Penicillin Susceptibility Research Articles

Penicillin susceptibility among Staphylococcus aureus skin and soft tissue infections at a children's hospital.

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children's Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ-negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤0.125 µg/mL were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). All PSSA underwent multilocus sequence typing. Medical records were reviewed. The median age of subjects was 4.2 years (IQR: 1.6-10.5). PSSA accounted for 9% of isolates during the study period. PSSA and PR-MSSA cases were similar with respect to age, demographics, and rates of prior antibiotic exposure. PSSA isolates less often had vancomycin MIC ≥1.5 µg/mL. Furthermore, 39% of PSSA were variants of sequence type 1. In multivariable analyses, penicillin susceptibility was independently associated with both hospital admission and surgical intervention. PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA SSTI is challenging. However, PSSA SSTI were independently associated with higher rates of hospital admission as well as the need for surgical intervention suggesting a significant clinical impact.IMPORTANCEThe vast majority of Staphylococcus aureus in the US are penicillin resistant with most clinical labs no longer reporting penicillin susceptibility for this organism. A number of centers, however, have reported increasing penicillin susceptibility among invasive S. aureus infections. Skin and soft tissue infections (SSTI) are far more common than invasive infections, yet the frequency and impact of penicillin-susceptible S. aureus (PSSA) in this population are uncertain. Through active surveillance at a children's hospital, we found that 9% of methicillin-susceptible S. aureus SSTI isolates were PSSA. PSSA were independently associated with hospital admission for the management of SSTI as well as the need for debridement in the operating room. Given that most SSTI are managed in the outpatient setting, these findings suggest a clinical impact of this phenotype and the need for a reassessment of the value in susceptibility testing and potentially even treatment with penicillin.

Endophthalmitis Caused by Bacillus cereus: Clinical Characteristics, Outcomes and Antibiotic Susceptibility.

Bacillus cereus endophthalmitis is a severe vision-threatening disease. This study aimed to analyze the clinical characteristics, antibiotic susceptibility, and risk factors for poor final visual acuity (VA) and enucleation or evisceration (ENEV) outcomes of B. cereus endophthalmitis patients. We retrospectively reviewed 52 cases (52 eyes) of culture-proven B. cereus endophthalmitis at Zhongshan Ophthalmic Center from January 2013 to December 2023. The mean age of the patients was 38.1 ± 20.1 years, and males composed the majority (90.4%) of the sample size; laborers (32.7%) and farmers (19.2%) were the primary occupations of the patients. All cases were caused by ocular trauma. Forty-one of 51 eyes (80.4%) had a final VA worse than the ability to count fingers (CFs), and 15 of the 52 total eyes (28.8%) underwent ENEV. Binary logistic forward (LR) regression analysis demonstrated that red eye (odds ratio [OR], 13.13; 95% confidence interval [CI], 1.58-108.80; p = 0.017), eye pain (OR, 22.87; 95% CI, 1.00-522.72; p = 0.050), and corneal edema/ulcer (OR, 13.13; 95% CI, 1.58-108.80; p = 0.017) were significant risk factors for poor VA outcomes. Conjunctival sac purulent discharge (OR, 10.08; 95% CI, 2.11-48.12, p = 0.004) and white blood cell (WBC) count (OR, 1.35; 95% CI, 1.06-1.72, p = 0.016) were significant risk factors for ENEV outcomes. B. cereus showed susceptibility rates of 100.0% to vancomycin and ofloxacin; 98.0% to levofloxacin; 93.3% to ciprofloxacin; 87.5% to imipenem; and 78.9% to tobramycin. The susceptibility to azithromycin and clindamycin was 66.7% and 50.0%, respectively. In contrast, B. cereus was resistant to penicillin (susceptibility at 3.8%), cefuroxime (5.6%), and cefoxitin (37.1%).

Genomic diversity and antimicrobial susceptibility of invasive Neisseria meningitidis in South Africa, 2016-2021.

Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016-2021. Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico. Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%) and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9 or penA14. IMD lineages circulating in South Africa were consistent with those circulating prior to 2008, however peni was higher than previously reported, and occurred in a variety of lineages.

High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland

BackgroundStreptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children. The CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/) collected nasopharyngeal swabs from children discharged from hospitals with clinically diagnosed CAP, and found no differences in pneumococci susceptibility between higher and lower antibiotic doses and shorter and longer durations of oral amoxicillin treatment. Here, we studied in-depth the genomic epidemiology of pneumococcal (vaccine) serotypes and their antibiotic resistance profiles.MethodsThree-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Genome heterogeneity analysis was performed using long-read sequenced isolates (PacBio, n = 10) and publicly available sequences.ResultsAmong 390 unique pneumococcal isolates, serotypes 15B/C, 11 A, 15 A and 23B1 were most prevalent (n = 145, 37.2%). PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%). STs associated with 19A and 19F demonstrated high genome variability, in contrast to serotype 3 (n = 13, 3.3%) that remained highly stable over a 20-year period. Non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low among the pneumococci analysed here and was independent of treatment dosage and duration. However, all 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible. This serotype was also identified in ST177, which is historically associated with the PCV13 serotype 19F and penicillin susceptibility, indicating a potential capsule-switch event.ConclusionsOur data suggest that amoxicillin use does not drive pneumococcal serotype prevalence among children in the UK, and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease CAP in this target population. Genotype 23B1 represents the convergence of a non-vaccine genotype with penicillin non-susceptibility and might provide a persistence strategy for ST types historically associated with vaccine serotypes. This highlights the need for continued genomic surveillance.

Characterization of invasive Group B Streptococcus isolates from Western Australian infants, 2004-2020.

Background. Invasive Group B Streptococcus (GBS; Streptococcus agalactiae) remains a leading cause of infant morbidity and mortality. Intrapartum antibiotic prophylaxis (IAP) has been implemented in many countries with a reduction in early-onset disease, but an effective vaccine may further reduce the disease burden. Candidate vaccines targeting capsular polysaccharides and surface proteins are now in clinical trials.Methods. Using whole-genome sequencing and phenotypic antimicrobial susceptibility testing, we characterized sterile-site GBS isolates recovered from Western Australian infants between 2004 and 2020. Characteristics were compared between three time periods: 2004-2008, 2009-2015 and 2016-2020.Results. A total of 135 isolates were identified. The proportion of serotype III (22.7 % in Period 1 to 47.9 % in Period 3, P=0.04) and clonal complex 17 (13.6-39.6 %, P=0.01) isolates increased over time. Overall coverage of vaccines currently being trialled was >95 %. No isolates were penicillin resistant (MIC>0.25 mg l-1), but 21.5 % of isolates had reduced penicillin susceptibility (MIC>0.12 mg l-1) and penicillin MIC increased significantly over time (P=0.04). Clindamycin resistance increased over time to 45.8 % in the latest period.Conclusions. Based on comprehensive characterization of invasive infant GBS in Western Australia, we found that coverage for leading capsular polysaccharide and surface protein vaccine candidates was high. The demonstrated changes in serotype and molecular type highlight the need for ongoing surveillance, particularly with regard to future GBS vaccination programmes. The reduced susceptibility to IAP agents over time should inform changes to antibiotic guidelines.

Clinical and microbiological profile of Viridans group streptococcal bacteraemia; experience from South India.

Viridans Group Streptococci (VGS) are a group of distinct species that can cause bacteraemia and other invasive infections. They are also among the common organisms causing infective endocarditis. Data on the epidemiology and clinical profile of VGS is limited, especially from India. We conducted an electronic medical record-based retrospective analysis of patients with VGS bacteraemia admitted to our hospital between January 2012 to December 2021. Blood cultures were incubated by BacT/ALERT system and bacterial identification and susceptibility testing were done by using the VITEK 2 microbial identification system. Susceptibility test reporting was as per Clinical and Laboratory Standards Institute (CLSI) guidelines. The incidence, clinical profile, source of bacteraemia, co-morbidities and antimicrobial resistance among VGS bacteraemia were analyzed. VGS were isolated in 219 patients, accounting for 3.2% of positive blood cultures during the period studied. The median age of the patients was 58 years and 69% were males. Diabetes mellitus was the most common co-morbidity (55%) followed by chronic kidney disease and chronic liver disease. Patients with haematological malignancy and neutropenia were few. Intra-abdominal infections were the most common source of infection and was noted in 26%. Infective endocarditis was diagnosed in only 10% of the cases. Streptococcus mitis was the most common species isolated followed by S. gallolyticus and S. sanguinis. 9.58% of the isolates could not be identified up to the species level. Overall penicillin susceptibility was 71% and ceftriaxone susceptibility was 92%, with individual species variation. In-hospital mortality was 19%. VGS are an important cause of bacteraemia and was associated with 19% mortality in our study. High rates of penicillin and ceftriaxone resistance are a reason of concern. Molecular diagnostics like matrix assisted laser desorption ionization-time of flight (MALDI-TOF) identification must be increasingly applied for species identification considering that a substantial number of isolates were not identified to species level.

Exploring Treatment Options for Methicillin-Resistant Staphylococcus Aureus through a Mixed Methods Approach

Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health concern, demanding multifaceted treatment strategies due to its complex nature. This study aimed to bridge the gap in understanding MRSA's clinical presentation, management, and outcomes by employing a mixed-methods approach. Through an extensive literature review and a singlecenter retrospective patient record review, the study offered insights into MRSA management, from diagnosis to treatment. The analysis included 44 patients, who presented to an outpatient dermatology practice. Results found a broad age range, revealing that 68.2% were treated with both topical and oral medications. Antibiotic susceptibility tests showed high resistance to Penicillin (84.1%) and high susceptibility to drugs like Linezolid (95.5%) and Moxifloxacin (97.7%). The literature review examined 22 relevant articles from the past decade. The study's findings emphasize the diversity of MRSA infections and the challenges in treatment, highlighting variations in antibiotic susceptibility and the urgent need for innovative approaches. It serves as a substantial contribution to the existing body of knowledge on MRSA and may inform future research and clinical practice.

184. Implications of Enterococcus faecalis penicillin susceptibility in patients with bacteremia

Abstract Background Enterococcus faecalis isolates with an elevated penicillin minimum inhibitory concentration (MIC) ≥ 4 mg/L have decreased in vitro ampicillin plus ceftriaxone bactericidal and synergistic activity, despite ampicillin susceptibility. This phenotype’s implication on patient outcomes and prevalence in the US is unknown due to limited penicillin susceptibility reporting. Methods This was a retrospective cohort study of adult patients with E. faecalis bacteremia between August 20, 2018 and May 13, 2021 from the Mount Sinai Health System in New York City. Patients were excluded if they were discharged or deceased within 48 hours of index blood culture, did not receive active definitive therapy, or the blood culture was determined to be contamination. The primary outcome was differences in 30-day and 90-day mortality based on the penicillin MIC and the secondary outcome was microbiological relapse. Multivariable logistic regression was used to identify risk factors for 90-day mortality. Corresponding blood isolates were tested for penicillin susceptibility by broth microdilution in accordance with CLSI. Results A total of 124 patients were included, with 27% having an elevated penicillin MIC ≥ 4 mg/L. Differences in baseline characteristics (Table 1) as well as source of infection and treatments received (Table 2) were similar between groups. Endocarditis infected 18.5% of patients and was less common in cases with an elevated penicillin MIC. Thirty-day and 90-day mortality, and microbiological relapse were higher in cases with an elevated penicillin MIC (14.4% vs. 20.6%, p=0.58; 20% vs. 26.5%, p=0.59; and 4.4% vs. 8.8%, p=0.39, respectively). Pitt bacteremia score and prior ceftriaxone usage had a higher odds of 90-day mortality (OR 1.2 [95% CI 1.03-1.4], p=0.02; OR 2.8 [95% CI 1.02-7.9], p=0.04, respectively), whereas definitive treatment with an aminopenicillin compared to piperacillin/tazobactam was protective of 90-day mortality (OR 0.21 [95% CI 0.05-0.93], p=0.04). Conclusion E. faecalis with an elevated penicillin MIC ≥ 4 mg/L is present in over a quarter of patients across New York City. Larger studies are warranted to determine the impact on patient outcomes. E. faecalis bacteremia treatment with piperacillin/tazobactam may be associated higher mortality. Disclosures Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant

A Multicenter Evaluation of Overall Susceptibility and Antimicrobial Resistance Among Streptococcus pneumoniae Isolates.

S. pneumoniae ranks as the fourth-most lethal pathogen globally in terms of fatalities associated with or attributable to resistance. In this study, the Antimicrobial Testing Leadership and Surveillance (ATLAS) analysis from India aims to study the overall antimicrobial susceptibility (AMS) among pneumococcal isolates collected between 2018 and 2021. Non-duplicate clinically significant S. pneumoniae isolates were collected between 2018 and 2021. In vitro activity of antibiotics was assessed against S. pneumoniae. Susceptibility was confirmed at an International Health Management Associates (IHMA) laboratory using supplied broth microdilution panels (Omron Microscan Systems, Inc., Omron Corp., Kyoto, Japan), according to the Clinical and Laboratory Standards Institute (CLSI) guidelines for all antibiotics. Of the total 86 non-duplicate isolates of Streptococcus pneumoniae collected from the tertiary care centers, the proportion of isolates increased from 8.14% (n=7) in 2018 to 43.02% (n=37) in 2020. Most isolates (n = 18; 48.65%) were collected from the age group of 31-60 years in the year 2020. Erythromycin revealed a decrease in susceptibility from the year 2018 (71.43%) to 2020 (16.22%). A decreased susceptibility of 90% was recorded for levofloxacin in the year 2021. Meropenem revealed a decrease in susceptibility from the year 2018 (85.71%) to 2020 (35.14%). Penicillin susceptibility decreased from 37.5% in 2019 to 27.03% in the year 2020. Clindamycin indicated a 100% susceptibility in the year 2018 which then decreased to 71.88% in 2019 and 56.76% in 2020. Linezolid and vancomycin were found to have uniform susceptibility of 100% throughout the years from 2018 to 2021. An increase in resistance to penicillin and macrolides among S. pneumoniae isolates was observed in the Indian population. Addressing the elevating rates of S. pneumoniae resistance may require pneumococcal conjugate vaccines (PCVs) with expanded serotype coverage and targeted antimicrobial stewardship efforts.

Antibiotic resistance, biofilm formation, and virulence genes of Streptococcus agalactiae serotypes of Indian origin

BackgroundGroup B Streptococcus (GBS) is a causative agent of various infections in newborns, immunocompromised (especially diabetic) non-pregnant adults, and pregnant women. Antibiotic resistance profiling can provide insights into the use of antibiotic prophylaxis against potential GBS infections. Virulence factors are responsible for host–bacteria interactions, pathogenesis, and biofilm development strategies. The aim of this study was to determine the biofilm formation capacity, presence of virulence genes, and antibiotic susceptibility patterns of clinical GBS isolates.ResultsThe resistance rate was highest for penicillin (27%; n = 8 strains) among all the tested antibiotics, which indicates the emergence of penicillin resistance among GBS strains. The susceptibility rate was highest for ofloxacin (93%; n = 28), followed by azithromycin (90%; n = 27). Most GBS strains (70%; n = 21) were strong biofilm producers and the rest (30%; n = 9) were moderate biofilm producers. The most common virulence genes were cylE (97%), pavA (97%), cfb (93%), and lmb (90%). There was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility, according to Spearman’s rank correlation analysis.ConclusionAbout a third of GBS strains exhibited penicillin resistance and there was a negative association between having a strong biofilm formation phenotype and penicillin susceptibility. Further, both the strong and moderate biofilm producers carried most of the virulence genes tested for, and the strong biofilm formation phenotype was not associated with the presence of any virulence genes.

