Treatment Of Pelvic Inflammatory Disease Research Articles

Intravenous azithromycin.

To review the pharmacology, microbiology, chemistry, pharmacokinetics, efficacy, safety, tolerability, dosage, administration, and economic issues of intravenous azithromycin. A MEDLINE search from 1978 to May 1998 of the English-language literature and an extensive review of journals and meeting abstracts was conducted. Due to the lack of published literature concerning the efficacy, safety, and pharmacokinetics of the intravenous formulation of azithromycin, the manufacturer was also contacted and requested to supply information concerning intravenous azithromycin. In vitro and preclinical studies were included, as well as data from Phase II and III clinical trials. Efficacy, pharmacokinetic, safety, and tolerability data were also supplemented with information from the manufacturer, due to the lack of published reports. Azithromycin, an azalide subclass of the macrolide antibiotics, is now available as an intravenous formulation. The intravenous form is approved for the treatment of community-acquired pneumonia caused by Chlamydia pneumoniae, Haemophilus influenzae. Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus (methicillin-sensitive), and Streptococcus pneumoniae, and for the treatment of pelvic inflammatory disease caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in situations in which intravenous therapy is required. Its spectrum of activity, unique pharmacokinetics, and high and sustained tissue penetration allow for once-daily dosing with monotherapy in many cases. Clinical and bacteriologic response rates as well as the adverse event profile have been similar to or better than comparative agents. Azithromycin offers advantages over other agents due to its unique pharmacokinetics, high and sustained tissue penetration, and spectrum of activity. This allows for monotherapy and once-daily intravenous dosing for mild-to-moderate community-acquired pneumonia or pelvic inflammatory disease in many instances. Future research should focus on total duration of antibiotic therapy and the need, or lack thereof, for extensive oral antibiotic follow-up.

Quinolones in sexually transmitted diseases: state of the art.

Progress in the development of fluoroquinolones for the treatment of sexually transmitted diseases has been slow. New compounds have appeared with good in vitro activity against the gonococcus, Chlamydia trachomatis and the genital mycoplasmas. However, there have been increasing reports of clinically relevant resistance by the gonococcus, and chlamydial and mycoplasmal resistance in vitro has been described. Formally reported treatment studies have not been forthcoming, despite an emerging role for the newer fluoroquinolones in the ambulatory treatment of pelvic inflammatory disease.

Correlates of Sexually Transmitted Bacterial Infections Among U.S. Women in 1995

Sexually transmitted diseases (STDs) of bacterial origin such as gonorrhea and chlamydial infection can lead to pelvic inflammatory disease (PID) and infertility. Identifying behaviors and characteristics associated with infection may assist in preventing these often asymptomatic diseases and their sequelae. Data from 9,882 sexually active women who participated in the 1995 National Survey of Family Growth describe the characteristics of women who report a history of infection with a bacterial STD or of treatment for PID. Multivariate analysis is used to determine which demographic characteristics and sexual and health-related behaviors affect the likelihood of infection or the occurrence of complications. Overall, 6% of sexually active women reported a history of a bacterial STD, and 8% reported a history of PID. Women who first had sexual intercourse before age 15 were nearly four times as likely to report a bacterial STD, and more than twice as likely to report PID, as were women who first had sex after age 18. Having more than five lifetime sexual partners also was associated with both having an STD and having PID. PID was more common among women reporting a history of a bacterial STD (23%) than among women who reported no such history (7%). In multivariate analyses, age, race, age at first intercourse and lifetime number of sexual partners had a significant effect on the risk of a bacterial STD. Education, age, a history of IUD use, douching and a history of a bacterial STD had a significant impact on the risk of PID, but early onset of intercourse did not, and lifetime number of partners had only a marginal effect. The pattern of characteristics and behaviors that place women at risk of infection with bacterial STDs is not uniform among groups of women. Further, the level of self-reported PID would suggest higher rates of gonorrhea and chlamydial infection than reported.

