BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P < 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z = -3.938; 11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z = -3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC > 8, cannot be reached.
Acinetobacter baumannii ; drug effects ; pathogenicity ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Ciprofloxacin ; pharmacokinetics ; pharmacology ; Female ; Gram-Negative Bacteria ; drug effects ; pathogenicity ; Humans ; Male ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; pathogenicity ; Respiratory Tract Infections ; drug therapy ; metabolism ; microbiology

PURPOSE: Colistin is used for the treatment of pneumonia associated with multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. However, the best route of administration and dosage is not known. We report our experience with aerosolized colistin in twelve patients with pneumonia caused by colistin-only-susceptible (COS) A. baumannii. MATERIALS AND METHODS: We retrospectively reviewed patients' medical records who were treated with aerosolized colistin for the treatment of pneumonia. RESULTS: Ten patients were treated only with aerosolized colistin inhalation and two patients received a 3-day course intravenous colistin, and then switched to colistin inhalation therapy. The median duration of aerosolized colistin therapy was 17 days (5-31 days). Four patients were treated only with aerosolized colistin, whereas 4 patients received concomitant glycopeptides, and 4 received concomitant levofloxacin or cefoperazone/sulbactam. At the end of the therapy, the clinical response rate and bacteriological clearance rate was 83% and 50%, respectively. Colistin-resistant strains were isolated from 3 patients after aerosolized colistin therapy; however, all of them showed favorable clinical response. The median interval between inhalation therapy and resistance was 7 days (range 5-19 days). Acute kidney injury developed in 3 patients. Two patients experienced Clostridium difficile associated diarrhea. One patient developed fever and skin rash after aerosolized colistin therapy. No patient developed neurotoxicity or bronchospasm. CONCLUSION: Colistin inhalation therapy is deemed tolerable and safe, and could be beneficial as an adjuctive therapy for the management of pneumonia due to COS A. baumannii. However, the potential development of colistin resistance cannot be overlooked.
Acinetobacter baumannii/drug effects/*pathogenicity ; Administration, Inhalation ; Aged ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Colistin/administration & dosage/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pneumonia/*drug therapy ; Retrospective Studies

Acinetobacter Infections ; drug therapy ; Acinetobacter baumannii ; drug effects ; pathogenicity ; Adult ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Burns ; drug therapy ; microbiology ; Cefoperazone ; administration & dosage ; therapeutic use ; Humans ; Middle Aged ; Minocycline ; administration & dosage ; therapeutic use ; Retrospective Studies ; Sulbactam ; administration & dosage ; therapeutic use ; Thienamycins ; adverse effects ; therapeutic use ; Young Adult

BACKGROUNDMultidrug-resistant Acinetobacter baumannii (MDRAB) is an important and emerging hospital-acquired pathogen worldwide. This study was conducted to identify the sources of MDRAB and its role in respiratory tract colonization and nosocomial pneumonia in intensive care unit (ICU) patients.

METHODSWe conducted a prospective active surveillance study of MDRAB in three ICUs at a Chinese Hospital from April to August 2011, to identify the sources of MDRAB and its role in respiratory tract colonization and nosocomial pneumonia.

RESULTSOne hundred and fourteen (13.0%) MDRAB isolates were detected from 876 specimens, with a sensitivity of 11.6% (55/474) in screening of the pharyngeal and tracheal swabs, and 14.7% (59/402) of the sputum/endotracheal aspirates. MDRAB colonization/infection was found in 34 (26.8%) of 127 patients, including 16 (12.6%) cases of pure colonization and 18 (14.2%) cases of pneumonia (two pre-ICU-acquired cases of pneumonia and 16 ICU-acquired cases of pneumonia). Previous respiratory tract MDRAB colonization was found in 22 (17.3%) patients: eight (6.3%) were pre-ICU-acquired colonization and 14 (11.0%) ICU-acquired colonization. Of eight pre-ICU-colonized patients, five were transferred from other wards or hospitals with hospitalization > 72 hours, and three came from the community with no previous hospitalization. Overall, 6/22 colonized patients presented with secondary pneumonia; only two (9.1%) colonized MDRAB strains were associated with secondary infections. Respiratory tract MDRAB colonization had no significant relationship with nosocomial pneumonia (P = 0.725). In addition, acute respiratory failure, mechanical ventilation, renal failure, and prior carbapenem use were risk factors for MDRAB colonization/infection.

CONCLUSIONSA high proportion of cases of MDRAB colonization/infection in ICU patients were detected through screening cultures. About one-third were acquired from general wards and the community before ICU admission. The low incidence of MDRAB colonization-related pneumonia questions the appropriateness of targeted antibiotic therapy.

Acinetobacter baumannii ; drug effects ; pathogenicity ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; therapeutic use ; Cross Infection ; drug therapy ; microbiology ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pneumonia ; drug therapy ; microbiology ; Prospective Studies ; Respiratory Tract Infections ; drug therapy ; microbiology

BACKGROUND/AIMS: Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. METHODS: Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital-onset MDR A. baumannii among patients in the ICUs. RESULTS: The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 +/- 82.26 defined daily doses per 1,000 patient-days to 94.85 +/- 50.98 defined daily doses per 1,000 patient-days (p = 0.016). CONCLUSIONS: Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year.
Acinetobacter Infections/epidemiology/microbiology/*prevention & control/transmission ; Acinetobacter baumannii/*drug effects/pathogenicity ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Carbapenems/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cross Infection/epidemiology/microbiology/*prevention & control/transmission ; Disinfection ; *Drug Resistance, Multiple, Bacterial ; *Endemic Diseases ; Hand Disinfection ; Humans ; Incidence ; Infection Control/*methods ; Microbial Sensitivity Tests ; Odds Ratio ; Patient Isolation ; Program Evaluation ; Republic of Korea/epidemiology ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome