Comparative study of oral microbiota in the experimental long-term opioid exposure, after its withdrawal and the use of complex drug correction.

OBJECTIVE: Aim: To study changes of dental biofilm microbiota composition during experimental opioid exposure, after its withdrawal and when using of complex drug correction.. PATIENTS AND METHODS: Materials and Methods: Microbiological studies (48 rats) included microscopic and bacteriological methods, as well as determination of antibiotic susceptibility of microbial isolates. Ceftriaxone and pentoxifylline were used to correction the changes. RESULTS: Results: The action of opioid for 10 weeks caused considerable changes in the microbiocenosis, which was illustrated by a significant increasing of the opportunistic pathogens quantitative indicators and the emergence of pathogenic microbiota. Changes in the microbiocenosis at 6 weeks of opioid exposure and after its withdrawal for 4 weeks were expressed in the appearance of pathogenic microbiota and the absence of significant differences in quantitative indicators of saprophytic and opportunistic microflora compared to similar indicators in animals with 10 weeks opioid exposure. This indicated a slow progression of dysbiotic changes and the inflammatory process in the oral cavity of rats. CONCLUSION: Conclusions: After 10 weeks of experiment with opioid administration for 6 weeks and the use of ceftriaxone and pentoxifylline on the background of 4-week opioid withdrawal, a significant reduction of quantitative indicators of opportunistic bacteria and elimination of pathogenic species of microorganisms was determined. The use of complex drug correction on the background of 10 weeks of opioid exposure led to a significant reduction in the quantitative indicators of opportunistic pathogens and contributed to the elimination of most pathogenic species of microbiota under the action of ceftriaxone.

Minimum inhibitory concentrations of Neisseria gonorrhoeae strains in clients of the Amsterdam sexual health clinic with a Dutch versus an international sexual network.

OBJECTIVES: International travel combined with sex may contribute to dissemination of antimicrobial-resistant (AMR) Neisseria gonorrhoeae (Ng). To assess the role of travel in Ng strain susceptibility, we compared minimum inhibitory concentrations (MICs) for five antibiotics (ie, azithromycin, ceftriaxone, cefotaxime, cefixime and ciprofloxacin) in strains from clients with an exclusively Dutch sexual network and clients with an additional international sexual network. METHODS: From 2013 to 2019, we recorded recent residence of sexual partners of clients (and of their partners) with Ng at the Center for Sexual Health of Amsterdam. We categorised clients as having: (1) exclusively sexual partners residing in the Netherlands ('Dutch only') or (2) at least one partner residing outside the Netherlands. We categorised the country of residence of sexual partners by World Bank/EuroVoc regions. We analysed the difference of log-transformed MIC of Ng strains between categories using linear or hurdle regression for each antibiotic. RESULTS: We included 3367 gay and bisexual men who had sex with men (GBMSM), 516 women and 525 men who exclusively had sex with women (MSW) with Ng. Compared with GBMSM with a 'Dutch only' network, GBMSM with: (1) a Western European network had higher MICs for ceftriaxone (ß=0.19, 95% CI=0.08 to 0.29), cefotaxime (ß=0.19, 95% CI=0.08 to 0.31) and cefixime (ß=0.06, 95% CI=0.001 to 0.11); (2) a Southern European network had a higher MIC for cefixime (ß=0.10, 95% CI=0.02 to 0.17); and (3) a sub-Saharan African network had a lower MIC for ciprofloxacin (ß=-1.79, 95% CI=-2.84 to -0.74). In women and MSW, higher MICs were found for ceftriaxone in clients with a Latin American and Caribbean network (ß=0.26, 95% CI=0.02 to 0.51). CONCLUSIONS: For three cephalosporin antibiotics, we found Ng strains with slightly higher MICs in clients with partner(s) from Europe or Latin America and the Caribbean. International travel might contribute to the spread of Ng with lower susceptibility. More understanding of the emergence of AMR Ng is needed.

A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Ceftriaxone-Resistant Gonorrhea - China, 2022.

Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis. The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxone-resistant clones, poses a formidable challenge to gonorrhea control. The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance. In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces. The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance. Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively. Only one case of spectinomycin resistance was reported. These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022. Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains. Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains.

