The guidelines on calculated parenteral initial treatment of bacterial infections in adults from 2018 were the first German language S2k guidelines for these infections. This article summarizes the experiences with respect to their practicality in the clinical routine and the resulting supplementations and comments. In view of the many different terms for soft tissue infections, the guidelines had to first establish some definitions and diagnostic criteria. Among others, the guidelines introduced the provisional term limited phlegmons (phlegmons are usually termed cellulitis in Angloamerican literature) for the frequent initially superficial soft tissue infections with Staphylococcus aureus, which do not always extend to the fascia, in order to differentiate them from erysipelas caused by Streptoccocus, which in contrast to phlegmons always respond to penicillin. The general symptoms present in erysipela are a practical differential criterion. Somewhat more complex are the definitions and recommendations for the severe forms of phlegmon, which involve the fascia and are accompanied by necrosis, so that here the practicality of the guidelines needs to prove its worth over time. The guidelines also give recommendations how to proceed in case of alleged or confirmed hypersensitivity to beta-lactam antibiotics. Currently, relevant guidelines recommend, and it is correspondingly here elaborated, that in acute cases a beta-lactam antibiotic with side chains other than those in the suspected drug may present an alternative without prior testing. Therefore, cefazolin, that does not share any side chains with other beta-lactam antibiotics, could be administered under appropriate precautionary measures. The term cellulitis is avoided in the guidelines. Since it is used frequently, and also for non-infectious dermatoses, the various meanings are discussed and distinguished from each other.
UNASSIGNED: Die Leitlinie „Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen“ von 2018 ist die erste deutschsprachige S2k-Leitlinie für diese Infektionen gewesen. In diesem Beitrag werden Erfahrungen zu ihrer Praktikabilität im klinischen Alltag und daraus rührende Ergänzungen und Kommentare zusammengefasst. Angesichts vieler verschiedener Begriffe zu Weichgewebeinfektionen musste die Leitlinie sich zunächst auf einige Definitionen und diagnostische Kriterien festlegen. Unter anderem hat sie für die häufigen, noch nicht die Faszie einschließenden Weichgewebeinfektionen mit Staphylococcus aureus den provisorischen Begriff „begrenzte Phlegmone“ eingeführt, um sie von den eher Streptokokken-bedingten Erysipelen zu unterscheiden, die im Gegensatz zu Phlegmonen immer auf Penizillin ansprechen. Die bei Erysipelen vorliegenden Allgemeinsymptome sind ein praktikables Unterscheidungskriterium. Etwas komplexer sind die Definitionen und Empfehlungen bei den Formen der schweren oder komplizierten Phlegmone, die bis zur Faszie reichen und mit Nekrosen einhergehen, sodass sich die Praktikabilität der Leitlinie hier noch bewähren muss. Die Leitlinie gibt auch jeweils Alternativen für den Fall einer vermeintlichen Allergie auf Betalaktamantibiotika. Inzwischen wird in einschlägigen Leitlinien empfohlen und entsprechend hier ausgeführt, dass im Akutfall auch ohne vorherige Testung ein Betalaktamantibiotikum mit anderen Seitenketten als bei dem in Verdacht stehenden Präparat in der Regel möglich ist und dass deswegen Cefazolin, das mit den anderen Betalaktamantibiotika keine Seitenkette teilt, unter entsprechenden Vorsichtsmaßnahmen eingesetzt werden kann. In den Leitlinien wird der Begriff „Zellulitis“ umgangen. Da er aber häufig und auch für nicht erregerbedingte Dermatosen gebraucht wird, werden seine unterschiedlichen Bedeutungen hier gegeneinander abgegrenzt.

In the present narrative review, we discuss the characteristics and differences between the Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines in terms on their recommendations/suggestions for the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii infections.
Treatment of severe infections caused by nonfermenting gram-negative bacteria (NF-GNB) is posing both novel hopes and novel challenges to physicians worldwide, and both the IDSA and the ESCMID have recently updated/released their guidelines or guidance documents, based on different philosophies and providing recommendations for the treatment of NF-GNB infections. In order to correctly exploit recent advances in the treatment of such infections, IDSA and ESCMID approaches should be viewed as complementary and evolving, and should not preclude further revision based on accumulating evidence on the use of novel β-lactams and β-lactam/β-lactamase inhibitor combinations.
A joint consideration of both philosophies should leave the door opened for the wise use of novel agents, ultimately building precious experience on their use that could favorably influence future guidelines revisions.

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI β-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

METHODS: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery.
METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development.
CONCLUSIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

The study purpose was to assess adherence to a local surgical prophylaxis guideline in patients with reported penicillin allergies, which recommends cephalosporins as first-line prophylaxis.
Adult patients with penicillin allergies admitted for a surgical procedure from July 2020 to June 2021 were retrospectively screened, and the first surgery per admission was included. The primary outcome was the proportion of surgeries using β-lactam prophylaxis. Additional outcomes included prophylaxis timing, hypersensitivity reactions, acute kidney injury, infectious complications, duration of stay, and 30-day mortality or readmission.
Among 597 procedures, 504 patients (84.4%) received a β-lactam for surgical prophylaxis, including 494 (82.3%) who received a cephalosporin. Patients in the non-β-lactam group were more likely to have a type I IgE-mediated penicillin allergy (48.4% vs 31.7%, P = .002); however, the majority with type I reactions still received β-lactams (78.0%), including in the setting of anaphylaxis or angioedema to penicillin (67.7%). Zero allergic reactions to prophylaxis antibiotics were reported in either group, and there were no significant differences in the proportion of patients receiving drugs associated with the management of allergic reactions. Receipt of non-β-lactams was associated with inappropriate prophylaxis timing (9.7% vs 3.2%, P = .005) and postprocedural acute kidney injury (7.5% vs 0.6%, P < .001). All other outcomes were nonsignificant between the groups.
Among surgical patients with a documented penicillin allergy, most received cephalosporin prophylaxis as recommended by institutional guidelines, with zero allergic reactions. Receipt of non-β-lactam prophylaxis was associated with worsened outcomes. Cephalosporin prophylaxis should be preferred for surgical patients, including in the setting of true penicillin allergy.