Penicillin-Susceptible Streptococcus pneumoniae Meningitis in Adults: Does the Ceftriaxone Dosing Matter?

The recommended empiric ceftriaxone dosing regimen for acute bacterial meningitis in adults is 2 g every 12 h. After penicillin-susceptible Streptococcus pneumoniae is isolated as a causative microorganism, the ceftriaxone dose may be continued or reduced to a single dose of 2 g every 24 h, per institutional preference. There is no clear guidance that indicates the superiority of one regimen over the other. The objective of this study was to evaluate the susceptibility of S. pneumoniae in the cerebral spinal fluid (CSF) of patients with meningitis and the relationship between ceftriaxone dose and clinical outcomes. We identified 52 patients with S. pneumoniae meningitis with positive CSF cultures who were treated at the University Hospital, Bern, Switzerland, over a 19-year period. We collected clinical and microbiological data for evaluation. Broth microdilution and Etest methods were performed to test penicillin and ceftriaxone susceptibility. All isolates were susceptible to ceftriaxone. Ceftriaxone was empirically used in 50 patients, with a starting dosing regimen of 2 g every 24 h in 15 patients and 2 g every 12 h in 35 patients. In 32 patients started on a twice-daily regimen (91%), doses were reduced to once daily after a median of 1.5 (95% CI 1-2) days. The overall in-hospital mortality was 15.4% (n = 8), and 45.7% of patients reported at least one sequela of meningitis at the last follow-up (median 375, 95% CI 189-1585 days). We found no statistical difference in outcome between the 2 g every 24 h and the 2 g every 12 h ceftriaxone dosing regimens. A ceftriaxone total daily dose of 2 g may be associated with similar outcomes to a 4 g total daily dose, provided that the causative organism is highly susceptible to ceftriaxone. The persistence of neurological and infection sequelae at the last follow-up underscores the need for optimal treatment of these complex infections.

A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus.

There is clinical uncertainty over the optimal treatment for penicillin-susceptible Staphylococcus aureus (PSSA) infections. Furthermore, there is concern that phenotypic penicillin susceptibility testing methods are not reliably able to detect some blaZ-positive S. aureus. Nine S. aureus isolates, including six genetically diverse strains harbouring blaZ, were sent in triplicate to 34 participating laboratories from Australia (n = 14), New Zealand (n = 6), Canada (n = 12), Singapore (n = 1) and Israel (n = 1). We used blaZ PCR as the gold standard to assess susceptibility testing performance of CLSI (P10 disc) and EUCAST (P1 disc) methods. Very major errors (VMEs), major error (MEs) and categorical agreement were calculated. Twenty-two laboratories reported 593 results according to CLSI methodology (P10 disc). Nineteen laboratories reported 513 results according to the EUCAST (P1 disc) method. For CLSI laboratories, the categorical agreement and calculated VME and ME rates were 85% (508/593), 21% (84/396) and 1.5% (3/198), respectively. For EUCAST laboratories, the categorical agreement and calculated VME and ME rates were 93% (475/513), 11% (84/396) and 1% (3/198), respectively. Seven laboratories reported results for both methods, with VME rates of 24% for CLSI and 12% for EUCAST. The EUCAST method with a P1 disc resulted in a lower VME rate compared with the CLSI methods with a P10 disc. These results should be considered in the context that among collections of PSSA isolates, as determined by automated MIC testing, less than 10% harbour blaZ. Furthermore, the clinical relevance of phenotypically susceptible, but blaZ-positive S. aureus, remains unclear.