Drug-induced Stevens-Johnson syndrome in Post traumatic facial injury.

Stevens-Johnson syndrome is a severe adverse drug reaction affecting the skin and mucous membrane. The causes include Sulfonamides, Anticonvulsants, etc. A patient developed ulcerations in the lips and oral cavity with difficulty in swallowing and rashes over the back, abdomen, and genitalia following administration of injection ceftriaxone 1 g intravenous (IV) b.i.d, injection pantoprazole 40 mg IV b.i.d, tablet aceclofenac + paracetamol 325 mg b.i.d, tablet cetirizine 10 mg b.i.d, chlorhexidine mouth wash, and injection metronidazole 500 mg IV t.i.d for the treatment of traumatic facial injury after 4 days of treatment. Injection ceftriaxone and tablet aceclofenac + paracetamol were suspected as the cause of this reaction. The two drugs were stopped. The patient was treated with corticosteroids, other antimicrobials, and oral topical anesthetics. Health-care providers should be careful about the possible adverse drug reactions even to commonly used drugs.

Tetralogy of Fallot complicated by multiple cerebral abscesses in a child: a case report.

INTRODUCTION: Brain abscesses are rare but potentially fatal condition and can be associated with cyanotic congenital heart disease of which 5-18.7% of these patients that develop cerebral abscess commonly have tetralogy of Fallot (TOF). CASE PRESENTATION: We report a case of 3-year-old Muganda male that presented with convulsions, cyanosis and difficulty in breathing. The patient had a combination intervention of medical treatment and surgical drainage of the abscess. Post-operative Computerized tomography scan images and pre-operative brain Computerized tomography scans were compared. The multiple rings enhancing lesions were reduced in number and sizes. The largest measured ring was 44 × 22.5×16mm compared to the previous; 42 × 41×36mm. The mass effect had reduced from 16 mm to 7.5 mm. The periventricular hypodensities persisted. Findings showed radiological improvement with residual abscesses, subacute subdural hematoma and pneumocranium. The patient was treated with intravenous ceftriaxone 1 g OD for six weeks and he showed marked improvement and was discharged home after 3 months. CONCLUSION: A comprehensive strategy involving medications, surgical drainage, and early neurosurgical consultation is vital in treating brain abscesses in uncorrected TOF. Early identification of the pathogen, appropriate antibiotic therapy, and vigilant follow-up through clinical assessments and imaging are crucial, potentially spanning a 4-8-week treatment.

Antibiotic Treatment in Complicated Appendicitis: Can It Be Optimized?

BACKGROUND: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment. OBJECTIVES: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis. METHODS: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012-2022 at a single tertiary medical center. RESULTS: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP. CONCLUSIONS: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization.

In vivo biodistribution and ototoxicity assessment of cationic liposomal-ceftriaxone via noninvasive trans-tympanic delivery in chinchilla models: Implications for otitis media therapy.

OBJECTIVES: We report the in vivo biodistribution and ototoxicity of cationic liposomal-ceftriaxone (CFX) delivered via ear drop formulation in adult chinchilla. METHODS: CFX was encapsulated in liposomes with size of ∼100 nm and surface charge of +20 mV. 100 µl liposomes or free drug was applied twice daily in both external ear canals of adult chinchillas for either 3 or 10 days. Study groups included free ceftriaxone (CFX, Day 3: n = 4, Day 10: n = 8), liposomal ceftriaxone (CFX-Lipo, Day 3: n = 4, Day 10: n = 8), and a systemic control group (Day 3: n = 4, Day 10: n = 4). Ceftriaxone delivery to the middle ear and systemic circulation was quantified by HPLC assays. Liposome transport was visualized via confocal microscopy. Auditory brainstem response (ABR) tests and cochlear histology were used to assess ototoxicity. RESULTS: Liposomal ceftriaxone (CFX-Lipo) displayed a ∼658-fold increase in drug delivery efficiency in the middle ear relative to the free CFX (8.548 ± 0.4638% vs. 0.013 ± 0.0009%, %Injected dose, Mean ± SEM). CFX measured in blood serum (48.2 ± 7.78 ng/ml) following CFX-Lipo treatment in ear was 41-fold lower compared to systemic free-CFX treatment (1990.7 ± 617.34 ng/ml). ABR tests and histological analysis indicated no ototoxicity due to the treatment. CONCLUSION: Cationic liposomal encapsulation results in potent drug delivery across the tympanic membrane to the middle ear with minimal systemic exposure and no ototoxicity.

