Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Study documents drug resistance in Chinese gonorrhea isolates

A surveillance study yesterday in BMC Infectious Diseases reports high levels of resistance to previously recommended antimicrobials in Neisseria gonorrhea isolates from a city in eastern China.

Antimicrobial susceptibility testing on 126 N gonorrhea isolates collected from men and women at a sexually transmitted disease (STD) clinic in Hefei, China, from January 2014 through November 2015 revealed that all isolates were resistant to ciprofloxacin, 73.8% (93 of 126) were resistant to penicillin, and 81.7% (103 of 126) were resistant to tetracycline. In addition, 28.6% (36 of 126) of the isolates were resistant to azithromycin and 11.1% (14 of 126) displayed reduced susceptibility to ceftriaxone and cefixime. Molecular testing showed that the isolates belonged to 86 different sequence types.

Penicillin, ciprofloxacin, and tetracycline are no longer used to treat gonorrhea in China, or elsewhere, because of resistance to those drugs. But the authors of the study note that the level of azithromycin resistance is higher than in other parts of the world, a significant finding given that the World Health Organization recommends dual therapy of ceftriaxone or cefixime combined with azithromycin as the standard treatment for gonorrhea.

According to the China Centers for Disease Control and Prevention, 100,245 cases of gonorrhea were reported in China in 2015.
May 25 BMC Infect Dis study

MCR-1 detected in Australian E coli isolates

Originally published by CIDRAP News May 24

Researchers have identified the colistin resistance gene MCR-1 in Escherichia coli samples from two patients in Australia, according to a report yesterday in Emerging Infectious Diseases.

The gene was detected in colistin-resistant E coli isolated from the urine of two patients in different cities in New South Wales, Australia, in 2011 and 2013. The first patient was a 70-year-old woman who had been in the intensive care unit of a large metropolitan hospital for 2 months; the other was a 71-year-old woman who had sought treatment from a community physician for a urinary tract infection. Neither woman had traveled outside the country in the previous 5 years.

The E coli isolates were among 4,555 Enterobacteriaceae isolates from 2007 through 2016 that were tested for colistin resistance. Overall, 96 isolates (2.1%) were found to be colistin resistant—44 Klebsiella pneumoniae, 18 E coli, 19 Enterobacter spp., 8 Klebsiella oxytoca, 5 Hafnia alvei, and 2 Citrobacter freundii.

Polymerase chain reaction testing confirmed the presence of the MCR-1 gene in the E coli isolates and identified them as belonging to sequence type (ST) 167 and ST93. The authors of the study note that ST167 isolates carrying MCR-1 have been found in chicken meat in China, and that ST93 is a known pathogenic strain that has been associated with transmission of MCR-1 from animals to humans in Laos and China. In addition, the plasmids carrying the gene are identical to previously described MCR-1–bearing plasmids from Asia and the Middle East.

The authors say the findings indicate that MCR-1 "is neither a key mechanism nor yet widely disseminated in this country despite multiple importation events."
May 23 Emerg Infect Dis dispatch

Study: Delayed antibiotics for respiratory infections may be preferable

Originally published by CIDRAP News May 24

A new study in The BMJ indicates that delaying antibiotic prescriptions for patients with uncomplicated lower respiratory tract infection is associated with a reduction in reconsultations for new or worsening symptoms and may be preferable to prescribing immediate antibiotics.

The prospective study evaluated 28,779 patients aged 16 and older in the United Kingdom who presented at primary care offices with acute lower respiratory infection, defined as an acute cough that had lasted for as long as 3 weeks. Patients with serious illness were excluded. The main outcomes measured were reconsultation in primary care or a visit to an emergency department with progression of illness in the 30 days after the initial visit, hospital admission, or death.

Of the patients in the study, 7,332 (25.5%) received no prescription for antibiotics, 17,628 (61.3%) received an immediate prescription, and 3,819 (13.3%) received a prescription for delayed antibiotics (median advised delay, 3 days). Subsequent hospital admission or death occurred in 26 of 7,332 patients (0.3%) after no antibiotic prescription, 156 of 7,628 patients (0.9%) after immediate antibiotic prescription, and 14 of 3,819 patients (0.4%) after delayed antibiotic prescription. Multivariable analysis showed that there was no reduction in hospital admission and death after immediate antibiotics (multivariable risk ratio 1.06) and a non-significant reduction with delayed antibiotics (0.81).

Reconsultation for new, worsening, or non-resolving symptoms occurred in 1,443 of 7,332 patients (19.7%) who received no antibiotics, 4,445 of 17,628 patients (25.3%) who received immediate antibiotics, and 538 of 3,819 patients (14.1%) who received delayed antibiotics. Multivariable analysis showed that reconsultation was significantly reduced by delayed antibiotics (multivariable risk ratio 0.64) but not by immediate antibiotics (0.98).

"Prescribing immediate antibiotics may not reduce subsequent hospital admission or death for young people and adults with uncomplicated lower respiratory tract infection, and such events are uncommon," the authors write. "If clinicians are considering antibiotics, a delayed prescription may be preferable since it is associated with reduced number of reconsultations with worsening illness."

An accompanying editorial says that the findings, combined with other studies, indicate that not offering an immediate antibiotic prescription for patients with common acute respiratory infections is a low-risk strategy. 
May 22 BMJ study
May 22 BMJ editorial 

Study: 1 in 4 pneumonia patients fail initial antibiotic therapy

Originally published by CIDRAP News May 22

Nearly one in four adult outpatients prescribed antibiotic monotherapy for community-acquired pneumonia (CAP) do not respond to treatment, according to a paper presented at the 2017 American Thoracic Society International Conference.

