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By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Plain Old Gonorrhea, Increasingly Difficult to Treat
Source: MMWR. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. 2007; 56:332-336.
Quinolone-Resistant Neisseria Gonorrhea (QRNG) continues to spread with alarming frequency across the United States. Quinolones were first recommended for the treatment of GC by the CDC in 1986. The first quinolone-resistant isolates were reported in Asia and Hawaii in 1991, and sporadic cases occurred in the United States between 1991-1999. However, since 2000, there has been a steady increase in QRNG cases, first in Hawaii, then in California and other Western states, then in men who have sex with men (MSM) throughout major cities in the United States, and now it is appearing with increasing frequency in heterosexual men. In 2003, the CDC revised the treatment recommendations, such that areas experiencing > 5% QRNG no longer used quinolones for first-line treatment of GC.
Surveillance for GC resistance in the United States began in 1986 through a CDC-sponsored program called GISP. Data is presently collected from urethral swabs from 6,000 males annually presenting to 26 to 30 STD clinics throughout the United States. The GISP program provides increasingly important resistance data on STDs in an era with declining use of cultures. Quinolone resistance is defined as an MIC > 1 microgram/mL to ciprofloxacin; intermediate resistance is defined as an MIC 0.125-0.500 microgram/mL.
Since 2001, the prevalence of QRNG in MSM has increased from 1.6% to 29% in 2005; preliminary data for 2006 suggests the current rate is much higher (38%). Resistance in heterosexual men has occurred more slowly, beginning with 0.6% in 2001 and increasing to 3.8% in 2005; preliminary 2006 data suggest the current rate is closer to 6.7%. Certain cities, like Philadelphia and Miami are experiencing even greater rates of resistance, especially in gay men.
The CDC now recommends a single dose of intramuscular ceftriaxone 125 mg for uncomplicated urogenital and anorectal GC. Alternate regimens would include a single dose of cefoxitin 2 grams with probenecid, ceftizoxime 500 mg, cefotaxime 500 mg, or cefiximine oral suspension 400 mg. For persons with severe penicillin or cephalosporin allergies, intramuscular spectinomycin 2 grams can be given (but would presently require being ordered through the public health department, resulting in a delay in treatment). A single oral dose of azithromycin 2 grams is another good option for patients with uncomplicated GC with severe PCN allergy. However, the routine use of azithromycin is not recommended because of concerns regarding the rapid emergence of resistance.
A single dose of intramuscular ceftriaxone 125 mg is also recommended for pharyngeal GC; the alternate regimens above may not be adequate for pharyngeal infection. In addition, quinolones are no longer recommended for treatment of conditions such as PID that may be caused by GC.
A test of cure 2-weeks post-treatment was previously required for persons receiving quinolone therapy. Since quinolones are no longer recommended, a test of cure is not necessary for treatment of uncomplicated GC. However, a culture and susceptibility studies should be obtained in any person with persistent symptoms. Keep in mind that the SF PHD identified 3 cases of combined quinolone and cephalosporin resistance in 2003. As of 2004, the IDSA has listed GC as one of the target organisms in their "Bad Bugs, No Drugs" campaign.
Find the LGV
Source: McLean CA, et al. Treatment of lymphogranuloma venereum. Clin Infect Dis. 2007; 44:S147-S152.
Beginning in 2003, clusters of cases of lymphogranuloma venereum were reported in several European and North American cities. Previously a third-world STD, it has since been occurring with increasing frequency in the United States, especially in men who have sex with men (MSM). LGV is caused by Chlamydia trachomatis serovars L1, L2, and L3. It typically presents with small genital papules or ulcers, although these can be readily missed or mistaken for other problems in half of patients. Patients with acute infection may develop inguinal lymphadenopathy, proctitis with rectal ulcerations, anal discharge, tenesmus, and lower abdominal crampy pain. As the infection progresses, fever, malaise, weight loss, chronic anal fissures, fistulas, and deep soft tissue abscesses and adhesions can develop in 25% of untreated persons. By then, the chronic inflammation, lymphatic scarring, and deep soft-tissue changes may not be reversible. Therefore treatment during the early stage of infection is important.
Having said this, the diagnosis of LGV remains problematical, and largely requires the heightened recognition of the clinical signs and symptoms of infection. Current DNA-based screening methods for Chlamydia fail to detect LGV (different serovar). Routine serologic testing for Chlamydia provides helpful supportive evidence if a titer is greater than or equal to 1:64 in the appropriate clinical setting. However, there is little data on the utility of this approach as a screening tool in high-risk patients. Cross-reaction with other chlamydial organisms is common, and serovar-specific testing is not readily available. Lesions and tissue from excisional biopsy of lymph nodes can be variously tested by culture, direct immunofluorescence, or nucleic acid testing, but such techniques have not been approved by the FDA for use on rectal swabs or rectal tissue biopsies.
Hence the diagnosis of LGV is to a large degree based on the prevalence of infection in your area, patient risk factors, and your clinical suspicion. Thus, any patient at risk with proctocolitis, inguinal adenopathy, or genital or rectal ulcers for which no other ready explanation exists should receive empiric doxycycline for 3 weeks. Some physicians advocate a longer course of therapy in patients with more severe symptoms. Only limited clinical data for the use of azithromycin and quinolones exists. Quinolones are probably highly effective but require a 3-week course, which is costly. Reports have found that a single dose of azithromycin 2 grams was effective in 2 patients, and this agent may be especially useful in pregnant women, although multiple doses over a > 3-week period would likely be necessary.
Cryptococcus gattii in North America
Source: Struck D. Washington Post Foreign Service, Sunday April 8, 2007, page D01; ProMED-mail post dated April 7 and April 12, 2007; www.promedmail.org.
Vancouver Island, off the coast of British Columbia, is experiencing an increasing number of unusual fungal infections in humans and pet dogs and cats due to Cryptococcus gattii. C. gattii is a yeast, distantly related to Cryptococcus neoformans, which is believed to have been brought to North America in the bark of imported eucalyptus trees. First identified in 1999 in pet dogs, and subsequently a number of porpoises with fatal pneumonia, the infection has resulted in more than 160 human infections and 8 deaths. While the infection typically occurs in persons with immune system dysfunction, such as those with HIV/AIDS, immune-competent hosts can be affected. Most of the human cases have occurred on Vancouver Island, although infections have been reported elsewhere in British Columbia, Washington, and Oregon, and a few tourists to the area have also been affected. The prevalence of infection on Vancouver Island is approximately 27 per million.
The basis for the increasing appearance of this fungal organism is not known, although some authorities have blamed global warming and a number of unusually warm summers. Epidemiologic investigation first focused attention on the eucalyptus trees in Rathtrevor Beach Provincial Park on the eastern side of the island, where the yeast was first isolated from swabs of tree bark, but has since been identified in about a 100 square km range along the eastern side of the island. The yeast may also be found in soil, water, and air. Dogs typically develop abscesses of the face and eyes, and have been identified with nasal colonization with the organism.
Cryptococcus gattii colonizing eucalyptus is not a newly recognized problem, although a cause of increasing concern in North America. It is endemic to Australia and other tropical zones, where it is frequently found in association with certain eucalyptus tree species. Rare cases of C. gattii infection are reported in Australia (5 cases per million), Eucalyptus were first brought to North America from Australia in the 19th century, ostensibly as another source of lumbar. But the trees proved to be too slow growing, and far too hard a wood for ordinary use as lumbar. At one point during the early days of the HIV/AIDS epidemic, it was thought the eucalyptus in San Francisco might be the source of Cryptococcal neoformans infection until it was recognized that the trees harbored a different species of yeast.