Bacterial and protozoal infections in pregnancy.pptx

bacterial and protozoal infections in pregnancy from williams gynaecology

1. BACTERIAL INFECTIONS

2. Group A Streptococcus Streptococcus pyogenes is the most frequent bacterial cause of acute pharyngitis. In most cases, streptococcal pharyngitis, scarlet fever, and erysipelas is seen Treatment, usually with penicillin, is equivalent for pregnant and nonpregnant women. S pyogenes produces toxins and enzymes responsible for its local and systemic toxicity. Pyrogenic exotoxin-producing strains are usually associated with severe disease

3. Group B Streptococcus Streptococcus agalactiae colonizes the gastrointestinal and genitourinary tract in 10 to 25 percent of gravidas . Group B Streptococcus (GBS) is isolated in a transient, intermittent, or chronic fashion during pregnancy. Although the organism is more likely always present in these same women, its isolation is not always consistent.

4. Maternal and Perinatal Infection Maternal and fetal GBS effects range from asymptomatic colonization to septicemia. S agalactiae can cause maternal bacteriuria, pyelonephritis, osteomyelitis, postpartum mastitis, and puerperal infections. GBS may also have the ability to overcome normally protective cervical mucus barriers during pregnancy to cause ascending antenatal infection. As such, GBS has also been implicated in preterm labor, prelabor rupture of membranes, chorioamnionitis, fetal infections, and stillbirth. Among newborns in the United States, GBS remains the leading infectious cause of morbidity and mortality . Infection <7 days after birth is defined as early-onset disease, although many investigators recognize a threshold of <72 hours of life as most compatible with intrapartum acquisition of disease.

5. In many neonates, septicemia involves signs of serious illness that usually develop within 6 to 12 hours of birth. These include respiratory distress, apnea, and hypotension. The mortality rate with early-onset disease has declined to approximately 4 percent, and preterm newborns are disparately affected. Late-onset disease caused by GBS is noted in 0.28 per 1000 live births and usually manifests as meningitis 1 week to 3 months after bir th. The mortality rate, is lower for late-onset meningitis than for early-onset sepsis.

6. Prophylaxis for Perinatal Infections Maternal intrapartum antibiotic administration is the main prevention of early-onset GBS disease.

7. Indications for Intrapartum Group B Streptococcal Infection prophylaxis GBS Bacteriuria Previous infant with invasive GBS disease Positive GBS screening culture during current pregnancy Unknown GBS status at labour onset and Birth at <37 wks , membrane rupture >18 hrs , intra partum temp >100.4•F , intra partum NAAT result positive for GBS , positive GBS status in prior pregnancy

8. Culture-based Prevention. The American College of Obstetricians andGynecologists (2020b) recommends universal vaginal-rectal culture screening for GBS at 36 to 38 weeks’ gestation. This is followed by intrapartum antibiotic prophylaxis for women identified to be carriers. Selective enrichment of the vaginal-rectal culture to favor GBS growth and then subculture improves detection. GBS isolates can also be tested for inducible clindamycin resistance in women with reported penicillin allergy. Updated guidance also recommends consideration of antenatal maternal penicillin-allergy testing in GBS-colonized women at high risk for anaphylaxis or IgE-mediated hypersensitivity. In a recent surveillance study of neonates with early-onset sepsis, 53 percent of those diagnosed with GBS disease were born to mothers with negative antenatal screening results

9. In women with heavy colonization, GBS may be specifically identified in a routine prenatal urine culture obtained to exclude asymptomatic bacteriuria (ASB). Cultures with ≥105 colony-forming units (cfu) should prompt treatment of ASB to reduce the risk of acute pyelonephritis in pregnancy. Values <105 do not require acute antepartum antibiotics for ASB. However, women are given GBS prophylaxis in labor. As a surrogate, we also consider a urine culture result that identifies gram-positive cocci, without further speciation, to be a presumptive positive result for GBS. Risk-based Prevention. This approach is recommended for women in labor and whose GBS culture results are not known. It relies on risk factors associated with intrapartum GBS transmission.

10. GBS Vaccine Serotype-specific capsular antibody concentrations clinically correlate with reduced rates of GBS neonatal disease. However, vaccine development is challenged by the diversity of GBS serotypes. Another hurdle is the bacterium’s ability to undergo serotype switching by altering its capsular polysaccharide. No vaccines are clinically available at this time.