Evaluation of Ofloxacin in the Treatment of Laparoscopically Documented Acute Pelvic Inflammatory Disease (Salpingitis)

Objective: To evaluate the safety and efficacy of intravenous and oral ofloxacin monotherapy in the treatment of laparoscopically documented acute pelvic inflammatory disease (PID).Methods: This study was conducted as an open‐label, phase‐III, uncontrolled, multicenter study. Patients identified with laparoscopic findings of salpingitis were treated with 400 mg of intravenous ofloxacin every 12 hours followed by 400 mg of oral ofloxacin every 12 hours for 10 to 14 days. Patients were evaluated five times for clinical and microbial efficacy. Since laparoscopy was performed only at admission, pathogens identified laparoscopically were presumed eradicated if they were present on the laparoscopic culture and the patient was clinically cured or improved at final evaluation.Results: Of the 70 patients evaluable for safety (intent‐to‐treat population), the mean age was 25.6 years. Sixty‐one of 70 patients (87%) were cured, one improved, one did not improve, and seven were unevaluable because they discontinued study participation. Fifty‐one were evaluable for clinical efficacy: 50 (98%) were cured and one did not improve. Sixteen were evaluable for expanded microbiological efficacy: three had documented Neisseria gonorrhoeae; 12, Chlamydia trachomatis; and one, a mixed infection of both organisms. All cervical, laparoscopic, and endometrial cultured pathogens, including N. gonorrhoeae and C. trachomatis, were eradicated or presumed eradicated at the posttherapy visit. No serious or unexpected adverse events occurred.Conclusions: Ofloxacin monotherapy was effective and well tolerated in the treatment of laparoscopically proven PID in a geographically diverse population. Future studies are necessary to evaluate long‐term outcomes and sequelae of PID treatment with single agent therapy. Infect. Dis. Obstet. Gynecol. 7:138–144, 1999.

When to Treat Adolescents With Pelvic Inflammatory Disease as Outpatients

Dr. Lydia Shrier and Dr. Michael Rich take opposing views on this issue. From my own practice, I have tended to err on side of the conservative approach with inpatient treatment. However, from some of more recent studies on effectiveness of oral antibiotic regimens in treatment of adults with pelvic inflammatory disease (PID), one may be able to extrapolate to adolescent population. Certainly Centers for Disease Control and Prevention (CDC) in publishing their 1998 guidelines on treatment of PID have removed criteria for admission of all adolescents. Unfortunately, compliance issues in adolescents have not changed since previous guidelines were published. Hospitalization gives practitioner opportunity to treat adolescent with antibiotics even if for a short time. Hospitalization also captures adolescent so that clinician can have, one hopes, opportunity to educate her regarding safe sex practices and to investigate other issues in adolescent's life that may make her susceptible to such a disease process. On other hand, hospitalization is expensive. It also makes issue of confidentiality more difficult for both practitioner and patient to maintain with parent and other significant others in adolescent's life. Each author makes a compelling argument for his or her opinion. I think that we should view new guidelines and treatment regimens as means for improving our treatment of adolescent with a sexually transmitted disease. It is apparent that more research is needed with this population. See what you think.

Pelvic Inflammatory Disease

1. Jonathan R. Pletcher, MD* 2. Gail B. Slap, MD* 1. 2. *Section of Adolescent Medicine, Division of General Pediatrics, Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA. 1. Pelvic inflammatory disease (PID) is a polymicrobial infection, usually initiated by endocervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis . 2. More than 25% of women affected with PID suffer one of several serious sequelae, including tubal infertility, tubo-ovarian abscess, chronic pelvic pain, or ectopic pregnancy. 3. PID is diagnosed primarily through clinical assessment, with laboratory and radiographic studies supporting or confirming it. 4. Treatment of PID includes broad-spectrum antibiotic coverage for anaerobic bacteria as well as for the causative organisms. 5. Primary and secondary prevention is paramount in reducing the social, emotional, and economic burden of PID and its sequelae. Pelvic inflammatory disease (PID) is an ascending polymicrobial genital tract infection that occurs in sexually active females. It includes an array of inflammatory disorders, including endometritis, parametritis, salpingitis, oophoritis, tubo-ovarian abscess (TOA), peritonitis, and perihepatitis. Neisseria gonorrhoeae and Chlamydia trachomatis are usually the causative agents of PID, but microflora from the vagina and the bowel also may contribute to its pathogenesis. The serious medical and social consequences of PID, including chronic pain, ectopic pregnancy, and infertility, demand improved efforts at prevention, recognition, and management. Given the declining age of sexual initiation in the United States, strategies designed to curtail PID and its sequelae begin in the pediatrician’s office. PID affects 1 million American women annually at an estimated annual cost of $4.2 billion. Sexually active adolescents account for 20% to 30% of cases and face a tenfold increase in risk compared with adults. PID results in more than 600,000 hospital admissions yearly and leads to serious long-term complications in 25% of women who are infected. The likelihood of sequelae is particularly high among adolescents because of late presentation, delayed diagnosis, and inadequate treatment. The increased risk of PID during adolescence reflects both the biologic susceptibility of the immature cervix and the high prevalence …