Rapid and simultaneous detection of viable S. aureus and its penicillin susceptibility by phage amplification techniques in different food matrices

Staphylococcus aureus, a zoonotic pathogen causes diseases in humans and animals, establishing a robust analytical method is crucial to minimize its adverse impacts. Phage amplification assay (PAA) is a method for indirect detection of target bacteria by detecting the progeny phage. In this study, we proposed a phage amplification assay based on Twortvirinae phage LSA2311 with a broad host range to indirectly detect S. aureus and penicillin-resistant S. aureus. PAA-based on the plaque counting could quantitatively detect viable S. aureus by forming progeny phage plaques on the culture medium within 6.5 h, with the detection limit of 10 CFU/mL. Progeny phages produced by PAA could be quantified by qPCR for the detection of viable S. aureus while reducing the detection time by 3 h (detection limit of 10 CFU/mL), and simple DNA extraction (thermolysis) process. It can be successfully applied to quantify viable S. aureus in spiked milk and lettuce. Moreover, this assay could rapidly detect its penicillin susceptibility within 13 h, and the results were in line with the standard paper disc diffusion method (DDM). These phage amplification techniques enable the rapid and accurate detection of viable S. aureus in food matrices, as well as drug-resistant S. aureus.

Penicillin-Binding Proteins and Alternative Dual-Beta-Lactam Combinations for Serious Enterococcus faecalis Infections with Elevated Penicillin MICs.

Ampicillin-ceftriaxone has become a first-line therapy for Enterococcus faecalis endocarditis. We characterized the penicillin-binding protein (PBP) profiles of various E. faecalis strains and tested for synergy to better inform beta-lactam options for the treatment of E. faecalis infections. We assessed the affinity of PBP2B from elevated-MIC strain E. faecalis LS4828 compared to type strain JH2-2 using the fluorescent beta-lactam Bocillin FL. We also characterized pbp4 and pbpA structures and PBP4 and PBP2B expression and used deletion and complementation studies to assess the impact of PBP2B on the levels of resistance. We tested penicillin-susceptible and -resistant E. faecalis isolates against ceftriaxone or ceftaroline combinations with other beta-lactams in 24-h time-kill studies. Two penicillin-susceptible strains (JH2-2 and L2052) had identical pbp sequences and similar PBP expression levels. One reduced-penicillin-susceptibility strain (L2068) had pbp sequences identical to those of the susceptible strains but expressed more PBP4. The second decreased-penicillin-susceptibility strain (LS4828) had amino acid substitutions in both PBP4 and PBP2B and expressed increased quantities of both proteins. PBP2B did not appear to contribute significantly to the elevated beta-lactam MICs. No synergy was demonstrable against the strains with both mutated PBPs and increased expression (L2068 and LS4828). Meropenem plus ceftriaxone or ertapenem plus ceftriaxone demonstrated the most consistent synergistic activity. PBP2B of strain LS4828 does not contribute significantly to reduced penicillin susceptibility. Neither the MIC nor the level of PBP expression correlated directly with the identified synergistic combinations when tested at static subinhibitory concentrations.

Amoxicillin and penicillin G dosing in pediatric community-acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines.

Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data. Using NONMEM v7.3, Monte Carlo simulations (N=10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval. In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens. Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.

National Surveillance of Tetracycline, Erythromycin, and Clindamycin Resistance in Invasive Streptococcus pyogenes: A Retrospective Study of the Situation in Spain, 2007-2020.

