OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3^rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ²=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.
Humans ; Carbapenems/therapeutic use* ; Pseudomonas aeruginosa ; Soft Tissue Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Hematologic Diseases ; Survival Analysis

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

OBJECTIVE: To evaluate the in vitro activity of ceftazidime-avibactam (CAZ-AVI) alone or in combination with colistin (COL) against clinically isolated extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). METHODS: Minimum inhibitory concentration (MIC) of 16 clinical XDR-PA isolates was determined by broth dilution method and chessboard design when CAZ-AVI and COL were used alone or in combination, then the combined inhibitory concentration index (FICI) was calculated. Class A [Klebsiella pneumoniae carbapenemase β-lactamase (bla_KPC), Guiana extended-spectrum β-lactamase (bla_GES)], Class B [imipenemase β-lactamase (bla_IMP), Verona-Integronmetallo β-lactamase (bla_VIM), New Delhi metallo β-lactamase (bla_NDM), German imipenemase β-lactamase (bla_GIM), Sao Paulo metallo-β-lactamase (bla_SPM)], Class C [AmpC β-lactamase (bla_AmpC)], Class D [oxacillinase β-lactamase (bla_OXA)] β-lactamase-related resistance genes were detected by polymerase chain reaction. Drug-resistant mutation frequencies of each strain were determined on a drug-containing plate. The time kill curves of three XDR-PA were plotted by colony counting method. A biofilm model was established in vitro, and the synergistic effect of CAZ-AVI and COL on biofilm inhibition was detected by methythiazolyl tetrazolium assay (MTT). RESULTS: The MICs of 16 XDR-PA for CAZ-AVI ranged from 1 mg/L to 128 mg/L, and three of the isolates showed resistance (MIC > 8 mg/L). The FICI range of CAZ-AVI combined with COL was 0.312-1.000. Four isolates were synergistic, while the other 12 isolates were additive. Three isolates resistant to CAZ-AVI contained Class B resistance genes such as bla_IMP and bla_VIM, while 13 susceptible isolates carried resistance genes belonging to Class A, C or D. The logarithm values of mutation frequencies of drug resistance in CAZ-AVI group, COL group and combination group were -4.81±0.88, -7.06±0.69 and -9.70 (-9.78, -9.53), respectively. There were significant differences among the three groups (H = 33.601, P < 0.001), and between every two groups (adjusted P < 0.05). In time kill curves, the phytoplankton load of three XDR-PA decreased more than 6 log CFU/L when these two drugs were used together, and number of PA1819 planktonic bacteria decreased more than 5.1 log CFU/L compared with monotherapy group. Viable quantity in biofilm (A₄₉₀) of normal saline group, CAZ-AVI group, COL group and CAZ-AVI-COL group were 0.665±0.068, 0.540±0.072, 0.494±0.642 and 0.317±0.080, respectively. There was significant difference between the other two groups (all P < 0.001), except for that between CAZ-AVI group and COL group (P = 0.109). CONCLUSIONS CAZ-AVI combined with COL can effectively improve the bactericidal effect of each drug alone on XDR-PA. The regimen can also reduce the production of drug-resistant bacteria and inhibit the formation of biofilm. Therefore, it is a potential treatment for XDR-PA infection.
Anti-Bacterial Agents/therapeutic use* ; Azabicyclo Compounds/therapeutic use* ; Ceftazidime/therapeutic use* ; Colistin/therapeutic use* ; Drug Combinations ; Drug Resistance, Bacterial/genetics* ; Microbial Sensitivity Tests ; Pseudomonas Infections/drug therapy* ; Pseudomonas aeruginosa ; beta-Lactamases

Actinomycosis ; complications ; drug therapy ; pathology ; Aged, 80 and over ; Amoxicillin-Potassium Clavulanate Combination ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Cephalexin ; therapeutic use ; Ciprofloxacin ; therapeutic use ; Clindamycin ; therapeutic use ; Coinfection ; drug therapy ; Drug Resistance, Bacterial ; Escherichia coli Infections ; complications ; drug therapy ; Humans ; Male ; Pseudomonas Infections ; complications ; drug therapy ; Skin Diseases, Bacterial ; complications ; drug therapy ; pathology ; Staphylococcal Skin Infections ; complications ; drug therapy ; Thigh ; Trimethoprim, Sulfamethoxazole Drug Combination ; therapeutic use

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

OBJECTIVETo investigate the effect of Qiguiyin Decoction, QGYD) on multidrug-resistant Pseudomonas aeruginosa infection in Sprague-Dawley (SD) rats.

