Pregnant women have increased susceptibility to infections due to the physiological and immunological changes discussed above. Similarly, these changes can enhance the risk of severe infections. Finally, there is a significant impact on the morbidity and mortality of the mother as well as the fetus. Infections with a disproportionate effect on pregnant individuals are not limited to those covered by vaccination. A common theme to the following infections is the necessity for a high suspicion, including attention to medical history and potential exposures, appropriate use of diagnostic testing, and prompt therapy when available.
Prenatal visits allow for preventative counseling regarding avoidance of foodborne or travel-associated exposures. These consults/visits are also an opportunity to evaluate reported penicillin allergies to determine if the allergy is consistent with an IgE-mediated anaphylactic allergy.34
Less than 10% of reported penicillin allergies are accurate, and the reported allergy is associated with suboptimal antibiotic therapy.35,36
In pregnancy, penicillin is the first-line treatment for group B Streptococcus
intrapartum prophylaxis, Listeria
, syphilis, and intrauterine inflammation and infection (chorioamnionitis), as alternative therapies are associated with increased complications and mortality.37,38
Patients with reported allergies can be referred to allergy or infectious disease consultation for penicillin skin tests.39
These tests are safe in pregnancy, have a high negative predictive value (97%-99%), and are associated with improved adherence to optimal antibiotic therapy.40
Urinary Tract Infections
UTIs are the most common bacterial infections in pregnancy due to increased urinary stasis.
Pregnancy is one of the few times asymptomatic bacteriuria should be treated due to the risk for progression to pyelonephritis and possible association with low birth weight and preterm births41,42,43,44
. Studies in the 1960s to 1980s showed that screening for and treatment of asymptomatic bacteriuria reduced the incidence of subsequent pyelonephritis from 20%-36% to 1%-4%, although current rates for progression to pyelonephritis may be as low as 2.5%.43,45,46
Screening at one of the initial visits with urine culture allows selection of antimicrobial therapy based on culture and antibiotic susceptibility results.
Asymptomatic bacteriuria is defined as ≥105
colony-forming units without dysuria, urgency, or other symptoms of a UTI.44
If symptomatic, empiric antimicrobial therapy based on local antibiograms can begin while awaiting culture results. Escherichia coli
is the most common infection isolated from women who have bacteriuria, followed by other Enterobacteriaceae
Common antibiotic choices include nitrofurantoin, fosfomycin (with the advantage of single dose treatment), penicillin (eg, amoxicillin-clavulanate), or cephalosporins (eg, cefpodoxime), with a treatment duration of 4 to 7 days depending on the antibiotic chosen.44,47
If progressed to pyelonephritis, blood cultures should precede antibiotics if possible, and therapy should be initiated with parenteral antibiotics (eg, ceftriaxone) while awaiting culture and susceptibility results. Once a patient has improved clinically, parenteral antibiotics can be transitioned to oral antibiotics based on susceptibility results to complete a 10- to 14-day course.41
Group B streptococcal (GBS) bacteriuria warrants particular attention as intrapartum colonization is associated with severe neonatal infections, and GBS bacteriuria is a risk factor for GBS intrapartum colonization.48
Detection of GBS bacteriuria is an indication for intrapartum prophylaxis with penicillin to prevent neonatal infection. In the case of penicillin allergies, intrapartum cefazolin can be used as second-line treatment if there is a low risk for anaphylaxis, or clindamycin or vancomycin if there is a high risk for anaphylaxis.49
Respiratory Tract Infections
Respiratory tract infections compose nearly half of self-reported infections during pregnancy in the United States and are the frequent causes of obstetric hospital admissions.50,51
In addition to the aforementioned immune modulations that may affect susceptibility to infections, the physiologic changes of pregnancy may increase the severity of respiratory infections. Pregnant individuals are more prone to aspiration pneumonia due to lower esophageal sphincter tone and increased intra-abdominal pressure, more readily develop respiratory acidosis due to decreased buffering ability (with resultant ready hypoxemia), and have increased risk for pulmonary edema.51,52,53
Therefore, a lower threshold exists for hospitalization of pregnant individuals with respiratory symptoms.
