Acute exacerbations contribute to the morbidity and mortality associated with COPD. This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.

Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N=573) or placebo (N=584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of 6 courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.

The results were that at 48 weeks the odds ratio (OR) for suffering an exacerbation favored moxifloxacin: per-protocol (PP) population (N=738, OR 0.75, 95% confidence interval (CI): 0.565-0.994, p=0.046), intent-to-treat (ITT) population (N=1149, OR 0.81, 95% CI: 0.645-1.008, p=0.059), and a post-hoc analysis of PP patients with purulent/mucopurulent sputum production at baseline (N=323, OR 0.55, 95% CI: 0.36-0.84, p=0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favor of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs. -3.8, p=0.009; PP: -8.8 vs. -4.4, p=0.006).

Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs. placebo largely due to gastrointestinal events (4.7% vs. 0.7%). Hence it was concluded that intermittent pulsed therapy with moxifloxacin reduces the odds of exacerbation by 20% in the ITT population, by 25% in the per-protocol (PP) population and by 45% in PP patients with purulent/ mucopurulent sputum at baseline and there were neither unexpected adverse events nor evidence of resistance development.

Source: Respir Res. 2010; 11(1):10

According to a study published in The Lancet, measuring levels of the biomarker procalcitonin in people in intensive care gives an accurate indication of the severity of bacterial infection they are experiencing which gives a clear indication as to the nature and length of any antibiotics course they require.

It was suggested that by using procalcitonin levels to prescribe antibiotics rather than the current arbitrary guidelines, people's exposure to antibiotics could be decreased, and the increasing rate of antibiotic resistance can be slowed.

Guidance about blood procalcitonin concentration has substantially reduced antibiotic use in patients presenting to the emergency department or admitted to hospital for lower-respiratory-tract infections. Despite these encouraging results, the potential usefulness of procalcitonin as an instrument to guide antibiotic use in all ICU's has not yet been shown. This was focused in looking at the effectiveness of using procalcitonin to reduce antibiotic exposure in intensive care.

In the randomised controlled trial, patients were assigned in a 1:1 ratio to procalcitonin (n = 311) or control (n = 319) groups. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician.

Patients were expected to stay in the ICU for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60, and number of days without antibiotics by day 28. Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in the final analyses. Mortality of patients in the procalcitonin group seemed to be no worse than the control group at day 28 (21% vs 20%) and day 60 (30% vs 26%). Patients in the procalcitonin group had almost 3 more days without antibiotics by day 28 (14.3 days vs. 11.6 days).

It was observed that, despite of lower antibiotic exposure in the procalcitonin group than in the control group, they were unable to show a between-group difference for the rates of emerging MDR bacteria. Moreover, a 3-day reduction of antibiotic use for only a small subset of admitted patients might not be sufficient to record a decreased resistance-emergence rate, especially for some intensive care units with high cross-transmission rates.

Hence it was concluded that a procalcitonin-guided strategy could reduce antibiotic selective pressure with potential benefits in the era of multiresistance.

Source: The Lancet 2010

The researchers at the University of Illinois and Weizman Institute of Science have found that two antibiotics working together might be more effective in fighting pathogenic bacteria than either drug on its own.

Individually, lankacidin and lankamycin, two antibiotics produced naturally by the microbe streptomyces, are marginally effective in warding off pathogens.

It was found that when used together, the two antibiotics are much more successful in inhibiting growth of dangerous pathogens such as MRSA , or methicillin-resistant Staphylococcus aureus, and possibly others. MRSA is a staph infection that is resistant to certain antibiotics.

Lankacidin and lankamycin act upon the ribosomes, the protein-synthesizing factories of the cell. A newly-made protein exits the ribosome through a tunnel through the ribosome body. Some antibiotics stave off an infection by preventing the ribosome from assembling proteins, while others bind in the tunnel and block the protein's passage.

Through the use of X-ray crystallography, which determines the arrangement of atoms in biological molecules the exact binding site of lankacidin in the ribosome was discovered. It was demonstrated that lankacidin prevents the ribosome from assembling new proteins.

When researchers realized that streptomyces also manufactures lankamycin, they became curious whether the two drugs might help each other. Biochemical analysis and molecular modeling showed that lankamycin binds in the ribosomal tunnel right next to lankacidin.

What was found to be most amazing is that the two antibiotics appeared to help each other in stopping pathogens from making new proteins and in inhibiting bacterial growth.

Source: Proceedings of the National Academy of Sciences 2010

Urinary tract infection (UTI) is common and bacteremia complicating this infection is frequently seen. Limited data is published that characterize bacteremic UTI in a population-based setting over an extended period. The incidence rate, microbiology, outcome, and in vitro antimicrobial resistance trends of bacteremic UTI due to gram-negative bacilli was examined in Olmsted County, Minnesota, from 1/1/1998 to 12/31/2007.

Kaplan-Meier method was used to estimate mortality rates, Cox proportional hazard regression to determine risk factors for mortality, and logistic regression to examine temporal changes in antimicrobial resistance rates.

The results were as follows; 542 episodes of bacteremic gram-negative UTI were identified during the study period. The median age of patients was 71 years and 65.1% were females. The age-adjusted incidence rate per 100,000 person-years was 55.3 (95% confidence interval [CI]: 49.5-61.2) in females and 44.6 (95% CI: 38.1-51.1) in males. Escherichia coli was the most common pathogen (74.9%). The 28-day and 1-year all-cause mortality rates were 4.9% (95% CI: 3.0-6.8) and 15.6% (95% CI: 12.4-18.8), respectively. Older age was associated with higher mortality; community-acquired infection acquisition and E. coli UTI were both independently associated with lower mortality. During the study period, resistance rates increased linearly from 10% to 24% for trimethoprim-sulfamethoxazole and from 1% to 8% for ciprofloxacin.

Hence it was concluded that since it is the first population-based study of bacteremic gram-negative UTI, the linear trend of increasing antimicrobial resistance among gram-negative isolates should be considered when empiric therapy is selected.

Source: J Infect. 2010; 1-8