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

INTRODUCTIONTreatment of acute lymphoblastic leukaemia (ALL) using intensive chemotherapy has resulted in high cure rates but also substantial morbidity. Infective complications represent a significant proportion of treatment-related toxicity. The objective of this study was to describe the microbiological aetiology and clinical outcome of episodes of chemotherapy-induced febrile neutropaenia in a cohort of children treated for ALL at our institution.

MATERIALS AND METHODSPatients with ALL were treated with either the HKSGALL93 or the Malaysia-Singapore (Ma-Spore) 2003 chemotherapy protocols. The records of 197 patients who completed the intensive phase of treatment, defined as the period of treatment from induction, central nervous system (CNS)-directed therapy to reinduction from June 2000 to January 2010 were retrospectively reviewed.

RESULTSThere were a total of 587 episodes of febrile neutropaenia in 197 patients, translating to an overall rate of 2.98 episodes per patient. A causative pathogen was isolated in 22.7% of episodes. An equal proportion of Gram-positive bacteria (36.4%) and Gram-negative bacteria (36.4%) were most frequently isolated followed by viral pathogens (17.4%), fungal pathogens (8.4%) and other bacteria (1.2%). Fungal organisms accounted for a higher proportion of clinically severe episodes of febrile neutropaenia requiring admission to the high-dependency or intensive care unit (23.1%). The overall mortality rate from all episodes was 1.5%.

CONCLUSIONFebrile neutropaenia continues to be of concern in ALL patients undergoing intensive chemotherapy. The majority of episodes will not have an identifiable causative organism. Gram-positive bacteria and Gram-negative bacteria were the most common causative pathogens identified. With appropriate antimicrobial therapy and supportive management, the overall risk of mortality from febrile neutropaenia is extremely low.

Candidiasis ; epidemiology ; Chemotherapy-Induced Febrile Neutropenia ; epidemiology ; microbiology ; Child ; Cohort Studies ; Escherichia coli Infections ; epidemiology ; Gram-Negative Bacterial Infections ; epidemiology ; Gram-Positive Bacterial Infections ; epidemiology ; Humans ; Influenza, Human ; epidemiology ; Klebsiella Infections ; epidemiology ; Mycoses ; epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Pseudomonas Infections ; epidemiology ; Retrospective Studies ; Singapore ; epidemiology ; Staphylococcal Infections ; epidemiology ; Virus Diseases ; epidemiology

BACKGROUNDHealthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis.

METHODSRetrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk).

RESULTSAmong 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with β-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP.

CONCLUSIONInitial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.

Acinetobacter baumannii ; pathogenicity ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Community-Acquired Infections ; drug therapy ; microbiology ; pathology ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Pneumonia ; drug therapy ; microbiology ; pathology ; Pseudomonas aeruginosa ; pathogenicity ; Retrospective Studies ; Staphylococcus aureus ; pathogenicity

BACKGROUND/AIMS: Whether the causative organism influences the clinical course of pneumonia in the intensive care unit (ICU) is controversial. We assessed the clinical manifestations and prognosis of pneumonia according to the causative pathogens in patients in a medical ICU. METHODS: A retrospective observational study was performed in a medical ICU. Among 242 patients who were admitted to the ICU, 103 who were treated for pneumonia were analyzed. RESULTS: The causative pathogen was identified in 50 patients (49.0%); 22 patients (21.6%) had multidrug-resistant (MDR) pathogens. The distribution of causative micro-organisms was Staphylococcus aureus (20%), Pseudomonas species (16%), Klebsiella pneumoniae (14%), and Acinetobacter baumannii (12%). No significant difference in ICU mortality rate, duration of ICU stay, duration of mechanical ventilation, or frequencies of re-intubation and tracheostomy were detected based on the identification of any pathogen. In sub-analyses according to the pneumonia classification, the number of pathogens identified did not differ between pneumonia types, and a higher incidence of identified MDR pathogens was detected in the hospital-acquired pneumonia group than in the community-acquired or healthcare- acquired pneumonia groups. However, the clinical outcomes of pneumonia according to identification status and type of pathogen did not differ significantly between the groups. CONCLUSIONS: Neither the causative micro-organism nor the existence of MDR pathogens in critically ill patients with pneumonia was associated with the clinical outcome of pneumonia, including ICU mortality. This result was consistent regardless of the pneumonia classification.
Acinetobacter Infections/diagnosis/*microbiology/mortality/therapy ; Aged ; Anti-Bacterial Agents/therapeutic use ; Critical Illness ; Drug Resistance, Multiple, Bacterial ; Female ; Hospital Mortality ; Humans ; Intensive Care Units ; Klebsiella Infections/diagnosis/*microbiology/mortality/therapy ; Length of Stay ; Male ; Middle Aged ; Pneumonia, Bacterial/diagnosis/*microbiology/mortality/therapy ; Proportional Hazards Models ; Pseudomonas Infections/diagnosis/*microbiology/mortality/therapy ; Respiration, Artificial ; Retrospective Studies ; Risk Factors ; Staphylococcal Infections/diagnosis/*microbiology/mortality/therapy ; Time Factors ; Tracheostomy ; Treatment Outcome

