Antibiotic Monotherapy Research Articles

P-1544. Outcomes of Multi-Drug Resistant Acinetobacter Baumannii (MDR-AB) Management in a Tertiary Care Hospital in Saudi Arabia: Retrospective Observational Study

Abstract Background Nosocomial infections caused by multi-drug resistant Acinetobacter baumannii (MDR-AB) are widespread and have been linked to numerous infections, resulting in high rates of morbidity and mortality globally. It has a mortality rate of 17.5%, a resistance rate of 74% to carbapenems, and has been found primarily in immunocompromised patients in Saudi Arabia. There is a lack of a defined treatment standard of care with a limited number of alternatives. To gain additional insight into managing MDR-AB, this study aimed to evaluate the clinical efficacy of various antibiotic regimens and compare the outcomes of monotherapy with those of antibiotic combinations Methods A five-years (2018 to 2023) retrospective observational study was conducted at a tertiary care hospital in Saudi Arabia. All patients with positive Acinetobacter baumannii culture were screened. Adult patients ( ≥ 18 years ) with MDR-AB isolated and had received a minimum of 72 hours of antibiotic treatment were included. The primary end point was clinical improvement. Adverse drug events and the 30-day overall mortality rate were evaluated as secondary end points Results One hundred patients met the study inclusion criteria. Of those, 45% were oncology or transplant patients and 80% were admitted to the intensive care unit. MDR-AB was associated with several infectious syndromes, including 44% pneumonia, 42% bacteremia, and 13% urinary tract infections. 30% of patients were given meropenem as an empiric treatment, with varying dosage regimens; 26% were given piperacillin/tazobactam. Based on culture sensitivity, 68% of the patients were treated with tigecycline, while 28% were retained on meropenem, despite the fact that 98% of the isolates were carbapenem-resistant. Antibiotic monotherapy has been given only to 39% of patients. Clinical improvement was reported in 66% of the patients with 80% achieved complete improvement. The 30-day mortality rate was 50%. Adverse drug events were rare, with only 3% GI symptoms Conclusion MDR-AB in our patients is mainly causing two infectious syndromes in 86%. A combination of antibiotics was used in 61%. High clinical improvement with a simultaneous high 30-day mortality rate highlighted the need for standardized guidelines for the management of MDR-AB infections Disclosures All Authors: No reported disclosures

P-935. Treatment and outcome characteristics in patients with Staphylococcus aureus Infective Endocarditis: A prospective observational study

Abstract Background Infective endocarditis (IE) is one of the most serious complication of Staphylococcus aureus bacteremia (SAB) and its incidence is on rise ranging from 10% to 46%.1 When present, it is linked to poor prognosis, with in-hospital mortality ranging from 20% to 30% highlighting to some extent the challenge in clinically diagnosing and treating the disease. 2There is lack of data focusing on the management of such cases in developing countries like India. The present observational study was carried out to determine the treatment and outcome characteristics in patients with IE due to SAB. Methods This was a prospective observational study carried in Division of Infectious diseases, Department of General Medicine, All India Institute of Medical Sciences, Jodhpur between January 2023 to October 2023. All consecutive cases diagnosed in-hospital with SAB related IE using modified Duke’s criteria were enrolled in the study. The demographic and clinical details of each patient, the diagnostic evaluation, treatment given and outcomes were recorded. All these patients were followed at 1 month, 3 and 6 months after discharge. Results A total of eight cases of SAB related definite IE were included. The most common presenting symptom was fever, present in all cases. Peripheral signs of IE were observed in only three cases having splinter haemorrhages, Osler’s nodes, and Roth spots. IV drug use, congenital heart disease and hemodialysis dependency were found to be risk factors. All the eight patients received only medical management with 5 of them receiving antibiotic monotherapy and 3 of them receiving combination therapy. The reason for combination therapy was persistent bacteremia, lack of fever defervescence. The duration of therapy varied between 6-8 weeks. Five cases underwent repeat follow – up TEE/TTE revealing no vegetation in 4 cases and reduction of vegetation size in one case. There was no in-hospital mortality seen. At 6 months of follow-up one patient expired which was not attributable to SAB IE. Table 1 summarises the clinical, diagnostic and treatment characteristics of cases. Figure 1 depicts detailed management of SAB related IE cases Conclusion This study underscores multifaceted nature of this disease and the use of systematic approach for its management can improve the patient outcomes. Disclosures All Authors: No reported disclosures

Advantages and Challenges of Using Antimicrobial Peptides in Synergism with Antibiotics for Treating Multidrug-Resistant Bacteria.

