Cluster of Nontoxigenic Corynebacterium diphtheriae Infective Endocarditis and Rising Background C. diphtheriae Cases-Seattle, Washington, 2020-2023.

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.

Doxycycline Prophylaxis for Skin and Soft Tissue Infections in Naval Special Warfare Trainees, United States1.

In 2015, several severe cases of skin and soft tissue infection (SSTI) among US Naval Special Warfare trainees prompted the introduction of doxycycline prophylaxis during the highest-risk portion of training, Hell Week. We performed a retrospective analysis of the effect of this intervention on SSTI incidence and resulting hospital admissions during 2013-2020. In total, 3,371 trainees underwent Hell Week training during the study period; 284 SSTIs were diagnosed overall, 29 of which led to hospitalization. After doxycycline prophylaxis was introduced, admission rates for SSTI decreased from 1.37 to 0.64 admissions/100 trainees (p = 0.036). Overall SSTI rates remained stable at 7.42 to 8.86 SSTIs/100 trainees (p = 0.185). Hospitalization rates per diagnosed SSTI decreased from 18.4% to 7.2% (p = 0.009). Average length of hospitalization decreased from 9.01 days to 4.33 days (p = 0.034). Doxycycline prophylaxis was associated with decreased frequency and severity of hospitalization for SSTIs among this population.

Applications of nitric oxide-releasing nanomaterials in dermatology: Skin infections and wound healing.

Nitric oxide (NO) is produced in most cells in the skin and is an important regulator of essential cutaneous functions, including responses to UV irradiation, microbial defense, wound healing, melanogenesis and epidermal permeability barrier homeostasis. Harnessing the physiological activities of NO for therapeutic use is difficult because the molecule is highly reactive and unstable. A variety of exogenous NO delivery platforms have been developed and evaluated; however, they have limited clinical applications in dermatology due to instability and poor cutaneous penetration. NO-releasing nanomaterials overcome these limitations, providing targeted tissue delivery, and sustained and controlled NO release. This review provides a comprehensive and up-to-date evaluation of the use of NO-releasing nanomaterials in dermatology for the treatment of skin and soft tissue infections and wound healing.

The diagnostic accuracy of Gram stain on formalin-fixed paraffin-embedded sections of skin tissue in the diagnosis of bacterial skin infection.

BACKGROUND AND OBJECTIVE: To evaluate the sensitivity, specificity, and likelihood ratios of Gram stain on formalin-fixed, paraffin-embedded (GS-FFPE) sections of skin in diagnosing bacterial skin infection. METHODS: We reviewed a retrospective series of skin specimens reported at our institution wherein histopathological assessment included Gram stain and fresh tissue was concurrently submitted for microscopy and culture. The clinicopathological correlation was the reference standard, whereby the presence of infection was deduced from the final diagnosis in each patient's case notes. RESULTS: Our sample included 168 cases (105 positive for infection). GS-FFPE showed a sensitivity of 0.43 (95% confidence interval 0.29, 0.57), a specificity of 0.98 (0.95, 1.01), a positive likelihood ratio of 21.50 (19.76, 23.24), and a negative likelihood ratio of 0.58 (0.41, 0.75). CONCLUSIONS: GS-FFPE has poor sensitivity, and a negative result should not be used as evidence to exclude infection. In contrast, it has excellent specificity and, unless the pretest probability of infection is very low, a positive result would make infection much more likely. The value of the GS-FFPE lies in cases where sterile tissue was not submitted for microbiological studies, or sterile tissue culture was negative, and there is at least a low-to-moderate pretest probability of infection.

Successful management of surgical site infection caused by Mycobacterium mageritense in a breast cancer patient.

Mycobacterium mageritense (M. mageritense), a nontuberculous mycobacterium, is classified as a rapidly growing mycobacterium, class IV in the Runyon Classification. This bacterium is found in soil, water, and other habitats. Infections caused by M. mageritense are relatively rare and no treatment protocol has been established. Herein, we report a case of skin and soft tissue infection caused by M. mageritense. A 49-year-old woman underwent surgery for right breast cancer. Four months after surgery, a surgical site infection was found, and M. mageritense was identified in the wound culture using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Based on the sensitivity results, the patient was treated with levofloxacin and doxycycline for 4 months. In addition to antimicrobial agents, aggressive surgical interventions led to a favorable course of treatment. In conclusion, successful treatment of skin and soft tissue infections with M. mageritense requires surgical intervention whenever possible, aggressive susceptibility testing, and appropriate antimicrobial therapy.

Case Commentary: Another prong of attack? Topical antibiotic instillation with negative pressure wound therapy for nontuberculous mycobacterial skin and soft tissue infections.