In the retrospective cohort analysis, researchers examined data on adult outpatients who received antibiotic treatment following an outpatient visit for CAP from 2011 through 2015. To be included in the study, patients were required to have a monotherapy antibiotic prescription claim for a single class of antibiotics (macrolides, fluoroquinolones, beta-lactams, or tetracyclines). Treatment was considered a failure if the patient had their antibiotic prescription refilled, switched to a different antibiotic, visited the emergency room (ER), or was hospitalized within 30 days of the receipt of the initial antibiotic prescription.

Among the 251,947 patients who met the criteria for the study, the mean age was 52.2 years. The majority of patients were prescribed azithromycin (40.3%) and levofloxacin (37.7%). The total antibiotic failure rate was 22.1% (55,741 patients), with 70.7% (39,397) of those patients switching to a different antibiotic, 20.6% (11,493) refilling their initial prescription, 5.4% (3,015) being hospitalized, and 3.3% (1,835) visiting the ER.

A multivariable logistic regression model revealed that diagnosis of pneumococcal pneumonia (p<0.02), older age (p<0.0001), and female gender (p<0.0001) were multivariate predictors of antibiotic failure. Comorbidities associated with higher rates of antibiotic failure included hemiplegia/paraplegia (odds ratio [OR] 1.33), rheumatologic disease (OR 1.28), chronic pulmonary disease (OR 1.25), cancer (1.14), diabetes (OR 1.07), and asthma (OR 1.05). After adjusting for baseline patient characteristics, beta-lactams were associated with the highest antibiotic failure rate (25.7%), followed by macrolides (22.9%), tetracyclines (22.5%), and fluoroquinolones (20.8%).

"Our findings suggest that the community-acquired pneumonia treatment guidelines should be updated with more robust data on risk factors for clinical failure," lead author James McKinnell, MD, an infectious disease specialist with LA BioMed, said in an American Thoracic Society (ATS) press release. In particular, he noted the greater risk of hospitalization for patients over 65. He also warned of the potential hazards of additional antibiotic therapy.

"The additional antibiotic therapy noted in the study increases the risk of antibiotic resistance and complications like C. difficile ("C diff") infection, which is difficult to treat and may be life-threatening, especially for older adults," McKinnell said.
May 21 abstract
May 21 ATS press release

Study finds directly observed therapy reduces mortality in MDR-TB patients

Originally published by CIDRAP News May 22

In another paper presented at the 2017 American Thoracic Society International Conference, researchers with the US Centers for Disease Control and Prevention (CDC) report that directly observed therapy (DOT) was associated with a 77% reduction in mortality among patients with multidrug-resistant tuberculosis (MDR-TB).

In an analysis of surveillance data for 3,434 MDR-TB patients treated in the United States from 1993 through 2013, the researchers found that 709 (21%) died during treatment. Among the patients with available data, 34% had an HIV infection, 18% had previous TB disease, and 17% had an additional drug resistance. DOT, a strategy that requires health workers, community volunteers, or family members to record patients taking their medicine, increased from 74% during 1993-2002 to 95% during 2002-2013, while all-cause mortality decreased from 31% to 11% during these periods.

Using Cox proportional hazard models to estimated adjusted hazard ratio (aHR), the researchers determined that older age (aHR 1.15) and reported HIV infection (aHR 7.11) were risk factors for all-cause mortality, while DOT (aHR 0.23) was protective.

"This protective effect may come from DOT alone or from other patient-centered measures, such as transportation assistance or food stamps given along with DOT by TB treatment facilities to improve treatment adherence," lead author Jorge Salinas, MD, said in an ATS press release. "The findings reinforce that all patients with MDR TB should receive DOT and other patient-centered measures to ensure patients complete their treatment."
May 21 abstract
May 21 ATS press release

Extensive multidrug resistance found in Salmonella from Ethiopian poultry

Originally published by CIDRAP News May 22

A new study in BMC Infectious Diseases has found extensive multidrug resistance in Salmonella isolates from poultry breeding, multiplication, and distribution centers in Ethiopia.

In the study, researchers from Addis Addaba University took fecal samples and cloacal swabs from chickens at two poultry multiplication centers and a commercial poultry farm, along with bedding samples and hand swabs from poultry workers. Salmonella was isolated in 45 of the 270 fecal samples (16.7%), 36 of 244 cloacal swabs (14.8%), 6 of 17 pooled bedding samples (35.3%), and 3 of 9 hand swabs (33.3%). Of the 45 Salmonella isolates subjected to antimicrobial susceptibility testing, 100% were resistant to at least three antimicrobials, with 93.3% exhibiting resistance to at least eight antimicrobials simultaneously, including all isolates from personnel and poultry bedding.

Interviews with center supervisors revealed that antimicrobials were routinely overprescribed to avoid the undetected spread of pathogens and onset of disease outbreak at the centers. In addition, the authors note the fact that Salmonella prevalence was higher in the bedding samples and hand swabs than in the chicken cloaca demonstrates the poor biosecurity and personnel hygienic practices at the facilities. Given the limited supply of personnel hygiene supplies and poor hand washing practices, hand contamination could lead to self-infection among poultry workers and spread of infection to family members and others.

"We conclude that the poultry breeding, multiplication and distribution centers in Ethiopia, as they currently stand, are a source for the dissemination of pathogens and drug resistant pathogens, at least Salmonella," the authors write.
May 18 BMC Infect Dis study