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Drug Resistance Patterns

Antibiotic stewardship vital

Link: HighWire Press -- Medline Abstract.

PURPOSE: To address how the high endemic levels of antimicrobial resistance and multidrug resistance in hospitals have challenged clinicians to select appropriate therapy for effectively treating bacterial infections among seriously ill patients. SUMMARY: Among gram-positive bacterial infections, differentiating between healthcare-associated and community-associated methicillin-resistant Staphylococcus aureus infections is becoming more difficult and can seriously impact therapeutic strategies and hence outcomes. Furthermore, the rising prevalence of multidrug-resistant gram-negative bacterial infections is increasing the pressure on proper antimicrobial selection given the dearth of new antimicrobial agents under development. Optimized dosing strategies will be instrumental in minimizing emergence of resistance and preserving the utility of currently available agents. Antimicrobial stewardship programs in conjunction with stringent infection control policies will be critical in improving the appropriate use of antimicrobials while reducing the spread of nosocomial pathogens. CONCLUSION: Addressing the challenges of antimicrobial resistance in hospitals will require a multidisciplinary approach, with clinical pharmacists taking a proactive role in ensuring the appropriate use of antimicrobials.

Bacteria beware: MIT graduate invents knock-out punch for antibiotic resistance

Link: Bacteria beware: MIT graduate invents knock-out punch for antibiotic resistance.

Working with his advisor, J.J. Collins, professor of biomedical engineering at Boston University, Lu developed two bacteriophage platforms to overcome antibiotic resistance. Bacteriophage are viruses that only infect bacteria, not human cells. They have been used since the early 20th century to treat bacterial infections; however, they fell out of favor in the United States due to the advent of antibiotics. Lu’s work represents an exciting application of synthetic biology, which is an emerging field focused on the rational engineering of organisms to achieve novel functions. Lu has engineered bacteriophage to boost antibiotic effectiveness. The bacteriophage carries DNA that codes for factors that target bacterial gene networks, which former treatments failed to reach, and destroys bacterial antibiotic resistance mechanisms. The weakened bacterial defenses enable antibiotics to perform better. Administered together, Lu’s bacteriophage and antibiotics have the potential to eliminate nearly 30,000 times more bacteria than antibiotics alone, including cells that survive antibiotic-only treatment. This combination treatment also thwarts development of stronger antibiotic resistance, which can extend the lifetime of existing and future antibiotic drugs. “While working at a hospital as part of a graduate course, I saw many patients who contracted new infections due to already-compromised immune systems or equipment that is extremely difficult to keep sterile,” Lu recalled. “Being infected by difficult-to-eradicate bacteria is a traumatic experience for patients and a serious public health issue that needs attention. I thought that there had to be a solution for these infections.”

The nightmare begins - CA MRSA that resists vancomycin

Link: Emergence of Multidrug-Resistant, Community-Associated, Methicillin-Resistant Staphylococcus aureus Clone USA300 in Men Who Have Sex with Men -- Diep et al., -- Annals of Internal Medicine.

The high incidence of multidrug-resistant USA300 among men who have sex with men has major implications for empirical treatment of skin infections among these patients. Several important antimicrobial classes for treatment of MRSA infections or eradication of colonization, including clindamycin, tetracycline, and mupirocin, may not be effective in this population. Resistance to trimethoprim–sulfamethoxazole and rifampin remains rare among USA300 isolates and was not seen in multidrug-resistant USA300 in our study (Table 1). However, prophylactic antimicrobial use has selected for the emergence of trimethoprim–sulfamethoxazole resistance in subclones genetically related to the USA300 lineage in patients from San Francisco and New York City who were infected with HIV (50–52). Prudent use of these antimicrobial agents for suspected MRSA disease in men who have sex with men is advisable to slow the emergence of even more resistant community-associated MRSA. The pUSA03 plasmid that determines multidrug resistance in multidrug-resistant USA300 belongs to a highly promiscuous class of conjugative plasmids that could readily accept transposons encoding resistance to aminoglycosides, trimethoprim, vancomycin, and other antimicrobials, potentiating the emergence of even more resistant community-associated MRSA (28, 53).

New Super Strength USA300 has been spreading since 2003

Link: S.F. gay community an epicenter for new strain of virulent staph.

But the latest problem is being caused by a new variant of USA300 that was first detected in a San Francisco patient in 2003. Among the six antibiotics it is resistant to are three that are normally considered for treatment of suspected MRSA. The study estimated that 200 cases of this highly drug-resistant variant are turning up in San Francisco each year, mostly among gay men. "We are nowhere near the peak," Diep said. "The peak will occur when it spreads into the general population."

The new variant of USA300 is resistant to the antibiotics erythromycin, clindamycin, tetracycline, Cipro-like antibiotics and drugs in the penicillin family. It also does not respond to mupirocin - a gel that is often used to kill MRSA growing in people's noses.