Nontuberculous mycobacteria (NTM) skin infections remain therapeutically challenging. Given the diversity in infections, host responses, and antimicrobials, clinical guidelines are often built on case series and observational studies. In this commentary, we respond to a paper by Stemkens et al. that introduces an emerging strategy: adjunctive negative pressure wound therapy with instillation and dwell time combined with topical antibiotics for refractory NTM skin and soft tissue infections. We delve into the primary considerations surrounding this innovative approach.

Does a Positive Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screen Predict the Risk for MRSA Skin and Soft Tissue Infection?

BACKGROUND: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited. OBJECTIVE: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs. METHODS: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel. RESULTS: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%. CONCLUSIONS: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

Botryomycosis: a rare mimic of sarcoma as an initial presentation of acquired immunodeficiency syndrome.

Botryomycosis is a rare granulomatous response to chronic bacterial infection most frequently associated with Staphylococcus aureus. This disease, which predominantly affects immunocompromised patients, may present with cutaneous, visceral, or soft tissue manifestations. Soft tissue involvement typically has an aggressive mass-like appearance on imaging which can be concerning for malignancy. In immunocompromised patients, botryomycosis can resemble fungal infection both clinically and histologically; therefore, definitive diagnosis requires tissue sampling along with histological and microbiological analysis. Presented here is a 25-year-old man with an enlarging intramuscular soft tissue mass of the right forearm as his first presentation of undiagnosed acquired immunodeficiency syndrome (AIDS). MR imaging showed a mildly T2 hyperintense and enhancing mass with infiltrative margins extending through tissue planes. Biopsy of the mass revealed Staphylococcus aureus-associated botryomycosis, which improved with nonsurgical treatment employing antibiotics. Unfortunately, the patient subsequently expired from other manifestations of his new AIDS diagnosis. This case describes the MR and PET-CT appearance of botryomycosis and also underscores that infection can mimic sarcoma, particularly in the setting of immunodeficiency.

Leclercia Adecarboxylata and Pseudomonas Oryzihabitans Infection after Achilles Tendon Repair: A Case Report and Literature Review.

Leclercia adecarboxylata and Pseudomonas oryzihabitans are two bacteria rarely seen in human infections. We present an unusual case of a patient who developed a localized infection with these bacteria after repair of a ruptured Achilles tendon. We also present a review of the literature regarding infection with these bacteria within the lower extremity.

Necrotizing Skin and Soft Tissue Infection after Gluteal Augmentation in a Perioperatively Asymptomatic COVID-19 Patient-Complications of the Post-Lockdown Era? A Case Report.

Introduction: Aesthetic surgery procedures are generally done in a relatively healthy population and carry a rather low risk compared to other surgical specialties. The incidence of complications in aesthetic surgery varies greatly depending on the type, wound cleanliness regarding the anatomical site, complexity of the surgery, patient's age, and comorbidities but is generally considered low. The overall incidence of surgical site infections (SSIs) in all aesthetic surgical procedures is around 1% in most of the literature while cases of necrotizing soft tissue infections are mostly found as individual reports. In contrast, treating COVID-19 patients is still challenging with many diverse outcomes. Surgical stress and general anesthesia are known mediators of cellular immunity impairment while studies regarding COVID-19 infection unquestionably have shown the deterioration of adaptive immunity by SARS-CoV-2. Adding COVID-19 to the modern surgical equation raises the question of immunocompetence in surgical patients. The main question of the modern post-lockdown world is: what could be expected in the postoperative period of perioperatively asymptomatic COVID-19 patients after aesthetic surgery? Case report: Here, we present a purulent, complicated, necrotizing skin and soft tissue infection (NSTI) after gluteal augmentation most likely triggered by SARS-CoV-2-induced immunosuppression followed by progressive COVID-19 pneumonia in an otherwise healthy, young patient. To the best of our knowledge, this is the first report of such adverse events in aesthetic surgery related to COVID-19. Conclusion: Aesthetic surgery in patients during the incubation period of COVID-19 or in asymptomatic patients could pose a significant risk for surgical complications, including severe systemic infections and implant loss as well as severe pulmonary and other COVID-19-associated complications.

Evaluating Differences in Opioid and Stimulant Use-associated Infectious Disease Hospitalizations in Florida, 2016-2017.

