Crystalline Retinopathy Following Intravitreal Clindamycin.

This case report describes a 74-year-old woman who developed a crystalline retinopathy following intravitreal injection of clindamycin. The patient presented with ocular toxoplasmosis in the left eye but was allergic to sulfa medications, so she was treated with intravitreal clindamycin. Subsequently, fine refractile yellow-white crystals were observed on examination of the left macula. Optical coherence tomography localized the crystals to the posterior hyaloid. Intravitreal clindamycin should be considered in the differential diagnosis of crystalline retinopathy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:168-170.].

Acute generalized exanthematous pustulosis associated with clindamycin in a patient with Hailey-Hailey disease.

A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.

Economic Viability of Penicillin Allergy Testing to Avoid Improper Clindamycin Surgical Prophylaxis.

OBJECTIVE: Patients mislabeled with a penicillin allergy are often unnecessarily given prophylactic clindamycin. Thus, otolaryngologists may cause harm due to clindamycin's associated risk of Clostridioides difficile infections (CDI) and surgical site infections (SSI). The objective of this study was to determine the economic feasibility of penicillin allergy testing in preventing unnecessary clindamycin use among patients with an unconfirmed penicillin allergy prior to otolaryngologic surgery. METHODS: A break-even analysis was performed using the average cost of penicillin allergy testing and a CDI/SSI to calculate the absolute risk reduction (ARR) in baseline CDI/SSI rate due to clindamycin required for penicillin testing to be economically sustainable. The binomial distribution was used to calculate the probability that current penicillin testing can achieve this study's ARR. RESULTS: Preoperative penicillin testing was found to be economically sustainable if it could decrease the baseline CDI rate by an ARR of 1.06% or decrease the baseline SSI rate by an ARR of 1.34%. The probability of penicillin testing achieving these ARRs depended on the baseline CDI and SSI rates. When the CDI rate was at least 5% or the SSI rate was at least 7%, penicillin allergy testing was guaranteed to achieve economic sustainability. CONCLUSION: In patients mislabeled with a penicillin allergy, preoperative penicillin allergy testing may be an economically sustainable option to prevent the unnecessary use of prophylactic clindamycin during otolaryngologic surgery. Current practice guidelines should be modified to recommend penicillin allergy testing in patients with an unconfirmed allergy prior to surgery. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1086-1091, 2023.

Safety of linezolid, rifampicin, and clindamycin combination therapy in patients with prosthetic joint infection.

We investigated adverse events in patients with prosthetic joint infections receiving combination therapy with linezolid, rifampicin, and clindamycin for ≥ 7 days. Twenty-two patients were evaluated. The combination therapy was administered for 15.5 (7-29) days at dosages of 1200, 450, and 450-1200 mg/day for linezolid, rifampicin, and clindamycin, respectively. Adverse events (gastrointestinal, eye, and skin disorders; liver damage; myelosuppression; hyponatremia, and others) were recorded. The incidence rates of leukopenia, neutropenia, anemia, thrombocytopenia, and hyponatremia were 36.4%, 31.8%, 40.9%, 18.2%, and 18.2%, respectively. Common Terminology Criteria for Adverse Events version 5.0 Grade 3 neutropenia, anemia, and hyponatremia were observed. The incidence rate of myelosuppression was higher following combination therapy compared with that previously reported following single-drug administration. All patients were discharged after the infection was under control. It is important to monitor these adverse events during combination therapy with the aforementioned agents; these conditions may be relieved by discontinuing linezolid.

Comparison of immediate hypersensitivity reactions to preoperative antibiotics in patients labeled as penicillin allergic.

BACKGROUND: Cefazolin is routinely recommended as the first-line agent for surgical antibiotic prophylaxis because it prevents more surgical site infections than second-line antibiotics. Clinicians often avoid administering cefazolin to patients who are labeled as penicillin allergic due to concerns of cross-reactivity. The aim of this study was to compare the incidence of hypersensitivity reactions between cefazolin and the second-line antibiotics vancomycin and clindamycin. METHODS: This retrospective study included patients who were labeled as penicillin allergic and received either cefazolin, clindamycin, or vancomycin as preoperative antibiotics. The primary outcome was intraoperative hypersensitivity reactions. RESULTS: A total of 734 surgical procedures in 690 patients were included. Fifteen immediate hypersensitivity reactions were identified. Probable hypersensitivity reactions occurred in 3 (0.9%) patients in the cefazolin group, 4 (1.4%) in the clindamycin group, and 1 (1.1%) in the vancomycin group. Seven of 8 patients reported allergies to additional medications beyond penicillin. There were seven cases of possible hypersensitivity reactions, 3 (0.9%) in the cefazolin group, 1 (1.1%) in the vancomycin group, and 3 (1.0%) in the clindamycin group. CONCLUSION: Our data suggest that perioperative hypersensitivity reactions are uncommon in patients labeled as penicillin allergic. The frequency of immediate hypersensitivity reactions was not different between patients receiving cefazolin, clindamycin, or vancomycin. Avoiding cefazolin in patients labeled as penicillin allergic may not be warranted.