That still leaves a variety of antibiotics that will kill the new USA300 strain, but they tend to be more expensive and require intravenous drips. One common oral antibiotic, Bactrim, is still effective against it.

Chambers also pointed out that researchers at San Francisco General have shown that many skin sores and boils caused even by these drug-resistant strains of staph often can be treated without any antibiotics, just by surgical drainage of pus.

One of the paradoxes of bacterial infections is that using antibiotics to treat them is one of the quickest ways to promote antibiotic resistance. Although the drugs sometimes are essential, overuse is weakening their effectiveness worldwide.

Drug resistance stands still in Texas hospital

Link: Inhibitory Activities of Eleven Antimicrobial Agents and Bactericidal Activities of Vancomycin and Daptomycin against Invasive Methicillin-Resistant Staphylococcus aureus (MRSA) from 1999 through 2006 -- Holmes and Jorgensen, 10.1128/AAC.00945-07 -- Antimicrobial Agents and Chemotherapy.

We assessed MICs and MBCs of vancomycin, daptomycin and nine other antimicrobials against methicillin-resistant Staphylococcus aureus isolates from 1999 through 2006. No vancomycin, daptomycin or linezolid resistance was observed. Clindamycin, gentamicin and ciprofloxacin resistance decreased significantly. No tolerance to vancomycin or daptomycin was observed, nor was MIC creep seen.

Antibiotic-Resistant "Superbugs" May Be Transmitted From Animals to Humans

Link: JAMA -- Antibiotic-Resistant "Superbugs" May Be Transmitted From Animals to Humans, November 14, 2007, Kuehn 298 (18): 2125.

The emergence of antibiotic resistance on farms where livestock are routinely treated with antimicrobials has been well documented, but whether it poses a human health threat has been controversial. Now, a growing body of evidence suggests these "superbugs" of animal origin are being transmitted to humans. A trio of posters presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy in September highlighted evidence that resistant bacteria themselves or bits of DNA containing genes encoding drug resistance can and do cross from animals to humans. Additionally, 2 recent epidemiological studies in distinct human populations suggest that bacteria are developing resistance to antibiotics on poultry farms and that these resistant bacteria are colonizing humans.

Researchers discover new strategies for antibiotic resistance

Link: Researchers discover new strategies for antibiotic resistance.

Drs. Michael R. Yeaman and Nannette Y. Yount present evidence that small proteins in the immune systems of humans and all kingdoms of life share fundamental structural and functional characteristics that enable these molecules to inhibit or kill microbial pathogens – even as these pathogens evolve to resist conventional antibiotics. "These findings reveal that nature uses a recurring molecular strategy to defend against infection," said Dr. Yeaman. "A clearer understanding of this strategy provides new opportunities to develop innovative anti-infective therapies to better prevent or treat life-threatening infections that resist current antibiotics." Most modern antibiotics work by targeting specific structures or functions in microbial pathogens. If the targets change due to mutation, pathogens can quickly become resistant to the antibiotics. In contrast, immune system molecules have retained the ability to fight infection – even as microbes evolve.

Clindamycin still very effective despite extensive CA MRSA Use

Link: HighWire Press -- Medline Abstract.

A previous study at our institution revealed 98% of methicillin-resistant Staphylococcus aureus (MRSA) isolates were susceptible to clindamycin; however, beta-lactams were then the predominant empiric treatment. This follow-up chart review study examined subsequent staphylococcal skin and soft tissue infection treatment and susceptibility patterns over a 2-year period. Of 296 S. aureus skin and soft tissue infections, 73% were MRSA, of which 87% were community-associated-MRSA; MRSA infections peaked in warm summer months. Despite a significant increase in empiric clindamycin use, 97% of community-associated-MRSA isolates retained susceptibility to clindamycin.

Hospital strains help community strains become resistant?

Link: HighWire Press -- Medline Abstract.

CONCLUSIONS: This study demonstrated that although CA-MRSA genotypes were heterogeneous, the predominant genotype that was circulating in our community was genotype A. Also, the multidrug resistance of CA-MRSA might be connected to the spreading of nosocomial strains in the community.

MRSA has creeping resistance to key drugs

Link: HighWire Press -- Medline Abstract.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 3,189) from 2,990 patients were investigated by agar screening and by the E-test(TM) macromethod for reduced susceptibility to glycopeptide. No vancomycin-resistant S. aureus or glycopeptide-intermediate S. aureus (GISA) were detected but 178 isolates were confirmed as hetero-GISA (hGISA) by vancomycin population analysis profile (PAP)-area under the curve (vPAP-AUC) ratio determination and/or teicoplanin PAP (tPAP) methods. Of 139 isolates detected using the recommended E-test(TM) macromethod cut-off values of >/=8 mg/L for both vancomycin and teicoplanin or >/=12 mg/L for teicoplanin alone, 73 were confirmed as hGISA by vPAP-AUC, 95 by tPAP and 108 by both methods.

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