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654 SECTION 11: Obstetrics and Gynecology TABLE 102-8 Treatment Regimens for Pinworms Agent and Dosage Comments Mebendazole 100 milligrams PO × 1 Repeated in 2 wk Teratogenic potential, only if benefits outweigh risk in pregnancy Albendazole 400 milligrams PO × 1 Repeated in 2 wk Contraindicated in pregnancy and 1 month prior to conception Pyrantel pamoate 11 milligrams/kg PO × 1 (maximum single dose = 1 gram) Repeat dose every 2 wk × 2 (total 3 doses) Available without prescription, no human data on safety VAGINAL FOREIGN BODIES Consider a vaginal foreign body in patients with chronic vaginal dis charge. Potential objects include tampons and toilet tissue, devices used for sexual stimulation, packets of illegal drugs, and various other objects. Premenarchal children presenting with vaginal discharge, especially if bloody or brown, should be evaluated for a vaginal foreign body. The discharge associated with a foreign body occurs daily and is often malodorous. 3 Potential foreign bodies include small pieces of toilet paper or cloth and small toys or objects. Vaginal irrigation with 0.9% normal saline can be attempted to visualize and remove a foreign body in cooperative children >7 years of age. Vaginoscopy under anesthesia in the operating room may be necessary for younger children. The use of imaging modalities is limited by the composition of the foreign body. Radiolucent foreign bodies are not seen on plain radiographs and may not be detected by pelvic ultrasound. MRI may aid in the localization of nonmetallic objects but is not always available and is not necessarily conclusive. Treatment is removal. PINWORMS Patients with pinworms (Enterobius vermicularis) complain of anal or vaginal pruritus, which is more intense at night (when the gravid female pinworms pass out from the intestinal tract to lay eggs on the perineal skin). The worms may migrate from the anus to the vagina in children. The diagnosis is made by visualization of 1-cm-long, thin, white worms exiting the anus. Alternately, a sample can be obtained on cellophane tape and used for identification of ova, which are large and double-walled in appearance, on microscopy. Treat the child and all family members and household contacts with an antiparasitic agent ( Table 102-8). Treatments are repeated because mature worms are more vulnerable to treatment than young worms. REFERENCES The complete reference list is available online at www.TintinalliEM.com Pelvic Inflammatory Disease Brian Weiss Suzanne M. Shepherd INTRODUCTION AND EPIDEMIOLOGY The term pelvic inflammatory disease (PID) comprises a spectrum of infections of the female upper reproductive tract.

o treatment than young worms. REFERENCES The complete reference list is available online at www.TintinalliEM.com Pelvic Inflammatory Disease Brian Weiss Suzanne M. Shepherd INTRODUCTION AND EPIDEMIOLOGY The term pelvic inflammatory disease (PID) comprises a spectrum of infections of the female upper reproductive tract. Although accurate estimates of the incidence and prevalence of PID in the United States are lacking due to lack of mandatory reporting and reliance on testing data, it is a common and serious disease initiated by ascending infection CHAPTER TABLE 103-1 Organisms Associated With Pelvic Inflammatory Disease Sexually transmitted organisms •  Chlamydia trachomatis •  Neisseria gonorrhoeae •  Herpes  simplex virus (types 1 and 2) •  Trichomonas vaginalis Endogenous genital tract Mycoplasma •  Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum Anaerobic bacteria • Bacteroides species, Peptostreptococcus, Prevotella bivia, Leptotrichia sanguinegens/ amnionii, Atopobium vaginae Aerobic bacteria • Gardnerella vaginalis, Haemophilus influenzae, Streptococcus agalactiae, Escherichia coli , and other gram-negative rods, Actinomyces israelii, Campylobacter fetus from the vagina and cervix. PID includes salpingitis, endometritis, myometritis, parametritis, oophoritis, and tubo-ovarian abscess and may extend to produce peri-appendicitis, pelvic peritonitis, and perihepatitis (Fitz-Hugh–Curtis syndrome). PID is the most common serious infection in sexually active women age 16 to 25 years. 1 In 2001, ambulatory data estimated that more than 750,000 cases of PID occurred in the United States. 2 The percentage of ED visits resulting in a diagnosis of PID decreased during 2006 to 2018 among females age 15 to 44 years (28.1% overall reduction, –4.3% annual change). Patients with less access to health care, including those without insurance or with public health insurance and those with lower median incomes, were the most likely to visit EDs. Long-term sequelae, including tubal factor infertility, implantation failure after in vitro fertilization, ectopic pregnancy, and chronic pain, may ultimately affect 11% of reproductive-aged women. 4 The most common cause of death is rupture of a tubo-ovarian abscess, with mortality associated with rupture remaining at 5% to 10%, even with current treatment methods. PATHOPHYSIOLOGY  ORGANISMS ASSOCIATED WITH PID Neisseria gonorrhoeae and Chlamydia trachomatis can be isolated in many cases of PID, and therapy is largely directed against these organ isms. Chlamydia has developed a number of mechanisms to avoid autophagy and destruction by the host immune system and is able to persist in a nonreplicative form in host epithelial cells. 