk factors for Group B Strep transmission and without previous screening (Abdelazim, 2013).
Screening method:
Sampling a swap from vaginal and rectal area yields a significantly higher percentage of indication of Group B Strep colonization. Because vaginal or cervical samples alone are predominant with that bacteria and lead to 40% fewer positive results (Ahmadzia and Heine, 2014).
Laboratory testing using culture media, which at least requires 36 to 48 hours of incubation time, remains the gold standard. Selective enrichment broth (e.g , Lim Broth, TransVag Broth, or Carrot Broth) is recommended to enhance Group B Strep growth initially for at least 18 to 24 hours . then, Subculture using selective media is performed for an additional 18 to 24 hours, and colonies undergo extraction for identification and susceptibility testing. Finally, to obtain the result by using current gold standard of testing “culturing”, it is at least take time around 36 to 48 hours of laboratory processing time (Ahmadzia and Heine, 2014).
CDC recommends screening of Group B Strep with a culture test at 35-37 weeks of pregnancy. This is done by swabbing the rectum and vagina with a Q-tip, and then waiting to see if Group B Strep grows in culture. This method consider as the ”gold standard”. But culture test during labor is not used in practice because it takes too long to get results back. And 91% of the women who screened negative for Group B Strep at 35-36 weeks were still give a negative result when the gold standard test was done during labor. The other 9% became Group B Strep positive. These 9% were “missed” GBS cases, meaning that these women had Group B Strep not early diagnosed and didn’t receive antibiotics. For those women it’s preferable if there is a rapid-test for the detection of that bacteria during labor (Young et al, 2011).
Rapid test for the diagnosis of group B streptococcus colonization:
Development of rapid testing technology for Group B Strep began in the 1980s. Methods such as latex agglutination, optical immunoassay, enzyme immunoassay, and DNA hybridization that included the bacterial unique antigens or RNA segments. Although these techniques reduced sample processing time significantly, and their accuracy was suboptimal or less than the highest standard or quality (Ahmadzia and Heine, 2014).
It was found that there are two tests which are polymerase chain reaction (PCR) and optical immunoassay (OIA) consider as rapid tests to identify maternal group B strep colonization at labor. Polymerase Chain Reaction was significantly more accurate than OIA for the detection of maternal Group B Strep colonization but it highly costing and expensive. To reduce the cost it is used for women who was negatively GBS testing. And for women diagnosed positively provide routine intravenous antibiotic prophylaxis “IAP” (Daniels et al., 2009).
Nucleic acid amplification testing or PCR have been intensely studied over the past 15 years. The 2 main tests, Xpert Group B Strep Assay and IDI-Strep, utilize primers targeting specific DNA regions unique of that bacteria and do not require incubation. The most recent versions of the tests consistently have sensitivities of greater than 90%. And the time for processing is variable, but on average takes about 1 hour (Ahmadzia and Heine, 2014).
New techniques are being developed that are hybrids of the culture and PCR methods. They include growth of the specimen in broth followed by PCR amplification. This combination of that two method takes about24 hours, but work to improves sensitivity and specificity compare to most of the current available testing. This test have a sensitivity of (98.6%) and specificity of (93.2%). An advantage of this hybrid testing is the ability to perform sensitivity testing from organisms isolated from the broth (Ahmadzia and Heine, 2014).
A new commercially available real-time PCR test used for the rapid detection of Group B Strep and accurately reflect intrapartum colonization with it.
There was a study designed to compare the intrapartum PCR test ” which is during labor” with the standard antepartum culture ” which is done before delivery” for detecting Group B Strep colonization. A total of 445 women in labor were register and having one of these criteria that is ;who had documented antepartum Group B Strep cultures, who did not receive either antepartum or intrapartum antibiotics, and who delivered their infant after the 4-hour threshold of 2 antibiotic doses. On labor and before the start of antibiotic prophylaxis, a vaginal specimen was collected, using two swabs, 1 swab for each testing method. With the use of intrapartum Group B Strep culture as the criterion standard test, the results of intrapartum PCR tests were compared with the results of antepartum culture to detect Group B Strep colonization. It was found that: the sensitivity and specificity of antepartum culture to diagnose Group B Strep colonization were 73% and 95.5%, respectively, compared with 98.3% and 99%, respectively, for the intrapartum PCR test. And the positive and negative predictive values of antepartum cultures to diagnose Group B Strep colonization were 83.9% and 91.6%, respectively, compared with 97.4% and 99.4% respectively for the PCR test.
They find that the intrapartum PCR test and antepartum culture had accuracy rates for detecting colonization of 98.8% and 90%, respectively. And the results suggest that the intrapartum molecular-based PCR test can be used to screen for GBS colonization very accurately than other methods (Abdelazim, 2013).
Prophylaxis and Treatment:
Intrapartum antibiotic prophylaxis in labor:
The recent guidelines from center of disease control and prevention CDC define adequate coverage for Group B Strep prophylaxis during labor. If a Group B Strep-positive woman receives penicillin G, ampicillin, or cefazolin at recommended doses for at least 4 hours before delivery, then the newborn probably does not need a diagnostic evaluation. Efficiency for penicillin G and ampicillin in reducing colonization have been shown by clinical trials that looked at the colonization, how to prevent transmission and not disease in the newborn.
Special consideration for prophylactic antibiotics must be given for women who have a penicillin allergy. Ideally, it should be clarified with a pregnant woman if she has a type I allergic reaction before labor begins. According to the CDC, type I reactions include anaphylaxis, angioedema, respiratory distress, and urticaria. If the allergy is not type I in nature, cefazolin can be used for prophylaxis (Ahmadzia and Heine, 2014).