Multidrug-resistant bacteria (MDR) have become a global threat, impairing positive outcomes in many cases of infectious diseases. Treating bacterial infections with antibiotic monotherapy has become a huge challenge in modern medicine. Although conventional antibiotics can be efficient against many bacteria, there is still a need to develop antimicrobial agents that act against MDR bacteria. Bioactive peptides, particularly effective against specific types of bacteria, are recognized for their selective and effective action against microorganisms and, at the same time, are relatively safe and well tolerated. Therefore, a growing number of works have proposed the use of antimicrobial peptides (AMPs) in synergism with commercial antibiotics as an alternative therapeutic strategy. This review provides an overview of the critical parameters for using AMPs in synergism with antibiotics as well as addressing the strengths and weaknesses of this combination therapy using in vitro and in vivo models of infection. We also cover the challenges and perspectives of using this approach for clinical practice and the advantages of applying artificial intelligence strategies to predict the most promising combination therapies between AMPs and antibiotics.

What is the most effective antibiotic monotherapy for severe Pseudomonas aeruginosa infection? A systematic review and meta-analysis of randomized controlled trials.

Severe infections caused by Pseudomonas aeruginosa are associated with significant morbidity and mortality, particularly in hospitalized and immunocompromised patients. Determining the optimal definitive monotherapy for these infections is critical. The main objective was to compile the evidence of subgroups of patients with Pseudomonas aeruginosa infection from randomized control trials (RCTs) evaluating different definite antipseudomonal monotherapies for severe P.aeruginosa infection. Systematic review and meta-analysis of RCTs that assessed monotherapy with an antipseudomonal drug versus another antipseudomonal for definite treatment, and reported on the subgroup of patients with P.aeruginosa infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS and the reference lists of included trials. Eligibility criteria included RCTs enrolling hospitalized adults (≥18 years) with microbiologically confirmed severe P. aeruginosa infections. Studies were excluded if they included >20% of patients receiving combination therapy or if patients had resistant P. aeruginosa strains at recruitment. Antipseudomonal drugs evaluated included cephalosporins, carbapenems, penicillins, quinolones and aztreonam. The primary outcome was 30-day mortality. Risk of bias was assessed using the Cochrane tool. Results were pooled using fixed-effects and random-effects models as appropriate. Relative risk (RR) and 95% CIs were calculated. Sensitivity analyses and subgroup analyses were performed when data were available. A total of 76 RCTs and 1681 patients with pseudomonal infection were included. Due to the low number of studies which reported our outcomes of interest, all subgroup analyses were underpowered. No difference in all-cause mortality was found for any direct antibiotic comparison. Higher clinical failure rates of carbapenems versus piperacillin-tazobactam were observed for pneumonia in two RCTs (RR, 2.55; 95% CI, 1.29-5.03; I2=0%, n=2), and higher microbiological failure rates with carbapenems versus other comparators (RR, 1.24; 95% CI, 1.02-1.51; I2=0%, n=23). Patients treated with imipenem were more likely to develop resistance to the study drug versus comparators (RR, 2.33; 95% CI, 1.61-3.38; I2=0%, n=7). In this systematic review and meta-analysis of definite antipseudomonal monotherapy for P.aeruginosa infection, we found no evidence of clinical benefit differences among direct antibiotic comparisons, but all subgroup analyses were underpowered to detect significant differences.

Bioinspired gelated cell sheet-supported lactobacillus biofilm for aerobic vaginitis diagnosis and treatment.

Aerobic vaginitis (AV) is a long-standing inflammatory disease that affects female patients. The use of antibiotics is a common means for AV treatment, but it will indiscriminately kill both pathogenic bacteria and beneficial strains, which easily causes vaginal dysbacteriosis and infection recurrence. Herein, we describe a bioinspired strategy for fabricating gelated cell sheet-supported lactobacillus biofilms (GCS-LBs) for AV treatment. Compared with common planktonic probiotic formulations, probiotic biofilms forming on a robust GCS exhibit enhanced stress tolerance and better colonization capacity in the mouse vagina. Moreover, DNA nanodevices are decorated on the GCS and dynamically report the microenvironment change of biofilms for timely evaluating bacterium activity, both in vitro and in vivo. Consequently, GCS-LBs are used for treating AV in an Escherichia coli-infected mouse model, which shows enhanced therapeutic efficacy compared with conventional antibiotic or lactobacillus monotherapy. Overall, the GCS-LB shows promise as a potent multifunctional tool to combat bacterial infection.

Which trial do we need? A randomized controlled trial comparing oral antibiotic monotherapy versus standard of care as antibiotic continuation treatment for the treatment of left-sided native valve bacterial endocarditis

Which trial do we need? A randomized controlled trial comparing oral antibiotic monotherapy versus standard of care as antibiotic continuation treatment for the treatment of left-sided native valve bacterial endocarditis

Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis.

The gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung axis and the interaction between the gut and the lung, which is related to the prognosis of critically ill patients; however, most of these studies focused on chronic lung diseases and influenza virus infections. The purpose of this study was to investigate the effect of faecal microbiota transplantation (FMT) on Klebsiella pneumoniae-related pulmonary infection via the gut-lung axis and to compare the effects of FMT with those of traditional antibiotics to identify new therapeutic strategies. We divided the mice into six groups: the blank control (PBS), pneumonia-derived sepsis (KP), pneumonia-derived sepsis + antibiotic (KP + PIP), pneumonia-derived sepsis + faecal microbiota transplantation(KP + FMT), antibiotic treatment control (KP+PIP+PBS), and pneumonia-derived sepsis+ antibiotic + faecal microbiota transplantation (KP + PIP + FMT) groups to compare the survival of mice, lung injury, inflammation response, airway barrier function and the intestinal flora, metabolites and drug resistance genes in each group. Alterations in specific intestinal flora can occur in the gut of patients with pneumonia-derived sepsis caused by Klebsiella pneumoniae. Compared with those in the faecal microbiota transplantation group, the antibiotic treatment group had lower levels of proinflammatory factors and higher levels of anti-inflammatory factors but less amelioration of lung pathology and improvement of airway epithelial barrier function. Additionally, the increase in opportunistic pathogens and drug resistance-related genes in the gut of mice was accompanied by decreased production of favourable fatty acids such as acetic acid, propionic acid, butyric acid, decanoic acid, and secondary bile acids such as chenodeoxycholic acid 3-sulfate, isodeoxycholic acid, taurodeoxycholic acid, and 3-dehydrocholic acid; the levels of these metabolites were restored by faecal microbiota transplantation. Faecal microbiota transplantation after antibiotic treatment can gradually ameliorate gut microbiota disorder caused by antibiotic treatment and reduce the number of drug resistance genes induced by antibiotics. In contrast to direct antibiotic treatment, faecal microbiota transplantation improves the prognosis of mice with pneumonia-derived sepsis caused by Klebsiella pneumoniae by improving the structure of the intestinal flora and increasing the level of beneficial metabolites, fatty acids and secondary bile acids, thereby reducing systemic inflammation, repairing the barrier function of alveolar epithelial cells, and alleviating pathological damage to the lungs. The combination of antibiotics with faecal microbiota transplantation significantly alleviates intestinal microbiota disorder, reduces the selection for drug resistance genes caused by antibiotics, and mitigates lung lesions; these effects are superior to those following antibiotic monotherapy.

Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance.

Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin (AMX) improves the treatment of primary pneumonia or superinfection caused by AMX-sensitive or AMX-resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and antibiotic-resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. A mathematical model was developed that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.

Selective bacteriophages reduce the emergence of resistant bacteria in bacteriophage-antibiotic combination therapy.

Escherichia coli O157:H7 is a globally important foodborne pathogen with implications for food safety. Antibiotic treatment for O157 may potentially contribute to the exacerbation of hemolytic uremic syndrome, and the increasing prevalence of antibiotic-resistant strains necessitates the development of new treatment strategies. In this study, the bactericidal effects and resistance development of antibiotic and bacteriophage monotherapy were compared with those of combination therapy against O157. Experiments involving continuous exposure of O157 to phages and antibiotics, along with genetic deletion studies, revealed that the deletion of glpT and uhpT significantly increased resistance to fosfomycin. Furthermore, we found that OmpC functions as a receptor for the PP01 phage, which infects O157, and FhuA functions as a receptor for the newly isolated SP15 phage, targeting O157. In the glpT and uhpT deletion mutants, additional deletion in ompC, the receptor for the PP01 phage, increased resistance to fosfomycin. These findings suggest that specific phages may contribute to antibiotic resistance by selecting the emergence of gene mutations responsible for both phage and antibiotic resistance. While combination therapy with phages and antibiotics holds promise for the treatment of bacterial infections, careful consideration of phage selection is necessary.IMPORTANCEThe combination treatment of fosfomycin and bacteriophages against Escherichia coli O157 demonstrated superior bactericidal efficacy compared to monotherapy, effectively suppressing the emergence of resistance. However, mutations selected by phage PP01 led to enhanced resistance not only to the phage but also to fosfomycin. These findings underscore the importance of exercising caution in selecting phages for combination therapy, as resistance selected by specific phages may increase the risk of developing antibiotic resistance.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis

Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. ClinicalTrials.gov Identifier: NCT03236961.