5-7 Polymicrobial infection, including infection with anaerobic and aerobic vaginal flora, is evident from cultured material from the upper reproductive tract. 8 Table 103-1 lists common pathogenic organisms associated with acute or subclinical PID. N. gonorrhoeae, C. trachomatis, and bacterial vaginosis–associated organisms are usually instrumental in initial infection of the upper genital tract. Approximately 15% of cases are due to enteric or respiratory organisms that have colonized the lower genital tract. 2 Anaerobes, facultative anaerobes, and other bacteria are isolated increasingly as inflammation develops and abscesses form. Bacterial vaginosis is frequently identified in women with PID, and the type of bacterial vaginosis–associated microorganism ( Gardnerella vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, pigmented or nonpigmented anaerobic gram-negative rods) may make a difference in the likelihood of developing PID.

esses form. Bacterial vaginosis is frequently identified in women with PID, and the type of bacterial vaginosis–associated microorganism ( Gardnerella vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, pigmented or nonpigmented anaerobic gram-negative rods) may make a difference in the likelihood of developing PID. 5,9,10 Sexually transmitted Mycoplasma genitalium has increasingly been implicated as contributory or causative to both cervicitis and ascending disease. 2,11-14 Infection with Trichomonas vaginalis is associated with a fourfold increase in the incidence of acute endometritis. Coinfection with herpes simplex virus type 2 and C. trachomatis, N. gonorrhoeae, or bacteria causing vaginosis is also associated with acute endometritis. Infection with herpes simplex virus type 2 causes fallopian tube inflammation and lower tract ulceration that may disrupt the endocervical canal mucous barrier. 15 Human immunodeficiency virus 1 (HIV-1) infection Tintinalli_Sec11_p0607-0668.indd 654 8/2/19 4:21 PM

g vaginosis is also associated with acute endometritis. Infection with herpes simplex virus type 2 causes fallopian tube inflammation and lower tract ulceration that may disrupt the endocervical canal mucous barrier. 15 Human immunodeficiency virus 1 (HIV-1) infection Tintinalli_Sec11_p0607-0668.indd 654 8/2/19 4:21 PM CHAPTER 103: Pelvic Inflammatory Disease 655 is associated with an increased incidence of C. trachomatis infection, increased incidence of coinfection with Candida and human papillomavirus, and increased risk of progression to PID.16 Chronic PID may result from Mycobacterium tuberculosis infection in endemic areas.17 Schistosomes can cause genital infection, including a PID-like tubal infection, infertility, and chronic abortion, and a recent report links schistosomiasis to HIV transmission in Africa. Actinomyces species have been identified almost exclusively in patients with intra uterine devices (IUDs).18  ASCENDING INFECTION Most cases of PID are presumed to originate with sexually transmitted infections of the lower genital tract, followed by ascending infection of the upper tract. The original sexually transmitted infection may be asymptomatic, as may the ascending infection (subclinical PID). 19 The precise mechanisms by which upper genital tract infection and inflam mation are initiated and propagated are not well understood. Although the cervical mucus serves as a functional barrier to ascending infec tion much of the time, its efficacy may be decreased by a number of factors, including enzymes produced by bacterial vaginosis–associated organisms that degrade cervical mucus and antimicrobial peptides, 20,21 hormonal changes during menstruation and ovulation, and retrograde menstruation. Intercourse may contribute to the ascent of infection due to rhythmic mechanical uterine contractions. Bacteria also may be carried by, or along with, sperm into the uterus and tubes. Uterine infection usually is limited to the endometrium, but can be more inva sive in a gravid or postpartum uterus. Tubal infection initially affects only the mucosa, but acute, complement-mediated transmural inflam mation may develop rapidly and increase in intensity with repeated infection. Inflammation may extend to uninfected parametrial struc tures, including the appendix and bowel. Infection may spread by direct extension of purulent material from the fallopian tubes or via lymphatic spread beyond the pelvis to involve the hepatic capsule with acute perihepatitis (Fitz-Hugh–Curtis syndrome) and produce acute peritonitis.  RISK FACTORS FOR PID Multiple risk factors are associated with development of PID (Table 103-2). 9,22-29 IUD use has been associated with an increased risk for PID. Although the majority of risk occurs within 21 days of insertion, the presence of an IUD is associated with complicated PID irrespective of the duration of use. 18,25-27 The risk of PID in IUD users is more related to the development of sexually transmitted infection than the IUD, 30,31 and sexually transmitted infection screening and treatment at the time of insertion can significantly decrease the likelihood that PID will develop. Pregnancy decreases the risk of PID because the cervical os is pro tected by the mucous plug. However, PID can occur during the first trimester and is associated with substantial fetal loss and preterm delivery.  COMPLICATIONS OF PID PID is associated with a number of serious clinical sequelae. Tuboovarian abscess is reported in up to one third of women hospital ized for PID.

