Prevention of Opportunistic Infections in Women With HIV Infection.

Opportunistic infections are those that are either more frequent or more severe as a result of the patient's immunosuppressed condition. Opportunistic infections are, of course, the distinguishing feature of HIV infection, and they can be the cause of serious morbidity and even mortality. Some opportunistic infections can be prevented by vaccination, for example, pneumococcal infection, meningococcal infection, influenza, hepatitis A and B, and varicella. Other major opportunistic infections require prophylactic antibiotics or antiviral medications. In obstetric patients, pneumocystis infections and toxoplasmosis are most effectively prevented by the administration of trimethoprim-sulfamethoxazole. The most effective agents for prevention of reactivation of tuberculosis are isoniazid, rifampin, and rifapentine. Fluconazole is of value in preventing cryptococcal infection and candidiasis. Acyclovir, valacyclovir, and famiclovir are effective in preventing recurrent outbreaks of herpes simplex virus. Ultimately; however, the best way to prevent opportunistic infections is to treat the patient with highly active antiretroviral agents and restore her immune competence.

Prevention of Infection After Cesarean Delivery.

The critical measures of importance in reducing the frequency of postcesarean infection are preoperative cleansing of the vagina with a povidone-iodine solution, administration of cefazolin plus azithromycin before surgery, preparation of the abdomen with a chlorhexidine solution, removal of the placenta by traction on the cord, closure of the deep part of the subcutaneous layer, and closure of the skin with sutures rather than staples.

Antibiotics for the Treatment of Staphylococcal Infections in the Obstetric Patient.

This review addresses current epidemiology and treatment of obstetric staphylococcal infections. It also examines current prophylaxis methods and the efficacy of universal screening.

Treatment and Prevention of Pneumococcal Infection.

Streptococcus pneumoniae, a gram-positive diplococcus, is the most common cause of bacterial pneumonia. The diagnosis of pneumococcal pneumonia is usually confirmed by chest x-ray and gram stain. The most appropriate antibiotics for treatment pneumococcal infection are macrolides, beta-lactams, and quinolones. Two vaccines, PPSV23 and PCV13, are highly effective in preventing infection.

Evidence for Use of Tenofovir in Pregnancy to Prevent Perinatal Transmission of Hepatitis B Infection.

Perinatal transmission of hepatitis B virus continues to be a serious global public health concern. Transmission failures are related to high maternal viremia. Several antiviral therapies reduce maternal viremia around the time of delivery and decrease maternal-to-child-transmission. This chapter is a review of current studies that, ultimately, have provided strong evidence for the efficacy and safety of 3 antiviral drugs in pregnancy-lamivudine, telbivudine and tenofovir. The latter drug is the particular focus of this chapter which will show that tenofovir is the preferred antiviral therapy in pregnant women because of its potency, safety profile, and low risk of resistance.

A comparison of 3 antibiotic regimens for prevention of postcesarean endometritis: an historical cohort study.