Safety of administering cefazolin versus other antibiotics in penicillin-allergic patients for surgical prophylaxis at a major Canadian teaching hospital.

BACKGROUND: Cefazolin surgical prophylaxis is associated with better patient outcomes; however, its use in penicillin-allergic patients is controversial. We evaluated the safety of cefazolin as surgical prophylaxis in penicillin-allergic patients, including those with anaphylaxis histories. METHODS: We conducted a pre and postintervention quality improvement evaluation of an institution-wide policy change at a tertiary-care hospital, before (October 2017-January 2018), during (February 2018-September 2018), and after (October 2018-October 2019) transition to routine cefazolin prophylaxis for penicillin-allergic patients, including those with anaphylaxis histories but excluding severe delayed reactions (eg, Stevens-Johnson syndrome). Retrospective data was collected on all surgical prophylaxis patients with penicillin-anaphylactic histories between October 2017 and September 2018. From October 2018, we prospectively reviewed adverse events with cefazolin. Primary outcome was adverse events in penicillin-allergic patients receiving cefazolin perioperatively. RESULTS: From October 2017 to October 2019, 27,467 operations were performed. Of 220 patients with penicillin-anaphylactic histories reviewed prior to the full policy change, no statistically significant differences were reported in allergic reactions (P = .70), surgical site infections (P = 1.00), or adverse events (P = .32) with cefazolin compared to other antibiotics. Postpolicy implementation, cefazolin usage increased 18.2%, while vancomycin and clindamycin decreased by 11.4% and 62.0%, respectively. No anaphylaxis was documented in penicillin-allergic patients receiving cefazolin in either the review or quality assurance follow-up after the change. Of 3 patients developing reactions to cefazolin, none had histories of penicillin allergy. Surgical site infection rates were similar between pre and postpolicy time periods (P = .842). CONCLUSION: Administration of cefazolin in penicillin-anaphylactic patients for surgical prophylaxis appears to be safe.

Clindamycin-induced acute generalized exanthematous pustulosis: A case report.

RATIONALE: Acute generalized exanthematous pustulosis (AGEP) is a severe pustular cutaneous adverse drug reaction. Sterile, non-follicular pustules overlying the erythematous skin characterize this reaction. PATIENT CONCERNS: A 30-year-old Asian women presented with sterile, non-follicular lesions with pus-fluid levels on her back 2 days after taking clindamycin. Skin biopsy revealed a spongiotic change in the epidermis with a focal subcorneal pustule and perivascular eosinophil and lymphocyte infiltration. DIAGNOSIS: Clindamycin-induced AGEP. INTERVENTIONS: We discontinued clindamycin treatment and prescribed systemic corticosteroids. OUTCOMES: The pustule stopped spreading within 1 day and the rash improved within 2 days. LESSONS: AGEP is a pustular cutaneous adverse drug reaction that can appear with pus-fluid levels, clinically mimicking Sneddon-Wilkinson disease. The differentiation between both conditions is a history of drug use, characteristic skin lesions and histopathology.

Microbiota in vitro modulated with polyphenols shows decreased colonization resistance against Clostridioides difficile but can neutralize cytotoxicity.