is pro tected by the mucous plug. However, PID can occur during the first trimester and is associated with substantial fetal loss and preterm delivery.  COMPLICATIONS OF PID PID is associated with a number of serious clinical sequelae. Tuboovarian abscess is reported in up to one third of women hospital ized for PID. Infection and inflammation can lead to loss of ciliated TABLE 103-2 Risk Factors Associated With Pelvic Inflammatory Disease 23-29 •  Multiple  sexual partners •  History  of sexually transmitted infection or pelvic inflammatory disease •  History  of sexual abuse •  Frequent  vaginal douching •  Intrauterine  device insertion within previous month •  Adolescence,  younger adulthood •  Lower  socioeconomic status •  Post-abortion epithelial cells in the fallopian tubes and to scarring and adhesions with obstruction within tubal lumens. Ectopic pregnancy is more frequent in women who have had PID than in those who have never had an ectopic pregnancy. Tubal factor infertility is increased by 12% to 50% in women with a past diagnosis of PID, and the incidence increases with the number and severity of past PID episodes. 33 Asymptomatic or silent PID also appears to be associated with tubal factor infertility. Sequelae of PID include recurrence of PID, chronic pelvic pain, menstrual disturbances, and chronic dyspareunia. Recurrence of PID may occur because of inadequately treated infection, nontreatment of partner(s), or reinfection from another sexual contact. In follow-up to the Pelvic Inflamma tory Disease Evaluation and Clinical Health trial, those with recurrence of PID were five times more likely to experience chronic pelvic pain. PID may also be associated with an increased risk of borderline ovarian tumors. CLINICAL FEATURES The clinical presentation of PID is variable. The most common presenting complaint is lower abdominal pain, most frequently described as bilateral and dull or crampy. Pain may be exacerbated by movement or by sexual activity. Other symptoms include abnormal vaginal discharge (75% of individuals), vaginal bleeding (including increased or prolonged menstrual bleeding) and postcoital bleeding (more than one third of patients), irritative voiding symptoms, and much less commonly sys temic signs of fever, malaise, nausea, and vomiting. 36 Symptoms usually occur early in the menstrual cycle or at the end of the menses and are attributed to low progesterone levels and coincident thinning of the cervical mucosal barrier. The physical examination usually is notable for lower abdominal tenderness, cervical motion tenderness, and uterine or adnexal tenderness. Involuntary guarding and rebound tenderness may be present and may indicate associated peritonitis. The positive predictive value of these findings varies depending on the prevalence of PID in a given clinical population. Adnexal tenderness appears to have a sensitivity of 95%. Mucopurulent cervicitis is common, and its absence should raise con sideration of another diagnosis. In women suspected of having PID and for whom there is no likely alternative diagnosis for abdominal pain, the presence of fever, adnexal tenderness, and an elevated erythrocyte sedi mentation rate are significant independent predictors of endometritis and correctly classify 65% of patients with laparoscopically proven PID (95% confidence interval, 61% to 99%). 37,38 Right upper quadrant tenderness, particularly with jaundice, may indicate perihepatic inflammation. Fitz-Hugh–Curtis syndrome (perihepatitis) is strongly suggested by right upper quadrant pain, and occasionally slightly elevated transaminases, in a woman with a clinical diagnosis of PID and no other cause for this pain. It is an uncommon complication and responds to standard antibiotic treatment for PID.