Most upper respiratory tract infections (rhinosinusitis, bronchitis) are viral, although the rare bacterial sinusitis may be treated with amoxicillin-clavulanate for a short (5- to 7-day) course.54
Molecular tests capable of identifying multiple viral respiratory pathogens should be used both for rapid diagnosis and to reduce unnecessary antibiotic use (and the associated risk of complications, including Clostridium difficile
infections). A prospective surveillance55
of viral respiratory illnesses in women in their second and third trimesters who presented to an outpatient urban clinic displayed a striking progression to lower respiratory tract illness (including wheezing, dyspnea, or cyanosis) in up to one-third of cases. Notably, the predominant viruses were rhinovirus, common coronaviruses, and respiratory syncytial virus—all managed with purely supportive care. Insufficient data are available at the time of this publication to evaluate the risks of coronavirus infectious disease 2019 (COVID-19) to pregnant women.
Influenza infections in pregnancy are associated with increased risk for hospitalization, acute respiratory distress syndrome, and death.56,57,58
Preventive care for pregnant individuals (and up to 2 weeks postpartum) includes vaccination and prophylactic therapy with oseltamivir after known exposure to individuals with influenza (dosed 75 mg daily for 1 week after last known exposure).59
Pregnant individuals presenting with influenza symptoms (including fever, cough, rhinorrhea, myalgias, headache, and/or malaise) should begin empiric antiviral therapy even if they had an influenza vaccine that season, as vaccine efficacy is not complete and early therapy is associated with reduced duration of hospitalization or risk of death.56,60,61
Oseltamivir is an oral neuraminidase inhibitor (NAI) that has extensive safety data in pregnancy and is the preferred antiviral agent for influenza. Zanamivir
(an inhaled NAI) is not preferred due to concerns about lower long volumes and bronchospasm, whereas peramivir (an intravenous NAI) and baloxavir (an oral endonuclease inhibitor) are not preferred due to a lack of pharmacokinetic and safety data in pregnant individuals. Amantadine and rimantadine are no longer used in any population due to the high (>99%) rates of resistance in circulating influenza strains.62
Treatment for community-acquired pneumonia is minimally changed in pregnant women compared to nonpregnant patients. Fluoroquinolones (such as levofloxacin) are generally avoided in pregnancy due to concerning cartilage toxicity in animal models, although a meta-analysis of fluoroquinolone exposures in pregnancy demonstrated no significant association with congenital abnormalities or adverse pregnancy outcomes.63
For clinically stable pregnant individuals without recent hospitalization, azithromycin monotherapy (500 mg daily for 3 days) is appropriate. If hospitalized, antimicrobials should expand to include a beta-lactam antibiotic (eg, ceftriaxone or ampicillin/sulbactam) for coverage of potentially macrolide-resistant Streptococcus pneumoniae
, and a history of recent antibiotics or hospitalization may necessitate the addition of an antipseudomonal beta-lactam (eg, piperacillin-tazobactam).47,64
is a gram-positive rod bacterium with a predilection for causing illness in pregnancy, with estimates of a 17- to 100-fold (or higher) increased risk over the baseline adult population.65,66
Although it rarely manifests as a gastrointestinal illness, most infections are foodborne and may occur in sporadic outbreaks. Historic outbreaks in the 1980s and 1990s were associated with delicatessen meats, with more recent outbreaks also associated with soft cheeses or produce such as cantaloupe.67,68
Invasive listeriosis results in bacteremia, meningitis, and, in a survey of US cases, progression to fetal loss or neonatal death.66,69
Maternal infections may present as fever or influenza-like illnesses, and Listeria
is readily identified in blood culture.70
In cases of meningitis or encephalitis, cerebrospinal fluid (CSF) analysis may show a neutrophilic or monocytic pleocytosis, Gram stain is often negative, and CSF culture sensitivity may be lower.71
Treatment includes high-dose ampicillin (minimum 2 g every 8 hours), with addition of gentamicin for synergy in severe illness (eg, meningitis). For patients with a penicillin allergy, ampicillin is substituted with trimethoprim/sulfamethoxazole (TMP/SMX) (10-20 mg/kg/d of trimethoprim component divided every 6 or every 12 hours).72,73,74
There have been concerns that TMP/SMX may be associated with congenital abnormalities due to interference with folate metabolism, although a meta-analysis showed no significant increase above the general population.75,76,77
Duration of therapy is a minimum of 2 weeks, with possible extension if the fetus survives.72
Prevention relies on supply chains reducing contamination of food products and avoidance for pregnant individuals.