While the knowledge on gut microbiota - C. difficile interactions has improved over the years, the understanding of the underlying mechanisms providing colonization resistance as well as preventative measures against the infection remain incomplete. In this study the antibiotic clindamycin and polyphenol extracts from pomegranate and blueberries were used individually and in combination to modulate fecal microbial communities in minibioreactor arrays (MBRA). Modulated communities were inoculated with C. difficile (ribotype 027). Subsequent 7-day periodical monitoring included evaluation of C. difficile growth and activity of toxins TcdA and TcdB as well as analysis of MBRA bacterial community structure (V3V4 16 S metagenomics). Polyphenols affected multiple commensal bacterial groups and showed different synergistic and antagonistic effects in combination with clindamycin. Exposure to either clindamycin or polyphenols led to the loss of colonization resistance against C. difficile. The successful growth of C. difficile was most significantly correlated with the decrease in Collinsella and Lachnospiraceae. Additionally, we demonstrated that Clostridium sporogenes decreased the activity of both C. difficile toxins TcdA and TcdB. The feature was shown to be common among distinct C. sporogenes strains and could potentially be applicable as a non-antibiotic agent for the alleviation of C. difficile infection.

Clostridioides difficile-Associated Antibiotics Alter Human Mucosal Barrier Functions by Microbiome-Independent Mechanisms.

A clinically relevant risk factor for Clostridioides difficile-associated disease (CDAD) is recent antibiotic treatment. Although broad-spectrum antibiotics have been shown to disrupt the structure of the gut microbiota, some antibiotics appear to increase CDAD risk without being highly active against intestinal anaerobes, suggesting direct nonantimicrobial effects. We examined cell biological effects of antibiotic exposure that may be involved in bacterial pathogenesis using an in vitro germfree human colon epithelial culture model. We found a marked loss of mucosal barrier and immune function with exposure to the CDAD-associated antibiotics clindamycin and ciprofloxacin, distinct from the results of pretreatment with an antibiotic unassociated with CDAD, tigecycline, which did not reduce innate immune or mucosal barrier functions. Importantly, pretreatment with CDAD-associated antibiotics sensitized mucosal barriers to C. difficile toxin activity in primary cell-derived enteroid monolayers. These data implicate commensal-independent gut mucosal barrier changes in the increased risk of CDAD with specific antibiotics and warrant further studies in in vivo systems. We anticipate this work to suggest potential avenues of research for host-directed treatment and preventive therapies for CDAD.

Perioperative Clindamycin Use in Penicillin Allergic Patients Is Associated With a Higher Risk of Infection After Shoulder Arthroplasty.

BACKGROUND: This study determines whether infection rates differ between prophylactic antibiotic use for patients with or without penicillin allergy before shoulder arthroplasty surgery. METHODS: Seven thousand one hundred forty primary shoulder arthroplasties operated between 2005 and 2016 were identified. We compared deep surgical site infection risk of patients who received perioperative vancomycin alone (6.2%, N = 444) or clindamycin alone (7.1%, N = 508) for penicillin allergy versus patients who received cefazolin alone without penicillin allergy (86.7%, N = 6,188). RESULTS: Seventy deep infections (1.2% 5-year cumulative incidence) were observed. The most common organism was Cutibacterium acnes (39.4%, N = 27). Compared with patients treated with cefazolin, infection risk was not different for those treated with vancomycin (hazard ratio = 1.17, 95% confidence interval 0.42 to 3.30, P = 0.8), but a higher risk of infection was identified for those treated with clindamycin alone (hazard ratio = 3.45, 95% confidence interval 1.84 to 6.47, P < 0.001). CONCLUSION: A higher risk of postoperative infection is found after prophylactic use of intravenous clindamycin antibiotic after shoulder arthroplasty. Vancomycin is preferred over clindamycin for patients with penicillin allergy. LEVEL OF EVIDENCE: III, retrospective cohort study.

Symmetrical drug-related intertriginous and flexural exanthema due to clindamycin.

Systemic drug exposure can produce a skin reaction consisting of symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) occurs after systemic exposure to a drug in which the patient was not previously sensitised, either in the first dose or after several doses. The mechanism of SDRIFE is unknown but is hypothesised to be the result of a delayed hypersensitivity response resulting in a cutaneous eruption some days after the exposure to the drug. The diagnosis should be clinical, based on the history and examination, but skin tests can also be performed to confirm sensitisation. But, as always, the gold-standard test is oral provocation. It is important to know this clinical entity to prevent re-exposure to the responsible allergen in the future.

Sinus Augmentation Failure and Postoperative Infections Associated with Prophylactic Clindamycin Therapy: An Observational Case Series.

