Cefotaxime Non-susceptibility Research Articles

Impact of Cefotaxime Non-susceptibility on the Clinical Outcomes of Bacteremic Pneumococcal Pneumonia.

Background: We aimed to analyze the impact of cefotaxime non-susceptibility on the 30-day mortality rate in patients receiving a third-generation cephalosporin for pneumococcal bacteremic pneumonia. Methods: We conducted a retrospective observational study of prospectively collected data from the Hospital Clinic of Barcelona. All adult patients with monomicrobial bacteremic pneumonia due to Streptococcus pneumoniae and treated with a third-generation cephalosporin from January 1991 to December 2016 were included. Risk factors associated with 30-day mortality were evaluated by univariate and multivariate analyses. Results: During the study period, 721 eligible episodes were identified, and data on the susceptibility to cefotaxime was obtainable for 690 episodes. Sixty six (10%) cases were due to a cefotaxime non-susceptible strain with a 30-day mortality rate of 8%. Variables associated with 30-day mortality were age, chronic liver disease, septic shock, and the McCabe score. Infection by a cefotaxime non-susceptible S. pneumoniae did not increase the mortality rate. Conclusion: Despite the prevalence of cefotaxime, non-susceptible S. pneumoniae has increased in recent years. We found no evidence to suggest that patients hospitalized with bacteremic pneumonia due to these strains had worse clinical outcomes than patients with susceptible strains.

Cefotaxime-non-susceptibility of Haemophilus influenzae induced by additional amino acid substitutions of G555E and Y557H in altered penicillin-binding protein 3

Cefotaxime-non-susceptible Haemophilus influenzae has rarely been isolated from clinical specimens. Although several reports have shown that amino acid (AA) alteration in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene, reduces activity of cefotaxime, precise mechanisms conferring the non-susceptibility have been unclear. We analyzed the ftsI gene of two clinically isolated cefotaxime-non-susceptible H. influenzae strains, 16-11 and 20-07 (minimum inhibitory concentrations [MICs]: 16 and 8 μg/mL, respectively), and found that their deduced AA sequences of PBP3 included two AA substitutions of G555E and Y557H in addition to previously described AA alterations. To clarify whether the two additional substitutions are requisite for cefotaxime non-susceptibility, we produced transformants of Rd KW20 (cefotaxime MIC: ≤0.06 μg/mL) with the ftsI gene of 16-11. Cefotaxime MICs against transformants M1 and M2, of which deduced PBP3s were altered with that of 16-11 entirely and partially (only the N-terminal side up to the AA position 519), were 8 and 0.25 μg/mL, respectively. We also produced M2-555/7 through site-directed mutagenesis inducing additional substitutions of G555E and Y557H into the PBP3 of M2, against which cefotaxime MIC was 8 μg/mL. These findings show that the additional substitutions of G555E and Y557H in PBP3 with previously described alterations cause cefotaxime non-susceptibility. An additional substitution of either G555E or Y557H alone in altered PBP3 reduced cefotaxime activity but the elevation of MICs were within the category of susceptibility. To our knowledge, this is the first study clarifying a genetic factor in the PBP3 causing cefotaxime non-susceptibility among H. influenzae strains.

Increasing Incidence of Penicillin- and Cefotaxime-resistant Streptococcus pneumoniae Causing Meningitis in India: Time for Revision of Treatment Guidelines?

Purpose: Pneumococcal meningitis is a life-threatening infection, requiring prompt diagnosis and effective treatment. Penicillin resistance in pneumococcal infections is a concern. Here, we present the antibiotic susceptibility profile of pneumococcal meningeal isolates from January 2008 to August 2016 to elucidate treatment guidelines for pneumococcal meningitis. Materialsand Methods: Invasive pneumococcal isolates from all age groups, were included in this study. Minimum inhibitory concentrations for the isolates were identified by agar dilution technique and VITEK System 2. Serotyping of isolates was done by co-agglutination technique. Results: Out of 830 invasive pneumococcal isolates, 167 (20.1%) isolates were from meningeal infections. Cumulative penicillin resistance in pneumococcal meningitis was 43.7% and cefotaxime non-susceptibility was 14.9%. Penicillin resistance amongst meningeal isolates in those younger than 5 years, 5–16 years of age and those aged 16 years and older was 59.7%, 50% and 27.3%, respectively, with non-susceptibility to cefotaxime in the same age groups being 18%, 22.2% and 10.4%. Penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016. Serotypes 14, 19F, 6B, 6A, 23F, 9V and 5 were the most common serotypes causing meningitis, with the first five accounting for over 75% of resistant isolates. Conclusions: The present study reports increasing penicillin resistance and cefotaxime non-susceptibility to pneumococcal meningitis in our setting. This highlights the need for empiric therapy with third-generation cephalosporins and vancomycin for all patients with meningitis while awaiting results of culture and susceptibility testing.