Combining antibiotic with anti-TLR2/TLR13 therapy prevents brain pathology in pneumococcal meningitis.

Despite effective antibiotic therapy, brain-destructive inflammation often cannot be avoided in pneumococcal meningitis. The causative signals are mediated predominantly through TLR-recruited myeloid differentiation primary response adaptor 88 (MyD88), as indicated by a dramatic pneumococcal meningitis phenotype of Myd88-/- mice. Because lipoproteins and single-stranded RNA are crucial for recognition of Gram-positive bacteria such as Streptococcus pneumoniae by the host immune system, we comparatively analyzed the disease courses of Myd88-/- and Tlr2-/- Tlr13-/- mice. Their phenotypic resemblance indicated TLR2 and -13 as master sensors of S. pneumoniae in the cerebrospinal fluid. A neutralizing anti-TLR2 antibody (T2.5) and chloroquine (CQ) - the latter applied here as an inhibitor of murine TLR13 and its human ortholog TLR8 - abrogated activation of murine and human primary immune cells exposed to antibiotic-treated S. pneumoniae. The inhibitory effect of the T2.5/CQ cocktail was stronger than that of dexamethasone, the current standard adjunctive drug for pneumococcal meningitis. Accordingly, TLR2/TLR13 blockade concomitant with ceftriaxone application significantly improved the clinical course of pneumococcal meningitis compared with treatment with ceftriaxone alone or in combination with dexamethasone. Our study indicates the importance of murine TLR13 and human TLR8, besides TLR2, in pneumococcal meningitis pathology, and suggests their blockade as a promising antibiotic therapy adjunct.

Isolated Intracranial Hypertension as a Presentation of Pediatric Lyme Borreliosis: A Case Report and Literature Review.

BACKGROUND: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial. METHODS: Case report and literature review. RESULTS: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months. CONCLUSIONS: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children.

Selection of Antibiotics as Prophylaxis for Close Contacts of Patients with Meningococcal Disease in Areas with Ciprofloxacin Resistance - United States, 2024.

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts. Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin. Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased. Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure. Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains. Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin. Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.

Ceftriaxone averts neuroinflammation and relieves depressive-like behaviors via GLT-1/TrkB signaling.

The beneficial effect of a beta-lactam antibiotic, Ceftriaxone (CEF), to improve depressive-like symptoms has been documented previously, attributed to its modulation of glutamate neurotransmission. Here, we aimed to determine whether CEF could improve LPS-altered glutamatergic signaling associated with neuroinflammation-allied depression. To assess our goals, we established a neuroinflammation-allied depression mice model by injecting lipopolysaccharides (LPS), followed by behavioral and biochemical analysis. LPS-treated mice displayed depressive symptoms, neuroinflammation, dysregulated glutamate and its transporter (GLT-1) expression, altered expression of astrocyte reactive markers (GFAP, cxcl10, steap4, GBP2, and SRGN), and dysregulated BDNF/TrkB signaling. However, these changes were rescued by CEF treatment, as we found decreased neuroinflammation, relief of depression symptoms, and improved GLT-1 and BDNF/TrkB signaling upon CEF treatment. Moreover, GLT-1 and BDNF/TrkB regulation role of CEF was validated by K252a and DHK treatment. In summary, the anti-depressive effects of glutamate modulators, like CEF, are closely related to their anti-inflammatory role.

The Management of Gonorrhea in the Era of Emerging Antimicrobial Resistance: What Primary Care Clinicians Should Know.

Gonorrhea rates continue to rise in the United States and Neisseria gonorrhoeae's propensity to develop resistance to all therapies used for treatment has complicated the management of gonorrhea. Ceftriaxone is the only remaining highly effective recommended regimen for gonococcal treatment and few new anti-gonococcal antimicrobials are being developed. The 2021 CDC STI Treatment Guidelines increased the dose of ceftriaxone to 500 mg (1 g if ≥ 150 kg) for uncomplicated infections. It is recommended that all clinicians should be aware of antimicrobial resistant gonorrhea and be able to appropriately manage any suspected gonorrhea treatment failure case.

Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.

OBJECTIVES: To investigate the genomic diversity and ß-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). METHODS: We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. RESULTS: Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. CONCLUSIONS: We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.

Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone.

The use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 hours. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Secondary outcomes included clinical cure, microbiologic cure, length of stay, ICU length of stay, mortality, 30-day readmission, and adverse events. In all, 137 patients were included, 34 of whom had a serum albumin of ≤2.5 g/dL. In a propensity-score-weighted analysis, clinical success was significantly more common among those without hypoalbuminemia (91.2%) as compared to those with hypoalbuminemia (77.8%) (P = 0.038). Death within 30 days (13.7% vs 0%, P < 0.001) and 30-day readmission (31.6% vs 12.0%, P = 0.008) were more common in the hypoalbuminemia group. In a univariate analysis, serum albumin and indication for ceftriaxone use were found to be predictors of clinical success. Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 g every 12 hours.

Detection of Salmonella typhi Isolates and Ceftriaxone Strains Harbouring CTX-M-15 Gene.

OBJECTIVE: To determine blaCTX-M-15(Cefotaxime-Munich) gene amongst the extensively drug resistant (XDR) Salmonella typhi (S. typhi) isolates by quantitative Polymerase Chain Reaction (qPCR). STUDY DESIGN: Observational, cross-sectional study. Place and Duration of the Study: PNS Shifa Hospital and Bahria University of Health Sciences (BUHS), from January to June 2022. METHODOLOGY: All the patients clinically suspected of enteric fever, whose blood culture specimens yielded growth of S. typhi were included in this study. These samples were confirmed by serotyping and biochemical reactions. The ceftriaxone resistance was evaluated by antibiotic susceptibility test according to CLSI 2020 guidelines, whereas blaCTX-M-15 gene was detected by (PCR) using gene-specific primers. RESULTS: Out of 149 S. typhi isolates, 87.2% were confirmed XDR S. typhi resistant to ceftriaxone (CRO). Among these, 83.9% harboured blaCTX-M-15 gene. CONCLUSION: There was a very high frequency of XDR S. typhi harbouring blaCTX-M-15 in Karachi, Pakistan. KEY WORDS: blaCTX-M-15, Salmonella typhi, Third generation cephalosporin, Typhoid fever, Extensively drug resistant.

Achromobacter pneumonia in a patient with advanced COPD, a diagnostic challenge.

Bacterial pneumonia causes significant morbidity and mortality especially in elderly and immunocompromised hosts. Achromobacter xylosoxidans denitrificans pneumonia is very rarely reported. However, the reported cases have been in patients who are either immunocompromised or have bronchiectasis. We hereby present a unique case of Achromobacter xylosoxidans denitrificans pneumonia in an immunocompetent patient with advanced chronic obstructive pulmonary disease (COPD). Our patient is a Caucasian male admitted with shortness of breath, fever and cough. Chest X-ray demonstrated right-sided infiltrates and he was treated with intravenous ceftriaxone and azithromycin. He was discharged home on oral amoxicillin-clavulanate 875-125 mg two times per day for a total of 7 days. Patient returned to emergency room after 5 weeks with persistent symptoms and chest X-ray revealed persistent right-sided infiltrate and sputum culture showed Achromobacter xylosoxidans denitrificans. The patient was started on oral levofloxacin 750 mg one time per day for 2 weeks with resolution of symptoms.

Prevalence and antimicrobial resistance profile of Salmonella typhi infection in Iraq, 2019-2021.