11. Intrapartum Antimicrobial Prophylaxis Penicillin remains the first-line agent for prophylaxis, and ampicillin is an acceptable alternative (American College of Obstetricians and Gynecologists, 2020b). Women with a penicillin allergy and at low risk for anaphylaxis are given cefazolin. Those at high risk for anaphylaxis or other life-threatening reaction, such as Stevens-Johnsonnsyndrome, should have antimicrobial susceptibility testing for erythromycin and clindamycin performed on GBS isolates. Clindamycin-sensitive but erythromycin-resistant isolates should undergo inducible clindamycin resistance testing. If clindamycin resistance is confirmed, vancomycin should be administered. Erythromycin is no longer used for penicillin-allergic patients.

12. Regimens Recommended : Penicillin G 5 Million units IV initial dose followed by 2.5 to 3 Million units IV 4 hrly Alternative : Ampicillin 2 gm IV initial dose , then 1 gm IV 4hr or 2gm every 6 hr

13. Methicillin-resistant Staphylococcus Aureus (MRSA) Staphylococcus aureus is a pyogenic gram-positive organism and is considered the most virulent staphylococcal species. It primarily colonizes the nares, skin, genital tissues, and oropharynx. MRSA infection may be hospital- or community-acquired MRSA (CAMRSA). CA-MRSA is diagnosed in an outpatient setting or within 48 hours of hospitalization in a person without health-care exposures in the past year. Exposures include prior hospitalization, dialysis or surgery, or indwelling catheters or device s .

14. MRSA and Pregnancy Skin and soft tissue infections are the most common presentation of MRSA in pregnant women. Mastitis and breast abscesses have been reported in up to a fourth of MRSA cases in pregnancy. Perineal or episiotomy abscess, abdominal surgical site infection, and rare placental abscess and chorioamnionitis have been associated with MRSA . Last, osteomyelitis and spinal-epidural abscess have been topics of case reports . Vertical transmission of MRSA is rare. Postnatal colonization and infection in the newborn are associated with maternal and health-care worker colonization or infection near the time of delivery .

15. Management Uncomplicated superficial infections are primarily managed by drainage and local wound care. E vidence suggests benefit from antibiotic therapy added to incision and drainage of smaller abscesses . Severe superficial infections, especially those that fail to respond to local care or those in patients with medical comorbidities, are treated with MRSA-appropriate antibiotics. Purulent cellulitis should be treated empirically for MRSA until culture and sensitivity results are available. Most CA-MRSA strains are sensitive to trimethoprim-sulfamethoxazole or clindamycin. Rifampin rapidly develops resistance and should not be used as monotherapy. Linezolid, although effective against MRSA, is expensive, and little information guides its use in pregnancy. Although effective for MRSA infections, doxycycline, minocycline, and other tetracyclines should not be used in pregnancy. Vancomycin remains a first-line therapy for inpatient treatment of serious MRSA infections.

16. The control and prevention of MRSA infection relies on appropriate hand hygiene and prevention of skin-to-skin contact. Routine screening of obstetrical patients for MRSA colonization is not recommended. That said, for women with culture-proven MRSA colonization or infection, we add a single dose of vancomycin to routine beta-lactam perioperative prophylaxis for cesarean deliveries and deep perineal lacerations. Breastfeeding in women colonized with MRSA is not prohibited, but optimal hygiene and attention to minor skin breaks is encouraged.

17. Listeriosis Listeria monocytogenes is a facultative intracellular gram-positive bacillus. Nearly all cases are thought to be foodborne. Outbreaks have been caused by contaminated dairy products, fruits and vegetables, and undercooked or processed meats Invasive listerial infections are more common in pregnant women, immunocompromised patients I nfection during pregnancy is 10 to 20 times more common than in the general population. Although pregnancy losses linked to listeriosis are more likely to be reported, another hypothesis is that pregnant women are more susceptible because of decreased cell-mediated immunity

18. Maternal and Fetal Infection Infections with Listeria may result in noninvasive, febrile gastroenteritis, sepsis, or CNS infection after a 2- to 4-week incubation. Listeriosis during pregnancy may be asymptomatic or may cause a febrile illness that is confused with influenza, pyelonephritis, or meningitis. Occult or clinical infection also may stimulate labor. Transplacental bacterial invasion leads to fetal infection, which can result in stillbirth or clinical illness similar to early-onset GBS sepsis. A classic description of overwhelming fetal infection is that of disseminated microabscesses and granulomas known as granulomatosis infantiseptica. Chorioamnionitis is common, and placental macroabscesses may be seen. Late-onset neonatal infection can also follow exposure at delivery.