PURPOSE: This observational study was based on a series of clinical cases in which failure of sinus augmentations occurred in patients who received prophylactic clindamycin therapy. MATERIALS AND METHODS: Between the years 2006 and 2010, a retrospective observational study was performed. The study consisted of 1,874 patients (723 males and 1,151 females) in whom sinus augmentations were performed prior to placement of dental implants. RESULTS: In nine (0.48%) patients (four males and five females), infection of the graft material inside the sinus floor occurred, and six patients developed an abscess in the site of surgery, 4 to 6 weeks postoperatively. In three patients, a buccal fistula with pus draining was observed 5 to 8 weeks postoperatively. In all patients, the source of infection was from the grafted material within the sinus. A common manifestation in all nine patients was that they had self-reported penicillin allergy and had been prescribed clindamycin (300 mg every 6 hours for 10 days). CONCLUSION: Prophylactic clindamycin therapy following sinus augmentation procedures seems to be a risk factor for infections and loss of grafting material following these surgical techniques.

Clindamycin-induced Maculopapular Exanthema with Preferential Involvement of Striae Distensae: A Koebner phenomenon?

Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier. Her past clinical history included hypertension, hypothyroidism, hyperuricemia, cholecystectomy, caesarean section, and endometriosis-related abdominal surgery, and she was taking levothyroxine, allopurinol, imidapril, and omeprazole. The skin rash first developed on her neck and back on the 3rd day of clindamycin oral treatment (300 mg every 6 hours), which was prescribed as antibiotic prophylaxis for a tooth implant. General malaise (but not fever) was also reported. Physical examination revealed an erythematous maculopapular eruption symmetrically distributed on the neck, abdomen, and back (Figure 1, A), with isolated lesions involving the proximal upper and lower limbs (Figure 1, B). There was a striking vertical distribution of skin lesions along the SD on the lateral sides of the abdomen (Figure 1, C). No mucosal involvement was found, and laboratory studies showed no abnormalities. Clindamycin withdrawal was followed by prescription of a course of oral deflazacort, starting at 30 mg daily and tapering down during a 9-day period. On the 5th day of treatment, the rash had almost cleared with minimal desquamation (Figure 1, D). Eight weeks after clearance of the skin rash, informed consent was obtained in order to perform an allergological evaluation of clindamycin, including prick and intradermal (ID) tests on the forearm and patch tests on the upper back (2). For patch testing, powder of the commercial capsules (Dalacin®) was diluted in petrolatum (pet.) and water (aq.), resulting in a final 1% clindamycin dilution. Parenteral clindamycin preparations were used in therapeutic concentrations for prick tests (150 mg/mL) and dilutions in saline of 1/100 and 1/10 for the ID test. Other authors have reported that these concentrations do not seem to irritate the skin (3-6). Prick and ID tests were assessed after 20 min and 24 hours, respectively. Patch tests were removed after the 2nd day, and late reactions were evaluated on day 2 and day 4. Prick and ID test results after 20 min were negative. Late results of ID tests with clindamycin (1.5 and 15 mg/mL) were positive: erythematous infiltrated papules about 7×7 mm and 18×15 mm were observed at 24 hours and lasted until the 8th day. Patch tests with clindamycin 1% in pet. and 1% in aq. were also positive (+ on day 2 and day 4). Positive late skin tests suggested delayed-type non-IgE-mediated allergic clindamycin hypersensitivity. Oral challenge tests are considered to be the gold standard to establish or exclude drug hypersensitivity. Due to the positive result of late skin test to clindamycin, oral challenge was not performed in our patient (3,5). The Koebner isomorphic phenomenon has been described in cutaneous reactions induced by drugs, such as antibiotics and chemotherapy. Chronic pressure on the skin is probably involved in the onset of skin lesions in hand-foot eruptions induced by tyrosine kinase inhibitors (sorafenib and sutinib). Solar exposure and cutaneous trauma also seem to play a role in the location of papulopustular eruptions caused by endothelial growth factor receptor inhibitors (erlotinib) (7). More frequent involvement in traumatized skin and surgical scars has been reported in the context of linear IgA bullous dermatosis and leukocytoclastic vasculitis triggered by vancomycin and cefuroxime (8). SD are produced by non-penetrating physical trauma, similar to friction or pressure. Different dermatoses can develop along SD skin lesions (like plaque psoriasis, pustular psoriasis, lichen planus, vitiligo, discoid lupus erythematosus, lupus vasculitis, urticarial vasculitis, or chronic graft-versus-host disease) (9). Bevacizumab, etretinate, and corticosteroid-induced ulcers, hyperpigmentation caused by bleomycin, and urticariform lesions triggered by diclofenac are examples of different type of drug-induced abnormalities involving SD (10). In summary, we identified clindamycin as the cause of the cutaneous reactions that occurred in our patient on the basis of the results of the skin tests and clinical history. Our findings confirmed a delayed-type hypersensitivity reaction, possibly involving a T-cell-mediated immunologic mechanism. Intradermal and patch tests were found to be useful in order to confirm the diagnosis (4,5). We did not find reports in the literature of drug-induced cutaneous eruptions along the SD as a manifestation of a Koebner phenomenon. Clinical underreporting of this phenomenon could explain the scarce literature on this cutaneous adverse reaction.