BACKGROUND: The opioid epidemic has led to increases in injection drug use (IDU)-associated infectious diseases; however, little is known about how more recent increases in stimulant use have affected the incidence and outcomes of hospitalizations for infections among people who inject drugs (PWID). METHODS: All hospitalizations of PWID for IDU-associated infections in Florida were identified using administrative diagnostic codes and were grouped by substance used (opioids, stimulants, or both) and site of infection. We evaluated the association between substance used and the outcomes: patient-directed discharge (PDD, or "against medical advice") and in-hospital mortality. RESULTS: There were 22 856 hospitalizations for infections among PWID. Opioid use was present in 73%, any stimulants in 43%, and stimulants-only in 27%. Skin and soft tissue infection was present in 50%, sepsis/bacteremia in 52%, osteomyelitis in 10%, and endocarditis in 10%. PWID using opioids/stimulants were youngest, most uninsured, and had the highest rates of endocarditis (16%) and hepatitis C (44%). Additionally, 25% of patients with opioid/stimulant use had PDD versus 12% for those using opioids-only. In adjusted models, opioid/stimulant use was associated with PDD compared to opioid-only use (aRR 1.28, 95% CI 1.17-1.40). Younger age and endocarditis were also associated with PDD. Compared to opioid-only use, stimulant-only use had higher risk of in-hospital mortality (aRR 1.26, 95% CI 1.03-1.46). CONCLUSIONS: While opioid use contributed to most IDU-associated infections, many hospitalizations also involved stimulants. Increasing access to harm reduction interventions could help prevent these infections, while further research on the acute management of stimulant use disorder-associated infections is needed.

HOME2 Study: Household Versus Personalized Decolonization in Households of Children With Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infection-A Randomized Clinical Trial.

BACKGROUND: A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members. METHODS: Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants' homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained. RESULTS: Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, -1.1% [95% confidence interval, -6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI. CONCLUSIONS: The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden. CLINICAL TRIALS REGISTRATION: NCT01814371.

Staphylococcus aureus Skin and Soft Tissue Infection Recurrence Rates in Outpatients: A Retrospective Database Study at 3 US Medical Centers.

BACKGROUND: Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) are common in healthcare and community settings, and recurrences occur at variable frequency, even after successful initial treatment. Knowing the exact burden and timing of recurrent disease is critical to planning and evaluating interventions to prevent recurrent SSTIs. METHODS: In this retrospective study, SSTI cases in patients aged ≥18 years at 3 US medical centers (Columbia, Chicago, Vanderbilt) between 2006 and 2016 were analyzed according to a biennial cohort design. Index SSTIs (with or without key comorbidities), either microbiologically confirmed to be SA-SSTI or not microbiologically tested (NMT-SSTI), were recorded within 1 calendar year and followed up for 12 months for recurrent infections. The number of index cases, proportion of index cases with ≥1 recurrence(s), time to first recurrence, and number of recurrences were collected for both SA-SSTI and NMT-SSTI events. RESULTS: In the most recent cohorts, 4755 SSTI cases were reported at Columbia, 2873 at Chicago, and 6433 at Vanderbilt. Of these, 452, 153, and 354 cases were confirmed to be due to S. aureus. Most cases were reported in patients without key comorbidities. Across centers, 16.4%-19.0% (SA-SSTI) and 11.0%-19.2% (NMT-SSTI) of index cases had ≥1 recurrence(s). In patients without key comorbidities, more than 60% of index SSTIs with recurrences had only 1 recurrence, half of which occurred in the first 3 months following primary infection. CONCLUSIONS: SA-SSTI recurrences are common among healthy adults and occur in at least 1 in 6 individuals during the 1 year following the primary event.

Evaluation of Linezolid Pharmacokinetics in Critically Ill Obese Patients with Severe Skin and Soft Tissue Infections.

Linezolid standard dosing is fixed at 600 mg every 12 h (q12h) for adults. Literature suggests critically ill, obese patients require higher doses. The study aim is 2-fold: (i) to describe linezolid pharmacokinetics (PK), and (ii) to evaluate if PK/pharmacodynamic (PD) target attainment is achieved with standard dosing in critically ill, obese patients with severe skin and soft tissue infections (SSTIs). Adult patients with a body mass index (BMI) of ≥30 kg/m2 and receiving intravenous (i.v.) linezolid from August 2018 to April 2019 were eligible for consent in this prospective study. Severe SSTIs were defined as necrotizing fasciitis, myonecrosis, or SSTI with sepsis syndrome. Four blood samples were collected at steady state at 1, 3, 5 h postinfusion and as a trough. Target attainment was defined as achieving area under the concentration-time curve from 0 to 24 h to MIC (AUC0-24h/MIC) of ≥100 h*mg/liter. Monte Carlo simulations were used to determine the probability of target attainment (PTA). Eleven patients were included in the study. The median BMI was 45.7 kg/m2, and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses, and four received 600 mg q8h. A one-compartment model described linezolid PK. Based on AUC0-24h/MIC targets, for noncirrhotic patients at 140 kg, the PTA with standard linezolid doses was 100%, 98.8%, 34.1%, and 0% for MICs of 0.5, 1, 2, and 4 mg/liter, respectively. In conclusion, target attainment of ≥90% is not achieved with standard linezolid doses for noncirrhotic patients ≥140 kg with MICs of ≥2 mg/liter. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.