METHODSA pseudomonal infection model in SD rats was established by injecting multidrug-resistant P. aeruginosa intraperitoneally. Infected rats were randomized into four groups treated with Pure water, QGYD, ceftazidime, or combined QGYD and ceftazidime. Blood samples were obtained from the abdominal aorta. Serum was then collected and analyzed by peptide array for immune responsiveness to multidrug-resistant beta-lactamase proteins, including Verona integronen-coded metallo-beta-lactamase 1 (VIM-1), Sao Paulo metallo-beta-lactamase 1 (SPM-1), and Temoniera (TEMs). Blood levels of interleukin-1β (IL-1β), interleukin-4 (IL-4), and interferon-γ (IFN-γ) were assessed by enzyme-linked immunosorbent assay.

RESULTSQGYD enhanced antibody reactivity against VIM-1 [epitopes 7-11 and 36-40] and TEM-1 [epitopes 26-27, 52-55, and 66-70]. QGYD treatment restored the compromised antibody reactivity against VIM-1 [epitopes 53-54 and 56-58] and SPM-1 [epitopes 16-19 and 82-85] following pseudomonal infection. Serum levels of IL-1β and Th1/Th2 in the rats were significantly elevated following pseudomonal infection (P<0.05 orP<0.01). In contrast, QGYD and combination QGYD and ceftazidime treatment restored the elevated serum IL-1β and Th1/Th2 levels to normal (P>0.05).

CONCLUSIONSQGYD improves the immune response to pseudomonal infection in rats by stimulating the production of protective antibodies against drug-resistant proteins VIM-1, SPM-1, and TEM-1. In addition, it protects the immune system and maintains immune responsiveness by restoring IL-1β and Th1/Th2 levels.

Animals ; Antibodies, Bacterial ; blood ; Drug Resistance, Multiple, Bacterial ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Interleukin-1beta ; blood ; Male ; Pseudomonas Infections ; drug therapy ; Pseudomonas aeruginosa ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; beta-Lactamases ; immunology

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

The trends and types of carbapenemase-producing Gram-negative bacilli were analyzed from clinical specimens collected between 2005 and 2012 at a Korean teaching hospital. The proportions of carbapenem-resistant Acinetobacter spp. increased markedly to 66%. Metallo-beta-lactamase producers significantly decreased and the majority shifted from the bla(VIM-2) type to the bla(IMP-1) type.
Acinetobacter/classification/drug effects/*enzymology ; Acinetobacter Infections/drug therapy ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins ; Carbapenems/*pharmacology ; Drug Resistance, Microbial ; Gram-Negative Bacteria/*drug effects/enzymology/isolation & purification ; Humans ; Incidence ; Microbial Sensitivity Tests/trends ; Population Surveillance ; Pseudomonas/classification/drug effects/enzymology ; Republic of Korea/epidemiology ; beta-Lactamases/biosynthesis/*drug effects

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

INTRODUCTIONPseudomonas aeruginosa (PA) bacteraemia is associated with high morbidity and mortality. We assessed clinical outcomes in patients with PA bacteraemia treated with piperacillin-tazobactam (TZP) versus other antibiotics, and monotherapy versus combination, all with proven activity by disc testing without minimum inhibitory concentration (MIC) data.

MATERIALS AND METHODSAll patients with PA bacteraemia in 2007 to 2008 were reviewed for demographic, comorbidity, clinical, laboratory, treatment and outcome data. Primary outcome was 30-day mortality. Secondary outcomes included microbiological clearance, clinical response and length of stay (LOS).

RESULTSMedian age for 91 patients was 65 years. Median Simplified Acute Physiology Score (SAPS) II score was 30. Monotherapy was used in 77 cases: 42 on ceftazidime, 17 on TZP, 10 on carbapenems, and 8 on other antipseudomonal antibiotics. The 30-day mortality was 20.9%, and similar between ceftazidime and TZP versus other antibiotics respectively. More patients in combination versus monotherapy group had cardiovascular diseases, diabetes mellitus and vascular access as source of bacteraemia. Patients on monotherapy had higher 30-day mortality (24.7% vs 0%, P = 0.037). Multivariate analysis identified SAPS II score (OR = 1.097, 95% CI, 1.032 to 1.166, P = 0.003) and cancer (OR = 4.873, 95% CI, 1.235 to 19.223, P = 0.024) as independent predictors of 30-day mortality.

CONCLUSIONTZP appeared to be an effective culture-guided antibiotic for PA bacteraemia. High 30-day mortality in monotherapy might be confounded by comorbidity, illness severity and sample size. Cancer patients and a high SAPS II score were independent predictors of 30-day mortality.

Aged ; Anti-Bacterial Agents ; therapeutic use ; Bacteremia ; drug therapy ; Ceftazidime ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Penicillanic Acid ; analogs & derivatives ; therapeutic use ; Piperacillin ; therapeutic use ; Pseudomonas Infections ; drug therapy ; Pseudomonas aeruginosa ; Retrospective Studies ; Treatment Outcome