High prevalence of cervical intra-epithelial neoplasia in women treated for pelvic inflammatory disease

Because human papillomavirus (HPV) is sexually transmitted, as are pelvic inflammatory disease (PID) agents, the authors investigated whether cervical intra-epithelial neoplasia (CIN) are more frequent in women under treatment for PID. The study involved 298 patients hospitalized for PID, in whom CIN were investigated by smears and colposcopy. CIN were diagnosed in 42 patients, i.e. in 14% of patients: 21 low-grade CIN and 21 high-grade CIN, including one case of early-stage microinvasion. These figures are to be compared to the 0.5–4% of pre-cancerous lesions found in the general population. Screening smears are frequently inaccurate and direct colposcopy appeared preferable. No clinical study of this type has been published before, but certain authors have mentioned a high CIN incidence in patients with PID histories or followed up in sexually transmitted disease centers. These results show that CIN are more frequent in patients treated for PID; CIN should be investigated systematically in this population.

Medically sound, cost-effective treatment for pelvic inflammatory disease and tuboovarian abscess

Objective: Our purpose was to determine the clinical effectiveness and cost-effectiveness of three antibiotic regimens for the treatment of pelvic inflammatory disease and tuboovarian abscess. Study Design: A review of all patients' hospitalized at Hutzel Hospital, Detroit, Michigan, for treatment of pelvic inflammatory disease and tuboovarian abscess between Jan. 1, 1993, and April 30, 1997, was performed. Demographic data, antibiotic choices, changes in therapy, operative interventions, and cost of therapy were assessed. Results: Two hundred three patients were admitted for treatment of pelvic inflammatory disease during the study period. We were able to evaluate the clinical efficacy of antibiotic treatment in 179 patients, including 105 patients with pelvic inflammatory disease alone (uncomplicated pelvic inflammatory disease) and 74 women whose infection was complicated by tuboovarian abscess. The three antibiotic regimens evaluated were cefotetan plus doxycycline, clindamycin plus gentamicin, and ampicillin plus clindamycin plus gentamicin. All regimens demonstrated comparable efficacy in treating uncomplicated genital tract infections. Ampicillin plus clindamycin plus gentamicin was significantly better than clindamycin plus gentamicin and cefotetan plus doxycycline in treatment of tuboovarian abscess ( p = 0.001). Fifteen women with tuboovarian abscess responded to a change to ampicillin plus gentamicin plus clindamycin antibiotic therapy alone. The hospital stay was prolonged by approximately 3 days in women failing to respond to initial antibiotic therapy, and operative interventions were common in this group of patients. Conclusions: Cefotetan plus oral doxycycline is the most cost-effective regimen for treating uncomplicated pelvic inflammatory disease, whereas triple-antibiotic therapy is the treatment of choice in women with tuboovarian abscess. (Am J Obstet Gynecol 1998;178:1272-8.)

C-reactive protein and the treatment of pelvic inflammatory disease

Objective: The significance of C-reactive protein (CRP) in assessing the treatment of pelvic inflammatory disease (PID) was established and compared with body temperature (BT), erythrocyte sedimentation rate (ESR) and serum leukocyte concentration (L). Method: In 51 patients with PID, 20 (39%) of them with tubo-ovarial abscess (TOA), measurement of BT and laboratory investigations were carried out on admission and during treatment on days 3–4, 6–8 and 18–21. The changes in these values were compared with the changes in clinical condition. Result: Prior to treatment, the majority — 49 patients or 96.1% — had increased CRP values. In successful treatment, the CRP values decreased significantly in PID patients without TOA on day 3–4, in patients with TOA on day 6–8 and reached normal values in both groups on day 18–21. Changes in clinical condition were most concurrent with changes in CRP. Conclusion: In assessing PID treatment, the determination of CRP has precedence over L, ESR and BT as the percentage of patients with increased CRP is higher and because the changes in value follow the changes in clinical condition more reliably.

