Intravenous plus intraventricular tigecycline-amikacin therapy for the treatment of carbapenem-resistant Klebsiella pneumoniae ventriculitis: A case report.

RATIONALE: Central nervous system infections (CNSIs) are one of the most serious complications after neurosurgery, especially carbapenem-resistant bacterial meningitis. Owing to the poor blood-brain barrier permeability of most antibiotics, the treatment of CNSIs by intraventricular (IVT) administration is becoming a hot topic in clinical research. Currently, the treatment of CNSIs caused by carbapenem-resistant Klebsiella pneumoniae is mainly based on intraventricular injection of an antibiotic combined with one or more other systemic intravenous (IV) antibiotics, whereas there are few case reports of intraventricular injection of 2 antibiotics. PATIENT CONCERNS: A 57-year-old man with an open craniocerebral injury presented with dyspnea, high fever, and seizures associated with surgery. DIAGNOSIS: Intracranial infection caused by carbapenem-resistant K. pneumoniae was diagnosed. INTERVENTIONS: On the advice of a clinical pharmacist, the patient was given tigecycline (100 mg IV + 3 mg IVT q12h) combined with amikacin (0.8 g IV + 30 mg IVT qd) antiinfective therapy. Ultimately, the pathogens in the cerebrospinal fluid were eradicated after 7 days, and the CNSIs were completely cured after 14 days. OUTCOMES: The patient recovered and was discharged from the hospital without adverse reactions. LESSONS: A series of in vitro and in vivo synergy tests of carbapenem-resistant K. pneumoniae showed that tigecycline combined with aminoglycosides had good synergistic effects and effectively suppressed bacterial resistance selection. Intravenous plus intraventricular tigecycline-amikacin seems to be a safe and effective treatment option for carbapenem-resistant K. pneumoniae CNSIs.

Carbapenem-Resistant Gram-Negative Bacteria-Related Healthcare-Associated Ventriculitis and Meningitis: Antimicrobial Resistance of the Pathogens, Treatment, and Outcome.

Carbapenem-resistant Gram-negative bacteria (CRGNB)-related health care-associated ventriculitis and meningitis (HCAVM) is dangerous. We aimed to report the antimicrobial resistance of the pathogens, treatment, and outcome. All cases with CRGNB-related HCAVM in2012-2020 were recruited. Antimicrobial agents were classified as active, untested, or inactive using antimicrobial susceptibility tests. The treatment stage was classified as empirical or targeted according to the report of pathogens. The treatment effect was classified as ineffective or effective according to HCAVM-related parameters. Overall, 92 cases were recruited. For most antimicrobial agents, the resistance rate was higher than 70.0%. The polymyxin resistance rate was the lowest at 11.6%. The chloramphenicol, trimethoprim-sulfamethoxazole, amikacin, levofloxacin, and tetracycline resistance rates were relatively low, ranging from 21.1% to 64.1%. The meropenem resistance rate was 81.9%. There was no significant trend for any antimicrobial agent tested. Meropenem was the most common antimicrobial agent used in empirical treatment; trimethoprim-sulfamethoxazole and polymyxin were the most used active antimicrobial agents, and meropenem/sulbactam and polymyxin were the most used untested antimicrobial agents in targeted treatment. In total, 42 (45.7%) cases received ineffective treatments. The ineffective treatment rate of cases that received active antimicrobial agents was lower than that of cases that received untested antimicrobial agents and cases that received inactive antimicrobial agents (29.3% [12/41] versus 46.2% [18/39] versus 100.0% [12/12], P < 0.001). Antimicrobial resistance was prevalent but without increasing trends. Active antimicrobial agents are necessary. Additionally, untested antimicrobial agents, including meropenem/sulbactam and polymyxin, might be optional. Inactive antimicrobial agents must be replaced. IMPORTANCE Carbapenem-resistant Gram-negative bacteria-related health care-associated ventriculitis and meningitis is a clinical threat because of the poor outcome and challenges in treatment. We reached several conclusions: (i) the antimicrobial resistance of pathogens is severe, and some antimicrobial agents represented by polymyxin are optional according to the antimicrobial susceptibility tests; (ii) in the background that the portion of carbapenems resistance in Gram-negative bacteria is increasing, there is no increasing trend for the antimicrobial resistance of carbapenem-resistant Gram-negative bacteria in the 9-year study; (iii) meropenem is the main antimicrobial agent in treatment, and trimethoprim-sulfamethoxazole, tigecycline, polymyxin, and meropenem/sulbactam are commonly used in the targeted treatment; (iv) the treatment effect was poor and affected by the treatment: timely active antimicrobial agents should be given. And untested antimicrobial agents represented by polymyxin and meropenem/sulbactam might be optional. Inactive antimicrobial agents must be replaced.

Multidrug-resistant Klebsiella oxytoca ventriculitis, successfully treated with intraventricular tigecycline: A case report.

A 38-year-old male presented to the hospital with headache, fever, and meningeal signs. He had undergone a surgical review of a ventriculoperitoneal shunt system one month earlier. A head computed tomography scan showed hydrocephalus. His medical history included a human immunodeficiency virus infection identified four years before and resolved cryptococcal meningitis, which had necessitated the implantation of the shunt system. Ventricular cerebrospinal fluid (CSF) was obtained, which showed inflammation and, in culture, grew a Gram-negative bacillus identified as multidrug-resistant Klebsiella oxytoca. The shunt was removed and a ventricular drain was installed. Treatment with meropenem and amikacin was established without a response; the CSF white blood cell count continued to increase, with cultures remaining positive. The patient's clinical condition deteriorated to stupor. With informed consent, intraventricular (ITV) treatment with tigecycline was initiated at a dose of 5 mg every 24 h and, three days later, the CSF cultures were negativized. Tigecycline levels in the CSF were quantified by liquid chromatography with ultraviolet detection and showed peak concentrations achieved at two hours after the dose of between 178 and 310 µg/mL. After 11 days of treatment with ITV tigecycline and eight negative CSF cultures, a new CSF shunt was installed. During follow-up review 10 months later, the patient reported he was working. The dose of tigecycline used in this study produced levels 15 to 20 times the minimum inhibitory concentration of the bacteria for up to six hours with adequate tolerance.

High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis.

A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.