BACKGROUND: Prophylactic antibiotics are of proven value in decreasing the frequency of postcesarean endometritis. The beneficial effect of prophylaxis is enhanced when the antibiotics are administered before the surgical incision as opposed to after the clamping of the umbilical cord. However, the optimal antibiotic regimen for prophylaxis has not been established firmly. OBJECTIVE: The purpose of this study was to compare 3 different antibiotic regimens for the prevention of postcesarean endometritis. STUDY DESIGN: This retrospective historical cohort study was conducted at the University of Florida, which is a tertiary care facility that serves a predominantly indigent patient population. In the period January 2003 to December 2007, our standard prophylactic antibiotic regimen for all women who had cesarean delivery was cefazolin (1 g) administered immediately after the baby's umbilical cord was clamped. In November 2008, we began to administer the combined regimen of cefazolin (1 g intravenously) plus azithromycin (500 mg intravenously); both were given 30-60 minutes before the skin incision. In the period of January-December 2014, we continued the dual agent regimen but based the dose of cefazolin on the patient's body mass index: 2 g intravenously if the body mass index was <30 kg/m(2) and 3 g if the body mass index was >30 kg/m(2). The surgical technique was consistent throughout all 3 time periods. Our primary endpoint was the frequency of endometritis in each time period. This diagnosis was based on fever ≥37.5°C, lower abdominal pain and tenderness, the exclusion of other localizing signs of infection, and the requirement for administration of therapeutic antibiotics. In the first year after beginning the new antibiotic regimen, we also monitored the frequency of neonatal sepsis evaluations and compared it with the frequency that was recorded during the year immediately preceding the change in antibiotic regimens. RESULTS: During the entire period 2003-2014, 29,633 women delivered at our institution; 6455 women (22%) had a cesarean delivery. In the period January 2003 to December 2007, 1034 women had a primary or repeat cesarean delivery. One hundred seventy women (16.4%; 95% confidence interval, 14.4-18.4%) developed endometritis. In the period November 2008 to December 2013, 4484 women had a primary or repeat cesarean delivery. Fifty-nine patients (1.3%; 95% confidence interval, 1.0-1.7%) developed endometritis (P < .0001 compared with period 1). In the year 2014, 937 women had a cesarean delivery; 22 of them (2.3%, 95% confidence interval, 1.3-3.3%) developed endometritis (P < .0001 compared with period 1 and P > .5 and <.10 compared with period 2). The frequency of evaluations for suspected neonatal sepsis in infants who were delivered to mothers who had cesarean delivery was 17.6% in the period January to December 2007 and 19.3% in the period November 2008 to November 2009 (relative risk, 1.1; 95% confidence interval, 0.7-1.9). One infant had proven sepsis in the former period; 2 infants had proven sepsis in the latter period (not significant). CONCLUSIONS: When administered before skin incision, the combination of cefazolin plus azithromycin was significantly more effective in the prevention of endometritis than the administration of cefazolin after cord clamping; the rate of endometritis was reduced to a very low level without increasing the rate of neonatal sepsis evaluations.

Autoimmune Hepatitis in Pregnancy: Hematological Perturbation and Management Dilemma. A Case Report.

BACKGROUND: Autoimmune hepatitis (AIH) is a progressive chronic hepatitis of unknown cause that occurs in children and adults, with a paucity of informa- tion of this disorder existing -__ in pregnancy. CASE: A primigravid pa- tient presented at 30 weeks with altered mental status, abdominal pain, vomiting, and epistaxis. Her history was significant for por- tal hypertension, encepha- lopathy, ascites, coagulopathy, hyperammonemia, and end-stage liver disease secondary to AIH. Ultrasound revealed cirrhosis, ascites, splenomegaly, and an appro- priately grown singleton gestation. She received 2 intra- muscular doses of betamethasone over 24 hours, subcuta- neous vitamin K, and oral prednisone. A lower extremity venous Doppler study was negative for thrombosis. She received ceftriaxone 1 g daily x 5 days to treat sponta- neous bacterial peritonitis. A unit of packed red blood cells and 1 unit of platelets were transfused prior to a primary cesarean 2 weeks after the initial presentation. Postoperative agitation was managed with risperidone, and wound infection was treated with vancomycinl metronidazole. She discharged herself against medical advice on postoperative day 15, and the infant was dis- charged to foster care on day 15 of life. CONCLUSION: Multiple management challenges usu- ally arise in pregnancies com- plicated by end-stage - liver disease. However, with com- prehensive multidisciplin- ary care a successful perina- tal outcome can be accom- - plished.

Blockade of GITR-GITRL interaction maintains Treg function to prolong allograft survival.