Invasive Pneumococcal Disease (IPD), Antibiotic Use, and Patterns of Penicillin and Cefotaxime Non-susceptibility Following Routine Use of 13-Valent Conjugate Pneumococcal Infant Vaccination in the United States

Invasive Pneumococcal Disease (IPD), Antibiotic Use, and Patterns of Penicillin and Cefotaxime Non-susceptibility Following Routine Use of 13-Valent Conjugate Pneumococcal Infant Vaccination in the United States

Vaccine-Type Pneumococcal Disease (IPD) and Patterns of Penicillin and Cefotaxime Non-susceptibility Following Routine Use of 13-Valent Conjugate Pneumococcal Infant Vaccination in the United States

Vaccine-Type Pneumococcal Disease (IPD) and Patterns of Penicillin and Cefotaxime Non-susceptibility Following Routine Use of 13-Valent Conjugate Pneumococcal Infant Vaccination in the United States

Daten zur Antibiotikaresistenzlage in Deutschland

In 2007, the Robert Koch Institute established the infrastructure for the national Antimicrobial Resistance Surveillance (ARS) system. Laboratories submit data of routine susceptibility testing of clinical samples from hospitals as well as from outpatient care settings in a standardized format to the Robert Koch Institute for central processing. The database for the period 2008–2011 comprises data of about 1.3 million samples from patients in hospital care and almost 800,000 samples from outpatients. Based on SIR interpretations of susceptibility, the trends of methicillin resistance of Staphylococcus aureus (MRSA) and cefotaxime non-susceptibility as an indicator of extended-spectrum beta-lactamases (ESBL) of Escherichia coli and Klebsiella pneumoniae were analyzed for four care settings or categories: hospital care, outpatient care, intensive care units, and isolates from blood cultures. After constant high levels of above 20%, the proportion of MRSA isolates showed a decline for the first time from 2010 to 2011 in hospital care overall, in intensive care units as well as in blood cultures; in outpatient care, MRSA proportions of about 13% were observed. Within the observed period, non-susceptibility to cefotaxime as an indicator of ESBL in E. coli showed an increasing trend in hospital care at a level above 10% in intensive care units, while cefotaxime non-susceptibility in K. pneumoniae was more frequent but without any trend. In outpatient care, the proportions of cefotaxime non-susceptibility increased year by year in both species resulting in nearly a doubling to 6%.

Nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Alloiococcus otitidis in young children in the era of pneumococcal immunization, Taiwan

We applied a multiplex polymerase chain reaction (PCR) and culture to detect Streptococcus pneumoniae and detected 3 other respiratory pathogens--Haemophilus influenzae, Moraxella catarrhalis, and Alloiococcus otitidis--simultaneously by PCR, in the nasopharynx of 386 children aged under 5 y. S. pneumoniae was the most common pathogen carried by children in all age groups, with the rate ranging from 15.8% in children aged 3-4 y to 28.6% in children aged 2-3 y. H. influenzae and M. catarrhalis showed similar carriage rates across all the age groups. Only 2 young children (0.5%) carried A. otitidis. Higher carriage of S. pneumoniae was found in children who had not received the heptavalent pneumococcal conjugate vaccine (PCV7). Cefotaxime non-susceptibility was high (51.4%) in S. pneumoniae nasopharyngeal isolates. Serotype 6B was the most common in fully immunized carriers and also in those who received catch-up immunization. Due to low PCV7 coverage in Taiwan, the carriage of vaccine and non-vaccine serotypes of S. pneumoniae in children remains common.

Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children in Spain, 1990 to 2008

The genetic structure and antibiotic nonsusceptibility of all serotype 19A Streptococcus pneumoniae pediatric pneumococcal isolates received at the Spanish Pneumococcal Reference Laboratory (1990 to 2008) were analyzed. Of them, 410 (79.8%) isolates belonged to 14 sequence types (STs) with >10 isolates each, and 104 to 73 STs (with 21 new STs, ST5141 to ST5161, with one isolate each). Time trends in 2000 to 2008 (n=471) were explored by lineal regression. Serotype 19A increased from 5.7% in 2000 to 16.8% in 2008 (R2=0.872; P=0.001). Decreasing trends (P<0.03) were found for ST202 (R2=0.774) and ST81 (R2=0.559), and increasing trends (P<0.03) for ST878 (R2=0.544) and ST320 (R2=0.530), both belonging to the clonal complex (CC) Denmark(14)-32 and first detected in 2003 and 2007, respectively, and ST2013 (R2=0.704) and ST4461 (R2=0.707), both appearing in 2004. Penicillin nonsusceptibility was clustered in ST81, ST276, ST320, ST878, ST2013, and ST4461 (>90% nonsusceptibility), and amoxicillin and cefotaxime nonsusceptibility in ST320: 87% amoxicillin (MIC50/MIC90=8/8 μg/ml) and 43.5% cefotaxime (MIC50/MIC90=1/2 μg/ml) nonsusceptibility. No trends were found for erythromycin nonsusceptibility (ranging from 38.5% to 66.7%) and cefotaxime nonsusceptibility (ranging from 0.0% to 7.8%), but increasing trends (P<0.02) were found for oral penicillin (from 16.7% in 2000 to 56.3% in 2008; R2=0.628) and amoxicillin (from 0.0% before 2007 to 13.8% in 2008; R2=0.628) nonsusceptibility. This study warns about the emergence of serotype 19A STs associated with high-level antibiotic nonsusceptibility, with a role for ST320 and ST878 occupying the niche left by some pneumococcal 7-valent conjugate vaccine (PCV7)-related resistant STs. The rapid expansion of serotype 19A and STs related to antibiotic resistance indicates that vaccines covering serotype 19A present advantages in countering invasive disease.

Serotype Distribution and Susceptibility of Streptococcus pneumoniae Isolates from Pleural Fluid in Spain from 1997 to 2008

Trends in serotype incidence and susceptibility (1997 to 2008) of Spanish Streptococcus pneumoniae pleural isolates (n = 831) were explored. Penicillin (oral) nonsusceptibility rates and the incidence of 7-valent pneumococcal conjugate vaccine (PCV-7) serotypes showed decreasing trends (R(2) ≥ 0.600; P ≤ 0.002). The incidence of serotypes 1 and 19A showed increasing trends (R(2) ≥ 0.759; P < 0.001), with no trends for serotype 3. Serotypes 19A, 1, and 3 represented 85% of pediatric isolates in 2008. In serotype 19A, the penicillin nonsusceptibility rate was 82.4% in 2008, associated with amoxicillin and cefotaxime nonsusceptibility in 21.4% of isolates. Inclusion of these serotypes in new vaccines offers the broadest coverage.

Multicenter surveillance of antimicrobial resistance of major bacterial pathogens in intensive care units in 2000 in Taiwan.

A susceptibility surveillance study of 1,274 bacterial isolates recovered from various clinical specimens from patients in intensive care units (ICUs) of five major teaching hospitals was carried out from March, 2000, to June, 2000, in Taiwan. This study demonstrated a high rate (66%) of oxacillin resistance in Staphylococcus aureus (ORSA), a high rate of nonsusceptibility to penicillin (intermediate, 50% and highly resistant, 8%), and high rates of cefotaxime nonsusceptibility for S. pneumoniae (intermediate, 29% and resistant, 4%), Enterobacter cloacae (57%), Serratia marcescens (34%), and Citrobacter freundii (60%). High rate of ceftazidime nonsusceptibility for Pseudomonas aeruginosa (22%), and high rates of imipenem nonsusceptibility for P. aeruginosa (15%) and Acinetobacter baumannii (22%) were also found. The percentage (11.9%) of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli was greater than that (11.3%) for Klebsiella pneumoniae. Rates of quinupristin-dalfopristin nonsusceptibility for S. pneumoniae (42%), Enterococcus faecium (71%), and ORSA (39%) were high, but no vancomycin-resistant enterococci were found in this study. The resistance rates of some pathogen varied by institution or type of ICUs. Surveillance for antimicrobial resistance among bacterial pathogens in hospitals, particularly in ICU settings with a preexisting higher resistance burden, is mandatory in establishing and/or modifying guidelines for empirical treatment of severe infections in ICU patients caused by these antimicrobial-resistant pathogens.