nflammation. Fitz-Hugh–Curtis syndrome (perihepatitis) is strongly suggested by right upper quadrant pain, and occasionally slightly elevated transaminases, in a woman with a clinical diagnosis of PID and no other cause for this pain. It is an uncommon complication and responds to standard antibiotic treatment for PID. The differential diagnosis of PID is broad and includes cervicitis, ectopic pregnancy, endometriosis, ovarian cyst, ovarian torsion, spontaneous abortion, septic abortion, cholecystitis, gastroenteritis, appen dicitis, diverticulitis, pyelonephritis, and renal colic. Look for signs of other sexually transmitted infections, such as herpes simplex, syphilis, and human papillomavirus infection. DIAGNOSIS The diagnosis is based on history and clinical findings. No single piece of historical, physical, or laboratory information is sensitive and specific for the disease. Laboratory evaluation of any woman of childbearing age in the ED always should include a pregnancy test. Consider the possibility of ectopic pregnancy or septic abortion. The most common alternative diagnosis in missed ectopic pregnancy is PID. Concurrent pregnancy also influences patient treatment and disposition. Current Centers for Disease Control and Prevention guidelines encourage initiation of empiric treatment in women at risk for PID who exhibit lower abdominal pain, adnexal tenderness, and cervical motion tenderness. Guidelines stratify diagnostic criteria into the three groups shown in Table 103-3. Tintinalli_Sec11_p0607-0668.indd 655 8/2/19 4:21 PM

ntrol and Prevention guidelines encourage initiation of empiric treatment in women at risk for PID who exhibit lower abdominal pain, adnexal tenderness, and cervical motion tenderness. Guidelines stratify diagnostic criteria into the three groups shown in Table 103-3. Tintinalli_Sec11_p0607-0668.indd 655 8/2/19 4:21 PM 656 SECTION 11: Obstetrics and Gynecology  LABORATORY TESTING Obtain saline- and potassium hydroxide–treated wet preparations of vaginal secretions to identify leukorrhea (more than one polymorpho nuclear leukocyte per epithelial cell) and trichomonads and to test for bacterial vaginosis (clue cells, pH, and a whiff test). If increased white blood cells are seen with clue cells, this increases the likelihood of accompanying cervicitis or PID, as bacterial vaginosis is not inflamma tory. Leukorrhea is sensitive but not specific for upper tract infection, and the absence of leukorrhea is a negative predictor for PID. Although endocervical swab specimens may be sent for culture and can be Gram stained for gonococci, nucleic acid amplification tests and DNA probes for N. gonorrhoeae and Chlamydia have replaced culture and Gram staining in many settings. If positive, the probability of PID increases significantly. Unfortunately, the latter results are not available to the ED at the time of initial evaluation. Several sensitive and specific diagnostic tests are currently available for Trichomonas testing, including a nucleic acid amplification test (Aptima ® ; GenProbe, San Diego, CA), approved in 2013, that is performed on the same clinical samples as those for Chlamydia and gonorrhea testing. 41,42 If PID is clinically suspected, an elevated WBC count, erythrocyte sedimentation rate, or C-reactive protein level supports the diagnosis. 40 Because a patient may have multiple sexually transmitted infections, also obtain a rapid plasma reagin test for syphilis. Test for HIV and hepatitis. Urinalysis can exclude urinary tract infection, but a positive urinalysis does not exclude PID, because any inflammatory process in the contiguous pelvis can produce WBCs in the urine. Blood cultures do not aid in diagnosis or treatment.  IMAGING AND OTHER DIAGNOSTIC MODALITIES Transvaginal pelvic US may demonstrate thickened (>5 mm), fluidfilled fallopian tubes or free pelvic fluid in acute severe PID. Pelvic or tubo-ovarian abscesses appear as complex adnexal masses with multiple internal echoes. Pelvic US can demonstrate as many as 70% of adnexal masses missed on physical examination. US also may be helpful in ruling in or out other causes in the differential diagnosis of pelvic pain, including ectopic pregnancy, ovarian torsion, hemorrhagic ovarian cyst, and possibly appendicitis or endometriosis. 43 The addition of power Doppler can identify increased blood flow, which is suggestive of inflammation and infection. Abdominopelvic CT and MRI may also be used to diagnose PID and tubo-ovarian abscess and to exclude other important causes of pelvic pain. If appendicitis or other surgical or GI diagnoses cannot be excluded, obtain an abdominopelvic CT. For further discussion, see Chapter 97, “ Abdominal and Pelvic Pain in the Nonpregnant Female. ” CT findings in PID include obscuration of the pelvic fascial planes, cervicitis, oophoritis, salpingitis, thickening of the uterosacral ligaments, and the presence of simple or complex pelvic fluid or abscess collections. Both PID and acute appendicitis may produce overlapping radiographic findings, but diagnosis can be improved by accounting for both appen diceal diameter and left tubal thickness. 44 Right tubal thickening does not distinguish the disorders, as inflammation from appendicitis can spread and cause right tubal thickening.

