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Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m2 administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m2 administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash—a class effect of EGFR antibodies—that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11·5 months [95% CI 10·4–12·6]) vs 9·9 months [8·9–11·1]; stratified hazard ratio 0·84 [95% CI 0·74–0·96; p=0·01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3–4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [<1%]). Including events related to disease progression, adverse events with an outcome of death were reported for 66 (12%) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 (11%) of 541 patients in the gemcitabine and cisplatin group; these were deemed to be related to study drugs in 15 (3%) and ten (2%) patients, respectively. Overall, we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations. Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease. Eli Lilly and Company.

Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea. G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227. Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group). Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea. UK National Institute for Health Research.

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti-type VII collagen autoantibodies in patients' blood or skin. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. ClinicalTrials.gov NCT02698735. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and VA Merit Award.

Few therapies for cutaneous leishmaniasis are available. In this phase 3 trial involving 375 patients with cutaneous leishmaniasis in Tunisia, paromomycin-based topical creams, as compared with a control agent, improved healing of lesions caused by Leishmania major . Leishmania, a genus of trypanosomatid protozoa, is endemic in 98 countries or territories worldwide, with infection transmitted by the bite of a female sand fly. The estimated yearly incidence of leishmania infection is 1.5 million cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis. 1 Cutaneous leishmaniasis results from the parasitization of skin macrophages and generally is manifested as a papule that enlarges to a nodule that often ulcerates during a period of 1 to 3 months. Diverse leishmania species cause cutaneous leishmaniasis. There are at least five species, including Leishmania major, on the Eurasian and African continents and seven . . .

Data on treatments for bubonic plague are limited. In this open-label, randomized, controlled trial in Madagascar, ciprofloxacin monotherapy was noninferior to a standard aminoglycoside–ciprofloxacin regimen.

Background This study aimed to elucidate the safety and intra-articular elution profiles of vancomycin and gentamicin bone cement in patients undergoing primary total knee arthroplasty (TKA), with a focus on serum safety thresholds and therapeutic efficacy. Methods Consecutive patients who underwent unilateral primary TKA were prospectively enrolled. The implants were fixed using gentamicin-impregnated bone cement, and after arthrotomy closure, 1000 mg of vancomycin suspended in 25 mL of normal saline was directly injected into the joint. Peripheral venous blood and drain fluid samples were collected 2, 8, and 24 h postoperatively. The serum and intra-articular concentrations of vancomycin and gentamicin were analyzed using liquid chromatography-tandem mass spectrometry within 24 h. Results Clinical data reflecting renal and liver function were recorded preoperatively, and at 24 and 72 h postoperatively. A total of 100 patients were included. At 2, 8, and 24 h postoperatively, the serum vancomycin concentration was 7.0 ± 2.0, 5.7 ± 1.8, and 3.6 ± 1.4 µg/mL, respectively, while the intra-articular concentration was 468.5 (interquartile range [IQR] 286.0 to 774.8), 139.5 (IQR 52.0 to 295.3), and 34.4 (IQR 22.2 to 56.8) µg/mL, respectively; 33.2 (IQR 19.5 to 80.5) mg vancomycin was lost in drainage fluid at 24 h postoperatively. For gentamicin, the overall intra-articular concentration was 70.4 (IQR 35.4 to 109.2), 33.8 (IQR 17.8 to 73.9), and 21.1 (IQR 12.2 to 36.0) µg/mL at 2, 8, and 24 h postoperatively, respectively, with an undetectable serum concentration. No cases of acute renal injury, liver injury, ototoxicity, or anaphylaxis were observed. Conclusions Intra-articular injection of 1000 mg vancomycin after arthrotomy closure combined with gentamicin-impregnated bone cement provided a therapeutic intra-articular concentration while avoiding systemic toxicity over the initial 24 h after primary TKA. Therefore, intra-articular vancomycin administration may offer a safer alternative to intravenous antibiotics, reducing systemic toxicity; however, further large-scale studies are necessary. Trial registration ClinicalTrials. Gov (registration number: NCT05338021).

Abstract Rationale Bronchiectasis is a chronic debilitating disease with few evidence-based long-term treatments. Objectives A randomized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non–cystic fibrosis bronchiectasis. Methods Sixty-five patients were randomized to either twice-daily nebulized gentamicin, 80 mg, or nebulized 0.9% saline, for 12 months. All were reviewed at three-monthly intervals during treatment and at 3 months' follow-up. Measurements and Main Results At each review the following were assessed: quantitative and qualitative sputum bacteriology; sputum purulence and 24-hour volume; FEV1, FVC, and forced expiratory flow, midexpiratory phase; exercise capacity; Leicester Cough Questionnaire and St. George's Respiratory Questionnaire; and exacerbation frequency. Fifty-seven patients completed the study. At the end of 12 months' treatment, compared with the saline group, in the gentamicin group there was reduced sputum bacterial density with 30.8% eradication in those infected with Pseudomonas aeruginosa and 92.8% eradication in those infected with other pathogens; less sputum purulence (8.7% vs. 38.5%; P < 0.0001); greater exercise capacity (510 [350–690] m vs. 415 [267.5–530] m; P = 0.03); and fewer exacerbations (0 [0–1] vs. 1.5 [1–2]; P < 0.0001) with increased time to first exacerbation (120 [87–161.5] d vs. 61.5 [20.7–122.7] d; P = 0.02). The gentamicin group had greater improvements in Leicester Cough Questionnaire (81.4% vs. 20%; P < 0.01) and St. George's Respiratory Questionnaire (87.5% vs. 19.2%; P < 0.004) score. No differences were seen in 24-hour sputum volume, FEV1, FVC, or forced expiratory flow, midexpiratory phase. No P. aeruginosa isolates developed resistance to gentamicin. At follow-up, all outcome measures were similar to baseline. Conclusions Regular, long-term nebulized gentamicin is of significant benefit in non–cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy. Clinical trial registered with www.clinicaltrials.gov (NCT00749866).