Clinical and laparoscopy diagnosis of acute pelvic inflammatory disease in Nigeria

Pelvic inflammatory disease (PID) is an important cause of morbidity in Nigeria. It is often the sequel to sexually transmitted diseases septic abortions and puerperal sepsis. The long term complications of PID such as infertility chronic pelvic pain and ectopic pregnancy constitute the bulk of the gynaecological workload in the country. Therefore at all levels of medical care in the country emphasis is placed on the prevention and treatment of PID by means of public health education use of appropriate antibiotics and the introduction of contraception to prevent unwanted pregnancies. However facilities for accurate diagnosis are inadequate in most hospitals and clinicians resort to diagnosis and treatment based mainly on clinical features or at best Gram stain of endocervical discharge where available. Laparoscopy is seldom performed. This study was carried out to assess the potential role of laparoscopy in the management of acute PID in Nigeria. (excerpt)

The aminoglycosides

The aminoglycosides are bactericidal drugs whose primary effect is irreversible inhibition of bacterial protein synthesis. Aminoglycoside efficacy is dependent on the presence of oxygen and the existence of the proper electrochemical gradient on each side of the cell membrane. Drug resistance to aminoglycosides can develop at several different sites of drug action. Aminoglycosides primarily are effective against the aerobic gram-negative bacilli, including most Pseudomonas species. Addition of clindamycin or metronidazole to drug regimens that include aminoglycosides adds anaerobic coverage. Aminoglycosides and β-lactam antibiotics are synergistic at many points in their activity, and addition of a β-lactam adds gram-positive coverage to drug regimens. Aminoglycosides are not absorbed well from the gastrointestinal tract and usually are administered either intravenously or intramuscularly. They are excreted almost exclusively by renal filtration. Only about 10% of an absorbed aminoglycoside dose is bound to plasma proteins, so liver disease has virtually no effect on aminoglycoside distribution. Aminoglycoside toxicities include ototoxicity and nephrotoxicity; drug hypersensitivity is rare. The combination of gentamicin plus penicillin or ampicillin is excellent therapy for chorioamnionitis in cases of vaginal delivery. Gentamicin plus clindamycin is one of two regimens recommended by the Centers for Disease Control and Prevention for parenteral treatment of pelvic inflammatory disease. This combination also is effective against most polymicrobial postoperative infections. Streptomycin may be used in the treatment of tuberculosis and other mycobacterial infections. The wholesale price of aminoglycosides, particularly gentamicin, is relatively low compared to other antibiotics. Once-daily aminoglycoside dosing has been introduced recently into the clinical setting. Animal studies indicate that this new regimen is equally effective when compared with divided dosing and appears to have lower toxicity in immunocompetent patients. Advantages of once-daily dosing of aminoglycosides include decreased toxicity, increased efficacy, and decreased cost.

Chlamydia trachomatis screening in family planning centers: a review of cost/benefit evaluations in different countries.

Chlamydia trachomatis is a primary cause of acute or silent salpingitis leading to infertility and ectopic pregnancy. The C. trachomatis epidemic, undiscovered in most cases, spreads, mostly in adolescents, during the years following the onset of sexual activity. As opposed to gonococcal infection which has greatly decreased, C. trachomatis cervical and urethral infection is common in young occidentals. More then 30 different studies covering 200-12,000 subjects screened in family planning centers, college women and men, students and military recruits in different parts of the USA, in Scandinavian countries and France, indicate a prevalence of 5-20% (mean 10%) in apparently healthy young females < 25 years and 5-10% in males. Female prevalence is strongly related to age, being highest (15-20%) in women < 20 years old. Several cost-benefit analyses show that the total cost of the general screening in young populations, which can easily be carried out for women in family planning centers, could save twice the cost of treatment for pelvic inflammatory disease caused by C. trachomatis and six times the total cost of C. trachomatis epidemics if late sequelae are taken into account (tubal infertility treatment, ectopic pregnancy). There is a debate among authors concerning the relative merits of total screening versus selective screening in family planning centers, the most common opinion being to do a total screening of women < 20 years old and selective screening of women 20-30 years of age with at least one risk factor, the most common risk factors being more than one partner in a year, purulent, cervical discharge, failure to use condoms and use of a contraceptive pill. Although the data clearly show that C. trachomatis screening is cost-effective, conducting of the diagnostic laboratory tests used in such screening programs should be carefully evaluated relative to cost, feasibility, specificity and sensitivity and should be adapted to the presumed prevalence in screened populations.

Role of Bacterial Vaginosis in Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is a frequent infection in sexually active young women and results in adverse sequelae, including tubal-factor infertility and ectopic pregnancy. In the 1970s investigations using culdocentesis demonstrated that anaerobic bacteria played an important role in the etiology of PID. This finding has subsequently been confirmed by studies utilizing laparoscopy and/or endometrial biopsy to obtain specimens directly from the upper genital tract (uterine cavity and fallopian tube) of patients with acute PID. Recently, several investigations have shown an association between bacterial vaginosis and the development of acute PID. The microorganisms associated with bacterial vaginosis include anaerobes such as Prevotella bivia, other Prevotella species, and Peptostreptococcus species. These studies that have demonstrated the presence of bacterial vaginosis-associated bacteria in addition to the sexually transmitted organisms Neisseria gonorrhoeae and Chlamydia trachomatis suggest that treatment of acute PID must be broad spectrum in nature and effective against anaerobic bacteria as well as N. gonorrhoeae and C. trachomatis.

Compliance With Doxycycline Therapy for Outpatient Treatment of Pelvic Inflammatory Disease

Women discharged from a municipal emergency department with the diagnosis of pelvic inflammatory disease were surveyed by telephone about their compliance with a standard 10-day regimen of doxycycline. Of the 386 women who completed the survey, 31% reported complete compliance; 28% reported that they did not fill their prescriptions for doxycycline. The most common reasons given for not filling prescriptions were cost, resolution of symptoms, and inconvenience. Forty-one percent reported that they stopped their medication early (average 4.1 +/- 1.4 days). Lack of symptoms, persistence of symptoms, and side effects were the major reasons given for the discontinuation of medications.

Characteristics Associated with Impaired Fecundity in the United States

The authors draw upon Cycle IV data from the 1988 National Survey of Family Growth a population-based nationally-representative sample of 8450 women aged 15-44 years as of March 15 1988 to examine the characteristics of US women who have reported impaired fecundity regardless of whether they have ever sought medical help or advice for these problems. The profile of women with impaired fecundity described in the article can help clinicians identify those who may be most likely to be infertile now or in the future and could thus be targeted for counseling and screening to reduce their risk of infertility problems. Study results on infecundity are based upon data for the subset of 5036 sexually experienced women who were not surgically sterile and whose partners were not surgically sterile. Approximately 15% of nonsterilized sexually experienced women aged 15-44 report impaired fecundity because they have difficulty conceiving or carrying a pregnancy to term or their partners have problems fathering a child. Multivariate logistic regressions found that older women childless women and married women are significantly more likely to report impaired fecundity but differences by race or ethnicity are not statistically significant. Furthermore women with an history of treatment for pelvic inflammatory disease or an history of diabetes hypertension or endometriosis are all significantly more likely than those without to report that they have impaired fecundity. Women who have never used a contraceptive method are more likely than users of the pill condom or IUD to report impaired fecundity.

Pelvic inflammatory disease in the adolescent

This article reviews new developments in the detection and treatment of pelvic inflammatory disease, including known risk factors, microbial etiologies, treatment standards, and associated morbidity. The use of transvaginal ultrasound and the role of the male partner in infection control is also discussed.

A comparison of pefloxacin/metronidazole and doxycycline/metronidazole in the treatment of laparoscopically confirmed acute pelvic inflammatory disease

A double-blind, randomised study was conducted to compare the efficacy and safety of a combination of pefloxacin and metronidazole versus doxycycline and metronidazole in patients with pelvic inflammatory disease (PID). The clinical diagnosis had to be confirmed by laparoscopy before patients were included. Of the 74 patients who fulfilled the clinical criteria for PID, laparoscopy confirmed the diagnosis in only 40 patients (54%). The microorganism most frequently found as causative pathogen was Chlamydia trachomatis. Both treatment groups showed a good response to the study-medication. At discharge 9 patients in the pefloxacin group (45%) were cured and 10 patients (50%) had improved. In the doxycycline group 7 patients (35%) were cured and 10 patients (50%) had improved. Obviously pefloxacin/metronidazole and doxycycline/metronidazole are equally effective in the treatment of PID.