Involvement of Treg in transplant tolerance has been demonstrated in multiple models. During the active process of graft rejection, these regulatory cells are themselves regulated and inactivated, a process termed counter-regulation. We hypothesize that ligation of the costimulatory molecule glucocorticoid-induced TNF receptor-related protein (GITR) on Treg inhibits their ability to promote graft survival, and by blocking GITR ligation graft survival can be prolonged. To this aim, we have designed a soluble GITR fusion protein (GITR-Fc), which binds GITR ligand and inhibits activation of GITR. Here, we show that GITR-Fc prolonged mouse skin graft survival, and this prolongation is dependent on Treg. In a full MHC-mismatched skin graft setting, GITR-Fc significantly improved graft survival when used in combination with MR1, anti-CD40L, while GITR-Fc alone did not demonstrate graft prolongation. These results demonstrate that disruption of binding of GITR with GITR ligand may be an important strategy in prolonging allograft survival.

5-Benzylidene, 5-benzyl, and 3-benzylthiazolidine-2,4-diones as potential inhibitors of the mitochondrial pyruvate carrier: Effects on mitochondrial functions and survival in Drosophila melanogaster.

A series of thiazolidinediones (TZDs) were synthesized and screened for their effect on the mitochondrial respiration as well as on several mitochondrial respiratory system components of Drosophila melanogaster. Substituted and non-substituted 5-benzylidene and 5-benzylthiazolidine-2,4-diones were investigated. The effect of a substitution in position 3, at the nitrogen atom, of the thiozolidine heterocycle was also investigated. The designed TZDs were compared to UK5099, the most potent mitochondrial pyruvate carrier (MPC) inhibitor, in in vitro and in vivo tests. Compared to 5-benzylthiazolidine-2,4-diones 6-7 and 3-benzylthiazolidine-2,4-dione 8, 5-benzylidenethiazolidine-2,4-diones 2-5 showed more inhibitory capacity on mitochondrial respiration. 5-(4-Hydroxybenzylidene)thiazolidine-2,4-dione (3) and 5-(3-hydroxy-4-methoxybenzylidene)thiazolidine-2,4-dione (5) were among the best compounds that compared well with UK5099. Additionally, TZDs 3 and 5, showed no effects on the non-coupled respiration and weak effects on pathways using substrates such as proline, succinate, and G3P. 5-Benzylidenethiazolidine-2,4-dione 3 showed a positive effect on survival and lifespan when added to Drosophila standard and high fat diet. Interestingly, analog 3 completely reversed the effects of high fat diet on Drosophila longevity and induced metabolic changes which suggests an in vivo inhibition of MPC at the mitochondrial level.

Single versus double-gloving for obstetric and gynecologic procedures.

OBJECTIVE: The purpose of this study was to compare the relative frequency of glove perforations in double-glove versus single-glove sets. STUDY DESIGN: In this prospective cohort study, surgeons single or double-gloved for pelvic surgery procedures at their own discretion. Gloves were collected at the end of each procedure and evaluated for perforations. RESULTS: We tested 1000 sets of gloves: 675 double-glove sets and 325 single-glove sets. The highest rate of perforation (19%) occurred during major gynecologic procedures. Surgical nurses were the most likely member of the surgical team to sustain a glove injury. There was no significant difference in the total perforation rate between double and single glove sets (10% vs 11%). However, there was a significantly greater potential for blood-skin exposure in the single glove sets. Eleven percent of single glove sets contained a perforation, whereas only 2% of double glove sets contained a corresponding defect in the inner and outer gloves (P < .01). CONCLUSION: Surgeons should double-glove for all pelvic surgery procedures.

Do U.S. medical licensure examination step 1 scores correlate with council on resident education in obstetrics and gynecology in-training examination scores and American board of obstetrics and gynecology written examination performance?