19. Treatment with ampicillin plus gentamicin is usually recommended because of its synergism against Listeria species . Trimethoprim-sulfamethoxazole can be given to penicillin-allergic women. Maternal treatment in most cases is also effective for fetal infection. No vaccine is available. Prevention is by washing raw vegetables, cooking all raw food, and avoiding the implicated foods listed previously .

20. Salmonellosis Six serotypes, including Salmonella subtypes typhimurium and enteritidis, account for most cases Nontyphoid Salmonella gastroenteritis is contracted through contaminated food. Symptoms that include nonbloody diarrhea, abdominal pain, fever, chills, nausea, and vomiting begin 6 to 48 hours after exposure. Diagnosis is made by stool studies . Treatment is with intravenous crystalloid solutions given for rehydration. Antimicrobials are not given in uncomplicated infections because they do not commonly shorten illness and may prolong the convalescent carrier state. If gastroenteritis is complicated by high fever or bacteremia, antimicrobials are given . Rare case reports have linked Salmonella enteritidis bacteremia with septic abortio n.

21. Typhoid fever caused by Salmonella typhi remains a global health problem. Infection is spread by oral ingestion of contaminated food, water, or milk. Severe complications among patients requiring hospitalization include gastrointestinal bleeding , intestinal perforatio n, encephalopath y, renal failur e, and cardiovascular collaps e . In pregnant women, the disease is more likely to be encountered during epidemics and in those with recent travel . Septic abortion is rare but reporte d. Fluroquinolones and third-generation cephalosporins are the preferred empirical treatment for enteric (typhoid) fever and invasive nontyphoidal Salmonella infectio n . Antimicrobial susceptibility testing is important to tailor the course of therapy, which typically lasts 1 to 2 weeks. T yphoid vaccine administration to pregnant women before travel is not linked to adverse outcomes.

22. Shigellosis Transmitted via the fecal–oral route, shigellosis is a common cause of diarrheal outbreaks in children attending day-care centers and in adults following international travel. Bacillary dysentery caused by Shigella species can range from mild diarrhea to severe dysentery with fever, bloody stools, abdominal cramping, and tenesmus. In immunosuppressed individuals, severe infection may lead to toxic megacolon, seizures or meningitis, or hemolytic uremic syndrome . Although mild infection is typically self-limited, treatment of dehydration is essential. Antimotility drugs are avoided, and meticulous hygiene is recommended to avoid transmission. Antimicrobial therapy during pregnancy includes fluoroquinolones, ceftriaxone, or azithromycin. Resistance is rapidly emerging, and antibiotic susceptibility testing can help guide appropriate therapy . Shigellosis can stimulate uterine contractions and cause preterm birth .

23. Lyme Disease Caused by the spirochete Borrelia burgdorferi, Lyme disease is a vector-borne illness . Lyme borreliosis results from tick bites of the genus Ixodes. There are three stages . Early infection—stage 1—causes a distinctive local skin lesion, erythema migrans, which may be accompanied by a flu-like syndrome and regional adenopathy. If untreated, early disseminated infection—stage 2—follows in days to weeks. Multisystem involvement is frequent, but skin lesions, neuropathies, myalgia, carditis, and meningitis predominate. If still untreated after months, late or persistent infection—stage 3—manifests in perhaps half of patients as a migratory arthritis. Native immunity is acquired, and the disease enters a chronic phase in approximately 10 percent.

24. Clinical diagnosis is important because serological and PCR testing have many pitfalls. IgM and IgG serological testing is recommended in early infection and is followed by a second test—either a second immunoassay or western blot—for confirmation. Ideally, acute and convalescent serological evaluation is completed if possible, however, rates of false-positive and -negative results are high. For erythema migrans, doxycycline for 10 days or amoxicillin or cefuroxime axetil for 14 days is recommended. However, doxycycline is usually avoided in pregnancy. Azithromycin for 7 days is a second-line regimen. For other manifestations, a 14- to 28-day oral or intravenous course of the same first-line drugs is recommended. No vaccine is commercially available. Avoiding areas with endemic Lyme disease and improving tick control in those areas is the most effective prevention. Selfexamination with removal of unengorged ticks within 36 hours of attachment reduces infection risk. For tick bites recognized within 72 hours, a single 200-mg oral dose of doxycycline may reduce infection development .

