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This study aimed to determine the bacterial isolates associated with postpartum endometritis among dairy cows in Western Australia and their antimicrobial susceptibility profiles. A cross-sectional study was conducted between June-October 2020. Endometritis was defined as evidence of mucopurulent to purulent vaginal discharge 60-100 days postpartum. Vaginal discharge samples were obtained, cultured, identified and tested for antimicrobial susceptibility. A total of 118 bacterial isolates were grown from 46 animals, representing 36 species. The bacteria isolated from both aerobic and anaerobic cultures included Bacillus (60.2%), Streptococcus (12.7%), Trueperella (10.1%), Escherichia (6.7%) and Staphylococcus (5.9%). The remaining genera5% were Histophilus, Aeroccocus, Enterococcus and Moraxella. Resistance was variable between isolates, but the highest resistance levels were observed in Streptococcal and Bacillus isolates to enrofloxacin, clindamycin and erythromycin, respectively. All Streptococcal isolates exhibited 100% resistance to enrofloxacin, and the greatest resistance levels were found in Streptococcus luteinises to trimethoprim-sulfamethoxazole 83%, clindamycin 66% and 33% quinupristin-dalfopristin. There was 84.5% resistance to clindamycin and 35.2% to erythromycin in the Bacillus isolates, with the highest resistance found in Bacillus licheniformis and Bacillus subtilis. Escherichia coli exhibited 12.5% resistance to gentamycin, ceftiofur, whereas amoxicillin-clavulanic acid exhibited 37.5%. Within the Staphylococcal isolates, 28.5%, 28.5%, 42.8% and 14.2% resistance to ceftiofur, erythromycin, cefoxitin, penicillin and tetracycline were observed, respectively. The presence of resistance to important antimicrobials for human use, such as cephalosporins, macrolides and fluoroquinolones, highlights the need for judicious use of antimicrobials in dairy cattle.

Cutibacterium acnes has been associated with chronic prostatitis, which can potentially favor the appearance of tumors in the prostate. Prostatitis is difficult to treat, and the drug needs to be able to penetrate the prostate. The aim was to investigate the pharmacokinetics of clindamycin in the interstitial fluid of rat prostate using microdialysis. Microdialysis probes were recovered in vitro and in vivo. Clindamycin was administered at 80 mg/kg iv bolus for plasma and tissue pharmacokinetic experiments. A microdialysis probe was implanted in the prostate gland for collections over an 8-hour period. The pharmacokinetic parameters were determined by both compartmental and non-compartmental approaches. Penetration was determined as the ratio between the area under the curve and the time of the clindamycin measurement in the prostate. The recovery of the in vivo probes was 38.11 ± 1.14%. The plasma profile was modeled by a two-compartment pharmacokinetic model. Clindamycin presented a prostate/plasma ratio of 1.02, with free concentrations above the minimum inhibitory concentration for Cutibacterium acnes isolates. This was the first study that determined clindamycin free concentrations in the prostatic fluid of rats. These findings suggest that clindamycin may be an effective alternative for the treatment of prostatitis caused by Cutibacterium acnes.

Clostridium difficile isolates from the environment are closely related to those from humans, indicating a possible environmental transmission route for C. difficile infection (CDI). In this study, C. difficile was isolated from 47.3% (53/112) of lake/pond, 23.0% (14/61) of river, 20.0% (3/15) of estuary and 0.0% (0/89) of seawater samples. The most common toxigenic strain isolated was C. difficile PCR ribotype (RT) 014/020 (10.5%, 8/76). All water isolates were susceptible to fidaxomicin, metronidazole, rifaximin, amoxicillin/clavulanic acid, moxifloxacin and tetracycline. Resistance to vancomycin, clindamycin, erythromycin and meropenem was detected in 5.3% (4/76), 26.3% (20/76), 1.3% (1/76) and 6.6% (5/76) of isolates, respectively. High-resolution core-genome analysis was performed on RT 014/020 isolates of water origin and 26 clinical RT 014/020 isolates from the same year and geographical location. Notably, both human and water strains were intermixed across three sequence types (STs), 2, 13 and 49. Six closely related groups with ≤10 core-genome single nucleotide polymorphisms were identified, five of which comprised human and water strains. Overall, 19.2% (5/26) of human strains shared a recent genomic relationship with one or more water strains. This study supports the growing hypothesis that environmental contamination by C. difficile plays a role in CDI transmission.

Oral tetracyclines have been used in clinical practice for over 60 years. One of the most common indications for use of oral tetracyclines is for treatment of adult outpatients with skin and soft infections (SSTIs), including acute bacterial skin and skin structure infections (ABSSSIs). The 2014 Infectious Diseases Society of America (IDSA) skin and soft tissue guideline strongly recommends sulfamethoxazole/trimethoprim, clindamycin, and tetracyclines as oral treatment options for patients with purulent SSTIs, especially when methicillin-resistant Staphylococcus aureus is of clinical concern. Despite the long-standing use of tetracyclines, practice patterns indicate that they are often considered after other guideline-concordant oral options for the treatment of patients with SSTIs. Clinicians may therefore be less familiar with the clinical data associated with use of commercially available tetracycline agents for treatment of patients with SSTI. This review summarizes the literature on the use of oral tetracyclines (ie, doxycycline, minocycline, and omadacycline) for the treatment of adult patients with SSTIs. As part of this review, we describe their common mechanisms of resistance, susceptibility profiles against common SSTI pathogens, pharmacokinetics and pharmacodynamics, and comparative clinical data.