Both PID and acute appendicitis may produce overlapping radiographic findings, but diagnosis can be improved by accounting for both appen diceal diameter and left tubal thickness. 44 Right tubal thickening does not distinguish the disorders, as inflammation from appendicitis can spread and cause right tubal thickening. 44 An appendiceal diameter cutoff of ≥7 mm in the Hentour cohort was sufficiently sensitive to capture all but one case of acute appendicitis, but left tubal enlargement to ≥10 mm was more suggestive of PID even in patients with dilation of the appendix to ≥7 mm. These measurements together resulted in a diagnostic algorithm with 98% accuracy in distinguishing PID from acute appendicitis. 44 MRI is especially helpful in characterizing complicated soft tissue masses, including dilated fallopian tubes and abscesses. MRI is more specific and accurate than US to assess PID, with a sensitivity of 95% and a specificity of 89%; however, it is often less available acutely in the ED. 45,46 Laparoscopy has been considered the gold standard for the diagno sis of PID. It is invasive, has a high interobserver variability, may not detect endometritis or early tubal inflammation, and often is not readily available for ED consultation. Transcervical endometrial aspiration and endometrial biopsy, although still invasive, may be more commonly used by consultants when the diagnosis is uncertain and the patient is ill. 2,38,47 TREATMENT Treatment is aimed at relieving acute symptoms, eradicating current infection, and minimizing the risk of long-term sequelae. From a public health perspective, another objective of treatment is to reduce the risk of transmission of infection to other new partners and to identify and treat past and current sexual partners to prevent disease spread. Early diagnosis and treatment are critical because duration of symptoms is an independent risk factor for infertility. Due to the difficulty of diagnosis and the potential for serious sequelae, the Centers for Disease Control and Prevention recom mends a low threshold for empiric treatment, with overtreatment preferred to a missed diagnosis with resultant delayed or no treatment. Provide adequate analgesia, control of emesis and fever, and fluid replacement in those with nausea, vomiting, and dehydration and in those who appear toxic. NSAIDs are very useful for the management of pain of pelvic origin. ED treatment should include empiric broad-spectrum antibiotic therapy to cover the full range of likely organisms. Screen for bacterial vaginosis and treat when screening is positive. Treatment regimens should follow both national guidelines from the Centers for Disease Control and Prevention and local health department surveillance reports. The Pelvic Inflammatory Disease Evaluation and Clinical Health trial, which included 654 females age 14 to 37 years old, demonstrated no differences between oral and parenteral regimens in women with mild to moder ately severe acute PID uncomplicated by pregnancy or the presence of a tubo-ovarian abscess. 49,50 Currently accepted inpatient and outpatient treatment regimens are summarized in Tables 103-4 and 103-5. Changing geographic patterns of drug resistance may alter recommendations. For example, worldwide resistance in gonorrhea has emerged over the past several decades by multiple molecular mechanisms to all the commonly used antibiotics. Patients with PID who require IV antibiotics initially can be switched to oral antibiotics after clinical improvement. SPECIAL CONSIDERATIONS  TREATMENT WITH IUD IN PLACE In the past, an IUD was generally removed, based on the belief that because it is a foreign body removal of the IUD would allow treatment to be more effective.