OBJECTIVEPseudomonas aeruginosa is an important cause of nosocomial infection, severe sepsis and death which associated with a trends of rising rates of resistance to a broad array of antimicrobial agents. To explore a feasible treatment protocol for such patients, we analyzed the susceptibility patterns of Pseudomonas aeruginosa in pediatric intensive care unit (PICU).

METHODThe age distribution, outcome of patients, sources of strains and susceptibility patterns of Pseudomonas aeruginosa in PICU from Jan 1, 2007 to Dec 31, 2011 were analyzed. Susceptibility to amikacin, piperacillin/tazobactam, aztreonam, ampicillin, ciprofloxacin, imipenem, meropenem, cefepime, cefoperazone, cefotaxime, ceftriaxone, ceftazidime, cefoperazone/sulbactam, cephazolin, cefuroxime, and polymyxin were determined by the disk-diffusion technique (K-B test method) and broth microdilution. P. aeruginosa ATCC 27853 was used as reference strain.

RESULTSeventy-five patients were Pseudomonas aeruginosa positive. 26(34.7%) were < 6 m, 49 (65.4%) were < 2 y. The percentages of cases who were Pseudomonas aeruginosa positive in different age groups in the same time was basically similar; 18 (24.0%) cases died. Pseudomonas aeruginosa accounted for 10.9% of G(-) germs, 6.5% of all pathogens in 2010 - 2011. Of the 126 strains, 83 (65.9%) were from sputum sample, 31 (24.6%) were from catheter sample of tracheal cannula, 10 (7.9%) were from blood sample and 2 (1.6%) were from secretion sample. The sensitivity to antibiotics of Pseudomonas aeruginosa in pediatric common treatments was 72.4% to cefoperazone/sulbactam, 71.5% to meropenem, 48.4% to imipenem, 66.7% to ceftazidime, 49.2% to piperacillin/tazobactam. Absolute resistance to ampicillin, cephazolin, cefuroxime and cefotaxime. Multiple-drug resistance was still severe, but a decreasing tendency was observed, 90.5% in 2007, 81.3% in 2008, 51.1% in 2009, 53.8% in 2010, 33.3% in 2011. Pan-drug resistance in different years was similar, 12.5% in 2008, 2.2% in 2009, 7.7% in 2010, 6.7% in 2011.

CONCLUSIONThe condition of drug resistance of Pseudomonas aeruginosa was still rigorous, we should conduct surveillance and prevent abusing antibiotics in order to avoid exacerbating drug resistance. We should improve testing technique, early and appropriate empirical antibiotics therapy is crucial according to clinical experience and antibiotic sensitivity. The effective treatment of P. aeruginosa is paramount to prevent multidrug resistance. The use of combination therapies for P. aeruginosa infection has been a long-advocated practice. To prevent hospital acquired cross infection, health care workers must pay close attention to hand sanitation and sterile operation strictly.

Adolescent ; Ampicillin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Cefazolin ; pharmacology ; Child ; Child, Preschool ; Cross Infection ; microbiology ; prevention & control ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Imipenem ; pharmacology ; Infant ; Intensive Care Units, Pediatric ; Male ; Microbial Sensitivity Tests ; Pseudomonas Infections ; drug therapy ; microbiology ; Pseudomonas aeruginosa ; drug effects ; isolation & purification

BACKGROUNDInfection due to pandrug-resistant Pseudomonas aeruginosa (PDRPA) has become a challenge in clinical practice. The aim of this research was to summarize the treatment of large-area burns (60% - 80%) with PDRPA infection and respiratory failure in our hospital over the last two years, and to explore a feasible treatment protocol for such patients.