Objectives To specify the concentration of the liquid antibiotics to be added to polymethylmethacrylate (PMMA) and its impact on the quality of the spacer is the purpose of this study with liquid clindamycin added to different cements. Methods In the present study, eight different cement mixtures were prepared and investigated. In the following, number 1 indicates the references, 2 all cements after liquid clindamycin was added to the liquid cement compound, 3 all cements after liquid clindamycin was added to the cement powder, and 4 all cements after liquid clindamycin was added to the cement dough. After curing, cements were filled into metal moulds and a pressure of 3 bar was maintained for 30 min. Mechanical investigations were carried out according to ISO 5833 (2002) and DIN 53435 (2007). For microbiological tests, standardized cylindrical mouldings (diameter: 25 mm, height: 10 mm) were produced and incubated in 10 ml buffer solution at room temperature for 24 h. All eluates were generated by spreading previously established suspensions of Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes and methicillin‐resistant Staphylococcus aureus (MRSA) with a 0.5 McFarland turbidity standard. Results Apparently, we found that in all investigated cases, the admixture of liquid antibiotic negatively affected the mechanical characteristics of the cement mould. Among the various test groups, the influence on the ISO compression strength and ISO flexural modulus of the investigated test groups was only minimal when liquid clindamycin was added to cement liquid. Compared to admixing of liquid clindamycin into cement powder or dough ISO compression strength and ISO flexural modulus and flexural strength showed the maximum reduction. The efficacy against chosen germs was reduced as well when liquid antibiotic was admixed instead of powder. This admixture of liquid anti‐infective agents resulted in a 234% enhanced elution after 10 days 29 a negative effect on the inhibition zones were detected during the previous period. Conclusion The admixture of powdery antibiotic is preferable to liquid antibiotics. If no powdery antibiotic is available, we can recommend the admixture of liquid antibiotic to liquid cement prior to dough production in case powdery antibiotics cannot be used. However, we discourage the admixture of liquid antibiotic to cement powder or cement dough during early low viscose phase., Experimental arrangement with Palacos R leading to the results.

Brain inflammation and apoptosis play crucial roles in the pathogenesis of various neurodevelopmental disorders. Probiotics have been shown to confer protection against many stresses, including apoptosis and inflammation, by modulating the gut function. The short‐chain fatty acid, propionic acid (PPA), plays an important intermediate of cellular metabolism. Although PPA exhibits numerous beneficial biological effects, its accumulation is neurotoxic. This study focused on the therapeutic potency of probiotics against PPA‐induced apoptosis and neuroinflammation in hamsters. Five groups of male golden Syrian hamsters were treated as follows: Group I as control; Group II as PPA‐treated with three doses of 250 mg PPA/kg/day; Group III as clindamycin‐treated with a single dose of 30 mg clindamycin/kg; Group IV as PPA–probiotic; and Group V as clindamycin–probiotic were two therapeutic groups which were treated with the same doses of PPA and clindamycin, respectively, followed by treatment with 0.2 g kg‐1 d−1 of probiotic (ProtexinR, Probiotics International Limited) for three weeks. Proapoptotic markers, such as caspases 3 and 7; neuroinflammation markers, such as interleukins 1β and 8; and heat shock protein 70 were measured in the brain. Significant increase of all measured markers (p ˂ .001) was observed in PPA and clindamycin‐treated hamsters compared with controls. Probiotics significantly reduced the damages and ameliorated all the test markers in both therapeutic groups compared with the control. Our results confirmed that probiotics can be utilized as a feasible strategy for managing apoptotic and inflammation‐related stresses in brain disorders by retaining the gut function., This study ascertained the role of neuroinflammation and apoptosis as neurotoxic effects in the PPA‐induced rodent model of autism. Clindamycin showed relatively fewer neurotoxic effects compared with orally administered PPA. Moreover, our study showed that probiotics exert ameliorative effects and may be used as a novel noninvasive and safe treatment strategy.

Background Surgical site infections (SSI) are common complications of free-flap reconstruction for head and neck cancer defects. This study aimed to identify risk factors for SSI following a significant change in local antibiotic prophylaxis practice. Methods A retrospective cohort study was conducted of 325 patients receiving free-flap reconstruction for head and neck cancer defects at a tertiary hospital in Melbourne, Australia between 2013 and 2019. Charts were queried for recipient SSI (primary outcome), donor SSI, other infections, antibiotic use, hospital length of stay, and mortality. Results Risk factors for SSI included female sex, T-classification, hardware insertion, clindamycin prophylaxis, and operative duration. There was a trend toward increased SSI with shorter ≤24 h prophylaxis (OR: 0.43). Conclusion Antibiotic duration and type were associated with SSI. Complexity of surgery, T-classification, hardware use, and operative duration were also independently associated with SSI. A prospective trial is indicated to elicit optimal prophylactic antibiotic duration.

Objectives To evaluate treatment outcomes in patients with severe maxillofacial infections requiring hospital care during a 17-year period. Methods A retrospective cohort study reviewed 5,465 medical records, and the following data were collected: the reason for infection, locations of inflamed regions, treatment provided, bacteriological findings, and treatment outcomes. Other information included sociodemographic characteristics (age, gender), presence of systemic diseases, and smoking history. Results The annual incidence rate of patients with acute maxillofacial infections was 206 ± 19 cases with a male to female ratio 1.4:1.0, a mean hospital stay of 7.9 ± 4.9 days. Older age (>65 years), smoking and systemic diseases (diabetes), the causative tooth (molar), and need for extraoral incision predicted longer hospitalization. Intravenous penicillin was the most common drug prescribed in 50.5% of cases. A total of 132 different microorganisms were identified. The highest microorganism resistance occurred for metronidazole and the highest sensitivity was to clindamycin. Conclusions Increased age, smoking, diabetes, causative tooth, and the occurrence of several infected spaces were associated with a longer hospital stay. Streptococcus α haemolyticus was the most common microorganism found in more than 70.0% of cases that were sensitive to intravenous penicillin.