Hepatitis E Virus
In areas in which hepatitis E virus (HEV) is endemic (including Southeast Asia and northern Africa), genotypes 1 and 2 are predominant, associated with waterborne transmission, and infection is associated with more severe illness.78
Genotypes 3 and 4 are responsible for sporadic cases in developed countries associated with undercooked meat (usually pork), tend to cause less severe illness, and tend to infect older men or individuals on immunosuppressive medications.79
A more detailed discussion of HEV infection and liver disease is provided in Chapter 34
, Liver Diseases.
Compared to hepatitis A, which similarly causes an acute but self-resolving hepatitis with a mortality rate less than 2%, the mortality rate for HEV is 1% to 4% in nonpregnant adults and 10-fold higher in pregnancy.78
A systematic review of adverse outcomes following HEV in pregnancy found a median case fatality rate of 26%, with the caveat that most studies are hospital based.80
Prevention remains in the realm of good sanitation, despite a promising vaccine with >95% efficacy that has not yet progressed to approval.78
Pregnant travelers should be advised as to the risks of HEV and the importance of hand hygiene and clean drinking water. Management is purely supportive, requiring a high degree of suspicion to diagnose (with positive IgM serology, rising IgG, or polymerase chain reaction [PCR]-based RNA detection).81
Lyme disease, caused by the spirochete Borrelia burgdorferi
, is a tick-borne disease usually presenting as a rash (erythema migrans) but with rare complications including Lyme carditis, neuroborreliosis, or
late manifestations of arthritis.82
No clear association exists between Lyme disease in pregnancy and adverse birth outcomes.83
In areas endemic for Lyme disease, nonpregnant individuals can receive prophylaxis for Lyme after a tick bite, but only doxycycline has demonstrated efficacy. Amoxicillin may be used for treatment of mild illness (500 mg three times daily for 14 days), and ceftriaxone may be used for meningitis.82
Importantly, persistent fevers despite treatment for Lyme disease warrant evaluation for alternate etiologies, including complete blood counts and blood smears to evaluate for coinfections, such as Babesia microti
or Anaplasma phagocytophilum
, that are transmitted by the same vector.
Although rickettsial infections, such as Rocky Mountain spotted fever (RMSF), anaplasmosis, or ehrlichia, do not appear to have increased susceptibility or severity in pregnancy, these are potentially life-threatening infections. Fever, headache, thrombocytopenia, and a history of tick bite are common for each of the rickettsial diseases.
The rash of RMSF often appears 2 to 4 days after the fever and may start as a blanching maculopapular rash before progressing to petechial involving the palms and soles. However, rash presentations may vary, thrombocytopenia may be delayed, and abdominal pain and vomiting may mimic gastroenteritis to delay diagnosis.84,85
For ehrlichia and anaplasma, rashes are rarer and variable. Serology is particularly sensitive 2 to 3 weeks after onset, with variable utility in acute illness, and therefore, both acute and convalescent specimens should be collected. PCR detection from whole blood is useful for ehrlichia and anaplasma, although less sensitive for RMSF. Blood smears or buffy coat preparations may identify ehrlichia or anaplasma, although not RMSF.84
First-line therapy is doxycycline (100 mg twice daily) and has been used successfully in a few cases of RMSF, ehrlichia, or anaplasma in pregnancy without evident sequelae in surviving cases.84,86,87,88
Initiation of doxycycline should be based on clinical suspicion, as delays in diagnosis are associated with increased mortality and most confirmatory tests are not rapid. A member of the tetracycline family, doxycycline is usually contraindicated in pregnancy as extended courses of tetracyclines were associated with of musculoskeletal and dental abnormalities in the fetus and fatty liver in the mother.89
However, a systematic review of doxycycline in pregnancy demonstrated that therapeutic doses of doxycycline were not associated with any increased risk to the fetus or mother.90
Doxycycline is the only therapy effective for Ehrlichia chaffeensis
or Anaplasma phagocytophilum
, and the alternate agent chloramphenicol, used for RMSF, is not as effective and is associated with increased mortality.84,91,92