Posts filed under ‘Bacteriemias’

CIM City: the Game Continues for a Better Carbapenemase Test

Clin. Microbiol. July 2019 V.57 N.7 P.1-5

The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing agree that carbapenemase testing is not necessary for clinical care, provided that the laboratory is up to date with current breakpoints. Nonetheless, publication on the development and modification of carbapenemase tests continues, as is the case in this issue of the Journal of Clinical Microbiology (R. W. Beresford and M. Maley, J Clin Microbiol 57:e01852-18, 2019, This commentary explores modifications to the carbapenem inactivation method—but is this the right focus for clinical laboratories?



June 26, 2019 at 4:19 pm

Gentamicin as an alternative treatment for gonorrhoea

LANCET June 22, 2019 V.393 N.10190 P.2474-2475


A high gonorrhoea disease burden, increasing rates, and growing antimicrobial resistance portend a developing global public health crisis.1 Gonorrhoea can cause reproductive complications such as pelvic inflammatory disease and infertility, blindness in infants born to infected mothers, and can facilitate HIV acquisition and transmission. Effective treatment prevents sequelae and transmission. Yet Neisseria gonorrhoeae has developed resistance to each antimicrobial used for treatment.2 Development of new antimicrobials has not kept pace…..




LANCET June 22, 2019 V.393 N.10190 P.2511-2520

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial


Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea.


G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227.


Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group).


Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea.


UK National Institute for Health Research.





June 22, 2019 at 7:59 pm

Listeriosis in Spain based on hospitalisation records, 1997 to 2015: need for greater awareness


Listeriosis is an infectious disease caused by bacteria of the genus Listeria spp. L. monocytogenes is the major pathogenic species in both animals and humans. L. monocytogenes is a Gram-positive, rod-shaped organism that can grow in aerobic and anaerobic conditions [1], is widely distributed in the environment and is able to contaminate a wide variety of foods or beverages (soft cheese, deli meats, unpasteurised milk, refrigerated smoked seafood, etc.) [2]. The bacteria can multiply at refrigerator temperatures [3]; therefore, contaminated products are often kept for several days or even weeks, e.g. in the household/restaurants, and may be eaten on multiple occasions, which can complicate the identification of the incriminated food source [4].

The clinical syndromes of listeriosis include: febrile gastroenteritis, sepsis, central nervous system (CNS) involvement in the form of encephalitis, meningoencephalitis and focal infections such as pneumonia myo-endocarditis and septic arthritis, etc [5]. Invasive listeriosis most commonly affects pregnant women, neonates, elderly people and people with chronic conditions or weakened immune response [6]. Listeriosis has one of the highest case fatality rates among all food-borne infections; when it affects the CNS, the mortality rate is above 50% and neurological sequelae are present in more than 60% of survivors [2]. Listeriosis is also associated with fetal and neonatal death.

Worldwide, listeriosis is an emerging infection of public health concern [7]. In Europe, human listeriosis peaked in incidence during the 1980s, showed a general decline during the 1990s and stabilised in the 2000s [8]. More recent data show an increasing trend since 2008 [9]. This increase seems to be related to the ageing of the population and the increase in life expectancy of immunocompromised patients, but also to changes in the ways food is produced, stored, distributed and consumed around the world [10]. Although listeriosis is often a sporadic disease [11], large food-borne outbreaks have occurred during the last decade in Europe and the United States (US) [12]. In South Africa, an outbreak with more than 1,024 laboratory-confirmed listeriosis cases, as at 2 May 2018, has been ongoing since the start of 2017, with a 28.6% case fatality rate [13].

In Spain, food safety criteria (FSC) for L. monocytogenes follow European Commission (EC) regulations [14,15]. Before 2015, when it was added to the list of mandatory notifiable diseases, regions could voluntarily report listeriosis to the Microbiological Information System (Sistema de Información Microbiológica, SIM) [16]. Using the centralised hospital discharge database (Conjunto Mínimo Básico de Datos, CMBD), we aimed to describe the epidemiology of listeriosis in Spain from 1997–2015.



June 21, 2019 at 7:49 am

Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting

European Journal of Clinical Microbiology & Infectious Diseases. June 2019 V.38 N.7

Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important.

Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock.

A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012–2013. The criterion “early appropriate antibiotic treatment” was defined as administration of the first dose of adequate antibiotics within 1 h, and the second dose given with less than 25% delay after the recommended dose interval.

A high-risk patient was defined as a septic patient with either shock within 24 h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality.

Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment.

Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.



June 20, 2019 at 7:01 pm

Meningococcal Disease Among College-Aged Young Adults: 2014–2016

Pediatrics January 2019  V.143  N.1


Freshman college students living in residence halls have previously been identified as being at an increased risk for meningococcal disease. In this evaluation, we assess the incidence and characteristics of meningococcal disease in college-aged young adults in the United States.


The incidence and relative risk (RR) of meningococcal disease among college students compared with noncollege students aged 18 to 24 years during 2014–2016 were calculated by using data from the National Notifiable Diseases Surveillance System and enhanced meningococcal disease surveillance. Differences in demographic characteristics and clinical features of meningococcal disease cases were assessed. Available meningococcal isolates were characterized by using slide agglutination, polymerase chain reaction, and whole genome sequencing.


From 2014 to 2016, 166 cases of meningococcal disease occurred in persons aged 18 to 24 years, with an average annual incidence of 0.17 cases per 100 000 population. Six serogroup B outbreaks were identified on college campuses, accounting for 30% of serogroup B cases in college students during this period. The RR of serogroup B meningococcal (MenB) disease in college students versus noncollege students was 3.54 (95% confidence interval: 2.21–5.41), and the RR of serogroups C, W, and Y combined was 0.56 (95% confidence interval: 0.27–1.14). The most common serogroup B clonal complexes identified were CC32/ET-5 and CC41/44 lineage 3.


Although the incidence is low, among 18- to 24-year-olds, college students are at an increased risk for sporadic and outbreak-associated MenB disease. Providers, college students, and parents should be aware of the availability of MenB vaccines.



June 17, 2019 at 6:59 pm

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrob. Agents Chemother. May 2019 V.63 N.5

Matthew Geriak, Fadi Haddad, Khulood Rizvi, Warren Rose, Ravina Kullar, Kerry LaPlante, Marie Yu, Logan Vasina, Krista Ouellette, Marcus Zervos, Victor Nizet and George Sakoulas

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at under identifier NCT02660346.)


May 21, 2019 at 3:53 pm

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents

Antimicrob. Agents Chemother. May 2019 V.63 N.5

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens” to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government.


May 21, 2019 at 3:52 pm

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