AIM The paediatric population has a low adherence and acceptance rate of unpalatable medicines. This study aimed to determine whether eating chocolate immediately prior to drug administration would help to mask the bitter taste of a drug. The difference in taste masking efficacy between white, milk and dark chocolate was a secondary measure outcome. METHODS A controlled repeated measures crossover taste trial was conducted using a taste panel of 29 young healthy adults who met the criteria to differentiate intensity in bitterness taste. Participants separately tasted solutions of quinine, flucloxacillin and clindamycin using the swill and spit method, singularly and following blinded prior administration of white, milk or dark chocolate. Drug solutions administered without prior chocolate served as controls. Bitterness score for each tasting was recorded using a 5-point scale. RESULTS Regardless of chocolate type, mean taste scores with prior chocolate for quinine (range 2.00-2.34), clindamycin (3.72-3.83) and flucloxacillin (3.38-3.45) were all lower than mean scores for respective drugs without chocolate (3.24, 4.75 and 4.28, respectively; P

BACKGROUND/OBJECTIVE: Pediatric patients hospitalized with bacterial infections often receive intravenous (IV) antibiotics. Early transition to enteral antibiotics can reduce hospital duration, cost, and complications. We aimed to identify opportunities to transition from IV to enteral antibiotics, describe variation of transition among hospitals, and evaluate feasibility of novel stewardship metrics. METHODS: This multisite retrospective cohort study used the Pediatric Health Information System to identify pediatric patients hospitalized with pneumonia, neck infection, orbital infection, urinary tract infection (UTI), osteomyelitis, septic arthritis, or skin and soft tissue infection (SSTI) between 2017 and 2018. Opportunity days were defined as days on which patients received both IV antibiotics and enteral medications, suggesting enteral tolerance. Percent opportunity was defined as opportunity days divided by days on any antibiotics. Both outcomes excluded IV antibiotics that have no alternative oral formulation. We evaluated outcomes per infection and antibiotic and assessed across-hospital variation. RESULTS: We identified 88,522 aggregate opportunity days in 100,103 hospitalizations. On 57% of the antibiotic days, there was an opportunity to switch patients to enteral therapy, with greatest opportunity days in SSTI, neck infection, and pneumonia encounters, and with clindamycin, ceftriaxone, and ampicillin-sulbactam. Percent opportunity varied by infection (73% in septic arthritis to 40% in pneumonia). There was significant across-hospital variation in percent opportunity for all infections. CONCLUSION: This multicenter study demonstrated the potential opportunity to transition from IV to enteral therapy in over half of antibiotic days. Opportunity varied by infection, antibiotic, and hospital. Across-hospital variation demonstrated likely missed opportunities for earlier transition and the need to define optimal transition times. Stewardship efforts promoting earlier transition for highly bioavailable antibiotics could reduce healthcare utilization and promote high-value care. We identified feasible stewardship metrics.

Blomfeldt A, Jorgensen SB, Helmersen K, Eskonsipo PKJ, Aamot HV. Is increased Staphylococcus aureus colonisation during military service caused by specific genotypes? Molecular examination of long-term carriage in a prospective cohort study A 22% increase in Staphylococcus aureus colonisation was observed in Norwegian recruits during first year of military service. The aim was to determine if specific genotypes caused the increase and to examine carriage status based on genotyping. Characterisation of S. aureus from nose, throat and perineum sampled at enrolment and discharge included spa typing, MLVA, detection of PVL genes and antimicrobial susceptibility testing. spa typing demonstrated high and stable genetic diversity. The three most frequent spa types were found in 15% of recruits at enrolment and in 29% at discharge. Only t084 increased significantly (p = 0.02). Subtyping revealed that t084, t065 and t002 consisted of 13, 6 and 11 different MLVA types, respectively, at discharge. The military cohort (n = 265) consisted of S. aureus carriers of identical genotype (n = 99, 38%), carriers of non-identical genotype (n = 52, 20%), intermittent carriers (n = 86, 33%) and non-carriers (n = 27, 10%). Carrier status was indefinable for one recruit due to unavailable isolates for genotyping. Antibiotic resistance towards erythromycin, fusidic acid and clindamycin increased significantly and above national surveillance levels. The observed increase in S. aureus colonisation during military service was caused by many different genotypes implying many transmission routes. Genotype did not correlate with colonisation niche or carriage status.

Aim We aimed at assessing the frequency of Community acquired Methicillin resistant Staphylococcus aureus (CA-MRSA) infections, identifying its risk factors and evaluating resistance patterns of Staphylococcus aureus to various antibiotics in order to recommend the optimal empirical treatment for suspected Staphylococcus aureus infections. Methods We reviewed the medical records of children who were treated at Shaare Zedek medical center, located in Jerusalem, Israel, over the years 2008-2019 and had a positive culture for Staphylococcus aureus. Patients with CA-MRSA infections were compared with Methicillin susceptible Staphylococcus aureus (CA-MSSA) infections. Results In this study, 620 pediatric patients were included. The number of children in the CA-MRSA study group was 124, while the MSSA control group consisted of 496 children. Risk factors for CA-MRSA infections included young age (1-5 years), female sex, Arab ethnicity and residence in East Jerusalem. The incidence of CA-MRSA increased over the past decade, with an average of 11.2%. An increase in MSSA resistance to clindamycin was noted while Trimethoprim-Sulfamethoxazole resistance remained low. Conclusion The incidence of CA-MRSA in Jerusalem was rising, along with changes in resistance patterns of both MSSA and MRSA to various antibiotic agents. In order to optimize empirical treatment for suspected staphylococcal infection, continued monitoring of CA-MRSA prevalence and resistance rates is essential.

