Maraviroc in Antiretroviral-Naïve HIV-1 Patients

New antiretroviral agents that are better tolerated with less side effects and novel resistance patterns are needed at all lines of human immunodeficiency virus (HIV) therapeutic strategies. The CC-chemokine receptor 5 (CCR5) antagonist maraviroc is a member of the novel class of “antiretroviral agents” that prevents the entry of HIV-1 into host cells by blocking the CCR5 coreceptor. In the MERIT (Maraviroc versus Efavirenz in Treatment-Naïve Patients) study in antiretrovial-naïve patients aged ≥16 years with CCR5-tropic HIV-1 infection, maraviroc showed noninferiority to efavirenz for virological endpoints. Evidences from trials suggest that maraviroc is effective at reducing HIV-1 viral load in antiretroviral-experienced and -naïve patients with CCR5-tropic virus, as well as in those with CCR5-tropic virus who have developed HIV-1 resistance to existing antiretroviral regimens. Recent in vitro study demonstrated that maraviroc was also active against CCR5-tropic HIV-2 strains

In-Vitro Efficacy of Cefiderocol in Carbapenem-Non-Susceptible Gram-Negative Bacilli of Different Genotypes in Sub-Region of North Rhine Westphalia, Germany

In the last two decades, the worldwide dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) has continued. Therapy options for such infections caused by MDR-GNB remain scarce, and only few new antimicrobial agents have been granted market approval. Cefiderocol has been approved for the treatment of infections associated with aerobic GNB with limited therapy options. This study evaluated the in vitro efficacy of cefiderocol against carbapenem-non-susceptible clinical GNB isolates from Germany. A total of 115 non-duplicate carbapenem-nonsusceptible GNB isolates, 61 (53.05%) of which were Enterobacterales species and 54 (46.95%) were non-fermenters (Acinetobacter baumanii and Pseudomonas aeruginosa), were investigated for their cefiderocol susceptibility. Minimum inhibitory concentrations (MICs) for cefiderocol were determined by disk diffusion, according to EUCAST (European committee for antimicrobial susceptibility testing). Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/-dynamic breakpoints were used. The most common pathogen was A. baumannii (33.91%), followed by Klebsiella pneumoniae (31.3%), P. aeruginosa (13.04%) and Escherichia coli (9.57%). Overall, 83.6% (51/61) of the Enterobacterales and 81.48% (44/54) of the non-fermenters were susceptible towards cefiderocol. In total, 20 species of Enterobacterales and non-fermenting GNB were resistant towards cefiderocol, irrespective of the isolation year (2014 to 2021). Moreover, the majority of the resistant isolates were among the OXA-23 producing A. baumannii (n = 7/26; 26.92%) from patients hospitalized during 2018 and 2019. Cefiderocol demonstrated high in vitro susceptibility rates against a wide range of carbapenem-non-susceptible GNB, including carbapenemase-producing isolates. Cefiderocol exhibited stability against hydrolysis by all carbapenemases, including metallo-β-lactamases (MBLs), except that few OXA-producing isolates exhibited resistance towards cefiderocol

Antibiotic Resistance of Pseudomonas aeruginosa in Pneumonia at a Single University Hospital Center in Germany over a 10-Year Period.