INTRODUCTION: Salmonella typhi could infect the intestinal tract and the bloodstream or invade body organs and secrete endotoxins. It is endemic in developing countries. It is increasingly evolving antimicrobial resistance to several commonly used antimicrobial agents. MATERIALS AND METHODS: A cross-sectional study was done at Iraqi Communicable Disease Control Center, where all confirmed cases of Salmonella typhi are reported, for a period 2019-2021. All demographic, epidemiological and clinical characteristics of patients, comorbidities, type of samples, distribution of S. typhi by age and gender, time distribution in each year and profile of bacterial resistance and sensitivity to antibiotics were gathered and analysed. RESULTS: Most samples were taken from blood. The mean age of cases during 2019, 2020 and 2021 was 18.7 ± 6.5, 17.7 ± 14.1 and 17.3 ± 12.8. Males constituted 56.7%, 58.5% and 39.8%, respectively. Some cases had comorbidities. Most cases had headache and fever. Some of them had nausea, diarrhoea, vomiting and epigastric pain. The age and sex were significantly associated with years of reporting. The most months of case reporting were June-July (2019 and 2021), Jan. -Feb. (2020). There was an obvious increase in S. typhi resistance to ceftriaxone (92.2%, 86.1%, 88.8%) and ampicillin (77.1%, 76.9%, 81.27%). There was a gradual increase in sensitivity to tetracycline (83.1%, 88.1%, 94%), cotrimoxazole (86.7%, 86.1%, 92.2%), ciprofloxacin (78.3%, 90.1%, 87.8%) and cefixime (77.7%, 72.3%, 72.7%). CONCLUSIONS: There was a sharp rise in resistance rates of the S. typhi in Iraq (during 2019-2021) to ceftriaxone and ampicillin, while there were highest sensitivity rates to imipenem, aztreonam and chloramphenicol. The following recommendations were made: (1) Improvement of general hygiene and food safety measures. (2) Emphasis on vaccination and surveillance of Salmonella infection. (3) Rational use of appropriate antibiotics through implementation of treatment guidelines. (5) Educate communities and travelers about the risks of S. typhi and its preventive measures.

Evaluating the efficacy of different antibiotics against Neisseria gonorrhoeae: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

BACKGROUND: With the widespread use of antibiotics, antimicrobial resistance in Neisseria gonorrhoeae is worsening. The objective of this study was to evaluate the efficacy changes of seven antibiotics in the treatment of N. gonorrhoeae by using Monte Carlo simulation combined with pharmacokinetics/pharmacodynamics/ (PK/PD). METHODS: The minimum inhibitory concentration (MIC) of antibiotics against clinical isolates from 2013 to 2020 in Nanjing, China, was determined by agar dilution method. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. RESULTS: All dosage regimens of seven antibiotics achieved PTAs ≥ 90% for MIC ≤ 0.06 µg/ml. But when the MIC was increased to 1 µg/ml, PTAs at each MIC value exceeded 90% only for ceftriaxone 1,000 mg and 2,000 mg, zoliflodacin 2,000 mg and 3,000 mg. Among them, the CFR values of each dosing regimen against N. gonorrhoeae only for ceftriaxone, cefixime and zoliflodacin were ≥ 90% in Nanjing from 2013 to 2020. CONCLUSIONS: Cephalosporins are still the first-line drugs in the treatment of gonorrhea. However, the elevated MIC values of cephalosporins can lead to decline in clinical efficacy of the conventional dose regimens, and increasing the dose of ceftriaxone to 1,000 mg-2,000 mg may improve the efficacy. In addition, zoliflodacin is possible to be a potential therapeutic agent in the future.

2023 Korean Association of Urogenital Tract Infection and Inflammation guidelines for gonococcal infection.

The incidence of gonorrhea has increased significantly in recent years in the United States, especially among sexually active twenty-year-olds. Although the incidence of gonorrhea has decreased in Korea since the early 2000s, it is still common among people in their twenties. Nucleic acid amplification test (NAAT) is the most sensitive diagnostic test for detecting gonococcal infection. Gram-staining is a simple and useful laboratory test for diagnosing symptomatic male gonococcal urethritis. Although bacterial culture can be used to detect antimicrobial susceptibility, its sensitivity is lower than that of NAAT. Treatment for uncomplicated gonorrhea infection is a single intramuscular injection of ceftriaxone 500 mg. Doxycycline (100 mg twice daily for 7 days) is added if there is a possibility of co-infection with chlamydia. If ceftriaxone is difficult to use, spectinomycin 2 g can be injected intramuscularly in Korea. Patients with gonorrhea should have repeated examinations within three months at the exposure site because of a high risk of re-infection. A person diagnosed with gonorrhea should discuss the nature of the infection, the importance of informing partners, when sexual activity can resume, and how to reduce the risk of sexually transmitted infections.