th PID who require IV antibiotics initially can be switched to oral antibiotics after clinical improvement. SPECIAL CONSIDERATIONS  TREATMENT WITH IUD IN PLACE In the past, an IUD was generally removed, based on the belief that because it is a foreign body removal of the IUD would allow treatment to be more effective. There is a low risk of PID from IUD insertion, TABLE 103-3 Diagnostic Criteria for Pelvic Inflammatory Disease (PID) Group 1: Minimum criteria. Empiric treatment if no other cause to explain findings. •  Uterine  or adnexal tenderness •  Cervical  motion tenderness Group 2: Additional criteria improving diagnostic specificity. •  Oral  temperature >101°F (38.3°C) •  Abnormal  cervical or vaginal mucopurulent secretions •  Elevated  erythrocyte sedimentation rate •  Elevated  C-reactive protein level •   Laboratory evidence of cervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis (i.e., culture or DNA probe techniques) Group 3: Specific criteria for PID based on procedures that may be appropriate for some patients. •  Laparoscopic  confirmation •   Transvaginal US (or MRI) showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex •  Endometrial  biopsy results showing endometritis Source: Reproduced with permission from Centers for Disease Control and Prevention, Workowski KA, Berman SM: Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 59(RR-12): 12, 2010. Tintinalli_Sec11_p0607-0668.indd 656 8/2/19 4:21 PM

rian complex •  Endometrial  biopsy results showing endometritis Source: Reproduced with permission from Centers for Disease Control and Prevention, Workowski KA, Berman SM: Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 59(RR-12): 12, 2010. Tintinalli_Sec11_p0607-0668.indd 656 8/2/19 4:21 PM CHAPTER 103: Pelvic Inflammatory Disease 657 especially when sexually transmitted infection testing is done con comitantly and immediate treatment is initiated. 32 Current Centers for Disease Control and Prevention guidelines suggest that there is insufficient evidence to recommend IUD removal before treatment for PID, because the device is usually not the source of infection. In those with an IUD who develop PID, there are no data to support the use of one treatment regimen over another. Studies were also performed on women with nonhormonal IUDs, with similar results. No data are available regarding treatment outcomes in those with levonorgestrelreleasing IUDs. Close clinical follow-up is prudent. If there is a concern regarding PID in a patient with an IUD newly placed in the past 3 weeks, it is reasonable to consult a gynecologist regarding removal.  TREATMENT IN HIV INFECTION Microbiologically, HIV-positive women are more likely to have con comitant Candida, M. hominis , HPV , and streptococcal infection. HIV-positive women with PID may experience more severe symptoms irrespective of CD4 count and are more likely to have sonographically diagnosed tubo-ovarian abscess. However, such patients appear to respond similarly to treatment for uncomplicated PID as do those not infected with HIV . 52-54 HIV-positive status alone is not a criterion for hospitalization.40,52,55,56  TREATMENT OF ADOLESCENTS Early and mid-adolescents were not well represented in the Pelvic Inflammatory Disease Evaluation and Clinical Health study, and of those enrolled, adolescents had increased risk of recurrent PID and a shorter time to pregnancy after an acute episode compared with adult enrollees. However, there is no robust evidence to suggest that adolescent outcomes are improved after hospitalization for PID management. Adolescents hospitalized in pediatric centers often receive services beyond IV antibiotics, including education on risk reduction and pregnancy prevention, emotional support, social work intervention, assistance with communicating the nature of their illness with parents, and assistance to arrange close follow-up. 57,58  ALTERNATIVE ANTIBIOTICS For those with severe cephalosporin allergy, spectinomycin is recommended in Canada and Europe but is not currently available in the United States. For more information, see the Centers for Disease Control and Prevention Web pages on antibiotic-resistant gonorrhea at http:// www.cdc.gov/std/Gonorrhea/arg/default.htm. Multiple studies have demonstrated poor compliance with doxycycline therapy (25%; 50% with partial compliance), and 20% to 25% of patients never fill their prescriptions. 59-61 Doxycycline also does not cover Mycoplasma genitalium. For PID treatment, azithromycin is an alternative, with studied dosing of 500 milligrams IV daily for one to two doses, followed by 250 milligrams once daily for 12 to 14 days, or in combination with metronidazole for anaerobic coverage, 250 milligrams PO once a day for 7 days or 1 gram once a week for 2 weeks. 59 The long half-life of azithromycin requires significantly fewer doses, which is thought to improve the likelihood of patient compliance. Azithromycin also provides intrinsic anti-inflammatory effects and may reduce local tissue damage.