Background Staphylococcal scalded skin syndrome (SSSS) is a toxin-mediated, blistering skin disorder that mainly affects infants and children. There is limited literature regarding pediatric SSSS. The purpose of this study was to describe the epidemiology, clinical features, and management of pediatric SSSS. Methods Retrospective cohort study of pediatric patients with a clinical diagnosis of SSSS seen at the Hospital for Sick Children in Toronto, Ontario, Canada, from January 1994 to March 2016. Results We included 84 patients with a clinical diagnosis of SSSS; 49/84 (58%) were male. Mean age of diagnosis was 3.1 ± 2.4 years. All patients presented with erythema and exfoliation, while 64/84 (76%) presented with vesicles/ bullae. Skin tenderness was the most common symptom, present in 68/84 (81%) subjects. Staphylococcus aureus was more commonly isolated from periorificial cultures than from bullae. Mean hospitalization was 4.7 ± 2.3 days. No difference was found in admission duration between children receiving clindamycin and those that did not (3.6 ± 2.2 vs 3.9 ± 2.34 days, P = .63). Skin debridement was the only risk factor leading to more complications and prolonged hospitalization (P = .03). Severe complications were seen in 4 (5%) cases, and no fatalities were observed. Conclusions Healthcare providers should be aware of SSSS and consider it in the differential diagnosis of infants and children with new onset erythema, exfoliation, and/or vesiculation. Suspected culprit pathogens were more often obtained from periorificial swabs; however, these isolates were not tested for exfoliative toxin to confirm causality. Antibiotic treatment should be guided by sensitivity testing. Addition of clindamycin as an anti-toxin agent had no effect on the duration of hospitalization, and this should be further investigated. Surgical debridement of the skin in patients with SSSS should be discouraged.

The current study compared the safety, tolerability, and pharmacokinetics of the new compound pharmaceutical preparation tazarotene clindamycin cream, and 2 single pharmaceutical preparations, tazarotene cream and clindamycin phosphate gel. Twelve healthy volunteers were enrolled in this single-center, single-blind, 3-treatment, 3-period crossover, single-dose randomized study. An 800-cm2 area on volunteers' backs was evenly smeared with 1.6 g of the test preparation to form a film. Blood samples were collected at predetermined time points for pharmacokinetic analysis. Safety and tolerability were assessed via skin reaction evaluation and clinical laboratory tests. The incidences of skin reactions were 18.2% for tazarotene clindamycin cream, 25.0% for tazarotene cream, and 18.2% for clindamycin phosphate gel. There were no significant differences in safety or tolerability among the 3 groups. Erythema, desquamation, and pruritus occurred in 7 volunteers, but no burning or tingling occurred. All adverse events were mild and resolved spontaneously, and there were no severe adverse events. The respective maximum plasma concentrations of tazarotenic acid after local administration of tazarotene clindamycin cream and tazarotene cream were 11 ± 5 pg/mL and 18 ± 12 pg/mL, and the areas under the curve within 72 hours were 444 ± 341 pg · h/mL and 692 ± 462 pg · h/mL.

A considerable number of prescriptions for antibiotics are issued by dentists. Educational institutions have a special responsibility to promote informed attitudes among dental students towards prescribing antibiotics. The purpose of this study was to analyze the antibiotic prescriptions issued during a 5-year period (2013-2017) at a University Dental Clinic (UDC) in Norway. All patient records containing prescriptions for patients ≥18 yr of age as of 2013-2017 were identified through an electronic search. In total, 6,014 patient record lines containing prescriptions were obtained, 1,047 (17.4%) of which were prescriptions for systemic antibiotics. These patient record lines were analysed to identify the specific antibiotic prescribed, the indication or diagnosis for which it was prescribed, and whether microbiological testing (to determine antibiotic sensitivity) had been carried out. Acute infections were the most common context for prescribing antibiotics. Surprisingly, prophylaxis was the second most frequent reason stated. Disease related to pulp necrosis (43%) and postoperative infections (26%) was the most common diagnosis for therapeutic antibiotic prescriptions. Antibiotic therapy was more commonly used to treat peri-implantitis than to treat periodontitis. Only 60% of the clindamycin prescriptions were issued to patients with penicillin allergy. Further studies are warranted concerning antibiotic use at UDC because this can probably be more restrictive, in particular concerning usage related to antibiotic prophylaxis. Microbiological testing should be performed before administration of antibiotic therapy for periodontitis and peri-implantitis. The reason for prescribing antibiotics should always be stated in the patient's record lines.

This study aimed to evaluate the antibacterial efficacy and discolouration potential of antibiotic pastes containing macrogol. Seventy single-rooted teeth were contaminated with a culture of Enterococcus faecalis for 30 days. Double (DAP) and triple antibiotic pastes (TAP) containing propylene glycol or macrogol as vehicles were applied. After 15 days, bacterial viability was compared. Change in teeth coronal colour was measured by a spectrophotometer. Statistical analysis was performed using anova and Tukey's test (P

We read with great interest the recent paper by Nenoff et al. regarding the antimicrobial activity of nadifloxacin against Cutibacterium acnes strains isolated from patients with acne1 . However, we would like to add a few points relevant to the subject. Whether C. acnes remains the most prevalent microorganism involved in acne, phylotype determination and potential correlation with some resistant lineages would have been of interest, especially with phylotype IA1 and clonal complex CC32 . We agree that a significant number of resistance with erythromycin and clindamycin are found clinically.