OBJECTIVE: The purpose of this study was to assess the possible association between scores of >200 on U.S. Medical Licensure Examination (USMLE) step 1 and the Council on Resident Education in Obstetrics and Gynecology (CREOG) in-training examinations and the pass rate on the American Board of Obstetrics and Gynecology (ABOG) written examination. METHODS: The USMLE step 1 and postgraduate year 1 to 4 CREOG in-training examination scores for the graduating chief residents in eight accredited obstetrics and gynecology residency programs were obtained. Performance on USMLE step 1 was correlated with ABOG examination performance and CREOG in-training examination scores. The correlations between USMLE step 1 and CREOG in-training examination scores and ABOG examination performance were analyzed by using the Spearman correlation coefficient. RESULTS: USMLE step 1 scores were significantly correlated with CREOG in-training examination scores (p < 0.000). None of the residents who scored >200 on USMLE step 1 and a mean of >200 on the CREOG in-training examinations failed the ABOG written examination. CONCLUSION: Program directors have used USMLE step 1 to identify trainees who are likely to perform well on the CREOG in-training examination. The CREOG in-training examination has been used to identify residents who are likely to pass the ABOG written examination. The results of this study document the strength of these associations.

Assessing the relationship between preterm delivery and various microorganisms recovered from the lower genital tract.

OBJECTIVE: To determine if the likelihood of preterm delivery is more dependent on the specific organisms present in the vagina than on the presence of bacterial vaginosis. METHODS: We evaluated the vaginal fluid of a prospective cohort of women at 23-32 weeks of gestation with signs and symptoms of preterm labor and intact membranes. Forward stepwise logistic regression models were used to evaluate the relationship between preterm delivery and the presence of anaerobic bacteria, Gardnerella, ureaplasmas and mycoplasmas, and sialidase. RESULTS: The cohort included 137 women, and complete delivery information was available for 134 of them. The rate of preterm delivery was 28% (37 of 134). Mycoplasma genitalium independently was associated with spontaneous preterm delivery (OR 3.48; 95% CI 1.41, 8.57). After controlling for this factor, none of the other variables were significantly prognostic for spontaneous preterm delivery (residual overall p = 0.19). CONCLUSION: The presence of Mycoplasma genitalium in the vagina of pregnant women is an independent risk factor for spontaneous preterm delivery.

Teaching and assessing professionalism in medicine.

Professionalism is the single most important of the clinical competencies. Lack of professional behavior, in turn, is the single most common cause for disciplinary action against third and fourth-year medical students, residents, fellows, and clinical practitioners. Desirable professional attributes include humility, honesty, responsibility, reliability, and accountability. The ability to preserve an appropriate balance between patient care responsibilities and personal commitments also is an important feature of professional behavior. Altruism, respectfulness, loyalty, compassion, sensitivity, and tactfulness are other desirable professional attributes. In addition, professionalism requires a heightened sense of intellectual curiosity, insight into personal strengths and weaknesses, maturity, and commitment to clinical excellence and self-directed learning. Professionalism can be taught and assessed through lectures, small-group seminars, role-playing exercises, directed reading, and one-on-one observation and counseling. However, the most effective way of teaching professionalism is for instructors to model appropriate behavior and to impose a consistent policy of zero tolerance for unprofessional behavior.

Professionalism in medicine: an A-Z primer.

To be successful as physicians, we should adhere to a simple, time-honored code of conduct. We must commit ourselves to a lifetime of self-directed learning. We must strive to be thoughtful, kind, and sensitive. We must avoid arrogance, dogmatism, and negativism. We must be honest, moral, tolerant, trustworthy, and above all else, humble and compassionate. Consistent adherence to these traits will help us maintain the nobility and credibility of the medical profession.

Single additional dose postpartum therapy for women with chorioamnionitis.