25. Several reports describe Lyme disease in pregnancy, although large series are lacking. Transplacental transmission has been confirmed, but no congenital effects of maternal borreliosis have been conclusively identified. Prompt treatment of early maternal infection prevent most pregnancy outcomes.

26. TUBERCULOSIS It is estimated that a third of the world population is infected with Mycobacterium tuberculosis . Infection begins with inhalation of mycobacteria, which incites a granulomatous pulmonary reaction.Active disease manifests usually as cough with minimal sputum production, low-grade fever, hemoptysis, and weight loss. Various infiltrative patterns are seen on chest radiograph, and cavitation or mediastinal lymphadenopathy may be associated. Stained smears of sputum reveal acid-fast bacilli (AFB) in approximately two thirds of culturepositive individuals. Forms of extrapulmonary tuberculosis include lymphadenitis, pleural, genitourinary, skeletal, meningeal, gastrointestinal, and miliary or disseminated . Silent endometrial tuberculosis can cause tubal infertility.

27. Treatment Latent Infection In nonpregnant, tuberculin-positive patients younger than 35 years with no evidence of active disease, treatment is given to substantially reduce the risk that their latent infection will progress to active disease. The preferred therapy is one of three rifamycin-based regimens with or without isoniazid for 3 to 4 months duration. Alternatively, isoniazid, 300 mg orally daily, is given for 6 to 9 months. Isoniazid has been used and it is considered safe in pregnancy. However, for gravidas with latent infection, most recommend that isoniazid therapy be delayed until after delivery. Some even recommend withholding treatment until 3 to 6 months after delivery because of a possibly increased isoniazid-induced hepatitis risk in postpartum women. Serum levels of hepatic transaminases should be monitored with isoniazid therapy.

28. Active Infection Regimens. Resistance to antituberculosis drugs has led to emergence of multidrug-resistant tuberculosis (MDR-TB) strains. The World Health Organization (2017) recommends isoniazid, rifampin, ethambutol, and pyrazinamide together for 6 months for nonpregnant persons. These are used until susceptibility studies are performed. Pyridoxine is added to help prevent isoniazid-associated neuropathy. A newer 4-month isoniazid, rifapentine, moxifloxacin, and pyrazinamide regimen was not inferior to the standard one. During pregnancy, in the first 2-month bactericidal phase, isoniazid, rifampin, and ethambutol are given. This is followed by a 7-month continuation phase with isoniazid and rifampi n . A few reports describe MDR-TB during pregnancy, and treatment options have been reviewed. Treatment should be undertaken in consultation with infectious disease and the local health department. Breastfeeding is not prohibited during antituberculous therapy. If neonatal therapy is indicated, medication levels in breast milk are inadequate for this.

29. Treatment of active disease is of special concern in HIV-infected women who are antiretroviral naïve. In these circumstances, beginning concomitant therapy with antituberculosis and antiretroviral therapy can cause the immune reconstitution inflammatory syndrome (IRIS) with toxic drug effects . If there is resistance to rifabutin or rifampin, then pyrazinamide therapy is given. Of the second-line regimens, the aminoglycosides—streptomycin, kanamycin, amikacin, and capreomycin —are ototoxic to the fetus and are contraindicated .

30. Transmission Prevention Inpatient airborne precautions should be initiated for any patient with suspected active pulmonary tuberculosis or for patients who remain infectious despite treatment. Precautions include rooming in a negative-pressure room. Patients are encouraged to wear surgical masks during interactions, and health-care workers should don personally fitted N95 respirator masks. Patients undergoing treatment can be considered noninfectious: (1) after 2 weeks of DOT treatment compliance, (2) after three consecutive AFB-negative sputum smears, or (3) after clinical improvement evidenced by absent fever and resolving cough .