This work reports on antimicrobial resistance data for invasive Streptococcus pyogenes in Spain, collected by the 'Surveillance Program for Invasive Group A Streptococcus', in 2007-2020. emm typing was determined by sequencing. Susceptibility to penicillin, tetracycline, erythromycin, and clindamycin was determined via the E-test. tetM, tetO, msrD, mefA, ermB, ermTR, and ermT were sought by PCR. Macrolide-resistant phenotypes (M, cMLSB, and iMLSB) were detected using the erythromycin-clindamycin double-disk test. Resistant clones were identified via their emm type, multilocus sequence type (ST), resistance genotype, and macrolide resistance phenotype. Penicillin susceptibility was universal. Tetracycline resistance was recorded for 237/1983 isolates (12.0%) (152 carried only tetM, 48 carried only tetO, and 33 carried both). Erythromycin resistance was detected in 172/1983 isolates (8.7%); ermB was present in 83, mefA in 58, msrD in 51, ermTR in 46, and ermT in 36. Clindamycin resistance (methylase-mediated) was present in 78/1983 isolates (3.9%). Eight main resistant clones were identified: two that were tetracycline-resistant only (emm22/ST46/tetM and emm77/ST63/tetO), three that were erythromycin-resistant only (emm4/ST39/mefA-msrD/M, emm12/ST36/mefA-msrD/M, and emm28/ST52/ermB/cMLSB), and three that were tetracycline-erythromycin co-resistant (emm11/ST403/tetM-ermB/cMLSB, emm77/ST63/tetO-ermTR/iMLSB, and emm77/ST63/tetM-tetO-ermTR/iMLSB). Tetracycline, erythromycin, and clindamycin resistance rates declined between 2007 and 2020. Temporal variations in the proportion of resistant clones determined the change in resistance rates.

Going Back in Time: Increasing Penicillin Susceptibility among Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children.

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children's and St. Louis Children's Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 μg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.

Changing Epidemiology of Pathogenic Bacteria Over the Past 20 Years in Korea.

The epidemiology of pathogenic bacteria varies according to the socioeconomic status and antimicrobial resistance status. However, longitudinal epidemiological studies to evaluate the changes in species distribution and antimicrobial susceptibility of pathogenic bacteria nationwide are lacking. We retrospectively investigated the nationwide trends in species distribution and antimicrobial susceptibility of pathogenic bacteria over the last 20 years in Korea. From 1997 to 2016, annual cumulative antimicrobial susceptibility and species distribution data were collected from 12 university hospitals in five provinces and four metropolitan cities in South Korea. The prevalence of Staphylococcus aureus was the highest (13.1%) until 2012 but decreased to 10.3% in 2016, consistent with the decrease in oxacillin resistance from 76.1% in 2008 to 62.5% in 2016. While the cefotaxime resistance of Escherichia coli increased from 9.0% in 1997 to 34.2% in 2016, E. coli became the most common species since 2013, accounting for 14.5% of all isolates in 2016. Pseudomonas aeruginosa and Acinetobacter baumannii rose to third and fifth places in 2008 and 2010, respectively, while imipenem resistance increased from 13.9% to 30.8% and 0.7% to 73.5% during the study period, respectively. Streptococcus agalactiae became the most common pathogenic streptococcal species in 2016, as the prevalence of Streptococcus pneumoniae decreased since 2010. During the same period, pneumococcal penicillin susceptibility decreased to 79.0%, and levofloxacin susceptibility of S. agalactiae decreased to 77.1% in 2016. The epidemiology of pathogenic bacteria has changed significantly over the past 20 years according to trends in antimicrobial resistance in Korea. Efforts to confine antimicrobial resistance would change the epidemiology of pathogenic bacteria and, consequently, the diagnosis and treatment of infectious diseases.