Effectiveness of oritavancin for management of skin and soft tissue infections in the emergency department: A case series.

Skin and soft tissue infections, such as cellulitis, are commonly diagnosed in the emergency department and these patients are often admitted to the hospital for intravenous antibiotic therapy. Oritavancin is a novel antibiotic approved for the treatment of skin and soft tissue infections that is administered as a one-time infusion. While oritavancin has demonstrated comparable efficacy with multi-dose parenteral antibiotics in clinical trials and has been proposed as an alternative to admission for emergency department patients, there is a paucity of available real world effectiveness data. In this case series, we describe the characteristics and outcomes of ten patients with high-risk skin and soft tissue infections who received oritavancin and were discharged from the emergency department.

Point-of-Care Ultrasound Used to Distinguish Between Superficial Skin Abscess and Deep Mediastinal Abscess: A Case Report.

BACKGROUND: Skin and soft tissue infections (SSTIs) are an increasingly common complaint in the emergency department (ED), but physical examination does not reliably identify abscesses or accurately determine which skin lesions require incision and drainage. Point-of-care ultrasound (POCUS) improves management of soft tissue skin infections by detecting occult abscess, preventing unnecessary procedures, and identifying more complex disease requiring further imaging. CASE REPORT: Here, we report a case in which POCUS drastically changed the management of what initially appeared to be an uncomplicated superficial skin abscess but was actually a much more serious mediastinal infection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case underscores the importance and utility of POCUS to enhance the physical examination in suspected SSTIs. Because POCUS is easy, accurate, low risk, and can change management, we recommend its consideration as a standard component of the ED work up for SSTIs.

The Use of Dalbavancin with a Dermal Substitute Application - a Case Report.

Skin and soft tissue infections (SSTIs) are a large group of diseases with a wide range of clinically different conditions, some of which can be immediately life-threatening. A number of bacteria play an important role in the etiology of SSTIs, especially gram-positive cocci Staphylococcus aureus and Streptococcus pyogenes. In this case report, a young woman with skin defects after a fasciotomy was treated using a dermal substitute application. Multiple infectious complications in the skin and soft tissues with a high risk of development of phlebitis and with significant intolerance to a variety of antimicrobials were observed. The dramatic SSTI was treated using intravenous administration of dalbavancin, a very potent bactericidal antibiotic representing a rational option in the treatment of SSTIs caused by gram-positive bacteria.

Skin and Soft Tissue Infection in People Living With Human Immunodeficiency Virus in a Large, Urban, Public Healthcare System in Houston, Texas, 2009-2014.

BACKGROUND: Skin and soft tissue infections (SSTIs) disproportionately impact patients with human immunodeficiency virus (HIV). Recent declines in the incidence of SSTIs have been noted in the non-HIV population. We sought to study the epidemiology and microbiology of SSTIs in a population of 8597 patients followed for HIV primary care in a large, urban county system from January 2009 to December 2014. METHODS: SSTIs were identified from the electronic medical record by use of International Classification of Diseases-9 billing codes. Charts were reviewed to confirm each patient's diagnosis of acute SSTI and abstract culture and susceptibility data. We calculated the yearly SSTI incidences using Poisson regression with clustering by patient. RESULTS: There were 2202 SSTIs identified. Of 503 (22.8%) cultured SSTIs, 332 (66.0%) recovered Staphylococcus aureus as a pathogen, of which 287/332 (86.4%) featured S. aureus as the sole isolated organism. Among the S. aureus isolates that exhibited antibiotic susceptibilities, 231/331 (69.8%) were methicillin resistant, and the proportion did not change by year. The observed incidence of SSTI was 78.0 per 1000 person-years (95% confidence interval 72.9-83.4) and declined from 96.0 infections per 1000 person-years in 2009 to 56.5 infections per 1000 person-years in 2014 (P < .001). Other significant predictors of SSTI incidences in both univariate as well as multivariate analyses included a low CD4 count, high viral load, and not being a Spanish-speaking Hispanic. CONCLUSIONS: SSTIs remain a significant problem in the outpatients living with HIV, although rates of SSTIs appear to have declined by approximately 40% between 2009 and 2014.

National Trends in Incidence of Purulent Skin and Soft Tissue Infections in Patients Presenting to Ambulatory and Emergency Department Settings, 2000-2015.

Nationally representative data from 2000-2015 demonstrated a rise in the incidence of outpatient visits for skin infections, peaking in 2010-2013, followed by a plateau. While cephalexin was the most frequently prescribed antibiotic at the beginning, trimethoprim-sulfamethoxazole was most frequently prescribed by the end of the study period.