Pseudomonas aeruginosa is a common cause of community-acquired and nosocomial-acquired pneumonia. The development of resistance of P. aeruginosa to antibiotics is increasing globally due to the overuse of antibiotics. This article examines, retrospectively, the antibiotic resistance in patients with community-acquired versus nosocomial-acquired pneumonia caused by P. aeruginosa or multidrug-resistant (MDR) P. aeruginosa.Data from patients with community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa and MDR P. aeruginosa were collected from the hospital charts at the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, between January 2004 and August 2014. An antibiogram was created from all study patients with community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa or MDR P. aeruginosa.A total of 168 patients with mean age 68.1 ± 12.8 (113 [67.3% males and 55 [32.7%] females) were identified; 91 (54.2%) had community-acquired and 77 (45.8%) had nosocomial-acquired pneumonia caused by P. aeruginosa. Patients with community-acquired versus nosocomial-acquired pneumonia had a mean age of 66.4 ± 13.8 vs. 70.1 ± 11.4 years [59 vs. 54 (64.8% vs. 70.1%) males and 32 vs. 23 (35.2% vs. 29.9%) females]. They included 41 (24.4%) patients with pneumonia due to MDR P. aeruginosa: 27 (65.9%) community-acquired and 14 (34.1%) nosocomial-acquired cases. P. aeruginosa and MDR P. aeruginosa showed a very high resistance to fosfomycin (community-acquired vs. nosocomial-acquired) (81.0% vs. 84.2%; 0 vs. 85.7%). A similar resistance pattern was seen with ciprofloxacin (35.2% vs. 24.0%; 70.4% vs. 61.5%), levofloxacin (34.6% vs. 24.5%; 66.7% vs. 64.3%), ceftazidime (15.9% vs. 30.9; 33.3% vs. 61.5%), piperacillin (24.2% vs. 29.9%; 44.4% vs. 57.1%), imipenem (28.6% vs. 27.3%; 55.6% vs. 50.0%), piperacillin and tazobactam (23.1% vs. 28.6%; 44.4% vs. 50.0%), tobramycin (28.0% vs. 17.2%; 52.0% vs. 27.3%), gentamicin (26.4% vs. 18.2%; 44.4% vs. 21.4%), and meropenem (20.2% vs. 20.3%; 42.3% vs. 50.0%). An elevated resistance of P. aeruginosa and MDR P. aeruginosa was found for cefepime (11.1% vs. 23.3%; 25.9% vs. 50.0%), and amikacin (10.2% vs. 9.1%; 27.3% vs. 9.1%). Neither pathogen was resistant to colistin (P = 0.574).While P. aeruginosa and MDR P. aeruginosa were resistant to a variety of commonly used antibiotics, they were not resistant to colistin in the few isolates recovered from patients with pneumonia

Drug sensitivity and drug resistance in different drug groups of patients with community-acquired compared to nosocomial-acquired pneumonia caused by multidrug-resistant <i>Pseudomonas aeruginosa</i>.

<p><b>Abbreviations:</b> CAP: community-acquired pneumonia; NAP: nosocomial-acquired pneumonia; MDR Pseudomonas: multidrug resistant <i>Pseudomonas</i>. <b>Note:</b> Significant <i>P</i> values are shown in bold.</p

Rate of development of antibiotic resistance over time for pneumonia due to <i>Pseudomonas aeruginosa</i> from 2004 to 2014.

<p>Rate of development of antibiotic resistance over time for pneumonia due to <i>Pseudomonas aeruginosa</i> from 2004 to 2014.</p

Drug sensitivity and drug resistance in different drug groups of patients with community-acquired compared to nosocomial-acquired pneumonia caused by <i>Pseudomonas aeruginosa</i> with MIC₅₀ and MIC₉₀ breakpoints of each antibiotic.

<p><b>Abbreviation</b>: CAP: community-acquired pneumonia; NAP: nosocomial-acquired pneumonia; MIC: minimum inhibitory concentration. <b>Note:</b> Significant <i>P</i> values are shown in bold.</p

Comparison of demographic data, length of hospitalization, and laboratory tests between patients with community-acquired and nosocomial-acquired pneumonia due to <i>Pseudomonas aeruginosa</i>.

<p><b>Abbreviations:</b> CRP: C-reactive protein; SD: standard deviation.</p

Comparison of demographic data, length of hospitalization, laboratory tests, specimens, and acute and chronic comorbidities between patients with community-acquired and nosocomial-acquired pneumonia due to multidrug-resistant <i>Pseudomonas aeruginosa</i>.

<p><b>Abbreviations:</b> CAP: community-acquired pneumonia; NAP: nosocomial-acquired pneumonia; SD: standard deviation.</p

Comparison of the susceptibility of antibiotics against isolates extracted from blood cultures with those from tracheal and bronchial sputum secretions and throat swabs in patients with pneumonia caused by <i>S</i>. <i>aureus</i> and MRSA.

<p><b>Abbreviations:</b> MRSA: methicillin-resistant <i>Staphylococcus aureus</i>, CI: confidence interval. <b>Note:</b> Statistically significant <i>P</i> values are shown in bold.</p><p>Comparison of the susceptibility of antibiotics against isolates extracted from blood cultures with those from tracheal and bronchial sputum secretions and throat swabs in patients with pneumonia caused by <i>S</i>. <i>aureus</i> and MRSA.</p

Acute and chronic comorbidities of patients with pneumonia caused by <i>S</i>. <i>aureus</i> compared to MRSA.

<p><b>Abbreviations:</b> MRSA: methicillin-resistant <i>Staphylococcus aureus</i>. <b>Note:</b> Statistically significant <i>P</i> values are shown in bold.</p><p>Comorbidities were only considered if they were more than 10% in one of the groups even if they were less than 10% in the other group.</p