Nadifloxacin (OPC-7251) represents an established antimicrobial agent belonging to the quinolone group and was developed exclusively for topical administration. Nadifloxacin is effective in treating a variety of bacterial skin infections and acne. Here, the in vitro activity of nadifloxacin was assessed and compared with those of erythromycin, clindamycin and tetracycline against Cutibacterium (C.) acnes, formerly Propionibacterium acnes, to gain a picture of the resistance situation in Germany. The study was approved by the Ethics Committee of the Bayerische Landesarztekammer (Munich, Germany; EC-No.17088) and registered at Deutsches Register Klinische Studien (ID:DRKS00014231).

The purpose of this statement is to debate the recommendations of the American Heart Association (AHA) for the prevention of infective endocarditis through an antibiotic prophylaxis protocol and its relation with bacterial resistance to antibiotics. Since dental infections involve biofilms that include several bacterial species (Gram-negative and Gram-positive), it is essential, from the dental point of view, to consider the frequency, magnitude, and duration of bacteremia associated with active dental infections before applying antibiotic prophylaxis. The actual guidelines for antibiotic prophylaxis should be revised according to recent evidence of bacterial resistance. Amoxicillin/clavulanic acid and moxifloxacin should be considered due to their effectiveness against bacteria associated with oral, GU, and GI infections and the low rates of antibiotic resistance associated with these antibiotics, instead of the actual protocol, which includes amoxicillin (2 g) or clindamycin (600 mg) administered an hour before the dental procedures. The breaking point to test the antibiotic bacterial resistance (ABR) had a wide range in the different studies that were analyzed, which could explain the widely varied ABR percentages reported for the various antibiotics used for antibiotic prophylaxis.

Background Controversy exists regarding the benefits of treating bacterial vaginosis (BV) during pregnancy to reduce the incidence of preterm labor (PTL). Objectives To evaluate whether treatment of BV with vaginal clindamycin or oral metronidazole before 28 weeks of pregnancy reduces PTL incidence. Search strategy PubMed, Scopus, Web of Science, Science Direct, CENTRAL, and SciELO databases were searched until December 30, 2017. Search terms included "bacterial vaginosis" and "preterm labor." No language restrictions were applied. Selection criteria Randomized clinical trials that evaluated treatment of BV with clindamycin or metronidazole to reduce PTL incidence. Data collection and analysis The risk of PTL was evaluated by the odds ratio (OR) and 95% confidence interval (CI). Dichotomous data from each study were combined for meta-analysis using the Mantel-Haenszel model. Main results Nine reports were included in the systematic review, with eight reports included in the meta-analysis. No reduction in the incidence of PTL was found for either metronidazole (OR 0.94, 95% CI 0.71-1.25) or clindamycin (OR 1.01, 95% CI 0.75-1.36). Conclusions Use of oral metronidazole or vaginal clindamycin to treat BV before 28 weeks of pregnancy did not reduce the incidence of PTL. PROSPERO registration: CRD42018086173.

Key Clinical Message Disseminated toxoplasmosis is a potentially fatal complication in dogs receiving immunosuppressive therapy, particularly if multiple immunosuppressive drugs are used. Toxoplasmosis should be considered if signs of acute respiratory or hepatic disease develop, and diagnosis would rely on demonstration of organisms via cytology or PCR rather than a single time‐point serological assay.

INTRODUCTION Amniotic fluid "sludge" has been associated with an increased rate of spontaneous preterm delivery before 35 weeks, a higher frequency of clinical and histologic chorioamnionitis in a high-risk population. Only one study evaluating the use of antibiotics in the presence of amniotic fluid "sludge" showed reduced rates of spontaneous preterm birth at

The objective of this study was to investigate a sudden increase in methicillin-resistant Staphylococcus aureus (MRSA) cases primarily in one maternity ward at the Center for Children's and Women's Health at Linköping University Hospital, Sweden. Approximately 300 individuals including patients, their family members, and healthcare workers were screened for MRSA. The antibiotic susceptibility was tested and isolates polymerase chain reaction (PCR)-positive for the mecA gene were spa typed. Isolates with the same antibiogram and spa type were further whole genome sequenced. Compliance to current cleaning and hygiene routines was also controlled, and environmental samples collected. The results showed that a total of 13 individuals were involved in the outbreak. It was caused by a t386 MRSA strain (ST-1, NCBI-accession AB505628) with additional resistance to erythromycin and clindamycin. All cases were epidemiologically connected to the index patient, who had recently emigrated from a high-endemic area for MRSA. With improved cleaning and better compliance to basic hygiene routines, no further cases were reported. This study demonstrates how rapid an MRSA strain can disseminate in a ward with susceptible patients and insufficient cleaning and hygiene. For a better control of MRSA, clinical cultures and screening samples need to be obtained early and more extensively than according to the current recommendations.

Since the level of antimicrobial resistance in Bacteroides fragilis has increased, monitoring the antimicrobial susceptibility could be necessary. The objectives of this study were to (i) investigate the prevalence of species, the occurrence of reduced antimicrobial susceptibility (E-test method), and antibiotic resistance genes in the B. fragilis group and (ii) evaluate the prevalence of enterotoxigenic B. fragilis and the distribution of bft gene subtypes in hospitalized patients. As many as 475 isolates out of 250 stool samples were detected to be B. fragilis group by using conventional biochemical tests (API-32A system) and multiplex-PCR. In addition, 48.2%, 13.9%, 76.6%, and 1.2% of B. fragilis group isolates were resistant (according to EUCAST breakpoint) to piperacillin-tazobactam, meropenem, clindamycin, and metronidazole, respectively. Six metronidazole-resistant strains were isolated; B. fragilis (n: 3), B. thetaiotaomicron, B. vulgates, and B. ovatus. The presence of the cfiA, cepA, ermF, and nim genes was observed in 3.8%, 15.9%, 34.1%, and 0.7% of the B. fragilis isolates, respectively. One hundred thirty-two B. fragilis isolates (27.8%)and 21 B fragilis isolates (15.9%) turned out to be bft gene positive by multiplex-PCR; eleven isolates (52.4%) harbored bft-1, eight isolates (38%) harbored bft-2 isotypes, and two isolates (9.5%) harbored bft-3 isotype (16.66%). These bacteria harbor antimicrobial resistance genes that could be transferred to other susceptible intestinal strains. Further investigations on lineage analysis are needed for a better understanding of these bacteria in Iran.