Postoperative surgical site infections (SSIs) in neurosurgery remain a significant concern due to their associated high morbidity and mortality. Consequently, implementing the most effective preventive measures is essential. One such strategy, intraoperative antibiotic irrigation, has been widely employed; however, its efficacy continues to be debated. Numerous studies have examined the use of various antibiotics, including streptomycin, bacitracin, gentamicin, rifamycin, amikacin, and vancomycin. Among these, gentamicin has shown promising results in reducing SSI rates, although other antibiotics have also demonstrated potential. Further research is required to determine the most effective method for minimizing SSIs in neurosurgical procedures. To compare the postoperative outcomes of gentamicin irrigation versus normal saline irrigation in the prevention of surgical site infections (SSIs) in neurosurgical procedures. A prospective randomized controlled trial was conducted at Rajavithi Hospital between 2023 and 2025. A total of 136 patients were enrolled and randomly assigned, using a block-of-four randomization method, into two groups: the gentamicin irrigation group (n = 68) and the normal saline irrigation group (n = 68). Postoperative surgical site infection (SSI) rates were monitored and statistically analyzed. A total of 136 patients were included in this study, with 68 patients (50 %) receiving gentamicin irrigation and 68 patients (50 %) receiving normal saline irrigation. There were no statistically significant differences between the two groups in terms of sex, age, body weight, underlying conditions, operative status, complications, operative time, length of hospital stay, or disease type. The postoperative surgical site infection (SSI) rate was 6 % in both groups (4 patients each; p = 0.443). In the gentamicin irrigation group, wound infection grade 3 was observed in 2 patients (3 %), and grade 4 in another 2 patients (3 %). In the normal saline group, 4 patients (6 %) developed grade 4 wound infections. Gentamicin irrigation did not demonstrate a significant advantage over normal saline irrigation in preventing postoperative surgical site infections when intravenous antibiotics were concurrently administered in neurosurgical patients. •Overall infection rates were similar between the two groups (6 %).•The incidence of meningitis was higher in the normal saline group compared to the antibiotic irrigation group.•No significant differences were found in baseline characteristics, operative conditions, complications, length of stay, or mortality between the groups.•The study's strengths include its prospective randomized design, standardized protocols, and careful analysis of clinically relevant outcomes.

Paromomycin-based topical treatments were shown to be effective in curing cutaneous leishmaniasis (CL) lesions caused by Leishmania major in Tunisia. Cure rates of an index lesion were approximately 80%. As a follow on, we conducted a similar Phase 3 trial in Panama to demonstrate the efficacy of these treatments against New World species. The primary objective was to determine if a combination topical cream (paromomycin-gentamicin) resulted in statistically superior final clinical cure rates of an index lesion compared to a paromomycin alone topical cream for the treatment of CL, primarily caused by Leishmania panamensis. We conducted a randomized, double blind, Phase 3 trial of topical creams for the treatment of CL caused by Leishmania spp. Three hundred ninety nine patients with one to ten CL lesions were treated by topical application once daily for 20 days. The primary efficacy endpoint was percentage of subjects with clinical cure of an index lesion confirmed to contain Leishmania with no relapse. The clinical cure of the index lesion for paromomycin-gentamicin was 79% (95% CI; 72 to 84) and for paromomycin alone was 78% (95% CI; 74 to 87) (p = 0.84). The most common adverse events considered related to study cream application were mild to moderate dermatitis, pain, and pruritus. Superiority of paromomycin-gentamicin was not demonstrated. However, the approximately 80% cure rates for both topical creams were similar to those demonstrated in Tunisia and previously reported with parenteral antimonials.

Surgical site infection (SSI) continues to be a common complication of surgery. The real benefit of using topical antibiotics for the prevention of SSI in abdominal hernia repair surgery is still unknown. This study aimed to evaluate the usefulness of topical gentamicin in SSI prophylaxis in incisional hernia repair with mesh. A randomized controlled trial was conducted in patients undergoing open incisional hernia repair. Patients were randomly assigned to one of two groups: in the gentamicin group, each layer of the abdominal wall was irrigated with gentamicin solution before wound closure, and in the saline solution group (placebo), each layer of the abdominal wall was irrigated with normal saline solution. The incidence of SSI and other surgical site complications was compared between both groups, and the presence of adverse effects with the use of topical gentamicin. Data from 146 patients were included for analysis: 74 in the gentamicin group and 72 in the saline solution group. SSI was observed in six patients (8.1%) in the gentamicin group and eight patients (11.1%) in the saline solution group, with no significant differences ( p  = 0.538) between both groups. No statistically significant differences were observed in the presentation of seroma, hematoma, and surgical wound dehiscence between both groups. No adverse effects were reported from topical application of gentamicin. In this clinical trial, the use of topical gentamicin in incisional hernia repair with mesh did not significantly reduce the incidence of SSI. EU Clinical Trials Register: EudraCT 2018-001860-45 (04/07/2019).