Serotype distribution of Streptococcus pneumoniae and pneumococcal vaccine coverage in adults in Turkey between 2015 and 2018

Objective To evaluate the serotype distribution and antibiotic resistance in pneumococcal infections in adults and to provide a perspective regarding serotype coverage of both current and future pneumococcal vaccines. Patients and methods This passive surveillance study was conducted with the Streptococcus pneumoniae strains isolated from the specimens of patients with pneumonia (materials isolated from bronchoalveolar lavage), bacteraemia, meningitis, pleuritis and peritonitis between 2015 and 2018. Serogrouping and serotyping were performed by latex particle agglutination and by conventional Quellung reaction using commercial type-specific antisera, respectively. The strains were analysed for penicillin, cefotaxime, erythromycin and moxifloxacin susceptibilities by E-test. Results In the whole study group (410 samples from adults aged ≥18 years), the most frequent serotypes were 3 (14.1%), 19 F (12%) and 1 (9.3%). The vaccine coverage for PCV13, PCV15, PCV20 and PPV23 was 63.9%, 66.6%, 74.1% and 75.9%, respectively, in all isolates. Penicillin non-susceptibility in invasive pneumococcal disease (IPD) was 70.8% and 57.1% in the patients aged <65 and ≥65 years, respectively. About 21.1% and 4.3% of the patients with and without IPD had cefotaxime resistance. Non-susceptibility to erythromycin and moxifloxacin was 38.2% and 1.2%, respectively. Conclusions The results revealed that novel PCV vaccines may provide improved coverage as compared with the currently available vaccine, PCV13. The significant antibiotic resistance rates imply the need to extend the serotype coverage of the vaccines. Continuing the surveillance in pneumococcal diseases is critical to explore the serotype distribution and incidence changes of IPD cases in the population and to inform policy makers to make necessary improvements in the national immunization programmes. Key messages This multicentre study demonstrated the most recent serotype distribution and antibiotic resistance in adult population in Turkey. Shifting from PCV13 to novel conjugated vaccines will significantly increase the coverage. Continuing the surveillance in pneumococcal diseases is critical to explore the serotype distribution changes and the incidence of cases with invasive pneumococcal disease in the population.

1324. Penicillin-Susceptibility among Staphylococcus aureus Skin-and-Soft-Tissue Infections at a Children’s Hospital

Abstract Background Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. By the 1960s, these strains became the dominant staphylococci in clinical practice. However, a number of centers have recently described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). In our center we have recently observed the emergence of PSSA in osteoarticular infections. Little data are available regarding the prevalence or impact of PSSA in pediatric skin-and-soft-tissue infections (SSTI). Methods MSSA SSTI isolates were obtained through an ongoing surveillance study at Texas Children’s (TCH) from 1/2017-12/2021. Twenty community-acquired MSSA SSTI isolates were chosen at random from every six-month interval during the study period, for a total of 200 isolates to be screened. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤ 0.125 μg/ml were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). Results During the study period 1701 MSSA SSTI isolates were collected with 200 examined for penicillin susceptibility. The overall median age of subjects was 4.1 years (IQR: 1.6-10.4). PSSA accounted for 9% of isolates during the study period; the annual frequency of PSSA varied from 5-17.5%. PSSA and PR-MSSA cases were similar with respect to age, demographics, anatomic site of infection and rates of prior antibiotic exposure. Subjects with SSTI secondary to PSSA more often had a prior history of SSTI, a diagnosis of abscess and were more often admitted to the hospital (Figure). Among PSSA, 94.4% belonged to agrI and 33.3% were PVL positive. Penicillin-Susceptible S. aureus (PSSA) vs. Penicillin-Resistant Methicillin-Susceptible S. aureus (PR-MSSA) Pediatric SSTI Isolates Comparison of the clinical features of PSSA and PR-MSSA SSTI isolates. PSSA were significantly associated with the diagnosis of abscess as well as hospital admission. Conclusion PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA is challenging. However, PSSA SSTI were associated with a greater rate of abscess formation and hospital admission, suggesting a high clinical impact of these infections. Further studies are needed to understand the optimal management of these infections. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Kristina G. Hulten, PhD, Me-med: Grant/Research Support|Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.