Aim The optimal antibiotic regimen for preterm premature rupture of membrane (pPROM) is still unclear. This study aimed to determine the effects of ampicillin-sulbactam (SBT/ABPC) and azithromycin (AZM) on the incidence of bronchopulmonary dysplasia (BPD). Methods This retrospective study included women with singleton gestations and a diagnosis of pPROM between 22 and 27 weeks of gestation. In patients presenting with a high risk of intra-amniotic infection between January 2011 and May 2013, piperacillin or cefmetazole + clindamycin (regimen 1 group; n = 11) was administered, whereas SBT/ABPC and AZM (regimen 2 group; n = 11) were administered in patients presenting a similar risk between June 2013 and May 2016. Results The incidence of moderate or severe infant BPD in the regimen 2 group was significantly lower than that in the regimen 1 group, even when adjusted for gestational age at the time of rupture of membrane, with an odds ratio (95% confidence interval) of 0.02 (1.8 × 10-5 -0.33). The incidence of BPD and total days on mechanical ventilation were significantly lower in the regimen 2 group than in the regimen 1 group. No significant differences were seen in other morbidities. Conclusion In patients with pPROM between 22 and 27 weeks of gestation, the administration of SBT/ABPC and AZM may improve the perinatal outcomes.

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.

The existence of alternative oral therapies could help clinicians to treat toxoplasmic encephalitis (TE) in the HIV patients. The combination of azithromycin and clindamycin may serve as an effective treatment for TE in HIV‐infected patients.

BACKGROUND: Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments. OBJECTIVES: To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of ’short cervix’ and/or physical examination. History‐indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound‐indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam‐indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster‐RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi‐RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross‐over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout. MAIN RESULTS: We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone ‐ this study did provide useable data for this review (and the study authors also provided additional data on request) but meta‐analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low‐certainty evidence); perinatal loss (data for miscarriage and stillbirth only ‐ data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low‐certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low‐certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17‐alpha‐hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega‐3 long chain polyunsaturated fatty acid supplementation and bed rest.

Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 μg/mL (plasma) and 0.05-1.0 μg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.

BACKGROUND: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland‐rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha‐hydroxy acid is unclear. OBJECTIVES: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha‐hydroxy acid, and sulphur) for acne. SEARCH METHODS: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self‐assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short‐term (less than or equal to 4 weeks), medium‐term (from 5 to 8 weeks), and long‐term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long‐term for the PGA outcome and mixed length (medium‐term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate‐quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low‐quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low‐quality evidence). Low‐quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low‐quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low‐quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low‐quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low‐quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low‐quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low‐quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low‐quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low‐quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low‐quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low‐quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha‐hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic‐mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low‐quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low‐quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low‐quality evidence). AUTHORS' CONCLUSIONS: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head‐to‐head trials against commonly used active drugs.

Pharmacokinetic/pharmacodynamic indices of anti-infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC-UV. The drugs were separated isocratically within 3-6 min on a C-18 column using mixtures of phosphate buffer-acetonitrile of pH 7.1-7.2. Sample treatment for the determination of total drug concentrations in plasma included extraction/back-extraction (clindamycin) or protein precipitation (flucloxacillin, tedizolid). The free drug concentrations were determined after ultrafiltration. An ultrafiltration device with a membrane consisting of regenerated cellulose proved to be suitable for all drugs. Maintaining a physiological pH was crucial for clindamycin, whereas maintaining body temperature was essential for tedizolid. The methods were applied to the analysis of total and free drug concentrations in clinical samples and were sufficiently sensitive for pharmacokinetic studies and therapeutic drug monitoring.

Background Multiple drug hypersensitivity syndrome (MDH) is used to describe persons with a drug hypersensitivity reaction (DHR) to at least two chemically unrelated drugs, confirmed by skin test or in vitro assay. Methods Medical records of 25 patients with MDH, tested and confirmed at our allergy division, were retrospectively evaluated in terms of clinical course, involved drugs, daily drug dose, latency periods, test results of skin test and cellular assays, and tolerated drugs in subsequent pharmacological treatments. Results Multiple drug hypersensitivity syndrome almost exclusively appeared as a delayed, often severe DHR and started in 14/25 with a drug reaction with eosinophilia and systemic symptoms (DRESS). Penicillins (13/25, 52.0%) and cephalosporins (6/25, 24.0%), typical high-dose drugs, were most often identified as elicitors of MDH, especially at the first DHR, followed by aromatic antiepileptics (7/25, 28.0%), vancomycin (4/25, 16.0%), and antibiotic sulfonamides (4/25, 16.0%). Cephalosporins, clindamycin, and radio contrast media (RCM) were mainly involved in subsequent DHR. The median daily drug dose of all drug trigger was 1875.0 mg (662.5; 2100.0) at the first DHR and 600.0 mg (300.0; 1300.0) at subsequent DHR, P = .0420. Conclusion High-dose drugs, especially beta-lactam antibiotics, RCM and clindamycin, are common elicitors of subsequent DHR in patients with MDH. Macrolides, quinolones, doxycycline, nonaromatic antiepileptics, and paracetamol were often tolerated. As the same drugs elicited both flare-up reactions and real DHR, drug-induced flare-up reactions may be precursors of a possible second DHR and MDH. The administration of highly dosed drugs should be avoided in patients at risk for MDH.

AIM Group B streptococcus (GBS) is a leading cause of life-threatening bacterial infections among newborns, and neonates born to heavily colonized women may be subject to vertical transmission. We sought to determine an appropriate detection method for genital GBS in pregnant women by comparing culture-based methods and real-time polymerase chain reaction (PCR). In addition, we performed molecular serotyping and multilocus sequence typing (MLST) on isolates. METHODS A total of 150 pregnant women were enrolled and underwent vaginal-rectal swabbing at 16-40 weeks of gestation. GBS was identified by conventional culture and real-time PCR with or without enrichment. Molecular serotyping and MLST were performed on isolates. RESULTS Overall genital GBS positive rate among the 150 study subjects was 17.3%. Direct culture identified 18 (12.0%) positive specimens, enrichment culture 22 (14.6%), direct PCR 24 (16.0%) and enrichment PCR 25 (16.6%). The sensitivity and specificity by direct and enrichment PCR were as follows: for direct PCR, 90.9% and 96.9%, respectively; and for enrichment PCR, 95.5% and 96.9%, respectively. Resistance rates to clindamycin and erythromycin were 33.3% and 19.1%, respectively. Serotype III-1 was the most common (26.3%), followed by serotype Ib (21.1%), III-3 (15.8%), V (15.8%), II (10.5%), IV (5.3%) and VI (5.3%). Most common sequence types (ST) were ST-1, ST-19 and ST-862 (15.8%), followed by ST-2 and ST-654 (10.5%). CONCLUSION Direct real-time PCR using vaginal-rectal specimen could be used for detecting GBS in emergent conditions. Molecular serotypes III, Ib and V were most common. MLST analysis frequently presented ST-1, ST-19 and ST-862.

Aim Community-acquired pneumonia (CAP) complicated by pleural empyema is an important paediatric problem. Antibiotic management decisions are made on the basis of little available data and without strong specific recommendations in guidelines. Methods This was an online survey of paediatric infectious diseases (PID) physicians disseminated by major international professional organisations, examining empiric and targeted antibiotic choice, switch to oral antibiotics and duration of treatment for two hypothetical cases of contrasting severity. Results This study included 183 responses, mostly from North America, Western Europe and Australia/New Zealand. Increased disease severity was significantly associated with broader-spectrum and combination empiric and targeted antibiotic treatment, empiric methicillin-resistant Staphylococcus aureus (MRSA) coverage and both longer intravenous (IV) and total duration of antibiotic treatment. Empirical MRSA coverage was also associated with local prevalence. Clinical progress was most important for determining the timing of the switch from IV to oral antibiotics. Few respondents chose antibiotics with activity against organisms associated with atypical pneumonia (e.g. Mycoplasma, Chlamydia), and most did not choose agents that inhibit protein synthesis (e.g. clindamycin), even in the case of a severe invasive group A streptococcal infection. Some variation in targeted treatment choices reflected areas of uncertainty, such as Streptococcus pneumoniae susceptibility breakpoints, comparative effectiveness of anti-staphylococcal penicillins and first-generation cephalosporins for serious S. aureus infections and linezolid and vancomycin for MRSA pneumonia. Conclusions This international survey of PID physicians highlights the priority targets for clinical research to improve antibiotic treatment of CAP complicated by empyema. Interventions that might be studied include empirical antibiotic guidelines stratified by case severity, adjunctive empirical use of agents that inhibit protein synthesis (e.g. clindamycin) and approaches to encourage rapid IV-to-oral switch and shorter total antibiotic treatment.

OBJECTIVE To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH ≥5.0. DESIGN Randomised double-blind placebo-controlled trial. SETTING Rural southern India. POPULATION Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks. METHODS Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (≥5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo. MAIN OUTCOME MEASURES The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks. RESULTS Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of

Adapalene 0.1% (ADA) with clindamycin phosphate 1.2% (CLNP; ADA + CLNP) and the fixed‐dose combination containing CLNP and benzoyl peroxide 3% (CLNP/BPO 3%) are strongly recommended for the early treatment of acne vulgaris in Japan. Here, we compare the early efficacy and safety of CLNP/BPO 3% with Japanese standard topical use of ADA + CLNP in the treatment of acne vulgaris. In this phase IV, multicenter study, 351 patients were randomized to receive CLNP/BPO 3% or ADA + CLNP for 12 weeks. The primary end‐point was percentage change from baseline in total lesion (TL) counts at week 2. Secondary end‐points included the percentage change from baseline in TL, inflammatory and non‐inflammatory lesion (IL and non‐IL) counts, Investigator's Static Global Assessment (ISGA), quality of life (QoL [Skindex‐16]) and patient preference. Local tolerability scores and adverse events were also recorded. CLNP/BPO 3% provided a significantly greater percentage reduction from baseline in TL compared with ADA + CLNP at week 2, and week 4. Compared with ADA + CLNP, CLNP/BPO 3% was superior at reducing IL (but not non‐IL) over weeks 2–12, was more effective at improving patient QoL and ISGA, and scored higher in patient‐preference assessments. Both treatments were well tolerated; adverse drug reactions occurred more frequently in patients receiving ADA + CLNP (37%) than in those receiving CLNP/BPO 3% (17%). In conclusion, CLNP/BPO 3% showed greater efficacy for the early treatment of acne vulgaris in Japan, with a more favorable safety profile compared with ADA + CLNP.