METHODSWe retrospectively analyzed the treatment of five patients with large-area burns accompanied by PDRPA infection and respiratory failure transferred to our hospital from burn units in hospitals in other Chinese cities from January 2008 to February 2010. Before PDRPA infection occurred, all five patients had open wounds with large areas of granulation because of the failure of surgery and dissolving of scar tissue; they had also undergone long-term administration of carbapenems. This therapy included ventilatory support, rigorous repair of wounds, and combined antibiotic therapy targeted at drug-resistance mechanisms, including carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors.

RESULTSFour patients recovered from burns and one died after therapy.

CONCLUSIONSFirst, compromised immunity caused by delayed healing of burn wounds in patients with large-area burns and long-term administration of carbapenems may be the important factors in the initiation and progression of PDRPA infection. Second, if targeted at drug-resistance mechanisms, combined antibiotic therapy using carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors could effectively control PDRPA infection. Third, although patients with large-area burns suffered respiratory failure and had high risks from anesthesia and surgery, only aggressive skin grafting with ventilatory support could control the infection and save lives. Patients may not be able to tolerate a long surgical procedure, so the duration of surgery should be minimized, and the frequency of surgery increased.

Adolescent ; Adult ; Anti-Bacterial Agents ; therapeutic use ; Burns ; drug therapy ; microbiology ; Carbapenems ; therapeutic use ; Ciprofloxacin ; therapeutic use ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Macrolides ; therapeutic use ; Male ; Middle Aged ; Pseudomonas Infections ; drug therapy ; Pseudomonas aeruginosa ; drug effects ; pathogenicity ; Respiratory Insufficiency ; drug therapy ; microbiology ; Retrospective Studies ; Young Adult

PURPOSE: The increasing prevalence of antimicrobial resistant bacteria has become a serious worldwide problem. The aim of this study was to analyze antimicrobial resistance data generated in 2009 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program. MATERIALS AND METHODS: Susceptibility data were collected from 24 hospitals and two commercial laboratories. In the analysis, resistance did not include intermediate susceptibility. Duplicate isolates were excluded from the analysis of hospital isolates, but not from the commercial laboratory isolates. RESULTS: Among the hospital isolates, methicillin-resistant Staphylococcus aureus, penicillin G-non-susceptible Streptococcus pneumoniae based on meningitis breakpoint, and ampicillin-resistant Enterococcus faecium remained highly prevalent. The proportion of vancomycin-resistant E. faecium gradually increased to 29%. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae increased to 17% and 33%, respectively, and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa increased to 33%, 67% and 39%, respectively. Amikacin-resistant Acinetobacter spp. increased to 48%. Imipenem-resistant Acinetobacter spp. and P. aeruginosa increased to 51% and 26%, respectively. Higher resistance rates were observed in intensive care unit (ICU) isolates than in non-ICU isolates among the isolates from hospitals. Resistance rates were higher in hospital isolates than in clinic isolates among the isolates from commercial laboratories. CONCLUSION: Among the hospital isolates, ceftazidime-resistant K. pneumoniae and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp., and P. aeruginosa further increased. The increase in imipenem resistance was slight in P. aeruginosa, but drastic in Acinetobacter spp. The problematic antimicrobial-organism combinations were much more prevalent among ICU isolates.
Acinetobacter/*drug effects/isolation & purification ; Acinetobacter Infections/drug therapy/microbiology ; Amikacin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Carbapenems/pharmacology ; Cross Infection/drug therapy/microbiology ; *Drug Resistance, Bacterial ; Fluoroquinolones/pharmacology ; Humans ; Pseudomonas Infections/drug therapy/microbiology ; Pseudomonas aeruginosa/*drug effects/isolation & purification ; Republic of Korea

This study aimed to evaluate the clinical profiles, antibiotic susceptibility, risk factors of multi-drug resistance (MDR) and outcomes of P. aeruginosa bacteremia in children by retrospective methods at a tertiary teaching children's hospital in Seoul, Korea during 2000-2009. A total of 62 episodes were evaluated and 59 patients (95.2%) had underlying diseases. Multivariate analysis demonstrated that an intensive care unit (ICU) stay within the previous one month was the only independent risk factor for MDR P. aeruginosa bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.3-35.8, P = 0.023). The overall fatality rate associated with P. aeruginosa bacteremia was 14.5% (9 of 62). The fatality rate in patients with MDR P. aeruginosa was 57.1%, compared with 9.1% in non-MDR patients (OR 13.3; 95% CI 2.3-77.2, P = 0.006). However, the presence of respiratory difficulty was the only independent risk factor for overall fatality associated with P. aeruginosa bacteremia according to multivariate analysis (OR 51.0; 95% CI 7.0-369.0, P < 0.001). A previous ICU stay and presentation with respiratory difficulty were associated with acquisition of MDR P. aeruginosa and a higher fatality rate, respectively. Future efforts should focus on the prevention and treatment of P. aeruginosa bacteremia in high-risk children.
Adolescent ; Bacteremia/*drug therapy/*epidemiology/microbiology ; Child ; Child, Preschool ; *Drug Resistance, Multiple, Bacterial ; Female ; Hospitals, Teaching ; Humans ; Infant ; Infant, Newborn ; Intensive Care Units, Pediatric ; Male ; Microbial Sensitivity Tests ; Pseudomonas Infections/*drug therapy/*epidemiology/microbiology ; Pseudomonas aeruginosa/*drug effects ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Treatment Outcome