In a population-based study of more than 7500 pregnant women, only 1% of women reported an allergy to penicillin with a “high risk” for anaphylaxis, whereas 8.1% reported an allergy to penicillin with “low risk” for anaphylaxis.50 Among the women with “low risk” for anaphylaxis, only 13.8% were given cefazolin as the second-line agent for prophylaxis. Usually, it is not recommended to give cefazolin for prophylaxis in the cases of a non–type I allergic reaction (Van Dyke et al., 2009).
For neonates whose mothers are receiving penicillin for less than 4 hours or who receive clindamycin, erythromycin, or vancomycin are considered inadequately treated and it is recommended they should be observed for 48 hours after delivery. However, if rupture of membranes around the fetus was longer than 18 hours or less there is clinical suspicion of disease. An inadequately treated infant should undergo further evaluation because they suspect that group B strep bacteria is transmitted from the mother to her baby. This evaluation includes a blood culture and a complete blood count within the first 6 to 12 hours of life. For that it is important to use the correct antibiotic and for varying obstetric events documenting the time (Ahmadzia and Heine, 2014).
Treatment of preterm labor/preterm premature rupture of membranes:
Preterm infants are at higher risk for mortality from having Group B Strep disease. Therefore, a strong and very effective antibiotics should be started on women who present in preterm labor (<37 weeks of gestation). Also, vaginal swab for group B strep should be collected at the time of admission .if either labor does not progress or the swab returns negative result, the antibiotics may be discontinued.
According to the CDC guidelines, a negative result is sufficient for 5 weeks after it is performed. However, recent evidence calls into question the sensitivity of results for that length of time (Baron, 2003).
In the situation of preterm premature rupture of membranes (less than 34 weeks of gestation), latency antibiotics typically include ampicillin are recommended. However, if there is an allergy concern or the woman is beyond 34 weeks gestation, one of the alternative CDC guidline should be started.
After antibiotics are continued for the standard 7 days, if a preterm premature rupture of membranes women enters into labor within 5 weeks of a negative Group B Strep swab the CDC does not recommend restarting antibiotics (Ahmadzia and Heine, 2014).
Resistance development against antibiotic for group B strep:
The widespread use of intrapartum antibiotic prophylaxis for the prevention of early-onset Group B Strep disease has increase concern about the development of antibiotic resistance among that bacterial isolates. Group B Strep continues to be susceptible to penicillin, ampicillin, and first-generation of cephalosporins. However, there was some isolates with increasing minimum inhibitory concentrations (MICs) to penicillin or ampicillin have been reported. Clinical and Laboratory Standards Institute guidelines do not specify susceptibility breakpoints for cefazolin, they recommend that all isolates susceptible to penicillin be considered susceptible to cefazolin (Dahesh et al., 2008).
The proportions of Group B Strep isolates from vitro resistance to clindamycin or erythromycin have increased over the past 20 years. Resistance to erythromycin is frequently but not always associated with resistance to clindamycin. One longitudinal study of GBS early-onset sepsis found that the overall rate of Group B Strep early-onset disease declined over time. Erythromycin-resistant Group B Strep caused an increasing proportion of sepsis disease during that time (Chen et al., 2005).
Vaccine to prevent Group B Strep disease:
There was a big push to search for Group B Strep vaccine for several reason. One of them because in-labor antibiotics do not prevent GBS infection 100% of time, and in-labor antibiotics can have side effects, also in-labor antibiotics do not prevent other Group B Strep problems, such as preterm labor (Dekker, 2013).
Group B Strep vaccines have been investigated as a tool for the reduction of maternal colonization and prevention of its transmission to neonates. However, no licensed vaccine is available currently. Sufficient amounts of Group B Strep capsular polysaccharide type-specific serum IgG in mothers have been shown high protection against invasive disease in their infants (Cdc.gov, 2016).
When administrating the vaccine during the third trimester of pregnancy the placenta will transfer the antibody to type ||| capsular polysaccharides in sufficient quantity to protect the fetus from invasive group B strep disease.Adult women who respond to the vaccine retained 40-60% peak of antibody concentration for at least 18-24 months of immunization.
Immunization with glycoconjugate vaccine provide protection against group B strep colonization in two distinct mechanism. First, the vaccine provide protection by eliciting antibody in concentration sufficient to prevent invasive infection. The second mechanism where group B strep vaccine protect against invasive infection by reducing vaginal and rectal acquisition of the organism (Edwards and Gonik, 2013).
Probiotics:
1-Lactobacilli:
people sometimes use Lactobacilli to eliminate Group B Strep in the vagina. In several studies, researchers have put vaginal lactobacilli (including a commercially available version) in a petri dish with different strains of Group B Strep. Then they found that the lactobacilli strongly inhibited the growth of Group B Strep by increasing the acidity of the vagina which is unsuitable to streptococcus agalactiae bacteria (Acikgov, 2005).
2-Colloidal silver:
A few websites mention that a colloidal silver can be used for preventing Group B Strep infection. Since the silver has anti-bacterial properties. Till now there is no known research studies have been conclude on taking colloidal silver to prevent a Group B Strep infection, and no studies have looked at the safety of colloidal silver in pregnancy. Because,The potential benefits and harms of this substance are unknown (Webmd.com, 2016).
3-Garlic:
One group of researchers put garlic extract and Group B Strep in a petri dish together They found that the garlic was able to kill group B strep within about 3 hours. Some recommend putting garlic or its extract in the vagina to eliminate Group B Strep growth. However, this treatment has never been tested in a scientific study with people (Dekker, 2013).
In the 1970’s when using penicillin during pregnancy, they found that it temporarily lower levels of Group B Strep, but the bacteria can grow up again by the time women go into labor. So by temporarily using garlic, this could help for getting a negative test result, but in long term the effect may be done very quickly (Cutler et al., 2009).
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