Hidradenitis suppurativa in children and young adults: a retrospective cross-sectional observational study in the United Kingdom.

Hidradenitis suppurativa (HS) in children and young adults (CYA) (<18 years) is uncommon. No previous observational studies have been carried out in a UK CYA HS population. This study was based on retrospective case note reviews of CYA HS patients attending tertiary-level care in the CYA HS service in a UK hospital. Patients <18 years old with a known diagnosis of HS were screened for inclusion. Exclusion criteria were those with less than one follow-up appointment. Twenty-eight CYA HS patients were identified, with an M:F ratio of 1:8.3. Mean BMI was 25.2 (SD: 7.6). 17 (61%) of cases had a relevant family history. Long-term antibiotic monotherapy was the most common treatment initiated. Lymecycline was the most commonly prescribed antibiotic, accounting for 23 (56%) of the 41 courses prescribed. Additional treatments initiated included dual therapy with rifampicin and clindamycin, isotretinoin, and adalimumab, which were more commonly prescribed in patients with Hurley Stage II or III. This group had a female predominance with an apparent strong genetic predisposition which is seen in other HS CYA cross-sectional research. Treatment was varied in this cohort, however long courses of antibiotics, including combined therapy with rifampicin and clindamycin, were the mainstay of treatment, similar to management in the adult population. This study therefore adds to the limited information on the demographics and management of the HS CYA population.

A smart sensor for monitoring antimicrobial interventions in wound infections

Effective therapeutic monitoring of wound infections is crucial for wound care. We explore a novel approach using a previously described 3D-printed, colourimetric indicator to non-invasively monitor antimicrobial interventions in wound infection. The indicator contains a pH-sensitive dye which detects carbon dioxide production from wound pathogens by changing colour from blue to yellow. The sensor accurately reported the minimum inhibitory concentration of antibiotic against Pseudomonas aeruginosa in a sealed 96-well plate. Subinhibitory antibiotic concentrations resulted in the sensor changing colour, whilst remaining blue for inhibitory concentrations. The sensor was applied to a porcine skin wound model with Pseudomonas aeruginosa biofilms, testing several antimicrobial treatments: antibiotic monotherapy, phage monotherapy, and a combination of both. After treatment, the sensor, sealed with the wound, enabled visual monitoring of antimicrobial efficacy. Through comparing post-treatment bioburden and sensor response, greater log-fold reductions in P. aeruginosa following antimicrobial treatment correlated with longer sensor response times. Sensors monitoring unsuccessfully treated biofilms changed colour, while those treated at or above the minimum biofilm eradication concentration elicited no colour change, indicating P. aeruginosa eradication. This sensor holds promise for monitoring wound infection treatment efficacy, improving patient outcomes, and promoting undisturbed wound healing as a non-invasive point-of-care tool.

Empiric antibiotic treatment for periprosthetic joint infections: a national survey in The Netherlands.

Early periprosthetic joint infection (PJI) is generally treated by means of debridement, antibiotics and implant retention (DAIR). Subsequently, empiric antibiotic therapy is commenced directly after surgery which is important for the successful treatment of PJI. The aim of this study is to evaluate current nationwide empiric antibiotic treatment regimens for PJI in the Netherlands. An electronic 15-question survey addressing the empiric antibiotic treatment strategy for PJI following THA or TKA was sent to orthopaedic surgeons in all Dutch hospitals in April 2019. Orthopaedic surgeons active in every single Dutch orthopaedic hospital (n=69) were approached. At least one surgeon in every hospital completed the survey (100% response rate). A protocol dictating the empiric antibiotic treatment following DAIR was used in 87% (60 hospitals). Among all hospitals, 72% (50 hospitals) used antibiotic monotherapy and 28% (19 hospitals) used combination therapy. Cefazolin was the most commonly used regimen in centres opting for monotherapy (42%, 29 hospitals). Similar regimens were used for the empiric treatment of suspected early PJI after revision surgery and for acute hematogenous PJI. In septic patients, combination therapy was preferred (64%). 81% (56 hospitals) incubated tissue biopsies for a minimum of 10 days whereas 16% (9 hospitals) indicated an incubation period of 7 days or less. Even in a small country such as the Netherlands there seems to be no uniformity regarding empiric antibiotic treatment for PJI. Increased uniformity regarding empiric treatment could be an important first step in improving PJI treatment.

Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease.

Lyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused by Borrelia burgdorferi (Bb) sensu lato which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics. However, 10-20% of patients experience chronic symptoms because of delayed or incomplete treatment, a condition called Post-Treatment Lyme Disease (PTLD). Some Bb persists in PTLD patients after the initial course of antibiotics and an effective treatment to eradicate the persistent Bb is needed. Other organisms that cause persistent infections, such as M. tuberculosis, are cleared using a combination of therapies rather than monotherapy. A group of Food and Drug Administration (FDA)-approved drugs previously shown to be efficacious against Bb in vitro were used in monotherapy or in combination in mice infected with Bb. Different methods of detection were used to assess the efficacy of the treatments in the infected mice including culture, xenodiagnosis, and molecular techniques. None of the monotherapies eradicated persistent Bb. However, 4 dual combinations (doxycycline + ceftriaxone, dapsone + rifampicin, dapsone + clofazimine, doxycycline + cefotaxime) and 3 triple combinations (doxycycline + ceftriaxone+ carbomycin, doxycycline + cefotaxime+ loratadine, dapsone+ rifampicin+ clofazimine) eradicated persistent Bb infections. These results suggest that combination therapy should be investigated in preclinical studies for treating human Lyme disease.

Inhibitors of the Elastase LasB for the Treatment of Pseudomonas aeruginosa Lung Infections.

Infections caused by the Gram-negative pathogen Pseudomonas aeruginosa are emerging worldwide as a major threat to human health. Conventional antibiotic monotherapy suffers from rapid resistance development, underlining urgent need for novel treatment concepts. Here, we report on a nontraditional approach to combat P. aeruginosa-derived infections by targeting its main virulence factor, the elastase LasB. We discovered a new chemical class of phosphonates with an outstanding in vitro ADMET and PK profile, auspicious activity both in vitro and in vivo. We established the mode of action through a cocrystal structure of our lead compound with LasB and in several in vitro and ex vivo models. The proof of concept of a combination of our pathoblocker with levofloxacin in a murine neutropenic lung infection model and the reduction of LasB protein levels in blood as a proof of target engagement demonstrate the great potential for use as an adjunctive treatment of lung infections in humans.

Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review.

Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Narrative review based on a literature search through PubMed and Cochrane using the following keywords: "multi-drug resistant (MDR)", "extensively drug resistant (XDR)", "pan-drug-resistant (PDR)", "difficult-to-treat (DTR) Gram-negative infection," "antibiotic duration therapy", "antibiotic combination therapy" "antibiotic monotherapy" "Gram-negative bacteremia", "Gram-negative pneumonia", and "Gram-negative intra-abdominal infection". Current literature data suggest adopting longer (≥10-14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45-50%), MDR (35%), XDR (15-20%), PDR (5.9-6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5-20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5-7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.

The management of acne vulgaris in young people in primary care: A retrospective cohort study.

Acne vulgaris (acne) is common among young persons (YPs). Clinical practice guidelines are available for acne management to minimize their physical and psychological impact. However, evidence of adherence to these guidelines is sparse in primary care practices. The study aimed to determine the demographic profile of YPs who sought primary care consultations for acne, their related prescriptions and referrals to specialists for further management. A retrospective study was conducted using data from a cluster of eight public primary care clinics in Singapore. Demographic, clinical, prescription, and referral data were extracted from the electronic health records of YPs aged 10-29 years with a documented diagnosis of acne (ICD-10 classification) from 1st July 2018 to 30th June 2020. The data were reviewed, audited for eligibility criteria, and de-identified before analysis. Complete data from 2,700 YPs with acne were analyzed. Male (56.1%) YPs and those of Chinese ethnicity (73.8%) had the most frequent attendances for acne. The mean and median age at presentation was 19.2 (standard deviation = 4.3) and 19 (interquartile range = 16-22) years, respectively. Only 69.7% of YPs received an acne-related medication; 33.5% received antibiotic monotherapy; 53.0% were prescribed oral doxycycline, 35.0% acne cream (combination of sulfur, salicylic acid, and resorcinol), and 28.4% benzoyl peroxide 5% gel; 54.3% of those treated with antibiotics were prescribed with a shorter duration than recommended; 51.3% were referred to a dermatologist on their first visit, and 15.8% had more than one visit. Acne management for YPs can be enhanced with refresher training among primary care physicians for better adherence to its clinical practice guidelines.