Identification of agricultural practices that mitigate the environmental dissemination of antibiotics is a key need in reducing the prevalence of antibiotic-resistant bacteria of human health concern. Here, we aimed to compare the effects of crop (lettuce [ L.] or radish [ L.]), soil amendment type (inorganic fertilizer, raw dairy manure, composted dairy manure, or no amendment), and prior antibiotic use history (no antibiotics during previous lactation cycles vs. manure mixed from cows administered pirlimycin or cephapirin) of manure-derived amendments on the incidence of culturable antibiotic-resistant fecal coliforms in agricultural soils through a controlled field-plot experiment. Antibiotic-resistant culturable fecal coliforms were recoverable from soils across all treatments immediately after application, although persistence throughout the experiment varied by antibiotic class and time. The magnitude of observed coliform counts differed by soil amendment type. Compost-amended soils had the highest levels of cephalosporin-resistant fecal coliforms, regardless of whether the cows from which the manure was derived were administered antibiotics. Samples from control plots or those treated with inorganic fertilizer trended toward lower counts of resistant coliforms, although these differences were not statistically significant. No statistical differences were observed between soils that grew leafy (lettuce) versus rooted (radish) crops. Only pirlimycin was detectable past amendment application in raw manure-amended soils, dissipating 12 to 25% by Day 28. Consequently, no quantifiable correlations between coliform count and antibiotic magnitude could be identified. This study demonstrates that antibiotic-resistant fecal coliforms can become elevated in soils receiving manure-derived amendments, but that a variety of factors likely contribute to their long-term persistence under typical field conditions.

Infection of the driveline or pump pocket is a common complication in patients with ventricular assist devices (VADs) and Staphylococcus aureus is the main pathogen causing such infections. Limited evidence is currently available to guide the choice of antibiotic therapy and the duration of treatment in these patients. Patients at the University Medical Center Utrecht who developed a VAD-related S. aureus infection between 2007 and 2016 were retrospectively assessed. Blood culture isolates were typed by whole genome sequencing to differentiate between relapses and reinfections, and to determine whether antibiotic therapy had led to acquisition of resistance mutations. Twenty-eight patients had S. aureus VAD infections. Ten of these patients also suffered S. aureus bacteremia. Discontinuation of antibiotic therapy was followed by relapse in 50% of the patients without prior S. aureus bacteremia and in 80% of patients with bacteremia. Oral cephalexin could ultimately suppress the infection for the duration of follow-up in 8/8 patients without S. aureus bacteremia and in 3/6 patients with S. aureus bacteremia. Clindamycin failed as suppressive therapy in 4/4 patients. Cephalexin appears an adequate choice for antibiotic suppression of VAD infections with methicillin-susceptible S. aureus. In patients without systemic symptoms, it may be justified to attempt to stop therapy after treatment of the acute infection, but antibiotic suppression until heart transplant seems indicated in patients with S. aureus bacteremia.

Regenerative endodontic procedures (REPs) are biologically based procedures planned to replace damaged tissues, including dentinee and root structures, as well as cells of the pulp-dentine complex. Effective sterilization of the root canal is essential in REPs, and antibiotics have been widely used to disinfect root canals. The aim of this paper was to review the scientific literature on (i) Effectiveness of antibiotics used in REPs against bacteria implicated in endodontic disease; (ii) Scientific evidence supporting the use of topical antibiotics in REPs; (iii) Clinical implications of the use of antibiotics in REPs and the possible side effects; (iv) Effect of antibiotics on dental pulp stem cells; and (v) Ongoing research on the use of antibiotics in REPs. Antibiotics used in REPs are effective against bacteria implicated in endodontic infections. Triple antibiotic pastes with minocycline attain complete disinfection of immature teeth with necrotic pulps, without affecting SCAP. Experimental studies carried out in dogs support the use of antibiotics in REPs. Clinical studies report high success rates of RET using antibiotics as intracanal dressings. However, tooth discolouration is an important side effect of the use of TAP. An antibiotic paste containing only metronidazole and ciprofloxacin could be a good alternative to the use of TAP. The use of antibiotic-containing scaffolds or clindamycin-modified triple antibiotic (metronidazole, ciprofloxacin and clindamycin) polymer could be a biologically safe antimicrobial drug delivery system in REPs.

BACKGROUND Clostridium difficile (CD) infection (CDI) increases patient morbidity, mortality and healthcare costs. Antibiotic treatment induces gut dysbiosis and is both a major risk factor for CD colonization and treatment of CDI. Probiotics have been trialed to support commensal gut microbiota and reduce CDI. This study investigated commensal microbe Faecalibacterium prausnitzii (FP) and a prebiotic, both known to yield butyrate and be anti-inflammatory and immunomodulatory, on CD colonization and gut integrity in mice. METHODS Mice were randomly grouped and supplemented daily with FP, prebiotic, FP + prebiotic, FP/prebiotic supernatant, or saline throughout the entire study. Following treatment with clindamycin for 3 days, mice were exposed to CD. Feces were collected at baseline, the day after antibiotic, and 1, 3, and 5 days after CD exposure and cultured for bacterial overgrowth and CD colonization. On days 1 and 5 after CD exposure, mice were randomly euthanized, and proximal colon was dissected for histological analysis and preparation of RNA for analysis of proinflammatory and anti-inflammatory cytokines. RESULTS Although all mice exhibited bacterial overgrowth and CD colonization, bacterial burden resolved quicker in the FP + prebiotic group. This was associated with induction and resolution of innate immune responses, anion exchanger, and tight junction protein preservation in proximal colon. CD toxin virulence potential was questionable as expression of CD toxin B receptor was depleted in the FP + prebiotic group. CONCLUSION Supplementation with anti-inflammatory butyrate-supporting commensal bacteria and prebiotic may support innate immune responses and minimize bacterial burden and negative effects during antibiotic and CD exposure.