OBJECTIVE: To determine whether a short course of antibiotics provides adequate treatment for chorioamnionitis. METHODS: Women received intravenous ampicillin, 2 g every 6 hours, and gentamicin, 1.5 mg/kg every 8 hours, when clinical chorioamnionitis was diagnosed. After delivery, subjects were randomized to continue this regimen until afebrile and asymptomatic for 24 hours (control group) or to receive only the next scheduled dose of each drug (study group). If delivered via cesarean, patients received clindamycin, 900 mg intravenously, at umbilical cord clamping. The control group continued receiving clindamycin every 8 hours until antibiotics were discontinued. The primary outcome was treatment failure, defined as a single temperature after the first postpartum dose of antibiotics of 39.0C or more, or two temperatures 38.4C or more at least 4 hours apart. To detect a 150% increase in rate of treatment failures from 8% in the control group to 20% in the study group, 292 subjects were needed (alpha = .05; 1 - beta = .80). RESULTS: From December 26, 1999, to March 18, 2003, a total of 292 women were enrolled in the study. In the intent-to-treat analysis, treatment failure rate did not differ between the control (n = 141) and study (n = 151) groups (3.5% versus 4.6%; P = .639). CONCLUSION: If treated promptly intrapartum, one additional dose of a broad-spectrum combination of antibiotics is sufficient postpartum therapy for immune-competent women with chorioamnionitis.

Vaginal-perianal compared with vaginal-rectal cultures for identification of group B streptococci.

OBJECTIVE: To estimate whether the rates of recovery of group B streptococci from combined vaginal and perianal cultures and combined vaginal and rectal cultures are equivalent. METHODS: We performed a prospective cohort study of vaginal-perianal versus vaginal-rectal culture for group B streptococci. Two hundred pregnant women in the third trimester were enrolled. Three specimens were collected from each patient in the following order: lower third of the vagina, perianal skin, and rectum. Each specimen was cultured serially in selective broth media, then on sheep's blood agar. Suspicious colonies were confirmed by latex agglutination. Culture positivity rates from the combined sites of vagina and perianal skin were compared with vagina and rectum. Laboratory personnel were blinded to the collection site of each individual swab. RESULTS: Of the 200 subjects, 71 (36%) had a positive culture from at least 1 site. Vaginal culture was positive in 55 patients (28%), compared with 48 patients (24%) with positive perianal cultures and 50 patients (25%) with positive rectal cultures. Results of combined vaginal and perianal cultures were positive in 68 patients (34%); results of combined vaginal and rectal cultures were positive in 67 patients (34%) (P = 1.0). CONCLUSION: The group B streptococci detection rate from vaginal-perianal specimens is not significantly different from the detection rate from vaginal-rectal specimens. Therefore, pregnant women do not need to be subjected to the discomfort of collection of a rectal specimen. LEVEL OF EVIDENCE: II-2.

Intrapartum antibiotic prophylaxis 2: positive predictive value of antenatal group B streptococci cultures and antibiotic susceptibility of clinical isolates.

OBJECTIVE: To estimate the probability of positive intrapartum group B streptococcus cultures among women previously identified as carriers of this organism, and to estimate the susceptibility of group B streptococci to six commonly used antibiotics. METHODS: We performed a prospective cohort study of women identified as carriers of group B streptococci by current pregnancy genital tract (group 1) or urine cultures (group 2), or a positive culture in a prior pregnancy (group 3). Intrapartum culture specimens were obtained, and isolates were tested for susceptibility to six antibiotics using the agar disk diffusion technique. RESULTS: Intrapartum cultures were positive for 68% (62, 73), 61% (49, 72), and 48% (36, 60) of groups 1 (n = 249), 2 (n = 69), and 3 (n = 59), respectively. Cultures were positive in 67% (61, 73) of women in group 1 whose cultures were done 42 days or less before delivery (n = 218). The proportion of isolates (n = 239) susceptible to penicillin, ampicillin, cefazolin, and vancomycin was 100% (98, 100). The proportion susceptible to clindamycin and erythromycin was 91% (87, 94) and 79% (73, 84), respectively. CONCLUSION: The positive predictive value of antenatal group B streptococci cultures is lower than was previously reported. Clindamycin and erythromycin are not optimal agents for prophylaxis against early-onset neonatal group B streptococcal infection in patients who are allergic to penicillin.