31. Neonatal Tuberculosis Congenital tuberculosis applies also to newborns who are infected by aspiration of infected secretions at delivery. Neonatal tuberculosis simulates other congenital infections and manifests with hepatosplenomegaly, respiratory distress, fever, and lymphadenopathy . Neonatal infection is unlikely if the mother with active disease is treated before delivery or if her sputum culture is negative. If the mother is infectious, 3 to 6 months of isoniazid prophylaxis is given to the newborn.

32. PROTOZOAL INFECTIONS

33. Toxoplasmosis The obligate intracellular parasite Toxoplasma gondii has a life cycle with two distinct stages . The feline stage takes place in cats—the definitive host—and their prey. Unsporulated oocysts are excreted in feces. In the nonfeline stage, tissue cysts containing bradyzoites or oocysts are ingested by the intermediate host, including humans. Gastric acid digests the cysts to release bradyzoites, which infect small-intestinal epithelium. Here, they are transformed into rapidly dividing tachyzoites, which can infect all cells within the host mammal. Humoral and cell-mediated immune defenses eliminate most of these, but tissue cysts develop. Their lifelong persistence is the chronic form of toxoplasmosis. Human infection is acquired by eating raw or undercooked meat infected with tissue cysts or by ingesting soil or water contaminated with oocysts from cat feces. Prior infection is confirmed by serological testing, and its prevalence depends on geographical locale and parasite genotype.

34. Maternal and Fetal Infection Most acute maternal infections are subclinical and are detected only by prenatal or newborn serological screening. In some cases, maternal symptoms may include a flu-like illness with lymphadenopathy. In immunocompetent adults, initial infection confers immunity, and prepregnancy infection nearly eliminates any risk of vertical transmission. Infection in immunocompromised women, however, may be severe, and reactivation may cause encephalitis, chorioretinitis, or mass lesions. Vertical transmission can cause fetal infection and then congenital toxoplasmosis. The latter is a fetopathy characterized by ocular or intracranial lesions and growth delay. Congenital toxoplasmosis is also associated with an increased risk for preterm delivery. The estimated rate of vertical transmission rises with gestational age. Transmission risk is lower in early pregnancy, sequelae of congenital toxoplasmosis are more likely to be severe .

35. Clinically affected neonates usually have generalized disease expressed as low birthweight, hepatosplenomegaly, jaundice, and anemia. Some primarily have neurological disease with intracranial calcifications, hydrocephaly, or microcephaly. Many eventually develop chorioretinitis and exhibit learning disabilities. This classic triad— chorioretinitis, intracranial calcifications, and hydrocephalus—is often accompanied by convulsions. Infected neonates with clinical signs are at risk for long-term complications .

36. Screening and Diagnosis With IgG antibody confirmed before pregnancy, there is no risk for fetal infection in immunocompetent hosts. Screening IgG serology tests should be performed in immunocompromised gravidas, including those with HIV infection. IgG antibodies against Toxoplasma develop within 2 to 3 weeks after infection, peak at 1 to 2 months, and usually persist for life—sometimes in high titers. Although IgM antibodies appear by 10 days after infection and usually become negative within 3 to 4 months, they may remain detectable for years. Thus, IgM antibodies are not used alone to diagnose acute toxoplasmosis. Toxoplasma IgG avidity increases with time. Thus, if a high-avidity IgG result is found, infection in the preceding 3 to 5 months is excluded

37. Congenital toxoplasmosis is suspected when sonography reveals findings such as hydrocephaly, intracranial or hepatic calcifications, ascites, placental thickening, hyperechoic bowel, and growth restriction. D iagnostic amniocentesis with PCR testing for toxoplasma as well as cytomegalovirus DNA is recommended, along with maternal serologic testing for both infections. The sensitivity of PCR for detection of toxoplasma DNA varies with gestational age and is lowest before 18 weeks’ gestation .

38. Management Prenatal treatment of acute maternal toxoplasmosis is based on two regimens. Spiramycin may be given alone, or a pyrimethamine plus sulfonamide combination is taken with folinic acid . These two regimens have also been used consecutively. S piramycin in women with acute infection early in pregnancy to reduce the risk of vertical transmission. Because it does not cross the placenta, spiramycin may not be used to treat fetal infection. Pyrimethamine plus sulfadiazine with folinic acid is selected for maternal infection after 18 weeks’ gestation or if fetal infection is suspected.