OBJECTIVETo study changes in the drug-resistance of Pseudomonas aeruginosa (PA) and the use of antibiotics in burn wards so as to optimize the use of antibiotic in the future.

METHODSBacteria were isolated from specimens of blood, venous catheter, stool, sputum, urine, wound tissue from 5717 patients hospitalized in our burn wards within the duration of January 2005 to December 2009. The number of specimens examined and positive rates of bacteria were calculated. Changes in constituent ratio of cocci and bacilli, spectrum of bacteria, the drug-resistance rate of PA, and the usage of antibiotics were analyzed. The number of specimens examined, constituent ratio of cocci and bacilli, drug-resistance rate were processed with chi-square test. Bivariate correlation analysis was performed between the usage of antibiotics and the drug-resistance rate.

RESULTS(1) The number of specimens examined showed no statistical difference during the five years (with rates from 73.2% to 76.1%, χ(2) = 5.583, P > 0.05), while constituent ratio of cocci and bacilli showed statistical difference (with ratios from 105:134 to 169:126, χ(2) = 14.806, P < 0.01). The positive rates of bacteria were increasing in the five years. (2) One thousand six hundred and seventy-five strains were identified during the five years from different kinds of specimens, with 29 from blood, 39 from venous catheter, 3 from stool, 157 from sputum, 13 from urine, and 1434 from wound tissue. Among them, Staphylococcus aureus accounted for 28% to 42%, PA accounted for 10% to 25%, Acinetobacter baumannii accounted for 10% to 19%, and they were the predominant strains. (3) The difference among drug-resistance rates of PA to each kind of 12 antibiotics during the five years were statistically significant (with χ(2) values from 47.911 to 308.095, P values all below 0.01). The drug-resistance rates of PA to some antibiotics showed downward trend in the former four years, including amikacin, ceftazidime, and imipenem/cilastatin, but it rebounded in the fifth year. (4) There was descending trend in usage of cefoperazone/sulbactam and levofloxacin, but vancomycin was always used widely. (5) Drug-resistance rates of PA to 7 antibiotics, including amikacin, imipenem/cilastatin, and ciprofloxacin, etc., were positively correlated with usage of various antibiotics (with r values from 0.879 to 0.978, P < 0.05 or P < 0.01).

CONCLUSIONSIn our burn wards, drug-resistant PA was prevalent. Disinfection and isolation measures, appropriate use of antibiotics, etc. can reduce PA infection.

Anti-Bacterial Agents ; therapeutic use ; Burn Units ; Burns ; drug therapy ; microbiology ; Drug Resistance, Bacterial ; drug effects ; Female ; Humans ; Male ; Pseudomonas Infections ; drug therapy ; microbiology ; Pseudomonas aeruginosa ; drug effects ; isolation & purification

Pseudomonas aeruginosa is an important pathogenic bacterium of nosocomial infections. The microbe easily produce biofilm which brings us much difficulties in clinical treatment. The formation processes of biofilm, including the stages of early bacteria planting, mushroom-like structure forming and extracellular matrix producing, are regulated by a series of molecules and genes. And quorum sensing system of the microbe is responsible for regulation of the whole process of biofilm formation. According to the process of biofilm formation and the mimitat associated regulation mechanism, several anti-biofilm therapeutic strategies have been applied in clinical medicine, and some novel drugs and methods are developed.
Biofilms ; growth & development ; Gene Expression Regulation, Bacterial ; Polysaccharides, Bacterial ; metabolism ; Pseudomonas Infections ; drug therapy ; microbiology ; Pseudomonas aeruginosa ; genetics ; physiology ; Quorum Sensing ; genetics ; physiology