Analyzing trends in treatment of acne vulgaris in pregnancy: a retrospective study.

Analyzing trends in treatment of acne vulgaris in pregnancy: a retrospective study.

Combined adipose-derived mesenchymal stem cell and antibiotic therapy can effectively treat periprosthetic joint infection in rats

Periprosthetic joint infection (PJI) is characterized by biofilm infection, which is difficult to alleviate while preserving implant integrity. Furthermore, long-term antibiotic therapy may increase the prevalence of drug-resistant bacterial strains, necessitating a non-antibacterial approach. Adipose-derived stem cells (ADSCs) exert antibacterial effects; however, their efficacy in PJI remains unclear. This study investigates the efficacy of combined intravenous ADSCs and antibiotic therapy in comparison to antibiotic monotherapy in a methicillin-sensitive Staphylococcus aureus (MSSA)-infected PJI rat model. The rats were randomly assigned and equally divided into 3 groups: no-treatment group, antibiotic group, ADSCs with antibiotic group. The ADSCs with antibiotic group exhibited the fastest recovery from weight loss, with lower bacterial counts (p = 0.013 vs. no-treatment group; p = 0.024 vs. antibiotic group) and less bone density loss around the implants (p = 0.015 vs. no-treatment group; p = 0.025 vs. antibiotic group). The modified Rissing score was used to evaluate localized infection on postoperative day 14 and was the lowest in the ADSCs with antibiotic group; however, no significant difference was observed between the antibiotic group and ADSCs with antibiotic group (p < 0.001 vs. no-treatment group; p = 0.359 vs. antibiotic group). Histological analysis revealed a clear, thin, and continuous bony envelope, a homogeneous bone marrow, and a defined, normal interface in the ADSCs with antibiotic group. Moreover, the expression of cathelicidin expression was significantly higher (p = 0.002 vs. no-treatment group; p = 0.049 vs. antibiotic group), whereas that of tumor necrosis factor (TNF)-α and interleukin(IL)-6 was lower in the ADSCs with antibiotic group than in the no-treatment group (TNF-α, p = 0.010 vs. no-treatment group; IL-6, p = 0.010 vs. no-treatment group). Thus, the combined intravenous ADSCs and antibiotic therapy induced a stronger antibacterial effect than antibiotic monotherapy in a MSSA-infected PJI rat model. This strong antibacterial effect may be related to the increased cathelicidin expression and decreased inflammatory cytokine expression at the site of infection.

Targeted Therapy of Severe Infections Caused by Staphylococcus aureus in Critically Ill Adult Patients: A Multidisciplinary Proposal of Therapeutic Algorithms Based on Real-World Evidence

(1) Introduction: To develop evidence-based algorithms for targeted antibiotic therapy of infections caused by Staphylococcus aureus in critically ill adult patients. (2) Methods: A multidisciplinary team of four experts had several rounds of assessment for developing algorithms concerning targeted antimicrobial therapy of severe infections caused by Staphylococcus aureus in critically ill patients. The literature search was performed by a researcher on PubMed-MEDLINE (until August 2022) to provide evidence for supporting therapeutic choices. Quality and strength of evidence was established according to a hierarchical scale of the study design. Two different algorithms were created, one for methicillin-susceptible Staphylococcus aureus (MSSA) and the other for methicillin-resistant Staphylococcus aureus (MRSA). The therapeutic options were categorized for each different site of infection and were selected also on the basis of pharmacokinetic/pharmacodynamic features. (3) Results: Cefazolin or oxacillin were the agents proposed for all of the different types of severe MSSA infections. The proposed targeted therapies for severe MRSA infections were different according to the infection site: daptomycin plus fosfomycin or ceftaroline or ceftobiprole for bloodstream infections, infective endocarditis, and/or infections associated with intracardiac/intravascular devices; ceftaroline or ceftobiprole for community-acquired pneumonia; linezolid alone or plus fosfomycin for infection-related ventilator-associated complications or for central nervous system infections; daptomycin alone or plus clindamycin for necrotizing skin and soft tissue infections. (4) Conclusions: We are confident that targeted therapies based on scientific evidence and optimization of the pharmacokinetic/pharmacodynamic features of antibiotic monotherapy or combo therapy may represent valuable strategies for treating MSSA and MRSA infections.