A Case of a Paediatric Patient With Allergic Contact Dermatitis to Benzoyl Peroxide.

Allergic contact dermatitis to benzoyl peroxide can occur in up to 6.5% of those with a history of exposure to this potential allergen. Conversely, irritant contact dermatitis is very common with benzoyl peroxide and can be differentiated from allergic contact dermatitis based on the patient's history and clinical signs and symptoms. We present a case of a paediatric patient with patch test-confirmed severe allergic contact dermatitis to benzoyl peroxide requiring hospitalisation and systemic treatment.

Antibiotic-Induced Depletion of Anti-inflammatory Clostridia Is Associated with the Development of Graft-versus-Host Disease in Pediatric Stem Cell Transplantation Patients.

Adult stem cell transplantation (SCT) patients with graft-versus-host-disease (GVHD) exhibit significant disruptions in gut microbial communities. These changes are associated with higher overall mortality and appear to be driven by specific antibiotic therapies. It is unclear whether pediatric SCT patients who develop GVHD exhibit similar antibiotic-induced gut microbiota community changes. Here, we show that pediatric SCT patients (from Children's Medical Center Dallas, n = 8, and Cincinnati Children's Hospital, n = 7) who developed GVHD showed a significant decline, up to 10-log fold, in gut anti-inflammatory Clostridia (AIC) compared with those without GVHD. In fact, the development of GVHD is significantly associated with this AIC decline and with cumulative antibiotic exposure, particularly antibiotics effective against anaerobic bacteria (P = .003, Firth logistic regression analysis). Using metagenomic shotgun sequencing analysis, we were able to identify specific commensal bacterial species, including AIC, that were significantly depleted in GVHD patients. We then used a preclinical GVHD model to verify our clinical observations. Clindamycin depleted AIC and exacerbated GVHD in mice, whereas oral AIC supplementation increased gut AIC levels and mitigated GVHD in mice. Together, these data suggest that an antibiotic-induced AIC depletion in the gut microbiota is associated with the development of GVHD in pediatric SCT patients.

Increased Surgical Site Infection Rates following Clindamycin Use in Head and Neck Free Tissue Transfer.

OBJECTIVE: The development of surgical site infections (SSIs) can put the viability of free tissue transfer reconstructions at risk, often resulting in considerable postoperative morbidity and prolonged hospitalization. Current antibiotic prophylactic guidelines suggest a first- or second-generation cephalosporin with metronidazole for clean-contaminated cases and recommend clindamycin as an alternative choice in penicillin-allergic patients. This study was designed to examine the rates of postoperative infection associated with prophylactic antibiotic regimens, including patients receiving clindamycin as an alternative due to penicillin allergy. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic medical center. SUBJECTS: Patients undergoing major ablative head and neck resection involving the pharynx and oral cavity reconstructed via free tissue transfer. METHODS: The sample included patients (n = 266) who underwent free tissue transfer involving the oral cavity and pharynx from 2009 to 2014. Data included demographic data, medical comorbidities, anatomic tumor subsite and surgical procedure, and prophylactic antibiotic regimen. SSI data were examined up to 30 days after the initial surgical procedure. Multivariate logistic regression analysis was performed to determine the overall risk for SSI. Culture data were also reviewed. RESULTS: The data indicated that clindamycin was associated with an approximate 4-fold increased risk for SSI (odds ratio, 3.784; 95% confidence interval: 1.367-10.470 [P = .010]) after controlling for possible confounding factors. CONCLUSION: For patients with a true penicillin allergy, we recommend broader gram-negative coverage with alternative antibiotics, such as cefuroxime, when undergoing free tissue transfer in the head and neck.