erage, 250 milligrams PO once a day for 7 days or 1 gram once a week for 2 weeks. 59 The long half-life of azithromycin requires significantly fewer doses, which is thought to improve the likelihood of patient compliance. Azithromycin also provides intrinsic anti-inflammatory effects and may reduce local tissue damage. Weigh these potential benefits against the lack of largescale or long-term studies comparing the effectiveness of azithromycin to doxycycline in the treatment of PID and the possibility of emerging resistance to azithromycin. 5,59,62-65 A recent meta-analysis of 37 randomized controlled trials, including multiple international trials, found that all Centers for Disease Control and Prevention–recommended regimens studied demonstrated fairly similar treatment efficacy, but that azithro mycin might be superior in those with mild to moderate PID. The authors point out the risk of bias in the trials studied and the need for high-quality randomized controlled trials to more robustly address this.  TUBO-OVARIAN ABSCESS Tubo-ovarian abscesses are most commonly a late complication of PID, and the majority have associated peritonitis. Tubo-ovarian abscess complicates about 2% of PID cases. Due to slower resolution of PID, women coinfected with HIV demonstrate an increased incidence of tubo-ovarian abscess. Disproportionate unilateral adnexal tender ness or adnexal mass or fullness may indicate a tubo-ovarian abscess (Figure 103-1). In women with clinical toxicity and asymmetric pelvic findings, obtain a pelvic US. Most tubo-ovarian abscesses (60% to 80%) resolve with antibiotic administration alone. 66-68 In the setting of tuboovarian abscess, oral therapy should be continued with clindamycin (450 milligrams PO four times per day) or metronidazole with doxy cycline for better anaerobe coverage for 14 days. Patients who do not improve after 72 hours of treatment should be reevaluated for possible CT- or US-guided percutaneous drainage, laparoscopic drainage, pos terior colpotomy with drainage, surgical intervention, or reconsideration of other possible diagnoses. Abscesses 9 cm or larger on imaging appear to have a higher likelihood of requiring surgical therapy. An enlarging pelvic mass may indicate bleeding secondary to vessel erosion or a ruptured abscess. TABLE 103-4 Parenteral Treatment Regimens for Pelvic Inflammatory Disease Cefotetan, 2 grams IV every 12 h, or cefoxitin, 2 grams IV every 6 h plus Doxycycline, 100 milligrams PO or IV every 12 h * Clindamycin, 900 milligrams IV every 8 h plus Gentamicin, 2 milligrams/kg IV or IM loading dose, followed by gentamicin, 1.5 milligrams/kg every 8 h maintenance dose † Alternative Parenteral Regimen (limited data on effectiveness) Ampicillin/sulbactam, 3 grams IV every 6 h plus Doxycycline, 100 milligrams PO or IV every 12 h * *PO doxycycline has the same bioavailability as IV doxycycline and avoids painful infusion. †Gentamicin dosing may be 3–5 milligrams/kg every 24 h. Source: Reproduced with permission from Centers for Disease Control and Prevention, Workowski KA, Berman SM: Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 64: 1, 2015. CDC.gov.

availability as IV doxycycline and avoids painful infusion. †Gentamicin dosing may be 3–5 milligrams/kg every 24 h. Source: Reproduced with permission from Centers for Disease Control and Prevention, Workowski KA, Berman SM: Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 64: 1, 2015. CDC.gov. TABLE 103-5 Oral and Outpatient Treatment Regimens for Pelvic Inflammatory Disease Ceftriaxone, 250 milligrams IM once, or cefoxitin, 2 grams IM once, and probenecid, 1 gram PO once administered concurrently Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) plus Doxycycline, 100 milligrams PO twice a day for 14 d with or without Metronidazole, 500 milligrams PO twice a day for 14 d If parenteral cephalosporin therapy is not feasible and community prevalence of fluoroquinolone resistance is low: Levofloxacin, 500 milligrams PO, or ofloxacin, 400 milligrams twice daily every day for 14 d with or without Metronidazole, 500 milligrams PO twice a day for 14 d Note: Other parenteral third-generation cephalosporins can be substituted for ceftriaxone or cefoxitin. Since the Centers for Disease Control and Prevention guidelines were published in 2006, clinically sig nificant resistance to the fluoroquinolones (6.7% of infections in heterosexual men, an 11-fold increase from 0.6% in 2001) has emerged in the United States. Fluoroquinolone antibiotics are no longer recom mended to treat gonorrhea in the United States. Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented. Source: Reproduced with permission from Centers for Disease Control and Prevention, Workowski KA, Berman SM: Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 64: 1, 2015. CDC.gov. Tintinalli_Sec11_p0607-0668.indd 657 8/2/19 4:21 PM