麻豆传媒

Amid growing concern about antimicrobial resistance, researchers have identified a potential alternative to current first-line antibiotic therapy for genital gonorrhea.

Results from G-ToG, the first randomized trial to compare gentamicin (Garamycin) with the current first-line option ceftriaxone (Rocephin), showed that gentamicin 240 mg was almost as effective as ceftriaxone 500 mg for clearing genital gonorrhea (94% of 174 patients vs 98% of 154 patients, respectively; adjusted risk difference, –4.4%).

But the efficacy of gentamicin did not match that of ceftriaxone for clearing either throat or rectal gonorrhea, Jonathan Ross, PhD, of the University Hospitals Birmingham NHS Foundation Trust, in England, and colleagues reported online in .

Both drugs were given as a single intramuscular injection combined with a 1 gram dose of oral azithromycin (Zithromax). Clearance of Neisseria gonorrhea was determined by negative nucleic acid amplification testing two weeks post-treatment.

"We were unable to conclude that gentamicin was non-inferior to ceftriaxone, and treatment failure with gentamicin was higher than with ceftriaxone for patients with extra-genital infections," the study authors wrote. "Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhea."

The investigators pointed out that globally, gonorrhea accounts for 78 million infections each year. What's more, there have been several reports of patients not responding to first-line ceftriaxone.

"Ceftriaxone should remain the first-line treatment for gonorrhea, with gentamicin reserved for use as a potential alternative, particularly for patients allergic or intolerant to ceftriaxone or those harboring a ceftriaxone-resistant isolate," Ross told the Reading Room.

The study showed that at a two week followup, pharyngeal infection had cleared in 108 patients (96%) receiving ceftriaxone compared to 82 (80%) on gentamicin (adjusted risk difference, –15.3%). In patients with rectal infection, infection cleared in 134 (98%) in the ceftriaxone group versus 107 (90%) treated with gentamicin (adjusted risk difference, –7.8%).

Although side effect profiles were similar in both groups, participants treated with gentamicin reported more severe pain at the injection site.

The investigators noted that combining azithromycin with either antibiotic was likely insufficient to prevent the development of antibiotic resistance, and recommended the use of azithromycin in combination therapy for gonorrhea to be reviewed. In fact, the British Association for Sexual Health and HIV changed its national gonorrhea treatment guideline, which now recommends that azithromycin be omitted as part of the first-line treatment standard for gonorrhea and that a larger dose of ceftriaxone be used instead.

In an accompanying , Robert D. Kirkcaldy, MD, MPH, of the Centers for Disease Control and Prevention in Atlanta, and Kimberly A. Workowski, MD, of Emory University, also in Atlanta, called the G-ToG findings "a welcome step forward."

However, new drugs that can clear infection at all sites are needed, Kirkcaldy and Workowski pointed out.

"A , increasing rates, and growing antimicrobial resistance portend a developing global public health crisis," they wrote. "Effective treatment prevents sequelae and transmission. Yet Neisseria gonorrhea has developed used for treatment. Development of new antimicrobials has not kept pace."

Noting that gentamicin cleared infection in only 80% of patients with pharyngeal gonorrhea, Kirkcaldy and Workowski warned that "gentamicin plus azithromycin is not a reliable treatment."

Pharyngeal infections can be more difficult to eradicate than infections at other sites. "[T]he pharynx might serve as a and resistant gonococci," they explained.

Better understanding of tissue penetration, particularly at extra genital disease sites, is needed to inform treatment duration, and given the current lack of treatment options for gonorrhea, "we might have to rethink existing efficacy standards for treatment recommendations," they suggested. Prevention programs will also need to be strengthened and new approaches, including vaccines, developed.

Reducing urinary tract infections

The hospital-wide use of 0.1% chlorhexidine solution for meatal cleaning prior to catheter insertion dramatically decreased the incidence of catheter-associated asymptomatic bacteriuria (CA-ASB) and catheter-associated urinary tract infection (CAUTI), Australian researchers published online in .

Results from the study -- a cross-sectional, open-label, randomized, controlled trial at three Australian hospitals -- showed that the intervention was associated with a 74% reduction in the incidence of CA-ASB (incident rate ratio [IRR], 0.26; P=0.026) and a 94% decrease in the incidence of CAUTI (IRR, 0.06; P<0·001), compared with 0.9% normal saline.

"Catheter-associated UTI [urinary tract infection] has substantial health and economic implications for patients and the health-care system," they wrote in The Lancet Infectious Diseases study. "Although less than a quarter of patients with catheter-associated asymptomatic bacteriuria develops , the excess costs, increased length of stay in hospital, and antimicrobial use for treatment, coupled with the frequency of these infections, provide a strong rationale to prevent its occurrence."

In addition to potentially increasing patient safety, the intervention is likely to be cost-effective and cost-saving, Brett Mitchell, PhD, of the Avondale College of Higher Education in Wahroonga, Australia, and colleagues, reported in a follow-up cost-effectiveness analysis, published in the . Using a cost-effectiveness accounting model in the follow-up study, the researchers determined this prevention strategy had a 100% probability of achieving cost savings.

In the U.S., related to CA-ASB and CAUTI suggest they can add up to more than $1,000 per patient.

Reducing the incidence of catheter-associated asymptomatic bacteriuria has the potential to decrease inappropriate antimicrobial use, which is important amidst multi-drug resistance, Mitchell and colleagues said.

"The impact of reducing the incidence of catheter-associated asymptomatic bacteriuria should not be underestimated, given that the who receive an indwelling urinary catheter is between 18% and 26%," they wrote. "We encourage an update of existing systematic reviews that inform international guidelines for the prevention and control of catheter-associated UTI, in addition to local hospital policies."

In an accompanying , Bart J. Laan, MD, PhD, and Suzanne E. Geerlings, MD, PhD, from Amsterdam UMC, and the University of Amsterdam, in the Netherlands, agreed that this study provides important evidence to decrease the incidence of catheter-assisted UTI.

However, they pointed out, restricting the use of urinary catheters and removing them as soon they are no longer needed remains "the most effective way to reduce the incidence of catheter-assisted UTI." The researchers demonstrated this point by assessing a de-implementation strategy in their recent .

The editorialists noted that the prevalence of health care-associated infections among inpatients varies from 3.2% in the U.S. to 15.5% in developing countries. Many of these infections, including catheter-associated UTIs which have a prevalence of 65–70%, are .

Laan and Geerlings, however, pointed to a number of issues with The Lancet Infectious Diseases study. The researchers questioned the choice of CA-ASB as co-primary endpoint, particularly since the Infectious Diseases Society of America (IDSA) state that the relationship between CA-ASB and UTI remains unclear. They also noted that in the current study's control period, 52% of catheters were removed before the end of follow-up while 79% of catheters were removed before the end of follow-up in the intervention period.

"Since a main risk factor for catheter-associated UTI is an increased number of consecutive catheter days, it is unclear whether a more frequent early removal of the catheter in the intervention period has introduced bias in the assessment of the primary outcome," they wrote.