39. Prevention No vaccine is available to prevent toxoplasmosis. Strategies to avoid infection include: (1) cooking meat to safe temperatures; (2) peeling or thoroughly washing fruits and vegetables; (3) cleaning all food preparation surfaces and utensils that have contacted raw meat or unwashed fruits and vegetables; (4) wearing gloves when changing cat litter or delegating this duty; and (5) avoiding feeding cats raw or undercooked meat and keeping cats indoors.

40. Malaria This protozoan infection remains a global health crisis. Sub-Saharan Africa and India carry the largest burden of cases. Transmitted by infected Anopheles mosquitoes, six species of Plasmodium cause human disease. Pregnant women have increased susceptibility . After infection, antibodies to the parasite surface antigen VAR2CSA help mediate placental accumulation of infected erythrocytes and lead to the harmful effects of malaria

41. Maternal and Fetal Infection Clinical manifestations are fever, chills, and flu-like symptoms, which may occur episodically. Symptoms are less severe with recurrences. Malaria may be associated with anemia and jaundice, and infections with Plasmodium falciparum may cause kidney failure, coma, and death. Pregnant women, although often asymptomatic, are said to be more likely to develop traditional symptoms. Malarial infections in pregnancy—either symptomatic or asymptomatic— are associated with higher rates of perinatal morbidity and mortality. Adverse outcomes include stillbirth, preterm birth, low birthweight, and maternal anemia. These correlate with high levels of placental parasitemia. The maternal anemia and low birthweight are documented . Effects stem from parasitized erythrocytes, monocytes, and macrophages that accumulate in the vascular areas of the placenta. Infections with P falciparum are the worst, and early infection raises the risk for abortion. The incidence of malaria increases significantly in the latter two trimesters and postpartum . Despite this, congenital malaria develops in <5 percent of neonates born to infected mothers.

42. Diagnosis and Management Identification of parasites by microscopic evaluation of a blood smear remains the diagnostic gold standard. In women with low parasite densities, however, the sensitivity of microscopy is poor. Malaria-specific antigens are now being used for rapid testing, which has become the diagnostic standard fo r treatment, the most frequently used antimalarial drugs are not contraindicated in pregnancy. The World Health Organization recommends that all infected patients living in or traveling from endemic areas be treated with an artemisinin-based regimen for uncomplicated falciparum malaria. The CDC (2020c) recommends that initial treatment be determined by where the infection was acquired.

43. Pregnant women diagnosed with uncomplicated malaria caused by P vivax, P malariae, P ovale, and chloroquine-sensitive P falciparum should be treated with hydroxychloroquine or chloroquine (Centers for Disease Control and Prevention, 2020c). For women infected with multidrug-resistant P falciparum, the first-line agent for gravidas in the second and third trimesters is a drug containing both artemether and lumefantrine. Chloroquine-resistant P vivax should be treated with mefloquine. Chloroquine-sensitive P vivax or P ovale should be treated with chloroquine throughout pregnancy and then primaquine postpartum. Resistance to all the antimalarial drugs has been reported, including the recently added artemisinin-based compounds. Treatment regimens for uncomplicated and severe malarial infections in pregnancy are detailed at: www.cdc.gov/malaria/diagnosis_treatment.

44. Prevention and Chemoprophylaxis Malaria control and prevention relies on chemoprophylaxis when traveling to or living in endemic areas. In secticidetreated netting, pyrethroid insecticides, and DEET-based insect repellent lower malarial rates in endemic areas. These are well tolerated in pregnancy. If travel is necessary, chemoprophylaxis is recommended. Chloroquine or hydroxychloroquine prophylaxis is safe and well tolerated in pregnancy. Atovaquone/proguanil use is approved for gravidas, however, primaquine and doxycycline are contraindicated. For women living in endemic areas, intermittent preventive treatment with sulfadoxine-pyrimethamine is superior to intermittent screening plus indicated treatment, although resistance is a growing concern

45. Amebiasis Approximately 10 percent of the world population is infected with Entamoeba histolytica, and most are asymptomatic . Amebic dysentery, however, may take a fulminant course during pregnancy. Symptoms are fever, abdominal pain, and bloody stools. Prognosis is worse if complicated by a hepatic abscess. Identifying E histolytica cysts or trophozoites within a stool sample is diagnostic. Therapy is similar to that for nonpregnant woman. For amebic colitis and invasive disease, tinidazole may be preferred over metronidazole