Multicenter Randomized Trial of Ofloxacin Versus Cefoxitin and Doxycycline in Outpatient Treatment of Pelvic Inflammatory Disease

A multicenter randomized comparative trial was done to assess the safety and efficacy of oral ofloxacin (400 mg twice daily for 10 days) versus cefoxitin (2 g intramuscularly) followed by doxycycline (100 mg twice daily orally for 10 days) for the outpatient treatment of uncomplicated pelvic inflammatory disease (PID). Neisseria gonorrhoeae (GC) grew on pretreatment endocervical cultures from 43 of 268 women (16%), and in 30 of 247 women (12%) cultures were positive for Chlamydia trachomatis (Ct). Ninety-five percent (122/128) of the women treated with the ofloxacin regimen and 93% (112/121) of those treated with the cefoxitin/doxycycline regimen had cure or improvement on examination at a minimum of one follow-up visit. All GC species were eradicated by both ofloxacin and cefoxitin. Among women who returned for follow-up, the eradication of C trachomatis was 88% (15/17) for the cefoxitin/doxycycline group and 100% (18/18) for ofloxacin. Side effects were more prevalent in the cefoxitin/doxycycline group (15%) than in the ofloxacin group (7%), nausea/vomiting being the most frequent adverse effect. In this study, it appears that ofloxacin and cefoxitin/doxycycline have similar clinical effectiveness for the outpatient treatment of uncomplicated pelvic inflammatory disease.

Gonorrhea, genital chlamydial infection, and nonspecific urethritis in male partners of women hospitalized and treated for acute pelvic inflammatory disease.

Acute pelvic inflammatory disease (PID) is often a complication to a sexually transmitted disease (STD), the most important agents being Neisseria gonorrhoeae and Chlamydia trachomatis. However, very little is known of the genitourinary status of the male partners of women with acute pelvic inflammatory disease (PID). To determine the presence of N. gonorrhoeae and/or C. trachomatis infection or nonspecific urethritis (NSU) in regular sexual male partners of women with acute PID. Two hundred regular sexual male partners to 196 women admitted to a hospital for treatment of acute PID were referred by contact tracing to the sexually transmitted disease outpatient clinic for clinical and laboratory examination regarding N. gonorrhoeae and/or C. trachomatis infection, or NSU defined as the presence of > 5 polymorphonuclear leukocytes per high-power field (x1,000) in > 4 fields and with negative laboratory tests for N. gonorrhoeae and C. trachomatis. The majority of the males was in the age group 20 to 29 years of age, female sexual partners in 15 to 24 years years of age. N. gonorrhoeae was demonstrated in 42.9% of the male partners to women with acute PID and concomitant gonorrhea. The corresponding figure for C. trachomatis was 43.7%. Nonspecific urethritis was diagnosed in 26 (33.8%) of the male partners to 77 women were diagnosed with N. gonorrhoeae and/or C. trachomatis infection, and in 45 (37.8%) partners of 119 women without such an infection. In all, N. gonorrhoeae, C. trachomatis or NSU were demonstrated in 117 (59.7%) of the 196 male partners, but only 32% of the males with N. gonorrhoeae or C. trachomatis and 8.5% of those with NSU presented subjective symptoms of urethritis. The findings of the study stress the need for routine clinical and laboratory examination and treatment of sexual male partners to women with acute PID.

Outpatient parenteral antibiotic therapy. Management of serious infections, Part II: Amenable infections and models for delivery. Pelvic inflammatory disease.

Due to its polymicrobial origins and potential for causing infertility and ectopic pregnancy, pelvic inflammatory disease (PID) is a particularly challenging infection to treat. Treatment of mild PID has long been standardized: a single dose of an IM antibiotic followed by oral therapy. Patients with advanced PID requiring long-term therapy may be candidates for outpatient parenteral therapy.